Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

On June 29, 626, a joint assault on the walls of Constantinople by the Allied forces began.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

At that time, there were about twelve thousand well-trained Byzantine cavalrymen (presumably dismounted) in the city, defending the city from the 80,000-strong army of Avars and Slavs [99].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Despite the constant bombing for a month, the morale of the Greeks remained high due to the religious zeal of Patriarch Sergius and his processions along the city walls with the icon of the Virgin, which convinced Byzantines that the city is under divine protection [138] [139].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

On August 7, the Persian army attempted to raft across the Bosphorus, but was surrounded and destroyed by Byzantine ships.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Slavs under the command of the Avars tried to attack the walls off the coast of Zolotoy Rog Bay, and the main troops of the Avar Khagan attacked from the land [140].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Then galleys under the command of Patrick Bon rammed and destroyed Slavic boats; the Avar attack from land (August 6-7) also failed [141].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Having received the news that Irakli's brother Theodore won a decisive victory over Shahin (presumably after that Shahin died, unable to withstand a crushing defeat), the Avars retreated deep within two days The Balkan Peninsula and never again seriously threatened Constantinople [142].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Although Shahrvaraz's army was still encamped in Chalcedon, the threat to the capital passed [137] [143].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In gratitude for the lifting of the siege and the patronage of the Most Holy Theotokos, an unknown author (possibly Patriarch Sergius or George Pisida) wrote the famous akathist [144] [145] [146].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Byzantine-Turkic Union


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

While the Avars and Slavs besieged Constantinople, Irakli made an alliance with Zievil, who ruled a people whom Byzantine sources call Turks or Khazars [147].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Most likely, the Khazars made up the bulk of the army, and Zievil was the Khagan of the Western Turkic Khaganate Tun-Jabgu Khan, whom the Byzantines persuaded to make peace in exchange for the fact that porphyrogenite will marry him [148].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Earlier in 568, the Turks, under the command of Yabgu Istemi Kagan, established relations with Byzantium when their relations with Persia deteriorated due to trade disagreements [149].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In 626, Turks based in the Caucasus sent forty thousand soldiers to ruin Persia, which marked the beginning [99].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Under the walls of Tiflis, they met with the army of the emperor, which came from Lazika [19].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The combined forces began to besiege Tiflis.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Byzantines used trebuchets to destroy walls; this was the first use by the Greeks of such siege weapons [150].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Then Khosrov sent a thousand horsemen under the command of Shahraplakan to strengthen the city [151], but this detachment was defeated, probably at the end of 628 [152].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Zievil died at the end of the same year, thereby saving Epiphany from the need to marry a barbarian [99].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Despite the fact that the siege continued, Irakli was also engaged in strengthening the base on the Upper Tigre [137].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Battle of Nineveh


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In mid-September 627, leaving Zievil to continue the siege of Tiflis, Irakli went with the army to the south, to the Dvin and further, to the ancestral Persian lands [19].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Edward Luttwak describes Heraclius's retreat during the winters of 624-626 and the unexpected campaign to Ctesiphon in 627 as “a big risk regarding the entire theater of operations”, because these maneuvers taught the Persians to strategically ineffective raids, which forced them to abandon the transfer of border troops to defend the central regions [153].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Byzantine army numbered from 25 to 50 thousand people, not counting reinforcements from 40 thousand Khazars, who quickly left the emperor due to unfamiliar natural conditions and constant persecution by Persians [154] [155].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Irakli advanced very quickly, but was tracked down by the Persian army under the command of an Armenian, which faced difficulties in supplying — the Byzantines devastated the entire neighborhood as they moved south to Assyria [156] [157].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

After that, the enemy troops began to maneuver; in the end, Rahzad perceived the movements of the Byzantines as a retreat and began to pursue [19].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

As a result, the Persian commander lost time, thereby allowing Irakli to bypass his army [19].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Seeing that the emperor was going to Ctesiphon, the Persians rushed in pursuit and, after a difficult march, still caught up with the Greeks at the ruins of the ancient city of Nineveh [19].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Irakli decided to fight the Persians before reinforcements approached them [158].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The battle of Nineveh took place in heavy fog, thereby reducing the Persian advantage of the presence of horse archers.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Irakli depicted a retreat, luring the Persians to the plains, and, to their great surprise, quickly deployed his troops into battle formation [159].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

After an eight-hour battle, the Iranians suddenly retreated to the nearby foothills, but did not flee [160].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

During the battle, approximately 6,000 Persians were killed [161].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Patriarch Nikephoros's “Brief History” reports that Rahzad challenged Irakli himself during the battle, and the emperor accepted the challenge and killed Rahzad on the first strike; two other opponents attacked him and also were defeated [162].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Irakli himself was wounded with a “spear in the lip” [163].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

According to Sebeos, after the battle, the emperor released all prisoners [164].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The end of war


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Persian army no longer existed.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Nothing could stop Irakli on his way to Ctesiphon.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Shahrbaraz and his own forces were returning too slowly from Asia Minor; the armies of Shahin and Rahzad were defeated and suffered serious losses.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Therefore, the remnants of the army of the deceased Rahzad withdrew to the capital to protect it from the Byzantines [19].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In January 628, Irakli crossed the Torna River and devastated the royal palaces of Beklal and Bebdah [163].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Then he looted the residence of Khosrov II Parviz — [165], where “three hundred Roman banners taken at different times were found, as well as stocks of rare works, lots of aloe and large aloe trees in eighteen liters, a lot of silk, pepper, shirt fabrics in excess of any number, sugar, ginger and many other things, found unfinished silver, silk clothes, bed carpets and colored carpets sewn, beautiful and in a great multitude”, but most of the prey was burned [163].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Khosrov had already fled to the Suziana Mountains to try to gather troops to protect Ctesiphon [137].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Then the emperor sent the following letter to the Persian king:


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Nevertheless, Irakli could not attack Ctesiphon, as the bridges over, located twenty kilometers from the capital, were destroyed, and on the other side stood the palace guard of the Persian king [165].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Bypassing or crossing the canal seemed extremely difficult maneuvers [166].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Therefore, the emperor decided to retreat to the north, ruining Persian villages on the way [19].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

On March 11, 628, the Byzantines entered Hansac [19].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

At this time, the Persian army rebelled and overthrew Khosrov II, proclaiming his son Kavad II, also known as Shiruye, king.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Khosrov was thrown into prison, where he was starved to death for five days, after which he was shot by archers [167].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The new ruler of Kavad sent an embassy to Irakli with a request for peace.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The emperor did not put forward strict demands, knowing that his own empire was also close to exhaustion.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Under the terms of the peace treaty, the border between the two states was restored as of 602, all prisoners were extradited to Byzantium, an indemnity was paid, and most importantly, the Life-Giving Cross was returned and other relics lost in Jerusalem in 614 [168] [169] [170].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

On April 8, 628, Irakli went from Hanzak to Armenia [117].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The route of the emperor's return journey from Armenia to Byzantium is unknown for sure, since sources practically do not mention it [171].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

However, it is known that Irakli went from Armenia to Upper Mesopotamia, where, in honor of his arrival in Amida, he founded a large temple (this happened in the winter of 628-629) [171].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The consequences


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Short-term effects


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

After several months of travel, Irakli triumphantly entered Constantinople.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

He was greeted by the residents of the city, his son Konstantin Irakli and Patriarch Sergius, who fell to their knees before him with joy [172].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Thanks to the alliance with the Persians, the Holy Sponge attached to the Life-Giving Cross was returned to the empire during a magnificent ceremony on September 14, 629 [173].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In the capital, a solemn parade, held on the occasion of the return of Irakli, went to Hagia Sophia.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

There, the Life-Giving Cross was slowly erected above the main altar.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

For many, this was a sign that a new golden age had begun for the Byzantine Empire [168] [174].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The victorious end of the war strengthened Irakli's commanding authority.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

He was nicknamed the “new Scipio” for his brilliant victories and for leading the Byzantine army to lands that the soldiers of the empire had never invaded before [91].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The triumphal rise of the Life-Giving Cross in Hagia Sophia was the culmination of the emperor's achievements.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

If Irakli had died in 629, according to Norman Davis, he would have gone down in history as “the greatest Roman military leader since Julius Caesar” [91].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

However, he lived to see the era of Arab conquest, lost a number of major battles, unsuccessfully trying to contain the onslaught of Muslims, and lost the fame of a successful military leader.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

John Norwich briefly described Irakli as “living too long” [175].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Meanwhile, the Sassanids struggled to create a stable and sustainable government.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

When Cavad II died a few months after assuming the throne, Persia was plunged into a civil war for several years caused by dynastic disputes.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In a short period from 628 to the winter of 632-633, four rulers changed on the Persian throne: Artashir III, commander Farrukhan Shahrvaraz who fought with Byzantium, two queens Borandokht and Azarmedokht.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

It was only when Yazdigerd III, grandson of Khosrov II, ascended the throne in 632 that some stability was established, but by that time it was too late to do anything to save the once powerful The Sassanid power, which soon collapsed under the blows of Muslim Arabs [176] [177].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Long term effects


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The war of 602-628 caused great damage to both empires due to its devastation and continuity.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Sassanids were also weakened by a decline in economic activity, heavy taxation to finance Khosrov II's campaigns, religious unrest and the growing influence of provincial landowners for Shah's score [178].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

According to, the victories over the Persians and their political consequences saved the main stronghold of Christianity in the Middle East and significantly weakened Zoroastrianism, but in the next two decades they turned out to be marred by the military achievements of the Arabs [179].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Nevertheless, the Byzantine possessions in the Balkans suffered greatly from the invasion of the Slavs, who conquered a significant part of this area [180].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In addition, Anatolia was devastated by numerous Persian raids, and the recently returned territories in the Caucasus, Syria, Mesopotamia, Palestine and Egypt have been weakened by years of Persian occupation [181 ].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Because of this, the Byzantines faced difficulties in paying for the service of veterans of the war with the Persians and recruiting new soldiers [24] [182].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Clive Foss called this war “the first stage in a process that marked the end of antiquity in Asia Minor” [183].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

None of the two empires was able to regain their former power due to the consequences of the war, as for several years they were seriously shocked by the onslaught of Arabs united by a single religion, Islam [184]; Howard-Johnston compared this invasion to a “human tsunami” [185].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

According to George Liski, “the excessively long Byzantine-Persian conflict has opened the way for Islam” [186].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Sassanid Empire was quickly defeated by the Arabs and was conquered by them.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

As a result of the Arab-Byzantine wars, the eastern and southern regions of Byzantium, recaptured from the Persians, were forever lost, and the area of the empire was reduced to a piece consisting of Anatolia, part of the Balkans, Italy and island groups [187].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

However, unlike Persia, Byzantium eventually survived Arab attacks, retained the remnants of its possessions and repelled two Arab sieges of the capital in 674—678 and 717—718 [188] [189].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Byzantine Empire also lost territories in Crete and southern Italy in later conflicts with the Arabs, although they were eventually returned [190].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Troop composition and strategy


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The elite of the Persian army was the Savaran cavalry [191].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Most likely, the main weapon of these cavalrymen was a long spear capable of piercing two people at the same time [192].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The horses were protected from enemy arrows by plate armor [193].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Another trump card of the Persians were the riflemen units.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Sassanid archers could aim from a distance of 175 meters and kill with an accurate shot from a distance of 50-60 meters [194].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

According to the Strategicon (warfare manual) of the Emperor of Mauritius, the Persians often used archers during battles and therefore avoided fighting in weather that prevented archery [ 195].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Mauritius also claims in its leadership that the Persians were built in such a way that the forces of the center and flanks were equal.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

They also seemed to avoid being attacked by Roman spearmen on rough terrain, as archers tried not to engage in hand-to-hand combat [196].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Thus, the Strategicon advised to fight the Iranians on flat terrain and attack quickly in order to avoid large losses from the shooting of Persian archers [196].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In addition, the Persians were considered masters of siege and achieved serious results with skillful leadership and careful planning [196].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The most important component of the Byzantine army was heavy cavalry — cataphractaries that became a symbol of Byzantium [197].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

They wore chain mail, engaged in battle on armored horses and used spears as their main weapon.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Cataphractaries were also armed with a small shield that was attached to the hand, and could also use swords, axes or bows [198].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The equipment of heavy Byzantine infantrymen (skutats) consisted of a large oval shield (scutum) and lamellar armor.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Scutats used spears against enemy cavalry to kill horsemen, and axes to injure horses [199].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Light Byzantine infantry (psyls) primarily used bows and wore only leather armor [200].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Byzantine infantry played a key role in strengthening the front line against enemy cavalry, and also served to support cavalry attacks.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

According to him, the heavy infantry of the empire “combined the best abilities of the Roman Legion with the old Greek phalanx” [201].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Avar army consisted of heavily armed archers and heavy cavalry fighting with spears.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Avars were skilled at siege and knew how to build trebuchets and siege towers.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

During the siege of Constantinople, they erected protective ramparts to prevent a counterattack and used large shields covered with animal skins to protect against archers.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In addition, like many nomads, the Avars used soldiers from subordinate peoples, such as the Gepids and Slavs, to support soldiers [202].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

But since the Avars depended on raids on the countryside for forage, they could not besiege cities for long, especially considering that their allies were less mobile [203].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

According to Kedzhi, the Byzantines had an almost obsessive desire to avoid changing essential elements of the status quo [204].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

They tried by all diplomatic means to find allies and divide enemies.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Although they failed in an attempt to prevent the unification of the Avars and Persians, their ties with the Slavs, who later became Serbs and Croats, and long negotiations with the Turks led to Slavic speeches against the Avar rule and the Empire's alliance with the Turks [205].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Logistics has always been a problem for Byzantines.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In his campaign on Byzantine territory, especially in Anatolia, Irakli most likely obtained food for his army by seizing it from the local population [206].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

During Heraclius's offensive campaigns against Persia, harsh winters each time forced him to abandon distant crossings, partly because both the Byzantine and Persian cavalry needed food for horses, which were kept in winter apartments [207].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Irakli feared forcing his troops to conduct campaigns in winter, since his closest predecessor Mauritius was overthrown precisely because of mistreatment of the army in winter [208].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Edward Luttwak believes that the Turks, with their hardy horses or ponies, which could survive in almost any terrain, played an important role in Heraclius's winter campaigns in hilly northwestern Persia in 627 [209].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

During campaigns on Persian lands, the Byzantines obtained food by robbery [210] [211].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

After the victory at Nineveh and the capture of the royal palace, the imperial army did not experience problems with supplying troops on foreign territory and in winter conditions [212]


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Historical sources


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The sources that report this war are mostly of Byzantine origin.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

First of all, among the modern events of Greek texts, it should be noted the Easter Chronicle, created by an unknown author around 630 [213] [214].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Giorgi Pisida wrote many poems and other works describing the events of the war.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Theophylact Simocatta is known as the author of many letters and History, which gives an idea of the political views of the Byzantines, but it covers only the period from 582 to 602 [215] [216].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Theodore Sinkell has preserved some speeches composed during the siege of Constantinople in 626 and containing useful information for studying some events.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Some Egyptian papyri of that time have also survived to us [215].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Persian archives have been lost, so there are no Persian sources modern to this war [51].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Non-Greek modern war sources include the Chronicle of John of Nikussky, which was written in Coptic, but survived only in Ethiopian translation.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

There are also some Syrian chronicles of the period, which Dogeon, Greytex and Lew call the most important sources of modern war [216] [217].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Among them, it is worth noting the “Chronicle of the Year 724", compiled in 640.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Guidi's Chronicle, or Khuzestan Chronicle, tells about the life of Nestorians in the Sassanid Empire [216].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Later Greek sources include The Chronicle by Theophanes the Confessor and A Brief History by Patriarch Nikephoros I.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The chronicle of Theophanes is very useful in recreating the course of the entire war [218].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

It is also usually supplemented by even later Syrian sources, such as the 1234 Chronicle and The Chronicle of Michael the Syrian [216].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

However, information from all these works, with the exception of Nikephoros's Brief History and the Book of Titles by the Christian-Arab historian Agapy of Manbij (Hierapolis), was drawn from a general source, from works by the historian of the VIII century Theophilos of Edessa [216] [219].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

From Armenian sources, the “History of Emperor Iraq” of the 7th century is known, attributed to Sebeos (there are disagreements about authorship).


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

This “History” is an Armenian compilation of various documents arranged in rough chronological order.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Because of this, the war is unevenly covered.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

In addition, this work was written, apparently, with the aim of correlating biblical prophecies and events that are modern to the author, but this is only an assumption [220].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The author of the work “History of the Artsruni House”, Tovma Artsruni, probably used sources similar to those used by Sebeos.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Another Armenian historian, Movses Kagankatvatsi, who wrote “The History of the Country of Aluank” in the 10th century, turned to unknown works, modern war [221].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Howard-Johnston considers the stories of Movses and Sebeos to be the most important surviving non-Muslim sources [222].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The History of Patriarch Eutychius of Alexandria, written in Arabic, contains many errors, but this work can still be used.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Quran also contains some details related to the conflict, but they should only be taken very carefully [219].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The 9th century Arab historian Al-Tabari, author of the book “” (“History of Prophets and Kings”), written on the basis of lost materials, described in it the history of the Sassanid state [223].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Byzantine lives of Saints Theodore of Sikeon and Anastasia Persiyanina are quite useful for studying the events of the war [219].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Life of George Khozevit gives an idea of the panic during the siege of Jerusalem [224].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

However, there are some suspicions that the texts of his life may have been distorted by corrections of the VIII or IX century [225].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Numismatics are useful for dating some events [226].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Sigillography, or the study of seals, is also used for this purpose.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Art and archaeological finds can also serve as grounds for reconstructing the course of the war.


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Epigraphic sources or inscriptions are of limited use [227].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

The Strategicon of the Emperor of Mauritius, which Edward Luttwak called “the most complete Byzantine field leadership” [228], contains valuable information about the military thought and customs of the time [229].


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Notes


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Literature


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

CS1 maint: multiple names: authors list (link)


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Cite journal requires |journal= (help) CS1 maint: date and year (link)


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

CS1 maint: multiple names: authors list (link) Template:Unavailable link


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

References


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

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Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Category:Byzantine Wars


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Category:Wars of the Sassanid State


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Category:7th-century wars


Question: At what age did Khosrov II Parviz become the ruler of Iran?

Iran—Byzantine War (602—628)

Category:Roman-Persian Wars


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute myeloid leukemia (also AML, acute non-lymphoblastic leukemia, acute myelogenous leukemia) is a malignant tumor of the myeloid blood germ in which altered white ones multiply rapidly blood cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

By accumulating in the bone marrow, they inhibit the growth of normal blood cells, which leads to a decrease in the number of red blood cells, platelets, and normal white blood cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The disease is manifested by fatigue, shortness of breath, frequent minor skin lesions, increased bleeding, frequent infectious lesions.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The clear cause of the disease is still unknown, but some risk factors have been identified.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

AML is an acute disease that develops rapidly and without treatment leads to the death of the patient in a few months, sometimes weeks.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

This is the most common type of acute leukemia in adults, and its incidence increases with age.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Although acute myeloid leukemia is a relatively rare disease, accounting for only 1.2% of malignant deaths in the US [1], it is expected to increase with aging of the population.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

There are several types of AML, the treatment and prognosis for them are different.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The survival rate for five years ranges between 15% and 70%, and the remission rate ranges from 78% to 33%, depending on the subspecies of the disease.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

At the beginning, AML is treated with chemotherapy drugs in order to achieve remission; then supportive chemotherapy may be performed, or hematopoietic stem cell transplantation is performed.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Grading


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The most commonly used AML classification schemes are the long-standing Franco-American-British (FAB) system and the more modern system of the World Health Organization (WHO).


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

World Health System Classification of Acute Myeloid Leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The WHO classification system for acute myeloid leukemia is developed taking into account the FAB system and is aimed at more effective clinical use and takes into account the most prognostically significant signs diseases.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Each of the types (categories) of AML according to the WHO classification includes several subspecies (subcategories) of a descriptive nature of interest to hematologists and oncologists; however, most clinically important information in the WHO classification is linked through distribution to the following subspecies.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

WHO subspecies of acute myeloid leukemia: [2]


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

There are subspecies of acute leukemia in which altered white blood cells cannot be defined as lymphocytes or granulocytes, or when malignant cells of both germs are present.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Such leukemia is sometimes referred to as biphenotype acute leukemia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Franco-American-British Classification


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The Franco-American-British Classification (FAB) system divides AML into 9 subspecies, from M0 to M8, based on the types of cells that are precursors of leukocytes, and the degree of maturity of the altered cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Determination of malignant cells is carried out on the basis of external signs by light microscopy and/or cytogenetically, revealing underlying changes in chromosomes.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Different AML subspecies have different prognosis and response to treatment.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Despite the advantages of the WHO classification, the FAB system is still widely used.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

According to FAB, there are nine subtypes of AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Unusual phenotypes of acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The morphological subtypes of AML include many extremely rare subtypes not included in the FAB classification.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

All of them, with the exception of acute myeloid dendritic cell leukemia, are included in the WHO classification.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

These subtypes are listed below.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute basophilic leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute eosinophilic leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute mast cell leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute myeloid dendritic cell leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute panmyelosis with myelofibrosis


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Myeloid sarcoma.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute myeloid leukemia manifestations


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Most of the symptoms of AML are caused by the replacement of normal blood cells by leukemia cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Insufficient formation of white blood cells causes a high susceptibility of the patient to infections - despite the fact that leukemic cells come from leukocyte precursors, the ability they do not have to resist infections.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[3] Decreased red blood cell count (anemia) can cause fatigue, pallor, and shortness of breath.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

A lack of platelets can lead to mild skin damage and increased bleeding.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Early signs of AML are often vague and non-specific, and may be similar to those of influenza or other common diseases.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Some common symptoms of AML are fever, fatigue, weight loss or decreased appetite, shortness of breath, anemia, increased damage to the skin and mucous membranes and bleeding, petechiae (flat, the size of pinhead spots inside the skin at the site of hemorrhages), hematomas, bone and joint pain, and persistent or frequent infections.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

With AML, there may be an enlargement of the spleen, but it is usually minor and asymptomatic.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Lymph node enlargement in AML occurs infrequently, unlike acute lymphoblastic leukemia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In 10% of cases, skin changes develop in the form of cutaneous leukemia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Occasionally, with AML, Sweet Syndrome occurs, which is also a paraneoplastic syndrome - inflammation of the skin around chloroma-affected areas.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Some AML patients develop swelling of the gums due to tissue infiltration by leukemia cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Occasionally, the first sign of leukemia is chloroma, a dense leukemic mass outside the bone marrow.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Sometimes the disease is asymptomatic, and leukemia is detected by a general blood test during a preventive examination.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The reasons


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

A number of factors were identified that contribute to the occurrence of AML — other disorders of the hematopoietic system, exposure to harmful substances, ionizing radiation, and genetic effects.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Pre-leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

“Pre-leukemia disorders of hematopoiesis, such as myelodysplastic syndrome or myeloproliferative syndrome, can lead to AML; the likelihood of disease depends on the form of myelodysplastic or myeloproliferative syndrome.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Exposure to chemicals


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Antitumor chemotherapeutic effects, especially alkylating substances, can increase the likelihood of AML in the future.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The highest chance of getting sick is 3-5 years after chemotherapy.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[6] Other chemotherapeutic drugs, especially epipodophylotoxins and anthracyclines, also bind to post-chemotherapeutic leukemia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

leukemia of this type is often explained by specific changes in the chromosomes of leukemia cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Occupational exposure to benzene and other aromatic organic solvents as a possible cause of AML remains controversial.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Benzene and many of its derivatives show carcinogenic properties in vitro.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Some observations confirm the possibility of occupational contact with these substances affecting the likelihood of developing AML, but other studies confirm that if there is such danger, it is only an added factor.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[8] [9]


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Ionizing radiation


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Exposure to ionizing radiation increases the likelihood of developing AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Hiroshima and Nagasaki atomic bomb survivors have an increased incidence of AML, [10] as well as radiologists who received high doses of X-rays at a time when radiological protection was insufficient.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Genetic factors


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

There is probably a hereditary increased likelihood of having AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

There are a large number of reports of many familial cases of AML, where the incidence was above the average.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[12] [13] [14] [15] The likelihood of developing AML in a patient's next of kin is three times higher.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

A number of congenital conditions can increase the likelihood of AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Most often, this is Down syndrome, in which the probability of AML is increased by 10 to 18 times.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Diagnostics


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Changes in the ratio of cellular elements in a general blood test are the first thing that suggests the possibility of AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The most common is leukocytosis, an increase in the total number of leukocytes, sometimes with the appearance of blast (immature) forms, but it happens that AML manifests itself as an isolated decrease in platelets, red blood cells, and the number of white blood cells may even be reduced (leukopenia).


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[18] A preliminary diagnosis of AML can be determined if blast forms of leukocytes are detected in peripheral blood smears, but appropriate changes in the analysis of bone marrow aspiration biopsy specimen.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Bone marrow and blood are examined by light microscopy and flow cytometry to diagnose and differentiate AML from other leukemia, for example, from acute lymphoblastic leukemia, and to clarify the AML subtype.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

A blood or bone marrow sample is usually tested for the presence of chromosomal translocations using conventional cytogenenitic methods, or by fluorescent hybridization in situ.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Genetic studies are also carried out to identify characteristic mutations that can affect the outcome of the disease — for example, in FLT3, nucleoplasmin, or KIT.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Cytochemical dyes for blood and bone marrow smears are very useful for the differential diagnosis of AML and ALL, as well as for the isolation of AML subtypes.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The combination of myeloperoxidase or Sudanese black dye and non-specific esterase dye provides the necessary information in most cases.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Myeloperoxidase or Sudanese black reactions are most useful for diagnosing AML and differentiating it from ALL.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Nonspecific esterase dye is used for monocytarone component of acute myeloid leukemia and for differentiation from the immature form of monoblastic leukemia from ALL.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The diagnosis and classification of AML can be a difficult task, this should be done by a qualified hematopathologist or hematologist.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In obvious cases, the presence of some characteristic morphological features, such as Auer bodies, or AML-specific results of flow cytometry make it possible to reliably separate AML from others leukemia; however, in the absence of such obvious signs, the diagnosis is significantly complicated.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In accordance with widely used WHO classification criteria, the diagnosis of AML is established if it is proved that more than 20% of cells in the blood and/or bone marrow are myeloblasts.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[21] AML should be carefully differentiated from so-called preleukemia conditions, in particular myelodysplastic syndrome or myeloproliferative syndrome, which are treated differently.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Since acute promyelocytic leukemia (OPL), requiring a unique treatment, responds very well to it, it is very important to quickly confirm or reject this subspecies of leukemia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

For this purpose, fluorescent hybridization in situ performed on blood or bone marrow is often used, since it easily detects chromosomal translocation (t [15; 17]) specific for OPL.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Pathophysiology


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Malignant cells in AML are myeloblasts.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In normal hematopoiesis, myeloblasts are immature precursors to myeloid leukocytes; normal myeloblasts gradually mature to become normal white blood cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

However, with AML, genetic changes accumulate in some of the myeloblasts, which “freeze” the cell in an immature state, stopping the process of cellular differentiation.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

By itself, this mutation does not cause leukemia, but when the “differentiation stop” is combined with other mutations that lead to the loss of genetic control over cell growth, the result there is an uncontrollable reproduction of an immature cell clone that determines the clinical essence of AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The great diversity and genetic heterogeneity of AML is due to the fact that leukemia transformation can occur at many stages of cell differentiation.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[25] Modern AML classification schemes recognize the dependence of the properties and behavior of leukemia cells, as well as the course of leukemia, on the stage at which differentiation stopped.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Specific cytogenetic abnormalities are found in many patients with AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The types of chromosome changes are often prognostically significant.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[26] Chromosomal translocations encode the synthesis of hybrid proteins, most often transcription factors — auxiliary proteins — assistants to RNA polymerases, the altered properties of which can lead to a halt differentiation.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[27] For example, in acute promyelocytic leukemia, translocation t (15; 17) causes the synthesis of the hybrid protein PML-RARα, which binds to the retinoic acid receptor in promoters of some genes specific for myeloid cells and stops differentiation in these cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The clinical manifestations and symptoms of AML occur because, as leukemia clone cells multiply, interfere with the activity of normal cells and tend to displace them from the bone marrow.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[29] This leads to neutropenia, anemia, and thrombocytopenia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Most often, the symptoms of AML are determined by a deficiency in normal blood cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In rare cases, patients develop chloromas, dense tumors from leukemia cells behind bone marrow fractures, which can cause various symptoms depending on the location of the chloroma.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Treatments


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The treatment of AML consists mainly of chemotherapy, and is divided into two stages: induction and postression treatment (or consolidation).


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The goal of induction therapy is to achieve complete remission by reducing the number of leukemia cells to an undetectable level; the goal of consolidating therapy is to eliminate residual, not detected by modern methods by remnants of the disease and cure.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Induction


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

For all AML subtypes, with the exception of FAB M3, induction chemotherapy with cytarabine and an anthracycline antibiotic (for example, daunorubicin or idarubicin) is usually used.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[31] This method of induction chemotherapy is known as “7+3”.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The name comes from the fact that this regimen provides for 7 days of continuous infusion of cytarabine, while in the first three days, an anthracycline antibiotic is simultaneously bolus administered.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

With this method of treatment, remission occurs in almost 70% of patients with AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[32] Other methods of induction treatment may be used, including FLAG, DAT, ADE regimens and the like, or monotherapy with high doses of cytarabine, or treatment with drugs that are at the stage research.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[33] [34] Due to the toxic effects of treatment, including suppression of myeloid germ and increased likelihood of infectious complications in very old patients, induction chemotherapy does not less intensive palliative treatment with chemotherapy drugs is proposed and prescribed.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

A subspecies of AML M3, also known as acute promyelocytic leukemia, is almost always treated with PTRK (fully transretinoic acid) in addition to induction therapy.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[35] [36] [37] In the treatment of acute promyelocytic leukemia, it is necessary to take into account the possibility of developing disseminated intravascular coagulation syndrome due to the intake of granule contents promyelocytes into peripheral blood.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The treatment of acute promyelocytic leukemia is extremely effective and has been reliably proven by many documented cases of treatment.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

On August 3, 2017, the US Food and Drug Administration (FDA) approved VYXEOS (Jazz Pharmaceuticals, Inc.) for the treatment of adults with recently diagnosed by two subspecies of AML (t-AML and AML-MRC).


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

VYXEOS is a liposomal combination of cytarabine and daunorubicin and has proven to be much more effective in treating these two subtypes than using the standard 7+3 combination.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The drug demonstrated an average overall survival of 9.6 months compared to 5.9 months for a combination of 7+3 [38]


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In 2018, the FDA approved the use of glasdegib (glasdegib) in combination with low-dose cytarabine to treat patients over 75 years of age who are unable to receive intensive chemotherapy.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The drug was approved on the condition of placing a warning about a high risk of toxicity to the fetus in the instructions.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The goal of the induction stage of treatment is to achieve complete remission.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Complete remission does not mean that the disease is fully cured.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Rather, the state of complete remission indicates that it is impossible to detect a sleeping disease by existing diagnostic methods.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[31] Complete remission is achieved in 50-70% of adult patients with newly diagnosed AML, the difference depends on the prognostic factors mentioned above.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[40] The duration of remission depends on the prognostic qualities of the initial leukemia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Basically, all cases of remission without additional, consolidating treatment are pumped by relapse.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Consolidation treatment


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Even after achieving complete remission, it is likely that few leukemia cells still survive.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

There are so few of them that it is impossible to detect them yet.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

If post-remission or consolidation treatment is not carried out, almost all patients eventually relapse.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[42] Therefore, in order to get rid of undetectable diseased cells and prevent relapse — that is, to achieve a complete cure, additional therapy is needed.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The type of treatment after achieving remission is determined individually depending on the prognostic factors and the general state of health of the patient.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

With prognostically favorable subspecies of leukemia (for example, with inv (16), t (8; 21) and t (15; 17), 3-5 additional courses of intensive chemotherapy, known as consolidation treatment, are usually prescribed.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Patients with a high risk of recurrence (for example, in the presence of cytogenetic changes associated with myelodysplastic syndrome, or with AML associated with previous treatment are usually recommended transplantation of allogeneic hematopoietic stem cells, if the general condition allows and there is a suitable donor.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[43] [44] In AML with an average probability of recurrence (with normal cytogenetic parameters or with such cytogenetic changes that do not fall into risk groups), the issue of consolidation treatment is not so clear and is determined by a number of specific indicators — the patient's age, general state of health, value system, and finally, the presence of a donor of suitable stem cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Those patients who are not indicated for stem cell transplantation after consolidation treatment undergo immunotherapy with a combination of histamine hydrochloride (ceplen) and proleukin.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Such treatment makes it possible to reduce the likelihood of relapse by 14%, prolonging remission by 50%.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Thus, high-intensity chemotherapy (VCT) and bone marrow transplantation are recognized as standard therapy for AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

However, the results of treatment, despite relatively high responses in young people, remain unsatisfactory in people over 65 years of age (30-50%) associated with early mortality (10%) and short duration remission.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

More than half of those with AML are older patients and/or with significant comorbidities, who, as a rule, cannot receive highly toxic chemotherapy regimens, so for their therapy low doses of cytarabine cytarabine and supportive treatment are used: antibiotics and blood transfusions.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Since 2010, hypomethylating agents (5-azacitidine, decitabine) have been recommended for the treatment of AML in patients who are not suitable for bone marrow transplantation/intensive chemotherapy.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[47] In the process of DNA methylation, hypomethylating agents covalently bind to DNA methyltransferase, which leads to gene reactivation, after which the differentiation of hematopoietic progenitor cells and normal hematopoiesis.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

5-azacitidine has a dual mechanism of action.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

It is embedded not only in the DNA molecule, but also into the RNA molecule.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Thus, 5-azacitidine reduces the amount of RNA in cells, which leads to a cytostatic effect regardless of the cell phase.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Based on the results of the Phase 3 study, AZA-001 is an international, multicenter, controlled study in parallel groups in which patients with high-risk MDS/AML (WHO criteria) were compared with standard therapy (accompanying therapy, intensive chemotherapy, low doses of cytarabine), azacitidine was registered, including in the Russian Federation, for the treatment of these groups patients.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

It has been shown that azacitidine increases the overall survival rate of AML patients by 2.5 times (WHO criteria).


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Recurrent AML


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In case of recurrence of AML, the only proven treatment that may be effective is stem cell transplantation, provided that it has not yet been used.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[49] [50] [51]


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In case of recurrence of AML, patients who do not plan hematopoietic stem cell transplantation or in case of relapse after stem cell transplantation can be offered treatment as part of a clinical trial, since the choice of conventional treatments is very limited.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Currently, the cytostatic substance clofarabin is undergoing clinical trials, and various methods of targeted therapy using farnesyltransferase inhibitors, decitabine and multidrug resistance protein inhibitors, cytarabine histone deacetylase inhibitors, angiogenesis blockers, deoxyadenosine analogues.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Sometimes a limited number of treatments for recurrent AML forces you to turn to palliative treatment.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

After clinical trials of arsenic trioxide, the Food and Drug Administration of the US has approved its use as a palliative treatment recurrent acute promyelocytic leukemia (OPL).


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

As well as ATGM, arsenic trioxide is ineffective in other AML subspecies.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In 2000, gemtuzumab ozogamycin (Milotarg) was allowed to be used in the United States to treat recurrent AML in patients over 60 years of age who cannot be treated with high doses of chemotherapy drugs, a drug in which , it was assumed that the cytotoxic substance, the anticancer antibiotic calichemicin, is associated with a monoclonal antibody that ensures the delivery of the antibiotic exactly to the leukemia cell.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

On July 20, 2018, the US Food and Drug Administration (FDA) registered the first inhibitor of the IDH1 gene ivosidenib (ivosidenib) for the treatment patients with recurrent AML and with a mutation in the oncogene IDH1.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Ivosidenib therapy allows patients to achieve complete remission of AML, as well as reduce the need for red blood cell and platelet transfusions.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

125 adult patients participated in the study of ivosidenib.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

CI showed a complete positive response to treatment in 30.4% of the subjects (also a response with partial hematological recovery in 8.8% of patients whose leukemia cell count was moderately low level).


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The drug was the first drug for the treatment of acute myeloid leukemia approved in the United States.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The registration certificate for the drug was issued to Agios Pharmaceuticals.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[54] [55]


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Prediction


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute myeloid leukemia is a curable disease.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The probability of recovery for each patient is different, as it is determined by a variety of prognostic factors.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Cytogenetics


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The most significant prognostic factor for AML is the cytogenetic factor, that is, the “construction” of chromosomes of leukemia cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Some cytogenetic abnormalities are associated with very favorable outcomes (for example, translocation 15; 17 in acute promyelocytic leukemia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In about half of AML patients, the cytogenetic condition looks normal, such patients are classified as in the group with an average probability of relapse.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

A number of cytogenetic changes are associated with an unfavorable prognosis and a high probability of relapse after treatment.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[57] [58] [59]


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The first publication examining the relationship between cytogenetic changes and prognosis appeared in a report by the Medical Research Council in 1998.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Later, the Southwest Cancer Group and the Eastern Cooperative Oncology Group, [61] and then Group B on Cancer and Leukemia Research published other, mostly matching lists prognostic cytogenetic changes in leukemia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Previous myelodysplastic syndrome and AML prognosis


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

AML that develops against the background of myelodysplastic syndrome or myeloproliferative syndrome (so-called secondary AML) has a worse prognosis than AML associated with previous treatment, which occurs after chemotherapy of another previous malignant disease.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Both of these conditions are associated with a high incidence of adverse cytogenetic changes.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[63] [64] [65]


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Other prognostic signs of AML


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Some studies have linked age after 60 years of age and elevated lactate dehydrogenase levels to an increased likelihood of an adverse outcome.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[66] As with most other malignant diseases, the general somatic status (that is, the general physical condition of the patient and his vital activity) is also of great prognostic importance.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

It has been proven that internal tandem doubling of FLT3 tyrosine kinase worsens the prognosis of AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[67] More aggressive treatment of such patients, in particular, stem cell transplantation in the first remission did not increase the duration of survival, so as a favorable prognostic sign doubling of FLT3 tyrosine kinase has no definite clinical significance.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[68] Internal tandem doubling of FLT3 tyrosine kinase may be associated with leukostasis.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Currently, studies of the clinical significance of mutations in the CD117 gene, responsible for the synthesis of stem cell growth factor C-kit receptor in AML, are widespread.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The importance of these studies is determined by the appearance in clinical practice of tyrosine kinase inhibitors, such as imatinib and sunitinib, which have the ability to stop the action of the C-kit receptor.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In addition, CEBPA, BAALC, ERG and NPM1 genes are studied as prognostic factors and objects of therapeutic effects.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Overall assessment of treatment results


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The effectiveness of treatment in clinical trials ranges from 20 to 45%.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[71] [72] However, it should be noted that young patients, as well as those who are able to endure aggressive treatments, participate in clinical trials.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The effectiveness of treatment for all patients, including the elderly and those for whom aggressive treatment is contraindicated, is likely to be lower.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In the case of acute promyelocytic leukemia, the effectiveness of treatment can reach 98%.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

epidemiology


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute myeloid leukemia is a relatively rare malignant disease.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Thus, 10,500 fresh cases of AML are detected annually in the United States, and the incidence remained unchanged from 1995 to 2005. The AML mortality rate accounts for 1.2% of all cancer deaths in the United States.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The incidence of AML increases with age, with the average age of detection of the disease being 63 years.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

AML accounts for about 90% of all acute leukemia in adults, but it is rare in children.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The incidence of AML associated with prior treatment (that is, AML caused by previous chemotherapy) is increasing.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Currently, such forms reach 10-20% of all cases of AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[74] AML is slightly more common in men, with a incidence of 1.3 to 1. [75]


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

There are some geographical differences in the incidence of AML.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In adults, the highest incidence is in North America, Europe and Oceania, while in Asia and Latin America, the incidence of AML is lower.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

76] [77] Conversely, children's AML is less common in North America and India than in other parts of Asia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[78] These differences can be determined by the genetic characteristics of the population and the characteristics of the environment.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

History


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The first description of leukemia in the medical literature dates back to 1827, when the French physician Alfred-Armand Louis-Marie Velpo described the disease of a 63-year-old gardener, which manifested itself as fever, weakness, kidney stones and a marked increase in the liver and spleen.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Velpo noticed that the patient's blood resembled “liquid oatmeal” in consistency, and suggested that this was due to white blood cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[79] In 1845, Edinburgh-based pathologist John Hughes Bennett published a report of several deaths of patients who had an enlarged spleen and “the blood was changed in color and consistency”.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Bennett used the term “leukocythemia” to describe changes in blood.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The term “leukemia” was coined by the famous German pathologist Rudolf Virchow in 1847.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

As the first researcher to use a light microscope in histopathology, Virchow was the first scientist to describe an excessive number of white blood cells in patients with clinical manifestations, as described by Velpo and Bennett.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Since Virkhov did not know the cause of the excess white blood cells, he used the exclusively descriptive term “leukemia” (Greek: “white blood”) to determine the condition.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

With the development of modern research methods, many details of the process of onset and development of leukemia have come


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Already in 1877, Paul Ehrlich developed a method for staining blood smears, which allowed him to describe in detail normal and altered white blood cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In 1889, Wilhelm Ebstein coined the term “acute leukemia” to separate rapidly developing deadly and relatively slowly flowing chronic leukemia.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[82] The term “myeloid” was coined by Neuman in 1869 when he discovered that white blood cells are formed in the bone marrow (ancient Greek: µuelos, myelos = bone marrow), and not in the spleen.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

A method for diagnosing leukemia by examining a bone marrow smear was first described by Mosler in 1879.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[83] Finally, in 1900, Negeli, who divided leukemia into myelocytic and lymphocytic leukemia, described the malignant cell of acute myeloid leukemia, myeloblast.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

[84] [85]


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

In 2008, the gene sequence in the genome of an AML patient was fully determined.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

The genome in AML was the first deciphered genome in malignant tumors.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

DNA obtained from leukemia cells was compared with DNA obtained from healthy skin [86], and mutations of several genes previously not considered to be associated with the disease were detected in leukemia cells.


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

See also


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Acute lymphoblastic leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Chronic myeloid leukemia


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Chronic lymphocytic leu


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Chlorome


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

References


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

at American Cancer Society


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

at Leukemia & Lymphoma Society


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

at cchs.net


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

at National Cancer Institute


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Notes


Question: Is acute myeloid leukemia a rare disease?

Acute myeloid leukemia

Category:Acute myeloid leukemia


Question: How did Max Linder die?

Max Linder

Gabriel-Maximilien Leuvielle (French: Gabriel-Maximilien Leuvielle), better known by his artistic pseudonym Max Linder (December 16, 1883 — October 31 (November 1?) 1925) is a French comedian actor, screenwriter and silent film director.


Question: How did Max Linder die?

Max Linder

Born in the Gironde department in western France.


Question: How did Max Linder die?

Max Linder

At the age of 18, he joined the theater troupe in Bordeaux, where he was engaged in the classical repertoire.


Question: How did Max Linder die?

Max Linder

In 1905, he became one of the main actors, and since 1908 he became the leading comedian at Pathé.


Question: How did Max Linder die?

Max Linder

More than 200 of his films are known [1] (although, for example, Rostislav Yurenev, Doctor of Art History, has at least 500 of them [2]), of which about half were created himself as a screenwriter and director.


Question: How did Max Linder die?

Max Linder

During the First World War, he participated in hostilities.


Question: How did Max Linder die?

Max Linder

He was wounded and also experienced a deep psychological shock.


Question: How did Max Linder die?

Max Linder

In 1916 he left for the United States.


Question: How did Max Linder die?

Max Linder

He shot medium-length and full-length films, but failed to achieve success comparable to the previous one.


Question: How did Max Linder die?

Max Linder

Destructive military memories, a period of creative lack of demand led the actor to a progressive depression.


Question: How did Max Linder die?

Max Linder

On the evening of October 30, 1925, together with his young wife, Helen Peters, committed suicide (physical death occurred only a day later).


Question: How did Max Linder die?

Max Linder

The character he created Max became the first screen image in international cinema, repeating from film to film, easily recognizable and memorable: an elegant suit, a top hat, a cane, dark antennae, a dazzling smile.


Question: How did Max Linder die?

Max Linder

His work is characterized by a transition from primitive, physiological comic of kicks and falls to the search for a character funny in character and psychology, humor of non-standard situations and circumstances.


Question: How did Max Linder die?

Max Linder

Their source was falling in love, intoxication, excessive activity of the hero Max Linder, his arrogance and frivolity.


Question: How did Max Linder die?

Max Linder

The actor's early work had a significant impact on Charlie Chaplin [3] [4] and Buster Keaton [5].


Question: How did Max Linder die?

Max Linder

Chaplin has repeatedly said that if at the age of twenty-third he had a desire to act in films, the reason for this was his admiration for the French actor Linder [6].


Question: How did Max Linder die?

Max Linder

Biography


Question: How did Max Linder die?

Max Linder

Early years


Question: How did Max Linder die?

Max Linder

Gabriel-Maximilian Leuviel was born on December 16, 1883 near Saint-Loubet in the Gironde department in western France [7] in the family of wealthy winemakers Jean and Suzanne Leuviel.


Question: How did Max Linder die?

Max Linder

In addition to him, brothers Maurice (born in 1881, in the future he will become a famous rugby player), Gerard and sister Marcel (born in 1884) grew up in the family.


Question: How did Max Linder die?

Max Linder

At the age of two, Gabriel contracted cholera.


Question: How did Max Linder die?

Max Linder

At the direction of a local doctor who arrived, the child was immersed in a heated oven, which made it possible to avoid death [8] [9].


Question: How did Max Linder die?

Max Linder

From early childhood, younger Leuviel was passionate about circus and farce, especially strong was the first impression of the Punch and Judy street theater [10].


Question: How did Max Linder die?

Max Linder

His parents categorically opposed his artistic aspirations.


Question: How did Max Linder die?

Max Linder

Against their will, Gabriel-Maximilian entered the Bordeaux Conservatory at the Faculty of Drama at the age of 16 (his parents believed that he was studying painting [11]).


Question: How did Max Linder die?

Max Linder

His interest became noticeable to a friend of the Leuviel family, the mayor of San Lube, Dr. Duncan, who secretly provided the student with all possible support.


Question: How did Max Linder die?

Max Linder

A couple of years later, he joined the main troupe of the local theater, where he played in plays by Moliere, Pierre Cornel and Alfred de Musset.


Question: How did Max Linder die?

Max Linder

He confronted his relatives with the fact of starting his artistic career.


Question: How did Max Linder die?

Max Linder

On stage, he had to perform under the pseudonym Max Lacerda, as his father categorically forbade him to use his real name on theater posters [8].


Question: How did Max Linder die?

Max Linder

During this period, he meets Comedy Francaise actor Charles Le Bargy, who recommends him to enter the Paris Conservatoire of Music and Dance.


Question: How did Max Linder die?

Max Linder

In 1904, Leuviel failed the entrance exam, but, not wanting to leave the capital, began to perform on the sidelines in small theaters in Paris.


Question: How did Max Linder die?

Max Linder

In 1905 and 1906, the actor repeated his attempts to enter the conservatory, but they were also unsuccessful.


Question: How did Max Linder die?

Max Linder

The artist's income was small, so Gabriel worked part-time with fencing lessons [2] and posed for promotional cards [8].


Question: How did Max Linder die?

Max Linder

Once at one of the performances, he was noted by director Louis Gagnier and offered several roles at the Pathé film studio.


Question: How did Max Linder die?

Max Linder

The actor himself described this engagement in several interviews as follows: “They brought a note to my dressing room: “Monsieur, I saw your performance yesterday and I'm ready to pay 100,000 francs just for mobility Your eyes. I'll double the amount if the contract with my studio is exclusive. Pathe. “” [12].


Question: How did Max Linder die?

Max Linder

French actor of the early 20th century, René Jean, in his book French: Max Linder et le théâtre (1965), called such memories a deliberately created myth.


Question: How did Max Linder die?

Max Linder

In 1905, no one would offer such a fee even to a famous artist.


Question: How did Max Linder die?

Max Linder

From his point of view, we could talk about 200,000 francs in 1909 or 1910 and only in relation to a three-year contract [10].


Question: How did Max Linder die?

Max Linder

Later, in an interview in the 1920s, the comedian cited the real amount of his fee for the beginning of his cinematographic career at 40 francs a day [13].


Question: How did Max Linder die?

Max Linder

Partnering with Pathé Studio


Question: How did Max Linder die?

Max Linder

Gabriel Leuviel, who was only 22 years old at the time, starred in several short films at Pathé without a well-formed image.


Question: How did Max Linder die?

Max Linder

Small stature (157 cm), with youthful features, he plays either teenagers or students (“First Schoolboy Exit”, French: La Première Sortie d'un collégien, 1905, “His First Cigar”, French: Le Premier Cigare d'un collégien, 1906), then a fussy half-blind old man (Duel of a Short-sighted Master, French: Le Duel d'un monsieur myope, 1910).


Question: How did Max Linder die?

Max Linder

At the same time, he participates not only in comedies, but also in melodramas (Poison, French: Le Poison, 1906; Two Great Grief, French: Deux grandes douleurs, 1908), drama Death of a Bullfighter, French: La Mort d'un toréador, 1907) and even in Segundo de Chaumont's mystical extravaganza “The Creation of the Serpentine” (French: Création de la serpentine, 1908).


Question: How did Max Linder die?

Max Linder

For the first time in the image of “dandy”, invented by him to enhance the comic effect, Gabriel Leuviel appears in French: Max patineur: Les Débuts d'un patineur, winter 1907.


Question: How did Max Linder die?

Max Linder

Here, again, for the first time, a pseudonym is used, the roots of which are not known for certain.


Question: How did Max Linder die?

Max Linder

Several versions are being considered at once.


Question: How did Max Linder die?

Max Linder

Relatives of the actor claim that already in 1904, theater posters were printed, on which the pseudonym was used [8].


Question: How did Max Linder die?

Max Linder

Gabriel Leuviel is quite successful at the Variety Theater, especially in Robert de Fleur and Gaston Armand de Cayave's plays Micetta and Her Mother (French: Miquette et sa mère, 1906) and The King (French: Le Roi , 1908).


Question: How did Max Linder die?

Max Linder

The troupe's actors included Max Dirley and Suzanne Lander.


Question: How did Max Linder die?

Max Linder

Georges Sadoul, an extremely authoritative film historian, is likely to believe that the combination of these names formed the basis of the comedian's future pseudonym, Max Linder [14].


Question: How did Max Linder die?

Max Linder

Other sources believe that the name was borrowed from actress Marcel Linder [7] or actor Marcel Linder [2].


Question: How did Max Linder die?

Max Linder

Finally, the Institut Max Linder cultural center, referring to the words of the artist himself, reports that the pseudonym was taken from the first sign of the shoemaker that caught my eye [8].


Question: How did Max Linder die?

Max Linder

At the same time, it is necessary to take into account the actor's propensity for hoaxes and jokes.


Question: How did Max Linder die?

Max Linder

Linder's success in Speed Skater's Debut almost coincided with the departure abroad of Pathé's leading comic actor Andre Dide (Andre de Chapé): Itala signed with him extremely a profitable contract.