Early deaths due to hemorrhage and leukostasis in childhood acute myelogenous leukemia. Associations with hyperleukocytosis and acute monocytic leukemia

Abstract

There were 294 children with acute myelogenous leukemia (AML) entered into the German AML Berlin, Frankfurt, and Münster hospitals (BFM) 78 and 83 studies. Thirty (10%) died as a result of hemorrhage and/or leukostasis prior to or in the first 12 days of therapy. The risk of early death due to hemorrhage and/or leukostasis is significantly greater when certain features are initially present: acute monocytic leukemia (French-American-British [FAB] M5), hyperleukocytosis (greater than or equal to 100,000/microliter), and extramedullary organ involvement (P less than 0.001). The risk increases sharply when these factors exist in combination: 72% mortality with FAB M5 and hyperleukocytosis, and 43% with FAB M5 and extramedullary organ involvement. In 11 patients leukostasis alone or in combination with hemorrhage was probably the cause of death during the first 3 days after diagnosis. All 11 children presented with hyperleukocytosis and were classified as monocytic subtype FAB M4 or M5. After induction, a close temporal association between rapid blast reduction and occurrence of fatal hemorrhage was established in five patients. Thrombocytopenic hemorrhages were controllable and, therefore, responsible for death only in exceptional cases. It is difficult to avoid these early fatal complications with current therapeutic measures. Early exchange transfusion together with special supportive care may be useful.

Risk score model for fatal intracranial hemorrhage in acute leukemia

“…9,[16][17][18][19][20][21][22][23][24] Most FICH occurred soon after diagnosis, 27 within 7 days, and 13 patients presented with FICH at diagnosis. Because the median interval from FICH to death was 2 days, we estimate that 1.6% of patients with acute leukemia die from FICH without any opportunity for proper management.…”

“…For example, although ATRA has been found to increase the remission rate, prolong survival and decrease hemorrhagic complications in APL, its effect on hemorrhagic death rates is not known. [4][5][6][7] Among the hemorrhagic complications in acute leukemia, intracranial hemorrhage (ICH) is the most serious and most common, 8,9 severely shortening the survival of patients with acute leukemia. Most fatal intracranial hemorrhages (FICH) occur during the early course of the disease (within 10 days of diagnosis), suggesting that early identification and management is crucial for preventing FICH.…”

Causes of death – other than progressive leukemia – in childhood acute lymphoblastic (ALL) and myeloid leukemia (AML): the Dutch Childhood Oncology Group experience

“…This may be related to the higher frequency of hyperleucocytosis in AML. 22 Moreover, AML blasts size is larger than in ALL, resulting in higher blood viscosity at similar WBCs. The higher rate of CRM in AML may be mainly due to the difference in treatment intensity, which is needed to cure these different types of leukemias.…”

Hyperleukocytosis and retinal hemorrhages after chemotherapy and filgrastim administration for peripheral blood progenitor cell mobilization

“…[7][8][9] Leukostasis is thought to be more commonly associated with myeloid than lymphoid leukemias because of the increased myeloblast's size and rigidity. 10 To the best of our knowledge, we believe that this is the first report of a patient with retinal hemorrhages and hyperleukocytosis secondary to chemotherapy and Filgrastim administration.…”