Early haemorrhagic morbidity and mortality during remission induction with or without all‐trans retinoic acid in acute promyelocytic leukaemia

Abstract

Summary. A total of 622 consecutive patients with acute promyelocytic leukaemia (APL) treated within the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group during 1989±97 have been reviewed to assess the clinical effectiveness of all-trans retinoic acid (ATRA) on the incidence of early haemorrhagic deaths and on APLassociated coagulopathy. Of them, 499 were treated with idarubicin plus ATRA (study A) and 123 with Idarubicin alone (study B). In both studies, similar guidelines for supportive treatment were used. Haemorrhagic symptoms were evaluated according to a reproducible score system. Deaths occurring within 10 d of starting treatment were 19 (3´8%) in study A and nine (7´3%) in study B (P 0´09), with 15 (3%) and ®ve (4´1%) (P not signi®cant) due to haemorrhage. Overall, induction mortality was 7´6% and 16´2% respectively (P < 0´003). In study A, days with platelet counts # 20´10 9 /l or with ®brinogen # 1 g/L were reduced by about 30%, the haemorrhagic score by 50% and the consumption of blood products by about 40%, and fewer patients were treated with antihaemorrhagic drugs (39% vs. 61%; P < 0´001). On multivariate analysis, early deaths were in¯uenced by blast count at diagnosis > 30´10 9

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG

“…2,[5][6][7][8]11 Patients with WBC counts X10 Â 10 9 /l had a higher risk of death due to fatal bleeding, as to be expected. 5,[30][31][32] The APL differentiation syndrome was diagnosed in 21.1% of our patients, which is in the range of other reports. [33][34][35][36] Possibly, the timing of ATRA and chemotherapy has contributed to the relatively high rate, as 60% of our patients received pretreatment with ATRA over a period of 7 days on average before the chemotherapy was started, as similarly observed by others.…”

Risk score model for fatal intracranial hemorrhage in acute leukemia

“…20,23,[39][40][41][42][43] In contrast to the improvement in survival and decrease of hemorrhagic complications resulting from the introduction of ATRA, changes in hemorrhagic mortality have been reported to be minimal. 10 In our study, FICH was not decreased after ATRA use (data not shown). Thus, despite the introduction of ATRA, APL is still a major risk factor for FICH.…”

“…Early hemorrhagic death in patients with APL has been reported to be influenced by higher blast cell count at diagnosis, higher hemorrhagic score, lower plasma fibrinogen level and lower platelet counts. 10,11 It is now known, however, whether these factors can be generalized to all patients with acute leukemia, whether some of these factors may affect FICH but not other hemorrhagic complications and whether risk strategies can reduce the incidence of FICH. To answer these questions, it is necessary to perform risk analyses for FICH and to develop an adequate risk model.…”

Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin

“…These data come from the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) group that carefully evaluated the cause of induction failure in 732 newly diagnosed APL patients who were treated with a combination of ATRA and idarubicin [16]. High blast count ([30 9 10 9 / L) was identified as a predictive factor for hemorrhagic death by PETHEMA as well as by the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group that evaluated early hemorrhagic death in 622 consecutive APL patients treated with ATRA either alone (n = 499) or in combination with idarubicin (n = 123) [13].…”

“…Approximately, 41 % of early deaths were related to hemorrhagic events, with intracranial hemorrhage being the most common cause of death (73 %) [6]. Incorporation of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO), into induction chemotherapy has revolutionized the treatment of individuals with APL, with 90-95 % of newly diagnosed APL patients achieving complete remission and over 85 % of patients surviving for longer than 5 years [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Despite the incorporation of ATRA, hemorrhage remains the major cause of early death (4.5 %); other causes of early death include infection (1.9 %) and differentiation syndrome (1.2 %) [20] (Table 1).…”