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

Abstract

The objective of this study for newly diagnosed acute promyelocytic Leukemia (APL) was to evaluate the efficacy of an intensified double induction chemotherapy including high dose ara-C (HD) and all-trans retinoic acid (ATRA) followed by consolidation and 3 years maintenance therapy. In contrast to APL studies stratifying therapy according to pretreatment white blood cell (WBC) count o and X10 Â 10 9 /l (low/intermediate and high risk according to the Sanz score), our patients received uniform therapy. From 1994 to 2005, 142 patients (age, 16-60 years) were enrolled. In the low/intermediate (n ¼ 105) vs high (n ¼ 37) WBC group, the rates of complete remission were 95.2 vs 83.8%, of induction death were 4.8 vs 16.2% (P ¼ 0.05) and of molecular remission were 87.5 vs 91.3% (P ¼ 1). Long-term overall survival was 84.4 vs 73.0% (P ¼ 0.12), event free survival was 78.3 vs 67.3% (P ¼ 0.11), relapse free survival was 82.1 vs 80.0% (P ¼ 0.83) and the cumulative incidence of relapse was 7.4 vs 11.4% (P ¼ 0.46). No relapse or death occurred after 4.7 years. ATRA and intensified chemotherapy including HD ara-C followed by prolonged maintenance therapy reduced the relapse risk in high risk patients. Pretreatment WBC count X10 Â 10 9 /l count was no relevant prognostic factor for relapse.

Clinical impact of FLT3 mutation load in acute promyelocytic leukemia with t(15;17)/PML-RARA

“…All patients received all-trans retinoic acid in combination with intensive chemotherapy according to standard study protocols. 1,5,17 This cohort is completely independent of a previously published one. 11 All patients gave informed consent to the use of laboratory data for research studies.…”

“…[6][7] Lengfelder et al observed no significant differences in survival outcomes and relapse incidence in 142 APL patients (who all received cytarabine within their induction and consolidation protocols) when they were separated according to a WBC threshold of 10¥10 9 /L . 5 The most suitable parameters for risk stratification in APL are, therefore, still under debate. It was discussed whether patients with the French-American-British (FAB) subtype M3v might have higher rates of early death because of hemorrhagic complications when compared to patients with the classical FAB M3 morphology, [8][9] but Tallman et al found that outcomes of patients with the two FAB subtypes did not differ significantly when adjustment for WBC counts or relapse risk scores was made.…”

“…Still, up to 15% of patients with APL develop clinical or molecular relapses. [4][5] A high white blood cell (WBC) count (>10¥10 9 /L) is supposed to be the main factor associated with relapse. The Sanz score subdivides APL patients according to peripheral blood counts into three risk groups: low (WBC ≤10¥10 /L).…”

Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry

“…[3][4][5][8][9][10] Recently, Jacomo et al reported an ED rate of 32% in a study of APL patients at 12 Brazilian institutions receiving treatment with ATRA and anthracyclines. Hemorrhages, caused by disseminated intravascular coagulation, hypercoagulability, fibrinolysis, proteolysis and thrombocytopenia, constitute the major cause of death with the central nervous system (CNS) being the most common site of bleeding.…”

Presenting features and treatment outcome of acute promyelocytic leukemia arising after multiple sclerosis

“…[12][13][14][15][16] These protocols included the AIDA 2000 of the Italian GIMEMA study group, 12 the PETHEMA LPA2005, 13 and the PETHEMA LPA 99, 14 UK MRC AML15 15 and the German AMLCG. 16 All protocols received approval from the corresponding IRB and/or ethical committees. Patients were enrolled in the respective trials prospectively and were treated accordingly after signing informed consent.…”