Outcome assessment of age group-specific (+/- 50 years) post-remission consolidation with high-dose cytarabine or bone marrow autograft for adult acute myelogenous leukemia

Abstract

BACKGROUND AND OBJECTIVE: To assess outcome of an age-adapted post-remission strategy for adult patients with acute myelogenous leukemia (AML, FAB-M3 excluded), including autologous bone marrow transplantation (ABMT) or high-dose cytarabine (HIDAC) consolidation. DESIGN AND METHODS: AML patients in first complete remission (CR) after doxorubicin-cytarabine-thioguanine (DoxAT) chemotherapy were scheduled to receive two identical early consolidation courses followed by HIDAC (1 g/m2/bd for 6 days), if aged > 50 years, or HiDAC plus total body irradiation (TBI) plus ABMT if aged < 50 years, the bone marrow being harvested prior to the HiDAC/TBI regimen and unpurged. Results were examined by treatment intention and in actual treatment groups, by selected pretreatment and therapy-related variables, and compared with age and disease matched historical patients treated with DoxAT consolidation without additional HIDAC or ABMT. RESULTS: One-hundred and eight (70%) of 153 patients achieved a response and were evaluable after a follow-up of 3.3-8.8 years. According to treatment intention, long-term relapse-free survival (RFS) was significantly improved in both age groups compared with controls (< 50 years: 41% vs 15%, p < 0.05; > 50 years: 33% vs 22%, p < 0.005). Actually, 41 patients proceeded to ABMT and 24 to the HIDAC cycle (including 5 aged < 50 years), 23 had early consolidation only (1: refusal; 1: inadequate marrow harvest; 21: complications), 10 relapsed and 2 died very early into remission, 7 were submitted to an allogeneic BMT, and one denied any post-remission therapy. The long-term RFS rates for ABMT and HIDAC groups were 53% and 54% (47% for 19 patients aged > 50), respectively, significantly better than for historical patients or those unable to go beyond early consolidation (p < 0.005, adjusted for early adverse events). Overall 5-year survival rate was 40% (p < 0.0001), 54% for CR patients, 60% after ABMT, and 65% after HIDAC. Relative to the ABMT and HIDAC intensive treatment groups, only the presence of hepatosplenomegaly at diagnosis was associated with a significantly worse outcome like that of the control study. INTERPRETATION AND CONCLUSIONS: This age-adapted double post-remission consolidation strategy with ABMT (allo-BMT) or HIDAC was applicable to only about two thirds of responders and was effective in about half these cases, regardless of patient age or specific treatment modality. While the loss of CR patients from treatment realization was unrelated to the study design and depended mainly on recurrence of AML and toxic complication, the exact place of ABMT vs HIDAC consolidation remains unsettled, calling for a new study in comparable patient and risk groups.