Allogeneic Stem Cell Transplantation (SCT) with Non Myeloablative Conditioning Regimen (NST) Following Intensive Consolidation May Be Equivalent to Conventional alloSCT and Superior to autoSCT for Patients over 50 with Acute Myeloid Leukemia (AML) in 1^stCR: First Results of the AML 2001 Trial.

From 11/01 until 04/05, 832 patients (median age 46, 18–60) with AML (previous diagnosis of myelodysplasia or myeloproliferative disorder, and M3 excluded) were included in prospective phase III AML 2001 trial. After achieving CR, research to identify an HLA-identical sibling was performed for all patients as they received low dose consolidation (Daunorubicin (D): 60 mg/m² × 2d OR Idarubicin (I): 12 mg/m² × 2d plus SC ARAC 100 mg/m² ×7d). 33 % patients had a donor then could proceed to a T-replete alloSCT: either conventional if age ≤ 50 (bone marrow graft; conditioning regimen: TBI (12 Gy 6 fractions over 3d) - cyclophosphamide (60 mg/kg × 2d); GvHD prophylaxis: ciclosporin-methotrexate d1+3+6) = arm M; or NST if age 51–60 (peripheral blood; Busulfan (oral Bu 4–8 mg/kg over 2d) - Fludarabin (30 mg/m² × 4d) – Thymoglobulin^® (2,5 mg/kg × 2d); ciclosporin alone), AFTER intensive consolidation (D: 60 mg/m² × 2d OR I: 12 mg/m² × 2d plus ARAC 3 g/m² × 8 doses over 4d) = arm m. A small group of patients with a donor but low-risk prognostic features (favorable cytogenetics, no hyperleucocytosis, CR after 1 induction = 3% CR1 patients) didn’t receive 1^st line alloSCT but intensive consolidation then a 2^nd HD ARAC course; alloSCT was therefore considered at relapse = arm C.

Patients without donor proceed to intensive consolidation then 1 or 2 autoSCT (1^st after HDM 200 mg/m² according to randomization, then Bu 16 mg/kg over 4d + HDM 140 mg/m² for all patients) = arms A + B; they were combined for analysis as no difference was observed for DFS and OS. Actual results concern 532 patients with 15 months follow-up (A + B = 367; M = 111; m = 54).

Median age was different between 3 groups (A + B = 46; M = 40; m = 54) as no difference was observed regarding leukocytosis or cytogenetic subgroups: favorable (t8;21) or inv16: A + B = 15%; M = 11%; m = 11%), intermediate (A + B = 72%; M = 78%; m = 67%), defavorable (5, 7, complex, 11q23 except t(9;11) or 3q; A + B = 13%; M = 11%; m = 22%).

Conventional alloSCT results in better 2y DFS than autoSCT arms (M 71% vs A+B 52%, p=0,007) thought 2y OS advantage remains non significant (M 77% vs A+B 68%, p=0,06) as toxic death rate is higher (36% all deaths in arm M vs 14 % in arms A + B). No significant difference was observed between conventional alloSCT and NST (2y DFS 62%, OS 68%). Advantage for NST over autoSCT arms was non significant for DFS (p=0,24) and OS. Same results are obtained if considering only patients aged > 50: 2y EFS (m 62% vs A+B 50%, p=0,27) and OS (m 68% vs A+B 65%). After NST, toxicity accounts for 25% deaths, as relapse rate is 40% at 2y with no late relapse thereafter (vs 48 % at 2y and 61 % at 4y in arms A + B).

In conclusion: 1) conventional alloSCT remains the best consolidation treatment for patients ≤ 50 with AML in CR1 despite higher toxicity; 2) NST after intensive consolidation seems promising: for older patients as toxicity is lower than conventional alloSCT, as few late relapse are observed in comparison with chemotherapy or autoSCT approaches; 3) NST may extend use of alternative sources of allogeneic hematopoietic stem cells to propose alloSCT approach for the majority of patients ≤ 60 with AML in CR1. Data with more than 2 years follow-up will be presented.