High-dose melphalan and autotransplantation followed by post transplant maintenance chemotherapy for acute lymphoblastic leukemia in first remission.
A total of 65 adults with acute lymphoblastic leukemia (ALL) received 200 mg/m2 melphalan and an autograft in first remission, with a plan to receive 6-mercaptopurine (6MP), methotrexate (MTX), and vincristine-prednisone (VP) for 2 years afterwards. There was no transplant-related mortality. In all, 69% of patients received 6MP, 54% received MTX, and 49% received VP. The cumulative incidence of relapse at 5 years was 52%. The 5-year probabilities of disease-free (DFS) and overall (OS) survival were 48 and 55%. Age >30 years, >4 weeks to attain remission, and t(9;22) or t(4;11) karyotypes were adverse prognostic features. Patients with 0 (standard risk), 1 (intermediate risk), and 2-3 (high risk) adverse features had 5-year cumulative incidences of relapse of 19, 59, and 100% (P<0.0001), and 5-year probabilities of DFS of 80, 41, and 0% (P<0.0001). The 5-year probabilities of DFS for patients receiving 0, 1, 2, and 3 maintenance therapy agents were 19, 40, 51, and 70% (P=0.0097). Maintenance therapy intensity was an independent determinant of outcome in Cox analysis. These data show that a high-dose melphalan-based autograft is safe and could be widely applicable in ALL in first remission, and that maintenance chemotherapy very likely contributes to improved outcome of autografted ALL patients.
Mehta
J
J
Leukaemia Unit, The Royal Marsden Hospital, Surrey, UK. j-mehta@northwestern.edu
Powles
R
R
Sirohi
B
B
Treleaven
J
J
Kulkarni
S
S
Singhal
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D014182:Transplantation, Autologous
D008558:Melphalan