Intensive Therapy before or during the Conditioning Regimen of Allogeneic Marrow Transplantation in Adult Acute Lymphoblastic Leukemia Patients: We Must Choose to Reduce Toxicity—A Groupe Ouest-Est d’Etude des Leucémies et Autres Maladies du Sang Study

Abstract Bone marrow transplantation (BMT) can cure patients with high-risk or recurrent acute lymphoblastic leukemia (ALL). Those lacking a related donor can receive either autologous or histocompatible unrelated donor (URD) marrow. Autotransplantation may result in higher risk of relapse, whereas URD allografts, although associated with serious posttransplant toxicities, may reduce relapse risk. Six years (1987 to 1993) of consecutive autologous BMT (University of Minnesota, Dana Farber Cancer Institute; n = 214) were compared with URD transplants (National Marrow Donor Program; n = 337). Most transplants (70% autologous, 48% URD) were in early remission (first or second complete remission [CR1 or CR2]); 376 patients (75% autologous, 64% URD) were less than 18 years old. Autologous BMT led to significantly lower transplant-related mortality (TRM; relative risk [RR] 0.35; P = .001). URD transplantation offered greater protection against relapse (autologous RR 3.1; P = .001). Patients greater than 18 years old, women, and BMT recipients beyond CR2 had higher TRM, whereas adults, BMT recipients in CR2+, or BMT recipients during 1991 through 1993 had significantly more relapse. After 25 months median follow-up, 100 URD and 56 autologous recipients survive leukemia free. URD BMT in CR2 resulted in superior disease-free survival (DFS), especially for adult patients. Multivariate analysis showed superior DFS for children, men, and BMT during CR1 or 2. Autologous and URD BMT can extend survival for a minority of patients unlikely to be cured by chemotherapy, and the results with either technique are comparable. Greater toxicity and TRM after URD BMT are counterbalanced by better protection against relapse. Prospective studies addressing additional clinical variables are needed to guide clinical decision making about transplant choices for patients with ALL.

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Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. The French Group on Therapy for Adult Acute Lymphoblastic Leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.1993.11.10.1990 ◽

1993 ◽

Vol 11 (10) ◽

pp. 1990-2001 ◽

Cited By ~ 137

Author(s):

D Fière ◽

E Lepage ◽

C Sebban ◽

C Boucheix ◽

C Gisselbrecht ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Lymphoblastic Leukemia ◽

Maintenance Chemotherapy ◽

Adult Acute Lymphoblastic Leukemia ◽

Postremission Therapy ◽

To Receive ◽

Group 1

PURPOSE In a prospective multicenter study, we analyzed the benefits of allogeneic bone marrow transplantation (BMT) in a nonselected group of adult patients with acute lymphoblastic leukemia (ALL) and, by a randomized trial, evaluated the effectiveness of autologous BMT over chemotherapy as postremission therapy in patients younger than 50 years who were not candidates for allogeneic BMT. PATIENTS AND METHODS After induction therapy that randomized patients to receive one of two anthracycline-containing regimens, either daunorubicin (DNR) or zorubicin (ZRB), patients were assigned to postremission treatment according to age and results of HLA typing. Patients younger than 40 years with an HLA-identical sibling (group 1) were scheduled to receive cyclophosphamide 60 mg/kg on days 1 and 2, total-body irradiation (TBI), and allogeneic BMT. Patients older than 50 years (group 2) received the chemotherapy arm composed of three monthly consolidation courses (DNR or ZRB, cytarabine, and asparaginase) followed by maintenance chemotherapy (modified L10 regimen). The remaining population (group 3) was randomly assigned to receive, after the three 1-month consolidation courses, either the chemotherapy arm or autologous BMT following a conditioning regimen similar to that of group 1. RESULTS Of the 572 assessable patients, 436 achieved complete remission (78% +/- 2% for DNR v 74% +/- 3% for ZRB; P = .3). The estimated 3-year disease-free survival (DFS) rate for the 116 patients included in group 1 was 43% +/- 5%. Both autologous BMT (95 patients) and chemotherapy (96 patients) produced comparable 3-year DFS rates (39% +/- 5% v 32% +/- 5%) and survival durations (49% +/- 5% v 42% +/- 5%). However, late relapses after 36 months were mainly observed in the chemotherapy arm. CONCLUSION This first interim analysis did not demonstrate a benefit of this autologous BMT procedure over classical maintenance chemotherapy in patients with ALL who received consolidation chemotherapy.

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