Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non-Hodgkin's lymphoma for patients <= 50 years old in first complete remission: results of the EORTC ALL-3 trial
[en] Background and Objectives. In the EORTC ALL-3 trial, the efficacy of allogeneic transplantation was compared with that of autologous marrow transplantation and maintenance chemotherapy in patients less than or equal to 50 years who reached CR. Design and Methods. Among 340 patients who entered the study, 279 were less than or equal to 50 years old. Out of these, 220 reached CR, 184 patients started consolidation and were HLA typed; 68 had a donor and 116 had no sibling donor. The median follow-up was 9.5 years; 93 patients relapsed, 26 died in CR, and overall 116 patients died. Allogeneic transplantation was performed in 47 (68%) patients with a donor while autologous transplantation or maintenance chemotherapy was given to 84 (72%) patients without a sibling donor. Results. The 6-year disease-free survival rate was similar in the groups with and without donor [38.2% (SE=5.9%) vs. 36.8% (SE=4.6%), hazard ratio 1.01, 95% CI 0.67-1.53]. Comparing the donor group with the no donor group, the former had a lower relapse incidence (38.2% vs. 56.3%, p=0.001), but a higher cumulative incidence of death in CR (23.5% vs. 6.9%, p=0.0004). The 6-year survival rates were similar [41.2% (SE=6.0%) vs. 38.8% (SE=4.6%)]. Interpretation and Conclusions. This trial did not show that allogeneic transplantation, when a sibling donor is available, produces a better outcome than the policy of offering autotransplantation or chemotherapy in the absence of a donor.
Disciplines :
Hematology
Author, co-author :
Labar, Boris
Suciu, Stefan
Zittoun, Robert
Muus, Petra
Marie, Jean-Pierre
Fillet, Georges ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie - Oncologie médicale
Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non-Hodgkin's lymphoma for patients <= 50 years old in first complete remission: results of the EORTC ALL-3 trial
Hoelzer D, Gökbuget N. New approaches to acute lymphoblastic leukemia in adults: where do we go? Semin Oncol 2000;27:540-9.
Rohatiner AZ, Bassan R, Battista R, Barnett MJ, Gregory W, Lim J, et al. High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukemia. Br J Cancer 1990;62:454-8.
Weiss M, Maslak P, Feldman E, Berman E, Bertino J, Gee T, et al. Cytarabine with high-dose mitoxantrone induces rapid complete remissions in adult acute lymphoblastic leukemia without the use of vincristine or prednisone. J Clin Oncol 1996;14:2480-5.
Gökbuget N, Hoelzer D. The role of high-dose cytarabine in induction therapy for adult ALL. Leuk Res 2002;26:473-6.
Kantarjian HM, O'Brien S, Smith TL, Cortes J, Giles FJ, Beran M, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 2000;18:547-61.
Linker CA, Levitt LJ, O'Donnell M, Forman SJ, Ries CA. Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 1991;78:2814-22.
Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood 2002;99:863-71.
Fière D, Lepage E, Sebban C, Bouchaix C, Gisselbrecht C, Vernant JP, et al. Adult acute lymphoblastic leukemia: a multicenter randomized trial testing bone marrow transplantation as postremission therapy. J Clin Oncol 1993;11:1990-2001.
Wheeler KA, Richards SM, Bailey CC, Gibson B, Hann IM, Hill FG, et al. Bone marrow transplantation versus chemotherapy in the treatment of very high-risk childhood acute lymphoblastic leukemia in first remission: results from Medical Research Council UKALL X and XI. Blood 2000;96:2412-8.
Ribera JM, Ortega JJ, Oriol A, Fontanillas M, Hernandez-Rivas JM, Brunet S, et al. Late intensification chemotherapy has not improved the results of intensive chemotherapy in adult acute lymphoblastic leukemia. Results of a prospective multicenter randomized trial (PETHEMA ALL-89). Haematologica 1998;83:222-30.
Larson RA, Dodge RK, Bloomfield CD, Schiffer CA. Treatment of biologically determined subsets of acute lymphoblastic leukemia in adults: Cancer and Leukemia Group B studies In: Buchner, T, Hiddeman, W, Wormann, B, et al. Acute Leukemias VI: Prognostic factors and treatment strategies, editors. Springer-Verlag, Berlin; 1997. p. 677.
Hoelzer D, Ludwig WD, Thiel E, Gassman W, Loffler H, Fonatsch C, et al. Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 1996;87:495-508.
Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M, et al. Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol 1999;17:2461-7.
Hoelzer D, Gökbuget N, Digel W, Faak T, Kneba M, Reutzel R, et al. Outcome of adult patients with T-lymphoblastic lymphoma treated according to protocols for acute lymphoblastic leukemia. Blood 2002;99:4379-85.
Stryckmans P, De Witte T, Marie JP, Fillet G, Peetermans M, Bury J, et al. Therapy of adult ALL: overview of 2 successive EORTC studies: (ALL-2; ALL-3). The EORTC Leukemia Cooperative Study Group. Leukemia 1992;Suppl 2:199.
Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft-versus-host disease after marrow transplantation for leukemia. N Engl J Med 1986;314:729-35.
De Witte T, Awwad B, Boezeman J, Schattenberg A, Muus P, Raemaekers J, et al. Role of allogenic bone marrow transplantation in adolescent or adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma in first remission. Bone Marrow Transplant 1994;14:767-74.
Gökbuget N, Hoelzer D, Arnold R, Bohme A, Bartram CR, Freund M, et al. Treatment of adult ALL according to the protocols of the German Multicenter Study Group for Adult ALL (GMALL). Hemat/Oncol Clin North Am 2000;14:1307-25.
Klein JP, Moeschberger ML. Survival analysis: techniques for censored and truncated data. Statistics for Biology and Health. Springer-Verlag, New-York. 1997.
Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988;16:1141-54.
Horowitz MM, Messerer D, Hoelzer D, Gale RP, Weiss A, Atkinson K, et al. Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission. Ann Intern Med 1991;115:13-8.
Zhang MJ, Hoelzer D, Horowitz MM, Gale RP, Messerer D, Klein JP, et al. Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. Ann Intern Med 1995;123:428-31.
Oh H, Gale RP, Zhang MJ, Passweg JR, Ino U, Murakami H, et al. Chemotherapy versus HLA-identical sibling transplants for adults with acute lymphoblastic leukemia in first remission. Bone Marrow Transplant 1998;22:253-7.
Thiebaut A, Vernant JP, Degos L, Huguet FR, Reiffers J, Sebban C, et al. Adult acute lymphocytic leukaemia study testing chemotherapy and autologous and allogeneic transplantation. Follow-up reports of the French protocol LALA 87 (Review). Hematol Oncol Clin North Am 2000;14:1353-66.
Gupta V, Yi QL, Brandwein J, Minden MD, Schuh AC, Wells RA, et al. The role of allogeneic bone marrow transplantation in adult patients below the age of 55 years with acute lymphoblastic leukemia in first complete remission: a donor vs no donor comparison. Bone Marrow Transplant 2004;33:397-404.
Horowitz MM, Rowlings PA. An update from the International Bone Marrow Transplant Registry and the Autologous Blood and Marrow Transplant Registry on current activity in hematopoietic stem cell transplantation. In: Current Opinion in Hematology, (Stossel TP, Goldman JM, Sander SG, editors). Rapid Science Publishers; Philadelphia: PA. 1997. p. 395-400.
Uderzo C, Balduzzi A, De Lorenzo P, Valsecchi MG, Gadner H, Klingebiel T, et al. EBMT Pediatric Working Group; I-BFM SG. Prospective study on allogeneic bone marrow transplantation (allo BMT) versus chemotherapy (chemo) for very high-risk (VHR) childhood acute lymphoblastic leukaemia in first complete remission. Bone Marrow Transplant 2001;28 Suppl 1:S22-4.
Weiner RS. Interstitial pneumonia following bone marrow transplantation. In: Recent Advances in Bone Marrow Transplantation, UCLA Symposia on Molecular and Cellular Biology, New Series, Volume 53, (Gale RP, Champlin RE, editors), Alan R. Liss, Inc., New York, NY, USA. 1987. p. 507-23. The Advisory Committee of the IBMTR.
Passweg JR, Tiberghien P, Cahn JY, Vowals MR, Camitta BM, Gale RP, et al. Graft versus leukemia effects in T-lineage and B-lineage acute lymphoblastic leukemia. Bone Marrow Transplant 1998;21:153-8.
Ringden O, Labopin M, Gorin NC, Schmitz N, Schaefer UW, Prentice HG, et al. Is there a graft-versus-leukaemia effect in the absence of graft-versus-host disease in patients undergoing bone marrow transplantation for acute leukaemia? Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. Br J Haematol 2000;111:1130-7.
Frassoni F, Labopin M, Gluckman E, Prentice HG, Vernant JP, Zwaan F, et al. Results of allogeneic bone marrow transplantation for acute leukemia have improved in Europe with time: a report of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 1996;17:13-8.