Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation.

This retrospective study assessed the outcome of 576 adult acute lymphoblastic leukemia patients aged ≥ 45 years, and who received a reduced-intensity conditioning (RIC; n = 127) or myeloablative conditioning (MAC; n = 449) allogeneic stem cell transplantation (allo-SCT) from a human leukocyte antigen-identical sibling while in complete remission. With a median follow-up of 16 months, at 2 years, the cumulative incidences of nonrelapse mortality and relapse incidence were 29% ± 2% (MAC) versus 21% ± 5% (RIC; P = .03), and 31% ± 2% (MAC) versus 47% ± 5% (RIC; P < .001), respectively. In a multivariate analysis, nonrelapse mortality was decreased in RIC recipients (P = .0001, hazard ratio [HR] = 1.98) whereas it was associated with higher relapse rate (P = .03, HR = 0.59). At 2 years, LFS was 38% ± 3% (MAC) versus 32% ± 6% (RIC; P = .07). In multivariate analysis, the type of conditioning regimen (RIC vs. MAC) was not significantly associated with leukemia-free survival (P = .23, HR = 0.84). Despite the need for randomized trials, we conclude that RIC allo-SCT from a human leukocyte antigen-identical donor is a potential therapeutic option for acute lymphoblastic leukemia patients aged ≥ 45 years in complete remission and not eligible for MAC allo-SCT.

[1]  J. Szer,et al.  The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission. , 2010, Blood.

[2]  D. Kaufman,et al.  Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  S. Lee,et al.  Reduced-intensity conditioning allogeneic stem cell transplantation is a potential therapeutic approach for adults with high-risk acute lymphoblastic leukemia in remission: results of a prospective phase 2 study , 2009, Leukemia.

[4]  D. Weisdorf,et al.  Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. , 2009, Blood.

[5]  J. Baars,et al.  Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. , 2009, Blood.

[6]  J. Cornelissen,et al.  Allogeneic stem cell transplantation in acute myeloid leukemia in first or subsequent remission: weighing prognostic markers predicting relapse and risk factors for non-relapse mortality. , 2008, Seminars in oncology.

[7]  M. Labopin,et al.  Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation , 2008, Haematologica.

[8]  M. Tallman,et al.  In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: fin , 2006, Blood.

[9]  F. Appelbaum,et al.  The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myelogenous leukemia in adults: an evidence-based review. , 2008, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[10]  G. Mufti,et al.  Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. , 2006, Blood.

[11]  H. Heslop,et al.  The clinical use of LMP2-specific cytotoxic T lymphocytes for the treatment of relapsed EBV +ve Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) , 2006 .

[12]  C. Pui,et al.  Treatment of acute lymphoblastic leukemia. , 2006, The New England journal of medicine.

[13]  R. Larson,et al.  The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[14]  A. Nagler,et al.  Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity , 2006, Leukemia.

[15]  J. Esteve,et al.  Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) , 2005, Leukemia.

[16]  M. Tallman,et al.  Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. , 2005, Blood.

[17]  G. Ledderose,et al.  Ph Philadelphia-positive acute lymphoblastic leukemia + outcome in MRD Early molecular response to posttransplantation imatinib determines , 2005 .

[18]  M. Sorror,et al.  Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. , 2005, Blood.

[19]  J. Hernández-Rivas,et al.  Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial. , 2005, Haematologica.

[20]  M. Béné,et al.  Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. , 2004, Blood.

[21]  H. Dombret,et al.  Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  K. Yamada,et al.  Eradication of residual bcr-abl-positive clones by inducing graft-versus-host disease after allogeneic stem cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia , 2002, Bone Marrow Transplantation.

[23]  S. Slavin,et al.  Immunotherapy of cancer with alloreactive lymphocytes. , 2001, The Lancet. Oncology.

[24]  J. Nomdedéu,et al.  Rituximab can be useful as treatment for minimal residual disease in bcr-abl-positive acute lymphoblastic leukemia , 2001, Bone Marrow Transplantation.

[25]  J Crowley,et al.  Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. , 1999, Statistics in medicine.

[26]  C. Sebban,et al.  Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia. , 1994, Journal of Clinical Oncology.