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)

Results of reduced intensity conditioning regimen (RIC) in the HLA identical haematopoietic stem cell transplantation (HSCT) setting have not been compared to those after myeloablative (MA) regimen HSCT in patients with acute myeloblastic leukaemia (AML) over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients. The majority of RIC was fludarabine-based regimen associated to busulphan (BU) (53%) or low-dose total body irradiation (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older, transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, acute GVHD (II–IV) and transplant-related mortality were significantly decreased (P=0.01 and P<10−4, respectively) and relapse incidence was significantly higher (P=0.003) after RIC transplantation. Leukaemia-free survival was not statistically different between the two groups. These results may set the grounds for prospective trials comparing RIC with other strategies of treatment in elderly AML.

[1]  A. Nagler,et al.  Non-myeloablative stem cell transplantation (NST): chimerism testing as guidance for immune-therapeutic manipulations , 2001, Leukemia.

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

[3]  N. Kröger,et al.  Hematopoietic stem-cell transplantation from unrelated donors in elderly patients (age>55 years) with hematologic malignancies: older age is no longer a contraindication when using reduced intensity conditioning , 2005, Leukemia.

[4]  M. Maris,et al.  Comparison of lung function after myeloablative and 2 Gy of total body irradiation-based regimens for hematopoietic stem cell transplantation. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[5]  E. Estey,et al.  Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. , 1997, Blood.

[6]  R. Storb,et al.  Serious graft-versus-host disease after hematopoietic cell transplantation following nonmyeloablative conditioning , 2005, Bone Marrow Transplantation.

[7]  J. Sierra,et al.  Effect of centre on outcome of bone-marrow transplantation for acute myeloid leukaemia , 2000, The Lancet.

[8]  A. Nagler,et al.  Non-myeloablative hematopoietic stem cell transplantation (NST) in the treatment of human malignancies: from animal models to clinical practice. , 2002, Cancer treatment and research.

[9]  R. Storb,et al.  Low-intensity allogeneic hematopoietic stem cell transplantation for myeloid malignancies: separating graft-versus-leukemia effects from graft-versus-host disease , 2005, Current opinion in hematology.

[10]  C. Flowers,et al.  Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. , 2004, Blood.

[11]  J P Klein,et al.  Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests. , 1999, Statistics in medicine.

[12]  E. Estey,et al.  Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years. , 2003, Blood.

[13]  A. Nagler,et al.  Nonmyeloablative stem cell transplantation: lessons from the first decade of clinical experience. , 2004, Current hematology reports.

[14]  Robert Gray,et al.  A Proportional Hazards Model for the Subdistribution of a Competing Risk , 1999 .

[15]  A. Rimm,et al.  Graft-versus-leukemia reactions after bone marrow transplantation. , 1990, Blood.

[16]  J. Gribben,et al.  Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age. , 2004, Blood.

[17]  C. Flowers,et al.  Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. , 2004, Blood.

[18]  P. Hougaard,et al.  Frailty models for survival data , 1995, Lifetime data analysis.

[19]  S. Slavin,et al.  Reduced-intensity conditioning for the treatment of malignant and life-threatening non-malignant disorders. , 2003, Clinical transplants.

[20]  D. Blaise,et al.  The role of reduced intensity conditioning allogeneic stem cell transplantation in patients with acute myeloid leukemia: a donor vs no donor comparison , 2005, Leukemia.

[21]  J. Radich,et al.  Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  M. Maris,et al.  Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. , 2003, Blood.

[23]  R. Champlin,et al.  Allogeneic hematopoietic transplantation for acute and chronic myeloid leukemia: Non-myeloablative preparative regimens and induction of the graft-versus-leukemia effect , 2000, Current oncology reports.

[24]  N. Ueno,et al.  Harnessing graft-versus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy. , 2000, British journal of haematology.

[25]  J. Finke,et al.  Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  H. Einsele,et al.  Outcomes for reduced-intensity allogeneic transplantation for multiple myeloma: an analysis of prognostic factors from the Chronic Leukaemia Working Party of the EBMT. , 2005, Blood.

[27]  J. Radich,et al.  Hematopoietic cell transplantation from HLA-identical sibling donors after low-dose radiation-based conditioning for treatment of CML , 2005, Leukemia.

[28]  M. Labopin,et al.  The highest leukaemia-free survival after allogeneic bone marrow transplantation is seen in patients with grade I acute graft-versus-host disease. Acute and Chronic Leukaemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT). , 1996, Leukemia & lymphoma.

[29]  R. Storb Nonmyeloablative preparative regimens: how relevant for acute myelogenous leukemia? , 2001, Leukemia.

[30]  K. Cleary,et al.  Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. , 2004, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[31]  A A Rimm,et al.  Outcome after allogeneic bone marrow transplant for leukemia in older adults. , 1993, JAMA.

[32]  A. Nagler,et al.  Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. , 1998, Blood.

[33]  S. Slavin Reduced intensity versus truly nonmyeloablative conditioning for stem-cell transplant recipients. , 2004, Transplantation.

[34]  J. Radich,et al.  Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. , 2001, Blood.

[35]  M. Sorror,et al.  Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning , 2004 .

[36]  M. Labopin,et al.  Retrospective evaluation of autologous bone marrow transplantation vs allogeneic bone marrow transplantation from an HLA identical related donor in acute myelocytic leukemia. A study of the European Cooperative Group for Blood and Marrow Transplantation (EBMT). , 1996, Bone marrow transplantation.