Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin’s lymphoma: identification of prognostic factors predicting outcome

The findings of this study suggest that for patients with Hodgkin’s lymphoma in whom an autologous transplant is deemed to be at high risk of failing, a reduced intensity conditioning allogeneic stem cell transplantation may represent a more effective therapy. Background The role of reduced intensity conditioning allogeneic stem transplantation (RICalloSCT) in the management of patients with Hodgkin’s lymphoma remains controversial. Design and Methods To further define its role we have conducted a retrospective analysis of 285 patients with HL who underwent a RICalloSCT in order to identify prognostic factors that predict outcome. Eighty percent of patients had undergone a prior autologous stem cell transplantation and 25% had refractory disease at transplant. Results Non-relapse mortality was associated with chemorefractory disease, poor performance status, age >45 and transplantation before 2002. For patients with no risk factors the 3-year non-relapse mortality rate was 12.5% compared to 46.2% for patients with 2 or more risk factors. The use of an unrelated donor had no adverse effect on the non-relapse mortality. Acute graft versus host disease (aGVHD) grades II–IV developed in 30% and chronic GVHD in 42%. The development of cGVHD was associated with a lower relapse rate. The disease progression rate at one and five years was 41% and 58.7% respectively and was associated with chemorefractory disease and extent of prior therapy. Donor lymphocyte infusions were administered to 64 patients for active disease of whom 32% showed a clinical response. Eight out of 18 patients receiving donor lymphocyte infusions alone had clinical responses. Progression-free and overall survival were both associated with performance status and disease status at transplant. Patients with neither risk factor had a 3-year PFS and overall survival of 42% and 56% respectively compared to 8% and 25% for patients with one or more risk factors. Relapse within six months of a prior autologous transplant was associated with a higher relapse rate and a lower progression-free. Conclusions This analysis identifies important clinical parameters that may be useful in predicting the outcome of RICaIICalloSCT in Hodgkin’s lymphoma.

[1]  N. Schmitz,et al.  Reduced-intensity conditioning compared with conventional allogeneic stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma: an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  J. Garcia-conde,et al.  Reduced‐intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long‐term outcomes , 2007, British journal of haematology.

[3]  J. Garcia-conde,et al.  Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[4]  G. Mufti,et al.  Reduced Intensity Allogeneic Transplantation Using BEAM-Alemtuzumab in Patients with Lymphoid Malignancy: Long Term Results and Impact of Intervention with DLI. , 2005 .

[5]  S. Mackinnon,et al.  Improved outcome following reduced intensity allogeneic transplantation in Hodgkin's lymphoma relapsing post-autologous transplantation , 2005 .

[6]  G. Hill,et al.  A prognostic model for prolonged event-free survival after autologous or allogeneic blood or marrow transplantation for relapsed and refractory Hodgkin's disease , 2005, Bone Marrow Transplantation.

[7]  A. Nademanee,et al.  Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study. , 2005, Blood.

[8]  N. Ueno,et al.  Reduced-intensity allogeneic stem cell transplantation in relapsed and refractory Hodgkin's disease: low transplant-related mortality and impact of intensity of conditioning regimen , 2005, Bone Marrow Transplantation.

[9]  J. Friedberg,et al.  Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  S. Mackinnon,et al.  Use of 18F‐FDG positron emission tomography following allogeneic transplantation to guide adoptive immunotherapy with donor lymphocyte infusions , 2005, British journal of haematology.

[11]  M. Czuczman,et al.  A prognostic model for prolonged event-free survival after autologous or allogeneic blood or marrow transplantation for relapsed and refractory Hodgkin's disease , 2005, Bone Marrow Transplantation.

[12]  J. Cox,et al.  Prognostic factors for disease progression after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for recurrent or refractory Hodgkin's lymphoma , 2004, Bone Marrow Transplantation.

[13]  S. Mackinnon,et al.  Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses. , 2004, Blood.

[14]  M. Maris,et al.  HLA-matched related (MRD) or unrelated donor (URD) nonmyeloablative conditioning and hematopoietic cell transplant (HCT) for patients with advanced Hodgkin disease (HD) , 2004 .

[15]  G. Mufti,et al.  BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients. , 2004, Blood.

[16]  N. Schmitz,et al.  Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. , 2002, Blood.

[17]  J. Garcia-conde,et al.  Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. , 2002, Blood.

[18]  C. Craddock,et al.  Role of nonmyeloablative allogeneic stem-cell transplantation after failure of autologous transplantation in patients with lymphoproliferative malignancies. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  Dirk Hasenclever,et al.  Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial , 2002, The Lancet.

[20]  C. Craddock,et al.  Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. , 2002, Blood.

[21]  I. Flinn,et al.  Long-term results of blood and marrow transplantation for Hodgkin's lymphoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  N. Keiding,et al.  Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling , 2001, Bone Marrow Transplantation.

[23]  A. López-Guillermo,et al.  Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  A. Romanelli,et al.  Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  N. Schmitz,et al.  High-Dose Therapy and Autologous Stem-Cell Transplantation for Adult Patients With Hodgkin's Disease Who Do Not Enter Remission After Induction Chemotherapy: Results in 175 Patients Reported to the European Group for Blood and Marrow Transplantation , 1999 .

[26]  N. Ueno,et al.  Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  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.

[28]  A. Fielding,et al.  Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin's disease. European Group for Blood and Bone Marrow Transplantation. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  J. Armitage,et al.  Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  S. Crawford,et al.  Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  D. Winfield,et al.  Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial , 1993, The Lancet.

[32]  S. Piantadosi,et al.  Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation. , 1991, Blood.