Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed, refractory, and transformed indolent non-Hodgkin's lymphoma.

PURPOSE Few effective treatment options exist for chemotherapy-refractory indolent or transformed non-Hodgkin's lymphoma (NHL). We examined the outcome of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in this setting. PATIENTS AND METHODS Sixty-two patients with indolent or transformed NHL were treated with allogeneic HCT from related (n = 34) or unrelated (n = 28) donors after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Nine unrelated donors were mismatched for >/= one HLA antigen. Sixteen patients had histologic transformation before HCT. Twenty patients (32%) had progressive disease after previous high-dose therapy with autologous HCT. Median age was 54 years, and patients had received a median of six lines of treatment before HCT. Median follow-up time after HCT was 36.6 months. RESULTS At 3 years, the estimated overall survival (OS) and progression-free survival (PFS) rates were 52% and 43%, respectively, for patients with indolent disease, and 18% and 21%, respectively, for patients with transformed disease. Patients with indolent disease and related donors (n = 26) had 3-year estimated OS and PFS rates of 67% and 54%, respectively. The incidences of grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 and 4 acute GVHD, and extensive chronic GVHD were 63%, 18%, and 47%, respectively. Among survivors, the median Karnofsky performance status at last follow-up was 85%. CONCLUSION Nonmyeloablative allogeneic HCT can produce durable disease-free survival in patients with relapsed or refractory indolent NHL, even in this relatively elderly and heavily pretreated cohort. Outcomes were particularly good in patients with untransformed disease and related donors, whereas patients with transformed disease did poorly. Long-term survivors reported good overall functional status.

[1]  A. Nademanee,et al.  Comparison of reduced-intensity and conventional myeloablative regimens for allogeneic transplantation in non-Hodgkin's lymphoma. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[2]  Y. Tanaka,et al.  Reduced-intensity hematopoietic stem-cell transplantation for malignant lymphoma: a retrospective survey of 112 adult patients in Japan , 2005, Bone Marrow Transplantation.

[3]  J. Radich,et al.  HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

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

[5]  C. Craddock,et al.  Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. , 2004, Blood.

[6]  R. Gascoyne,et al.  Long‐term disease‐free survival of patients with advanced follicular lymphoma after allogeneic bone marrow transplantation , 2004, British journal of haematology.

[7]  P. Mclaughlin,et al.  Nonmyeloablative allogeneic hematopoietic transplantation: a promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  Ruta Bajorunaite,et al.  Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. , 2003, Blood.

[9]  R. Storb,et al.  Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. , 2003, Blood.

[10]  S. Heimfeld,et al.  HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. , 2003, Blood.

[11]  E. Jaffe Pathology and Genetics: Tumours of Haematopoietic and Lymphoid Tissues , 2003 .

[12]  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.

[13]  B. Quesnel,et al.  Allogeneic bone marrow transplantation in patients with follicular lymphoma: a single center study , 2002, Bone Marrow Transplantation.

[14]  P. Mclaughlin,et al.  Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. , 2001, Blood.

[15]  P. Bierman Allogeneic bone marrow transplantation for lymphoma. , 2000, Blood reviews.

[16]  J. Armitage,et al.  Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Anajane G. Smith,et al.  Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. , 1998, Blood.

[18]  J. Armitage,et al.  Allogeneic bone marrow transplantation for low-grade lymphoma. , 1998, Blood.

[19]  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.

[20]  L. Verdonck,et al.  Allogeneic versus autologous bone marrow transplantation for refractory and recurrent low-grade non-Hodgkin's lymphoma. , 1997, Blood.

[21]  B. Nathwani,et al.  A clinical evaluation of the International Lymphoma Study Group Classification of non-Hodgkin's lymphoma: a report of the Non-Hodgkin's Lymphoma Classification Project , 1997 .

[22]  E D Thomas,et al.  1994 Consensus Conference on Acute GVHD Grading. , 1995, Bone marrow transplantation.

[23]  K. Sullivan,et al.  Chronic graft-versus-host disease and other late complications of bone marrow transplantation. , 1991, Seminars in hematology.

[24]  E. Berg,et al.  World Health Organization Classification of Tumours , 2002 .

[25]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.