Treatment-related mortality and graft-versus-leukemia activity after allogeneic stem cell transplantation for chronic lymphocytic leukemia using intensity-reduced conditioning

Autor: Giorgio Lambertenghi Deliliers, Donald Milligan, Peter Dreger, Rodrigo Martino, Nigel H. Russell, Dietger Niederwieser, Paolo Corradini, Jürgen Finke, A. van Biezen, Mauricette Michallet, J Hansz, Ronald Brand
Rok vydání: 2003
Předmět:
Adult
Male
Melphalan
Cancer Research
medicine.medical_specialty
Transplantation Conditioning
medicine.medical_treatment
Lymphocyte
Chronic lymphocytic leukemia
Graft vs Host Disease
Gastroenterology
Disease-Free Survival
Lymphocyte Depletion
Cohort Studies
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Transplantation
Homologous
Busulfan
Aged
Neoplasm Staging
Retrospective Studies
Chemotherapy
business.industry
Remission Induction
Hazard ratio
Hematopoietic Stem Cell Transplantation
Hematology
Middle Aged
Total body irradiation
medicine.disease
Leukemia
Lymphocytic
Chronic
B-Cell
Surgery
Survival Rate
Transplantation
Leukemia
Treatment Outcome
medicine.anatomical_structure
Oncology
Female
Neoplasm Recurrence
Local
business
Vidarabine
Whole-Body Irradiation
medicine.drug
Zdroj: Leukemia. 17:841-848
ISSN: 1476-5551
0887-6924
DOI: 10.1038/sj.leu.2402905
Popis: Allogeneic stem cell transplantation (SCT) using reduced-intensity conditioning (RIC) has potential to be a promising treatment of aggressive chronic lymphocytic leukemia (CLL). Since available clinical data obtained with this novel approach are very limited, we have performed a survey on this issue. Data of 77 patients were collected from 29 European Group for Blood and Marrow Transplantation centers. Median age was 54 (30-66) years, and the median number of previous chemotherapy regimens was 3 (0-8). HLA-identical sibling donors were used in 81% of the cases. Moderate conditioning regimens (mainly low-dose total body irradiation (TBI) or fludarabine-cyclophosphamide combinations) were administered to 56% of the patients, whereas the remainder received more intense conditioning consisting of fludarabine-busulfan or high-dose melphalan combinations. In 40% of the patients, in vivo T-cell depletion (TCD) with anti-thymocyte globulin or CAMPATH-1H was part of the conditioning regimen. Cumulative treatment-related mortality (TRM) was 18% (95% CI 9; 27) after 12 months. Complete chimerism as well as best response was not achieved immediately post-transplant but took a median of 3 months to develop. The 2-year probability of relapse was 31% (95% CI 18; 44), with no event occurring later than 12 months post transplant in the absence of TCD. With one exception, relapses were not observed after onset of chronic graft-versus-host disease. Event-free and overall survival at 24 months were 56% (95% CI 43; 69) and 72% (95% CI 61; 83), respectively. The median follow-up was 18 (1-44) months. Donor lymphocyte infusions or secondary transplants were performed in 19 patients with insufficient disease control and/or incomplete donor chimerism post-transplant, leading to a response in seven patients (37%). Preliminary multivariate analysis identified less than PR at transplant (hazard ratio (HR) 3.5; P0.01) and alternative donor (HR 3.1; P=0.02) as significant risk factors for relapse, whereas number of previous regimens2 (HR 5.4; P=0.03), TBI (HR 2.5; P=0.05), and alternative donor (HR 2.3; P=0.08) were risk factors for survival. We conclude that RIC might favorably influence the outcome after allogeneic SCT for CLL by reducing TRM while preserving graft-versus leukemia activity.
Databáze: OpenAIRE
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