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

Leukemia. 2003 May;17(5):841-8. doi: 10.1038/sj.leu.2402905.

Abstract

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; P&<0.01) and alternative donor (HR 3.1; P=0.02) as significant risk factors for relapse, whereas number of previous regimens >2 (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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Busulfan / administration & dosage
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / mortality*
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / etiology
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality*
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / etiology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / therapy
  • Neoplasm Staging
  • Remission Induction
  • Retrospective Studies
  • Survival Rate
  • Transplantation Conditioning*
  • Transplantation, Homologous
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives*
  • Whole-Body Irradiation

Substances

  • Vidarabine
  • Busulfan
  • fludarabine