Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning

J Clin Oncol. 2005 Mar 20;23(9):1993-2003. doi: 10.1200/JCO.2005.08.136.

Abstract

Purpose: We have used a nonmyeloablative conditioning regimen consisting of total-body irradiation (2 Gy) with or without fludarabine (30 mg/m(2)/d for 3 days) for related and unrelated hematopoietic cell transplantation (HCT) in patients with hematologic malignancies who were not candidates for conventional HCT because of age, medical comorbidities, or preceding high-dose HCT. This approach relied on graft-versus-tumor (GVT) effects for control of malignancy.

Patients and methods: We analyzed GVT effects in 322 patients given grafts from HLA-matched related (n = 192) or unrelated donors (n = 130).

Results: Of the 221 patients with measurable disease at HCT, 126 (57%) achieved complete (n = 98) or partial (n = 28) remissions. In multivariate analysis, there was a higher probability trend of achieving complete remissions in patients with chronic extensive graft-versus-host disease (GVHD; P = .07). One hundred eight patients (34%) relapsed or progressed. In multivariate analysis, achievement of full donor chimerism was associated with a decreased risk of relapse or progression (P = .002). Grade 2 to 4 acute GVHD had no significant impact on the risk of relapse or progression but was associated with increased risk of nonrelapse mortality and decreased probability of progression-free survival (PFS). Conversely, extensive chronic GVHD was associated with decreased risk of relapse or progression (P = .006) and increased probability of PFS (P = .003).

Conclusion: New approaches aimed at reducing the incidence of grade 2 to 4 acute GVHD might improve survival after allogeneic HCT after nonmyeloablative conditioning.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Comorbidity
  • Female
  • Graft Rejection
  • Graft vs Tumor Effect / drug effects*
  • Graft vs Tumor Effect / radiation effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Leukemia / mortality
  • Leukemia / therapy*
  • Male
  • Middle Aged
  • Probability
  • Transplantation Conditioning / methods*
  • Treatment Outcome
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Vidarabine
  • fludarabine