Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality

Blood. 2002 Dec 1;100(12):3919-24. doi: 10.1182/blood-2002-04-1150. Epub 2002 Aug 8.

Abstract

We investigated the feasibility of unrelated stem cell transplantation in 21 patients with advanced stage II/III multiple myeloma after a reduced-intensity conditioning regimen consisting of fludarabine (150 mg/m(2)), melphalan (100-140 mg/m(2)), and antithymocyte globulin (ATG; 10 mg/kg on 3 days). The median patient age was 50 years (range, 32-61 years). All patients had received at least one prior autologous transplantation, in 9 cases as part of an autologous-allogeneic tandem protocol. No graft failure was observed. At day 40 complete donor chimerism was detected in all patients. Grade II to IV acute graft-versus-host disease (GVHD) was seen in 8 patients (38%), and severe grade III/IV GVHD was observed in 4 patients (19%). Six patients (37%) developed chronic GVHD, but only 2 patients (12%) experienced extensive chronic GVHD. The estimated probability of nonrelapse mortality at day 100 was 10% and at 1 year was 26%. After allografting, 40% of the patients achieved a complete remission, and 50% achieved a partial remission, resulting in an overall response rate of 90%. After a median follow-up of 13 months, the 2-year estimated overall and progression-free survival rates are 74% (95% CI, 54%-94%) and 53% (95% CI, 29%-87%), respectively. A shorter progression-free survival was seen in patients who already experienced relapse to prior autograft (26% versus 86%, P =.04). Dose-reduced conditioning with pretransplantation ATG followed by unrelated stem cell transplantation provides durable engraftment and donor chimerism, reduces substantially the risk of transplant-related organ toxicity, and induces high remission rates.

Publication types

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

MeSH terms

  • Adult
  • Antilymphocyte Serum / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Feasibility Studies
  • Female
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation Conditioning / mortality
  • Transplantation, Homologous / adverse effects
  • Transplantation, Homologous / methods
  • Transplantation, Homologous / mortality
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives*

Substances

  • Antilymphocyte Serum
  • Vidarabine
  • fludarabine
  • Melphalan