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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-04-1150.
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Blood, 1 December 2002, Vol. 100, No. 12, pp. 3919-3924
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Unrelated stem cell transplantation in multiple myeloma after a
reduced-intensity conditioning with pretransplantation antithymocyte
globulin is highly effective with low transplantation-related
mortality
Nicolaus Kröger,
Herbert Gottfried Sayer,
Rainer Schwerdtfeger,
Michael Kiehl,
Arnon Nagler,
Helmut Renges,
Tatjana Zabelina,
Boris Fehse,
Francis Ayuk,
Georg Wittkowsky,
Norbert Schmitz, and
Axel Rolf Zander
From the Department of Bone Marrow Transplantation,
University Hospital Hamburg-Eppendorf, and Department of Hematology,
A. K. St Georg, Hamburg, Germany; Department of Oncology and
Hematology, University of Jena, Germany; Department of Bone Marrow
Transplantation, DKD-Clinic, Wiesbaden, Germany; Bone Marrow
Transplantation Clinic, Idar-Oberstein, Germany; and Chaim Sheba
Medical Center, Tel Hashomer, Israel.
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/m2), melphalan (100-140 mg/m2), 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.
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