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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-04-1150.
Submitted April 16, 2002
Accepted July 3, 2002
Unrelated stem cell transplantation in multiple myeloma after a reduced intensity conditioning with pretransplant anti-thymocyte globulin is highly effective with low transplantation related mortality
Nicolaus Kroger*, 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
Bone Marrow Transplantation, University Hospital Hamburg, Hamburg, Germany
Department of Oncology and Hematology, University Jena, Jena, Germany
Department of Bone Marrow Transplantation, Wiesbaden, Wiesbaden, Germany
Department of Bone Marrow Transplantation, Idar-Oberstein, Idar-Oberstein, Germany
Department of Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel
Department of Hematology, AK St. Georg, Hamburg, Germany
* Corresponding author; email: nkroeger{at}uke.uni-hamburg.de.
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 anti-thymocyte globulin (ATG: 3x10mg/kg). The median patient age was 50 years (range 32-61). 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-IV acute Graft versus host disease (GvHD) was seen in 8 (38%), while severe grade III/IV GvHD was observed in 4 patients (19%). Six patients (37%) developed chronic GvHD, but only two patients (12%) experienced extensive chronic GvHD. The estimated probability of non-relapse mortality at day 100 was 10% and at one year 26%. After allografting 40% of the patients achieved a complete remission, while 50% achieved a partial remission, resulting in an overall response rate of 90%. After a median follow-up of 13 months, the 2 years estimated overall and progression-free survival is 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% vs 86%, p=0.04). Dose-reduced conditioning with pretransplant 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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