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

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. (Blood. 2002;100:3919-3924)

High‐dose therapy and autologous peripheral blood stem cells transplantation followed by a very low reduced intensity regimen with fludarabine + cyclophosphamide and allograft improve complete remission rate in de novo multiple myeloma patients

“…The median OS was 15 months and it was better in patients who received the RICT as planned consolidation of a single autograft. The two-step approach was also employed with success by Kro¨ger et al [21] in 42 patients with unrelated/mismatched donors. Carella et al [22] confirmed the feasibility of the sequential combination of APBSCT and RICT.…”

Allo-SCT for multiple myeloma in the era of novel agents: a retrospective study on behalf of Swiss Blood SCT

“…23,24,[40][41][42][43][44] This is not surprising, because irrespective of the treatment modality analyzed, relapsed and refractory patients will inherently have a shorter PFS and OS than patients in first remission. However, in contrast to earlier studies, new agents were available to most of our patients who relapsed after allogeneic transplantation.…”

In pursuit of the allo-immune response in multiple myeloma: where do we go from here?

“…Encouraging results have been reported, with a TRM of B20-21% at 2 and 3 years. 34,35 Clearly, further prospective trials are warranted to define better the role of RIC MUD Allo SCT for patients with myeloma.…”

“…33 The role of RIC MUD AlloSCT remains to be defined although recent results have reported a TRM of B20%. 33,34 Clearly, further prospective trials are warranted to better define the role of RIC MUD Allo SCT for patients in the first treatment phase for myeloma. Similarly, the use of umbilical cord stem cells as a source for GvM has been reported in a limited number of case reports, but only in patients with advanced disease, 39,40 and again should be explored only as part of a clinical study protocol.…”