High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions

Standard allogeneic stem cell transplant (allo-SCT) regimens have been asso ciated with a high transplant-related mortality (TRM) in multiple myeloma ( MM). Non-myeloablative therapy can establish stable engraftment after allo- SCT and maintain the antitumor effect with less toxicity, which is importan t in heavily pretreated and elderly patients. We report on 16 poor-risk MM patients receiving allo-SCT from an HLA-matched (n = 14) or mismatched (0 = 2) sibling following conditioning with melphalan 100 mg/m(2) (MEL-100). Te n patients had refractory relapse, 4 responsive relapse, and 2 patients wer e in near complete remission (nCR) with poor-prognosis disease. Patients ha d received 1 (n = 9) or 2 (n = 7) prior autotransplants. Donor lymphocyte i nfusions (DLIs) were given to 14 patients with no clinical evidence of graf t versus host disease (GVHD) either to attain full donor chimerism (0 = 4) or to eradicate residual disease (n = 10). Fifteen patients showed myeloid engraftment, and 12 patients were full donor chimeras at day +21. No TRM wa s observed during the first 100 days. Acute GVHD developed in 10 patients; 1 had fatal grade IV GVHD, Seven progressed to chronic GVHD, limited in 3 a nd extensive in 4 patients. At a median follow-up of 1 year, 5 patients ach ieved and sustained CR, 3 nCR, and 4 partial remission. Of 4 patients progr essing after transplantation, 3 achieved a remission following further chem otherapy and DLI. Remarkable graft versus myeloma responses were seen in ch emotherapy-refractory patients. Two patients died of progressive disease, a nd 3 died of GVHD complications without active disease. GVHD remains a majo r problem with this procedure. (Blood, 2001;97: 2574-2579) (C) 2001 by The American Society of Hematology.