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

• Published in: Blood 2001-05, Vol.97 (9), p.2574-2579
• Main Authors: Badros, Ashraf, Barlogie, Bart, Morris, Christopher, Desikan, Raman, Martin, Sara R., Munshi, Nikhil, Zangari, Maurizio, Mehta, Jayesh, Toor, Amir, Cottler-Fox, Michele, Fassas, Athanasios, Anaissie, Elias, Schichman, Steven, Tricot, Guido
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Lymphocyte Transfusion; Male; Medical sciences; Middle Aged; Multiple Myeloma - pathology; Multiple Myeloma - therapy; Myeloablative Agonists - therapeutic use; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Homologous; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V97.9.2574

Standard allogeneic stem cell transplant (allo-SCT) regimens have been associated with a high transplant-related mortality (TRM) in multiple myeloma (MM). Nonmyeloablative therapy can establish stable engraftment after allo-SCT and maintain the antitumor effect with less toxicity, which is important 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 (n = 2) sibling following conditioning with melphalan 100 mg/m2 (MEL-100). Ten patients had refractory relapse, 4 responsive relapse, and 2 patients were in near complete remission (nCR) with poor-prognosis disease. Patients had received 1 (n = 9) or 2 (n = 7) prior autotransplants. Donor lymphocyte infusions (DLIs) were given to 14 patients with no clinical evidence of graft versus host disease (GVHD) either to attain full donor chimerism (n = 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 was 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 and extensive in 4 patients. At a median follow-up of 1 year, 5 patients achieved and sustained CR, 3 nCR, and 4 partial remission. Of 4 patients progressing after transplantation, 3 achieved a remission following further chemotherapy and DLI. Remarkable graft versus myeloma responses were seen in chemotherapy-refractory patients. Two patients died of progressive disease, and 3 died of GVHD complications without active disease. GVHD remains a major problem with this procedure.