TY - JOUR
T1 - Nonmyeloablative Unrelated Donor Hematopoietic Cell Transplantation to Treat Patients with Poor-Risk, Relapsed, or Refractory Multiple Myeloma
AU - Georges, George E.
AU - Maris, Michael B.
AU - Maloney, David G.
AU - Sandmaier, Brenda M.
AU - Sorror, Mohamed L.
AU - Shizuru, Judith A.
AU - Lange, Thoralf
AU - Agura, Edward D.
AU - Bruno, Benedetto
AU - McSweeney, Peter A.
AU - Pulsipher, Michael A.
AU - Chauncey, Thomas R.
AU - Mielcarek, Marco
AU - Storer, Barry E.
AU - Storb, Rainer
N1 - Funding Information:
This work was supported in part by National Institute of Health grants CA78902, CA18029, CA15704, and CA92058. The authors are very grateful to all of the patients and donors who participated in this study. They also thank research nurses John Sedgwick, Mary Hinds, and Steve Minor and data coordinator Debbie Bassuk for their invaluable help in making the study possible; Drs. Leona Holmberg and William Bensinger for their thoughtful review of the manuscript; Helen Crawford and Bonnie Larson for their help with manuscript preparation; and all physicians, nurses, and support personnel for their very dedicated care of the patients in this study.
PY - 2007/4
Y1 - 2007/4
N2 - The purpose of this study was to determine long-term outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in patients with poor-risk multiple myeloma. A total of 24 patients were enrolled; 17 patients (71%) had chemotherapy-refractory disease, and 14 (58%) experienced disease relapse or progression after previous autologous transplantation. Thirteen patients underwent planned autologous transplantation followed 43-135 days later with unrelated transplantation, whereas 11 proceeded directly to unrelated transplantation. All 24 patients were treated with fludarabine (90 mg/m2) and 2 Gy of total body irradiation before HLA-matched unrelated peripheral blood stem cell transplantation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median follow-up was 3 years after allografting. One patient experienced nonfatal graft rejection. The incidences of acute grades II and III and chronic graft-versus-host disease were 54%, 13%, and 75%, respectively. The 3-year nonrelapse mortality (NRM) was 21%. Complete responses were observed in 10 patients (42%); partial responses, in 4 (17%). At 3 years, overall survival (OS) and progression-free survival (PFS) rates were 61% and 33%, respectively. Patients receiving tandem autologous-unrelated transplantation had superior OS and PFS (77% and 51%) compared with patients proceeding directly to unrelated donor transplantation (44% and 11%) (PFS P value = .03). In summary, for patients with poor-risk, relapsed, or refractory multiple myeloma, cytoreductive autologous HCT followed by nonmyeloablative conditioning and unrelated HCT is an effective treatment approach, with low NRM, high complete remission rates, and prolonged disease-free survival.
AB - The purpose of this study was to determine long-term outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in patients with poor-risk multiple myeloma. A total of 24 patients were enrolled; 17 patients (71%) had chemotherapy-refractory disease, and 14 (58%) experienced disease relapse or progression after previous autologous transplantation. Thirteen patients underwent planned autologous transplantation followed 43-135 days later with unrelated transplantation, whereas 11 proceeded directly to unrelated transplantation. All 24 patients were treated with fludarabine (90 mg/m2) and 2 Gy of total body irradiation before HLA-matched unrelated peripheral blood stem cell transplantation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median follow-up was 3 years after allografting. One patient experienced nonfatal graft rejection. The incidences of acute grades II and III and chronic graft-versus-host disease were 54%, 13%, and 75%, respectively. The 3-year nonrelapse mortality (NRM) was 21%. Complete responses were observed in 10 patients (42%); partial responses, in 4 (17%). At 3 years, overall survival (OS) and progression-free survival (PFS) rates were 61% and 33%, respectively. Patients receiving tandem autologous-unrelated transplantation had superior OS and PFS (77% and 51%) compared with patients proceeding directly to unrelated donor transplantation (44% and 11%) (PFS P value = .03). In summary, for patients with poor-risk, relapsed, or refractory multiple myeloma, cytoreductive autologous HCT followed by nonmyeloablative conditioning and unrelated HCT is an effective treatment approach, with low NRM, high complete remission rates, and prolonged disease-free survival.
KW - Allogeneic hematopoietic cell transplantation
KW - Chronic graft-versus-host disease
KW - Graft-versus-tumor effect
KW - Multiple myeloma
KW - Nonmyeloablative conditioning
KW - Peripheral blood stem cell transplantation
KW - Unrelated donor
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U2 - 10.1016/j.bbmt.2006.11.011
DO - 10.1016/j.bbmt.2006.11.011
M3 - Article
C2 - 17287157
AN - SCOPUS:33947240964
SN - 1083-8791
VL - 13
SP - 423
EP - 432
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 4
ER -