Originally published as JCO Early Release 10.1200/JCO.2006.06.9914 on August 8 2006

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Factors Associated With Outcomes in Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning After Failed Myeloablative Hematopoietic Cell Transplantation

Frédéric Baron, Rainer Storb, Barry E. Storer, Michael B. Maris, Dietger Niederwieser, Judith A. Shizuru, Thomas R. Chauncey, Benedetto Bruno, Stephen J. Forman, Peter A. McSweeney, Richard T. Maziarz, Michael A. Pulsipher, Edward D. Agura, James Wade, Mohamed Sorror, David G. Maloney, Brenda M. Sandmaier

From the Fred Hutchinson Cancer Research Center; University of Washington School of Medicine; Veterans Affairs Puget Sound Health Care System, Seattle, WA; Stanford University, Stanford; City of Hope Comprehensive Cancer Center, Duarte, CA; Rocky Mountain Cancer Center, Denver, CO; Oregon Health and Science University, Portland, OR; University of Utah, Salt Lake City, UT; Baylor University, Dallas, TX; Medical College of Wisconsin, Milwaukee, WI; University of Liège, Liège, Belgium; University of Leipzig, Leipzig, Germany; and the University of Torino, Torino, Italy

Address reprint requests to Brenda M. Sandmaier, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024; e-mail: bsandmai{at}fhcrc.org

Purpose: Several studies have investigated the feasibility of allogeneic hematopoietic cell transplantations (HCTs) after reduced-intensity conditioning in patients who experienced relapse after myeloablative HCT. Although most studies showed relatively low nonrelapse mortality (NRM) rates and encouraging short-term results, it has yet to be defined which patients would benefit most from these approaches.

Patients and Methods: We analyzed data from 147 patients with hematologic malignancies who experienced treatment failure with conventional autologous (n = 135), allogeneic (n = 10), or syngeneic (n = 2) HCT and were treated with HLA-matched related (n = 62) or unrelated (n = 85) grafts after conditioning with 2 Gy of total-body irradiation with or without fludarabine.

Results: Three-year probabilities of NRM, relapse, and overall survival were 32%, 48%, and 27%, respectively, for related recipients, and 28%, 44%, and 44%, respectively, for unrelated recipients. The best outcomes were observed in patients with non-Hodgkin's lymphoma, whereas patients with multiple myeloma and Hodgkin's disease had worse outcomes as a result of high incidences of relapse and progression. Being in partial remission (PR) or complete remission (CR) at HCT (P = .002) and developing chronic graft-versus-host disease (GVHD; P = .03) resulted in lower risks of relapse and progression. Factors associated with better overall survival were PR or CR (P = .01) and lack of comorbidity (P = .03) at HCT and absence of acute GVHD after HCT (P = .06).

Conclusion: Encouraging outcomes were seen with allogeneic HCT after nonmyeloablative conditioning in selected patients who had experienced relapse after a high-dose HCT, particularly in patients with non-Hodgkin's lymphoma. Results with unrelated grafts were comparable with results with related grafts.

published online ahead of print at www.jco.org on August 7, 2006

Supported in part by Grants No. HL36444, CA78902, CA92058, CA18029, CA49605, and CA15704 from the National Institutes of Health, Department of Health and Human Services, Bethesda, MD. F.B. is a research associate of the National Fund for Scientific Research Belgium and is supported in part by postdoctoral grants from the Fulbright Commission and from the Centre Anticancéreux près l'Université de Liège.

Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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