Originally published as JCO Early Release 10.1200/JCO.2006.07.0953 on January 16 2007

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Partially Matched, Nonmyeloablative Allogeneic Transplantation: Clinical Outcomes and Immune Reconstitution

David A. Rizzieri, Liang Piu Koh, Gwynn D. Long, Cristina Gasparetto, Keith M. Sullivan, Mitchell Horwitz, John Chute, Clayton Smith, Jerald Z. Gong, Anand Lagoo, Donna Niedzwiecki, Jeannette M. Dowell, Barbara Waters-Pick, CongXiao Liu, Dawn Marshall, James J. Vredenburgh, Jon Gockerman, Carlos Decastro, Joseph Moore, Nelson J. Chao

From the Department of Medicine, Division of Cellular Therapy; Department of Biostatistics; Department of Pathology, Division of Hematopathology; and Department of Medicine, Division of Oncology, Duke University Medical Center, Durham, NC; and the Department of Medicine, Division of Stem Cell Transplantation, Vancouver University, Vancouver, British Columbia, Canada

Address reprint requests to David A. Rizzieri, MD, Box 3961, Duke University Medical Center, Durham, NC 27710; e-mail: rizzi003{at}mc.duke.edu

PURPOSE: Allogeneic transplantation is typically limited to younger patients having a matched donor. To allow a donor to be found for nearly all patients, we have used a nonmyeloablative conditioning regimen in conjunction with stem cells from a related donor with one fully mismatched HLA haplotype.

PATIENTS AND METHODS: Fludarabine, cyclophosphamide, and alemtuzumab were used as the preparatory regimen. Additional graft-versus-host disease (GVHD) prophylaxis included mycophenolate with or without cyclosporine. Patients with persistence of disease had a donor lymphocyte boost planned. Toxicities, engraftment, response, survival, and immune recovery are reported.

RESULTS: Forty-nine patients with hematologic malignancies or marrow failure and no other available donors were enrolled. Ninety-four percent of patients had successful engraftment, and 8% had secondary graft failure. The treatment-related mortality rate was 10.2%, and 8% of patients had severe GVHD. Encouraging evidence of quantitative lymphocyte recovery through expansion of transplanted T cells was noted by 3 to 6 months. Seventy-five percent of patients attained a complete remission, and 1-year survival rate was 31% (95% CI, 18% to 44%). A standard-risk group of 19 patients with aplasia or in remission at transplantation demonstrated a 63% 1-year survival rate (95% CI, 38% to 80%) and 2.9-year median overall survival time (95% CI, 6.2 to 48 months).

CONCLUSION: Nonmyeloablative therapy using haploidentical family member donors is feasible because the main obstacles of GVHD and graft rejection are manageable, allowing readily available stem-cell donors to be found for nearly all patients. Further qualitative and quantitative improvement in immune recovery is needed to address the high rate of relapse and risk of severe infections.

published online ahead of print at www.jco.org on January 16, 2007.

Supported in part by National Institutes of Health Grants No. 5K23RR16063-01 (D.A.R.), 2PO-1CA47741 (N.J.C.), and M01-RR30 (National Center for Research Resources, Clinical Research), the Lisa Stafford Memorial Young Investigator Award (D.A.R.), Amgen Inc, and Berlex Laboratories Inc.

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

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