Originally published as JCO Early Release 10.1200/JCO.2005.03.962 on July 25 2005

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Unrelated Donor Marrow Transplantation for B-Cell Chronic Lymphocytic Leukemia After Using Myeloablative Conditioning: Results From the Center for International Blood and Marrow Transplant Research

From the National Cancer Institute, Bethesda, MD; M.D. Anderson Cancer Center, Houston, TX; Center for International Blood and Marrow Transplant Research; National Marrow Donor Program; University of Minnesota, Minneapolis, MN; University of Nebraska Medical Center, Omaha, NE; City of Hope National Cancer Center, Duarte, CA; Ohio State University, Columbus, OH; Karolinska University Hospital, Huddinge, Sweden; Mayo Clinic, Jacksonville; Massachusetts General Hospital, Boston, MA; Washington University School of Medicine, St Louis, MO; Roswell Park Cancer Institute, Buffalo, NY; and Hospital Clinic, IDIBAPS, University of Barcelona, Spain; H. Lee Moffitt Cancer Center, Tampa, FL

Address reprint requests to Steven Pavletic, MD, Graft-versus-Host and Autoimmunity Unit, Experimental Transplantation and Immunology Branch, National Cancer Institute, 9000 Rockville Pike, Building 10, Room CRC 3-3330, Bethesda, MD 20892-1907; e-mail: pavletis{at}mail.nih.gov

PURPOSE: To determine the role of myeloablative conditioning and unrelated donor (URD) bone marrow transplantation in the treatment of patients with advanced B-cell chronic lymphocytic leukemia (CLL).

PATIENTS AND METHODS: A total of 38 CLL patients received a matched URD transplant using bone marrow procured by the National Marrow Donor Program. The median age was 45 years (range, 26 to 57 years), the median time from diagnosis was 51 months, and the median number of prior chemotherapy regimens was three. Fifty-five percent of patients were chemotherapy refractory and 89% had received fludarabine. Conditioning included total-body irradiation in 92% of patients. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate with cyclosporine or tacrolimus for 82% of patients.

RESULTS: Twenty-one patients (58%) achieved complete response and six (17%) achieved partial response. Incidences of grades 2 to 4 acute GVHD were 45% at 100 days and incidences of chronic GVHD were 85% at 5 years. Eleven patients are alive and disease free at a median of 6 years (range, 3.0 to 9.0 years). Five-year overall survival, failure-free survival, disease progression rates, and treatment-related mortality (TRM) were 33%, 30%, 32%, and 38% respectively.

CONCLUSION: These data demonstrate that lasting remissions can be achieved after URD transplantation in patients with advanced CLL. High TRM suggest that myeloablative conditioning and HLA-mismatched donors should be avoided in future protocols, and it is mandatory to investigate transplant strategies with a lower morbidity and mortality, including the use of nonmyeloablative regimens.

Supported by funding from the National Marrow Donor Program, the Health Resources and Services Administration grant No. 240-97-0036 and the Office of Naval Research grant No. N00014-93-0658 to the National Marrow Donor Program.

Presented in part as an oral presentation at the 36th Annual Meeting of the American Society of Oncology Meeting, May 20 to 23, 2000, New Orleans, LA (abstr 8).

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

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