Originally published as JCO Early Release 10.1200/JCO.2005.04.569 on April 4 2005

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Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning for Advanced Chronic Lymphocytic Leukemia

From the Fred Hutchinson Cancer Research Center; University of Washington; VA Puget Sound Health Care System; Hematologics Inc, Seattle, WA; Stanford University, Stanford, CA; University of Leipzig, Leipzig, Germany; Baylor University, Dallas, TX; Oregon Health & Science University, Portland, OR; University of Utah, Salt Lake City, UT; University of Colorado, Denver, CO; Medical College of Wisconsin, Milwaukee, WI; University of Torino, Torino, Italy; and Emory University, Atlanta, GA

Address reprint requests to David Maloney, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA 98109-1024; e-mail: dmaloney{at}fhcrc.org

PURPOSE: Patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) have a short life expectancy. The aim of this study was to analyze the outcome of patients with advanced CLL when treated with nonmyeloablative conditioning and hematopoietic cell transplantation (HCT).

PATIENTS AND METHODS: Sixty-four patients diagnosed with advanced CLL were treated with nonmyeloablative conditioning (2 Gy total-body irradiation with [n = 53] or without [n = 11] fludarabine) and HCT from related (n = 44) or unrelated (n = 20) donors. An adapted form of the Charlson comorbidity index was used to assess pretransplantation comorbidities.

RESULTS: Sixty-one of 64 patients had sustained engraftment, whereas three patients rejected their grafts. The incidences of grades 2, 3, and 4 acute and chronic graft-versus-host disease were 39%, 14%, 2%, and 50%, respectively. Three patients who underwent transplantation in complete remission (CR) remained in CR. The overall response rate among 61 patients with measurable disease was 67% (50% CR), whereas 5% had stable disease. All patients with morphologic CR who were tested by polymerase chain reaction (n = 11) achieved negative molecular results, and one of these patients subsequently experienced disease relapse. The 2-year incidence of relapse/progression was 26%, whereas the 2-year relapse and nonrelapse mortalities were 18% and 22%, respectively. Two-year rates of overall and disease-free survivals were 60% and 52%, respectively. Unrelated HCT resulted in higher CR and lower relapse rates than related HCT, suggesting more effective graft-versus-leukemia activity.

CONCLUSION: CLL is susceptible to graft-versus-leukemia effects, and allogeneic HCT after nonmyeloablative conditioning might prolong median survival for patients with advanced CLL.

Supported by grant Nos. CA78902, CA92058, CA18029, CA49605, and CA15704 from the National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Leukemia and Lymphoma Society Specialized Center of Research grant 7040. M.S. was supported in part by a grant from the Oncology Research Faculty Development Program of the Office of International Affairs of the National Cancer Institute. B.B. was supported by a grant from Ministero dell'Istruzione, dell'Università, della Ricerca, Italy.

Presented in part at the Tandem Bone Marrow Transplantation meeting, February 13-17, 2004, Orlando, FL (for part of the patient population).

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

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