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Prospective Trial of Chemotherapy and Donor Leukocyte Infusions for Relapse of Advanced Myeloid Malignancies After Allogeneic Stem-Cell Transplantation

From the University of Michigan, Ann Arbor, MI; Ohio State University, Columbus, OH; University of Utah, Salt Lake City, UT; Indiana University, Indianapolis, IN; Hospital de Sant Pau, Barcelona, Spain; Medical College of Wisconsin and International Bone Marrow Transplant Registry, Milwaukee, WI; National Heart, Lung and Blood Institute, Bethesda, MD; University of Pennsylvania, Philadelphia, PA; M.D. Anderson Cancer Center, Houston; Baylor-Sammons Cancer Center, Dallas; and University of Texas Southwestern Medical Center, Dallas, TX; and Oregon Health Sciences University, Portland, OR.

Supported by the Leukemia Association of North Central Texas.Address reprint requests to John E. Levine, MD, Blood and Marrow Stem Cell Transplantation Program, B1-207 CCGC/Box 0914, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0914; email: jelevine{at}umich.edu

PURPOSE: Patients with advanced myeloid malignancies who experience relapse after allogeneic bone marrow transplantation (BMT) have a poor prognosis. Long-term survival after chemotherapy alone, second myeloablative transplant, or donor leukocyte infusions (DLIs) alone is unusual. DLIs may have minimal effectiveness in advanced disease because adequate cellular responses are not able to develop in the presence of bulky, fast-growing disease. A chemotherapy strategy was used to debulk disease before administration of granulocyte colony-stimulating factor (G-CSF)–primed DLIs.

PATIENTS AND METHODS: Sixty-five patients experiencing hematologic relapse of myeloid malignancy after HLA-matched sibling BMT were prospectively treated with cytarabine-based chemotherapy, then G-CSF–primed DLIs. No prophylactic immunosuppression was provided.

RESULTS: Twenty-seven of 57 assessable patients experienced a complete response. Graft-versus-host disease (GVHD) was observed in 56% of the patients. Treatment-related mortality was 23%. Overall survival at 2 years for the entire cohort was 19%. Patients with a complete response were more likely to survive, with 1- and 2-year survival rates of 51% and 41%, respectively, with a median follow-up of more than 2 years. The 1-year survival for nonresponders was 5%. A posttransplant remission lasting more than 6 months before relapse was associated with a higher likelihood of response. GVHD was not required for durable remission.

CONCLUSION: Salvage treatment with chemotherapy before DLI can help some patients with advanced myeloid relapse and is not dependent on GVHD. Patients with short remissions after BMT are unlikely to benefit from this approach, and the approach is associated with significant treatment-related mortality. Modifications of this approach or entirely different approaches will be required for most patients with this difficult clinical problem.

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