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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2254-2262.
Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2004-04-1506.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning
Frédéric Baron,
Jennifer E. Baker,
Rainer Storb,
Theodore A. Gooley,
Brenda M. Sandmaier,
Michael B. Maris,
David G. Maloney,
Shelly Heimfeld,
Dmitrij Oparin,
Eustacia Zellmer,
Jerald P. Radich,
F. Carl Grumet,
Karl G. Blume,
Thomas R. Chauncey, and
Marie-Térèse Little
From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle; the Department of Hematology, University of Liège, Belgium; the University of Washington School of Medicine, Seattle, WA; Stanford University, Stanford, CA; and the Veterans Affairs Medical Center, Seattle, WA.
We analyzed the kinetics of donor engraftment among various peripheral blood cell subpopulations and their relationship to outcomes among 120 patients with hematologic malignancies given hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning consisting of 2 Gy total body irradiation (TBI) with or without added fludarabine. While patients rapidly developed high degrees of donor engraftment, most remained mixed donor/host chimeras for up to 180 days after HCT. Patients given preceding chemotherapies and those given granulocyte colony-stimulating factor–mobilized peripheral blood mononuclear cell (G-PBMC) grafts had the highest degrees of donor chimerism. Low donor T-cell (P = .003) and natural killer (NK) cell (P = .004) chimerism levels on day 14 were associated with increased probabilities of graft rejection. High T-cell chimerism on day 28 was associated with an increased probability of acute graft-versus-host disease (GVHD) (P = .02). Of 93 patients with measurable malignant disease at transplantation, 41 achieved complete remissions a median of 199 days after HCT; 19 of the 41 were mixed T-cell chimeras when complete remissions were achieved. Earlier establishment of donor NK-cell chimerism was associated with improved progression-free survival (P = .02). Measuring the levels of peripheral blood cell subset donor chimerisms provided useful information on HCT outcomes and might allow early therapeutic interventions to prevent graft rejection or disease progression.
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