Anti-CD45 radioimmunotherapy without TBI before transplantation facilitates persistent haploidentical donor engraftment.

Autor:	Orozco JJ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Hematology Division, Department of Medicine, University of Washington School of Medicine, Seattle, WA;, Kenoyer A; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;, Balkin ER; Radiation Oncology, University of Washington, Seattle, WA;, Gooley TA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;, Hamlin DK; Radiation Oncology, University of Washington, Seattle, WA;, Wilbur DS; Radiation Oncology, University of Washington, Seattle, WA;, Hylarides MD; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;, Frost SH; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;, Mawad R; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA; and., O'Donnell P; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;, Sandmaier BM; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA; and., Fuchs EJ; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD., Luznik L; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD., Green DJ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA; and., Gopal AK; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA; and., Press OW; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA; and., Pagel JM; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA; and.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2016 Jan 21; Vol. 127 (3), pp. 352-9. Date of Electronic Publication: 2015 Nov 17.
DOI:	10.1182/blood-2014-12-617019
Abstrakt:	Many patients with hematologic malignancies cannot tolerate hematopoietic cell transplantation (HCT), whereas others may not have a compatible human leukocyte antigen-matched donor. To overcome these limitations, we optimized a conditioning regimen employing anti-CD45 radioimmunotherapy (RIT) replacing total body irradiation (TBI) before haploidentical HCT in a murine model. Mice received 200 to 400 μCi (90)Y-anti-CD45 antibody (30F11), with or without fludarabine (5 days starting day -8), with cyclophosphamide (CY; days -2 and +2) for graft-versus-host disease prophylaxis, and 1.5 × 10(7) haploidentical donor bone marrow cells (day 0). Haploidentical bone marrow transplantation (BMT) with 300 μCi (90)Y-anti-CD45 RIT and CY, without TBI or fludarabine, led to mixed chimeras with 81.3 ± 10.6% mean donor origin CD8(+) cells detected 1 month after BMT, and remained stable (85.5 ± 11% mean donor origin CD8(+) cells) 6 months after haploidentical BMT. High chimerism levels were induced across multiple hematopoietic lineages 28 days after haploidentical BMT with 69.3 ± 14.1%, 75.6 ± 20.2%, and 88.5 ± 11.8% CD3(+) T cells, B220(+) B cells, and CD11b(+) myeloid cells, respectively. Fifty percent of SJL leukemia-bearing mice treated with 400 μCi (90)Y-DOTA-30F11, CY, and haploidentical BMT were cured and lived >200 days. Mice treated with 200 μCi (90)Y-DOTA-30F11 had a median overall survival of 73 days, while untreated leukemic mice had a median overall survival of 34 days (P < .001, Mantel-Cox test). RIT-mediated haploidentical BMT without TBI may increase treatment options for aggressive hematologic malignancies. (© 2016 by The American Society of Hematology.)
Databáze:	MEDLINE
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