Anti-CD45 radioimmunotherapy without TBI before BMT facilitates persistent haploidentical donor engraftment in a murine model.

Publication Type:

Journal Article

Source:

Blood (2015)

Abstract:

Many patients with hematologic malignancies cannot tolerate hematopoietic cell transplantation (HCT), while 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) prior to haploidentical HCT in a murine model. Mice received 200-400 μCi (90)Y-anti-CD45 antibody (Ab; 30F11), with or without fludarabine (FLU; 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 FLU, led to mixed chimeras with 81.3 ± 10.6% mean donor origin CD8(+) cells detected one 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 (OS) of 73 days, while untreated leukemic mice had a median OS of 34 days (p<0.001, Mantel-Cox test). RIT-mediated haploidentical BMT without TBI may increase treatment options for aggressive hematologic malignancies.