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

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 mCi 90Y-anti-CD45 antibody (30F11), with or without fludarabine (5 days starting day -8), with cyclophosphamide (CY; days -2 and 12) for graft-versus-host disease prophylaxis, and 1.5 3 107 haploidentical donor bone marrow cells (day 0). Haploidentical bone marrow transplantation (BMT) with 300 mCi 90Y-anti-CD45 RIT and CY, without TBI or fludarabine, led to mixed chimeras with 81.3 6 10.6% mean donor origin CD81 cells detected 1 month after BMT, and remained stable (85.5611% mean donor origin CD81 cells) 6 months after haploidentical BMT. High chimerism levels were induced across multiple hematopoietic lineages 28 days after haploidentical BMT with 69.3 6 14.1%, 75.6 6 20.2%, and 88.5 6 11.8% CD31 T cells, B2201 B cells, and CD11b1 myeloid cells, respectively. Fifty percent of SJL leukemia-bearing mice treated with 400 mCi 90Y-DOTA-30F11, CY, and haploidentical BMT were cured and lived >200 days. Mice treated with 200 mCi 90Y-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.