Abstract
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.
Original language | English (US) |
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Pages (from-to) | 352-359 |
Number of pages | 8 |
Journal | Blood |
Volume | 127 |
Issue number | 3 |
DOIs | |
State | Published - Jan 21 2016 |
ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology