title: Double haploidentical hematopoietic stem cell transplantation results in successful engraftment of bone marrow from both donors without graft-versus-host or graft-versus-graft effects.
abstract: We established double-haploidentical (DH) hematopoietic stem cell transplantation (HSCT) murine models to explore competitive engraftment, graft-versus-graft effect and graft-versus-host disease (GVHD). T cell-depleted (TCD) bone marrow (BM) cells from B6SJF1 (donor 1 [D1]) and B6D2F1 (donor 2 [D2]) mice achieved >90% donor engraftment when transplanted into B6CBAF1 mice. B6CBAF1 recipients survived without evidence of GVHD when undergoing HSCT with TCD-BM from 2 haploidentical donors, D1 and D2. DH-HSCT recipients had significantly higher leukocyte and neutrophil counts than single-haploidentical HSCT recipients from either D1 or D2. DH recipients consistently showed successful mixed chimerism in both BM and spleen. Two other DH-HSCT models, B6D2F1 + C3D2F1→B6C3F1 and B6CBAF1 + B6SJLF1→B6D2F1, showed similar engraftment patterns. Low-dose T cell infusion from both D1 and D2 increased the degree of early engraftment of the respective donors in BM and spleen; however, this early engraftment pattern did not determine long-term engraftment dominance. In the long term, minimally engrafted D1 BM recovered and comprised >50% of all donor- derived B, T, and natural killer cells. We conclude that early BM engraftment is determined by donor T cell immunodominance, but long-term engraftment is related to the engraftment potential of stem cells after DH-HSCT.
authors.affiliation: Department of Medical Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Biswas
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Sauter
authors.forename: Cavan P
authors.initials: CP
authors.lastname: Bailey
authors.forename: Daniel
authors.initials: D
authors.lastname: Rittenberg
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Luo
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Panis
authors.forename: Tulin
authors.initials: T
authors.lastname: Budak-Alpdogan
authors.forename: Dolores
authors.initials: D
authors.lastname: Grosso
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
authors.forename: Onder
authors.initials: O
authors.lastname: Alpdogan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D014019:Tissue Donors