Donor HLA mismatch promotes full donor T-cell chimerism in the allogeneic stem cell transplant with reduced-intensity conditioning and post-transplant cyclophosphamide GVHD prophylaxis

• Published in: Annals of hematology Vol. 102; no. 3; pp. 613 - 620
• Main Authors: Cioccio, Joseph, Rakszawski, Kevin, Zheng, Hong, Nickolich, Myles, Naik, Seema, Wirk, Baldeep, Rybka, Witold, Ehmann, Christopher, Silar, Brooke, Vajdic, Caitlin, Shah, Neal, Tuanquin, Leonard, Greiner, Robert, Brown, Valerie, Hohl, Raymond, Claxton, David, Mineishi, Shin, Minagawa, Kentaro, Shike, Hiroko
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2023; Springer Nature B.V
• Subjects: Chimerism; Cyclophosphamide - therapeutic use; Graft vs Host Disease - etiology; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; HLA Antigens; Humans; Lymphocytes; Medicine; Medicine & Public Health; Oncology; Original Article; Retrospective Studies; Stem cell transplantation; Stem Cell Transplantation - adverse effects; T-Lymphocytes; Transplantation Conditioning - adverse effects; Unrelated Donors; Mixed chimerism; Lymphocyte recovery; Lymphopenia; Lymphocyte count; PTCy
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-022-05077-2

Full donor T-cell chimerism (FDTCC) after allogeneic stem cell transplant (allo-SCT) has been associated with improved outcomes in hematologic malignancy. We studied if donor human leukocyte antigen (HLA) mismatch improves achievement of FDTCC because mismatched HLA promotes donor T-cell proliferation where recipient T-cells had been impaired by previous treatment. Patients (
N
 = 138) received allo-SCT with reduced-intensity conditioning (RIC) from 39 HLA mismatched donors (16 unrelated; 23 haploidentical) with post-transplant cyclophosphamide (PTCy) or 99 matched donors (21 siblings; 78 unrelated) with PTCy (
N
 = 18) or non-PTCy (
N
 = 81). Achievement of FDTCC by day 100 was higher with HLA mismatched donors than matched donors (82.1% vs. 27.3%,
p
 < 00,001), which was further improved with 200 cGy total body irradiation (87.9%) or lymphoid (versus myeloid) malignancy (93.8%). Since all mismatched transplants used PTCy, FDTCC was higher with PTCy than non-PTCy (68.4% vs. 25.7%,
p
 < 0.00001), but not in the matched transplant with PTCy (38.9%), negating PTCy as the primary driver. Lymphocyte recovery was delayed with PTCy than without (median on day + 30: 100 vs. 630/µL,
p
 < 0.0001). The benefit of FDTCC was not translated into survival outcomes, especially in myeloid malignancies, possibly due to the insufficient graft-versus-tumor effects from the delayed lymphocyte recovery. Further studies are necessary to improve lymphocyte count recovery in PTCy transplants.