TY - JOUR
T1 - 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
AU - Cioccio, Joseph
AU - Rakszawski, Kevin
AU - Zheng, Hong
AU - Nickolich, Myles
AU - Naik, Seema
AU - Wirk, Baldeep
AU - Rybka, Witold
AU - Ehmann, Christopher
AU - Silar, Brooke
AU - Vajdic, Caitlin
AU - Shah, Neal
AU - Tuanquin, Leonard
AU - Greiner, Robert
AU - Brown, Valerie
AU - Hohl, Raymond
AU - Claxton, David
AU - Mineishi, Shin
AU - Minagawa, Kentaro
AU - Shike, Hiroko
N1 - Funding Information:
This work was supported by the Arlene Witmer Memorial Fund for Bone Marrow Cancer Research, the John and Denise Gilliland Fund for the Cancer Genetics Program, G. R. Sponaugle Employee Cancer Research Fund, Earl “Bumps” Clouser Memorial Lymphoma Research Endowment, and Richard E. and Stephanie A. Ziegler Charitable Foundation Endowment in Hematology.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
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U2 - 10.1007/s00277-022-05077-2
DO - 10.1007/s00277-022-05077-2
M3 - Article
C2 - 36527460
AN - SCOPUS:85144217604
SN - 0939-5555
VL - 102
SP - 613
EP - 620
JO - Annals of Hematology
JF - Annals of Hematology
IS - 3
ER -