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

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.

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00277-022-05077-2

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Work Title 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
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Open Access
Creators
  1. Joseph Cioccio
  2. Kevin Rakszawski
  3. Hong Zheng
  4. Myles Nickolich
  5. Seema Naik
  6. Baldeep Wirk
  7. Witold Rybka
  8. Christopher Ehmann
  9. Brooke Silar
  10. Caitlin Vajdic
  11. Neal Shah
  12. Leonard Tuanquin
  13. Robert Greiner
  14. Valerie Brown
  15. Raymond Hohl
  16. David Claxton
  17. Shin Mineishi
  18. Kentaro Minagawa
  19. Hiroko Shike
Keyword
  1. PTCy
  2. Lymphocyte recovery
  3. Lymphopenia
  4. Lymphocyte count
  5. Mixed chimerism
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. Annals of Hematology
Publication Date December 17, 2022
Publisher Identifier (DOI)
  1. https://doi.org/10.1007/s00277-022-05077-2
Deposited February 27, 2023

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Version 1
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  • Created
  • Added HLA_mismatch_outcome_revision_102022.docx
  • Added PTCy_fig_091522.pptx
  • Added Table_1.docx
  • Added Table_2.docx
  • Added Table_3.docx
  • Added Table_4.docx
  • Added Creator Joseph Cioccio
  • Added Creator Kevin Rakszawski
  • Added Creator Hong Zheng
  • Added Creator Myles Nickolich
  • Added Creator Seema Naik
  • Added Creator Baldeep Wirk
  • Added Creator Witold Rybka
  • Added Creator Christopher Ehmann
  • Added Creator Brooke Silar
  • Added Creator Caitlin Vajdic
  • Added Creator Neal Shah
  • Added Creator Leonard Tuanquin
  • Added Creator Robert Greiner
  • Added Creator Valerie Brown
  • Added Creator Raymond Hohl
  • Added Creator David Claxton
  • Added Creator Shin Mineishi
  • Added Creator Kentaro Minagawa
  • Added Creator Hiroko Shike
  • Published
  • Updated Keyword, Publication Date Show Changes
    Keyword
    • PTCy, Lymphocyte recovery, Lymphopenia, Lymphocyte count, Mixed chimerism
    Publication Date
    • 2022-01-01
    • 2022-12-17
  • Updated