Adverse impact of a high CD4/CD8 ratio in the allograft may be overcome by methotrexate‐ but not mycophenolate‐ or post‐transplant cyclophosphamide‐based graft versus host disease prophylaxis

Adverse impact of a high CD4/CD8 ratio in the allograft may be overcome by methotrexate‐ but not mycophenolate‐ or post‐transplant cyclophosphamide‐based graft versus host disease prophylaxis

Introduction A high CD4/CD8 T cell ratio in hematopoietic stem cell transplant (HSCT) allografts was observed to predict graft‐versus‐host disease (GVHD) and nonrelapse mortality (NRM) but has not been comparatively examined in settings of various GVHD‐prophylaxis regimens. Methods This retrospectiv...

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Published in:European journal of haematology Vol. 110; no. 6; pp. 715 - 724
Main Authors: Nikoloudis, A., Buxhofer‐Ausch, V., Aichinger, C., Binder, M., Hasengruber, P., Kaynak, E., Wipplinger, D., Milanov, R., Strassl, I., Stiefel, O., Machherndl‐Spandl, S., Petzer, A., Weltermann, A., Clausen, J.
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01-06-2023
Subjects:
allograft composition
Allografts
CD4 antigen
CD4-Positive T-Lymphocytes
CD4/CD8 ratio
CD8 antigen
CD8-Positive T-Lymphocytes
Cyclophosphamide
Cyclophosphamide - adverse effects
Cyclosporine - therapeutic use
Cyclosporins
Disease prevention
Graft versus host disease
Graft vs Host Disease - diagnosis
Graft vs Host Disease - etiology
Graft vs Host Disease - prevention & control
Graft-versus-host reaction
Hematopoietic Stem Cell Transplantation - adverse effects
Hematopoietic stem cells
Histocompatibility antigen HLA
Humans
Immunosuppressive Agents - therapeutic use
Lymphocytes T
Methotrexate
Methotrexate - therapeutic use
Mortality
Mycophenolic acid
Mycophenolic Acid - therapeutic use
Peripheral blood
Prophylaxis
Retrospective Studies
Risk factors
Stem cell transplantation
survival
Tacrolimus
CD4/CD8 ratio
survival
allograft composition
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Summary:Introduction A high CD4/CD8 T cell ratio in hematopoietic stem cell transplant (HSCT) allografts was observed to predict graft‐versus‐host disease (GVHD) and nonrelapse mortality (NRM) but has not been comparatively examined in settings of various GVHD‐prophylaxis regimens. Methods This retrospective monocentric study included all consecutive HSCT performed with peripheral blood stem cells between January 2000 and June 2021. The impact of the graft CD4/CD8 ratio was analyzed in three cohorts with different GVHD‐prophylaxis platforms. Results In the cyclosporine/mycophenolate‐mofetil (CSA/MMF) cohort (n = 294, HLA‐matched HSCT), a high (>75th percentile) CD4/CD8 ratio was associated with increased overall mortality (HR: 1.56; p = .01), increased NRM (HR: 1.85; p = .01) and GVHD‐associated mortality (HR: 2.13; p = .005). In the post‐transplant cyclophosphamide (PTCy)/tacrolimus/MMF cohort (n = 113, haploidentical‐related or mismatched‐unrelated HSCT), a high CD4/CD8 ratio was associated with increased overall mortality (HR 2.07; p = .04) and aGVHD3‐4 (HR: 2.24; p = .02). By contrast, in the CSA/methotrexate (CSA/MTX) cohort (n = 185, HLA‐matched HSCT) the CD4/CD8 ratio had no significant impact on any of the investigated endpoints. Conclusion A high CD4/CD8 ratio in the allograft has an adverse impact on GVHD and survival in CSA/MMF‐ and PTCy‐based HSCT, while MTX‐based prophylaxis may largely alleviate this important risk factor.
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ISSN:0902-4441
1600-0609
DOI:10.1111/ejh.13956