Impacts of Posttransplant Cyclophosphamide Dose on Graft-versus-leukemia Effects via HLA-B Leader in HLA-haploidentical Peripheral Blood Stem Cell Transplantation.
Acta Haematol
; 2024 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-38432202
ABSTRACT
INTRODUCTION:
The graft-versus-leukemia effect of HLA-B leader dimorphism, i.e. methionine (M) or threonine (T) at position -21 of the leader sequence, has been observed in HLA-haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide (PTCy-haplo). However, the biological mechanism has been unclear, and the contributions of HLA-B leader genotype to risk reduction of relapse might be dependent on posttransplant cyclophosphamide (PTCy) doses.METHODS:
To investigate whether the effect of HLA-B leader dimorphism was modified by the PTCy dose, we retrospectively analyzed 99 patients who received PTCy-haplo.RESULTS:
In the low-dose PTCy group, the patient M+ HLA-B leader genotype did not significantly affect the cumulative incidence of relapse (CIR) but negatively impacted the overall survival (OS) compared to the M- genotype. In contrast, in the high-dose PTCy group, patients with the M+ genotype had a decreased CIR, but no significant difference in the OS was observed between patients with the M+ and M- genotypes. Regardless of PTCy doses, the patient M+ genotype had detrimental effects on nonrelapse mortality.CONCLUSION:
Our findings suggest that the effect of the patient HLA-B leader genotype is modified by the PTCy dose, providing immunological insight into the PTCy dosage and supporting further studies to investigate the underlying mechanisms.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Acta Haematol
Ano de publicação:
2024
Tipo de documento:
Article