A novel approach to hematopoietic stem cell transplantation: The effect of CMV infection and HLA genotypes on chimerism status in Egyptian patients

Over the past three decades, hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for patients with certain malignant and non-malignant hematological disorders. Complete remission was associated with complete chimerism (CC), which is considered one of the indicators of regeneration and reconstitution of bone marrow. Persistent complete donor chimerism reflects full hematopoietic conversion and sustained remission following allogeneic HSCT (allo-HSCT) [1,2].

The precise immune mechanisms underlying allo-immune responses against host cells, leading to CC after allo-HSCT, remain unclear. Allo-immune responses mediated against host cells eliminated host hematopoietic cells through targeting minor histocompatibility antigens which were mismatched in the recipients. There are many variables which affect the immune system driving it toward CC like graft versus host disease (GvHD) [3,4] and donor lymphocyte infusions [5,6] which ultimately aim to eliminate host hematopoietic cells. On the opposite side, there are other factors which delay the conversion to complete donor chimerism as immunosuppressive regimens and graft T cell depletion [7,8]. CMV reactivation post transplantation was repeatedly reported to be one of the driving forces toward CC through eliciting an immune reaction against host cells that result from proinflammatory response mediated by CMV-specific immunity [9]. Many reports studied the direct effect of alloreactive T cells directed against CMV on chimerism status and overall T cell reconstitution. They found that certain human leukocyte antigens (HLA) alleles were associated with CMV reactivation modifying the immune system and acting indirectly to affect chimerism status. Previous literature has encouraged and recommended examining the role of specific HLA alleles in CMV immunity due to racial diversity among populations. This recommendation also aligns with the conclusion of studies that investigated this relationship before [10]. The current study aims to investigate the association of CMV with certain HLA alleles, examining their effect on chimerism status post transplantation and identifying other factors influencing chimerism status.

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