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Dynamics of polyclonal immuno-reconstitution after allogeneic transplant with post-transplant cyclophosphamide and letermovir.

Giorgio OrofinoElisabetta XueMatteo DoglioMaddalena NovielloElena TassiMatteo CristanteAndrea AcerbisDaniela ClericiFrancesca FarinaEdoardo CampodonicoAlessandro BrunoSimona PiemonteseSara MastaglioElisa DiralRaffaella MilaniAnnalisa RuggeriConsuelo CortiLuca VagoChiara BoniniJacopo PeccatoriFabio CiceriMaria Teresa Lupo StanghelliniRaffaella Greco
Published in: Bone marrow transplantation (2023)
Cytomegalovirus (CMV) reactivations are strong stimulators of immune-reconstitution (IR) in hematopoietic stem cell transplantation (HSCT) recipients. Herein, we analyzed 317 CMV-seropositive consecutive patients (n = 109 letermovir, LTV; n = 208 no-LTV), undergoing HSCT with post-transplant cyclophosphamide (PTCy) and calcineurin inhibitor- (CNI) free graft-versus-host-disease (GvHD) prophylaxis. At day+90, median CD19 + /mm 3 was higher in LTV-cohort: 5.5 [0;439] versus 2 [0;294], p = 0.008; median CD3+/mm 3 counts were lower in LTV-cohort, with no differences in CD4 + , CD8 + and NK-cells. At day+180 median CD3 + , CD4 + and CD8 + /mm 3 values were comparable between groups. Higher CD19 + /mm 3 counts were observed in LTV-cohort: 62 [0; 2983] versus 42 [0; 863]. Significantly higher median NK/mm 3 values were seen in LTV-cohort: 225.5 [0;763] versus 163.5 [0;1181], p = 0.0003. The impact of LTV on B-cell IR at 3 months and NK-cell levels at 6 months was retained in multivariate analysis (p < 0.01), whereas the effect on T-cells was not confirmed. Moreover, we confirmed a significant reduction of clinically-relevant CMV, and moderate-to- severe chronic GvHD in LTV-cohort. Overall, in our study the use of LTV was associated with a slight improvement of B-cell and NK-cells reconstitution, with only minor impact on T-cell subsets, giving new insights on polyclonal IR for HSCT recipients in the LTV era.
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