Post-Transplant Cyclophosphamide-Based Prophylaxis and Its Impact on Infectious Complications and Immune Reconstitution According to Donor Type

<b>Background/Objectives:</b> This study evaluated infectious complications and immune reconstitution in 253 adults undergoing peripheral blood allogeneic hematopoietic cell transplantation (allo-HCT) with post-transplant cyclophosphamide (PTCY)-based GVHD prophylaxis. <b>Methods:</b> Patients received grafts from HLA-matched donors (47.4%), mismatched unrelated donors (MMUD, 33.2%), or haploidentical donors (19.4%). <b>Results:</b> The estimated 2-year non-relapse mortality (NRM) was 11.8%, 26.4%, and 22.4%, respectively (<i>p</i> = 0.0528). The cumulative incidence (Cum.Inc) of acute and chronic GVHD, immunosuppression duration, and post-transplant outcomes were similar across donor types. The day +30 Cum.Inc of bacterial bloodstream infections (BSI) tended to be higher in HLA-matched transplants (49.2%, <i>p</i> = 0.073), while HHV-6 reactivation showed a trend toward higher frequency in haploidentical transplants (22.4%, <i>p</i> = 0.068). Cytomegalovirus (CMV) reactivation occurred between days +30 and +100, with the highest Cum.Inc in MMUD (59.5%, <i>p</i> = 0.033). BK virus-associated hemorrhagic cystitis showed a trend toward higher incidence in MMUD (22.3%, <i>p</i> = 0.056). Respiratory and fungal infections were most frequent in the first 100 days, with comparable rates across donor types. By day +180, most patients achieved immune reconstitution, with normalization of CD4+ T cells, CD8+ T cells, and IgG levels, independent of donor type. <b>Conclusions:</b> Patients undergoing allo-HCT with PTCY-based prophylaxis experience a high infectious density rate early post-transplant, which decreases after 6 months as immune reconstitution progresses, regardless of donor type.