Background/Objectives: 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. Methods: Patients received grafts from HLA-matched donors (47.4%), mismatched unrelated donors (MMUD, 33.2%), or haploidentical donors (19.4%). Results: The estimated 2-year non-relapse mortality (NRM) was 11.8%, 26.4%, and 22.4%, respectively (p = 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%, p = 0.073), while HHV-6 reactivation showed a trend toward higher frequency in haploidentical transplants (22.4%, p = 0.068). Cytomegalovirus (CMV) reactivation occurred between days +30 and +100, with the highest Cum.Inc in MMUD (59.5%, p = 0.033). BK virus-associated hemorrhagic cystitis showed a trend toward higher incidence in MMUD (22.3%, p = 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. Conclusions: 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.

Background: Even though venetoclax in combination with azacitidine (VenAza) is considered a low-intensity regimen, its patients present a high incidence of cytopenia and infections during the first courses, making the initial management a challenging phase. Methods: This difficulty in our center led to the establishment of an At-Home (AH) program for ramp-up and follow-up patients during the VenAza combination induction phase focused on therapy administration, patient and caregiver education, and management of adverse events (AEs). A total of 70 patients with newly diagnosed acute myeloid leukemia (ND-AML) or relapsed/refractory AML (R/R AML) were treated with VenAza from March 2019 to May 2022. We compared outcomes between patients managed with a hospital-based (inpatient) approach and those managed through the AH program. Results: Despite most patients experiencing grade 3–4 cytopenias (96.9%), the incidence of serious infections and other AEs was comparable between both groups, with no significant difference in febrile neutropenia (42.3% vs. 27.8%, p = 0.38). Overall, the AH cohort demonstrated a significantly lower hospital readmission rate after ramp-up (29.5% vs. 84.6%, p = 0.001). Moreover, the inpatient cohort’s admission days were longer than in the AH cohort (13 vs. 8, p = 0.28). Conclusions: AH management was feasible and safe, leading to better resource use, enhanced patient comfort, and improved treatment compliance. The potential of AH programs for managing low-intensity chemotherapy regimens can reduce hospital admissions and subsequently improve patient and caregiver well-being.