Severe infections and infection-related mortality in a large series of haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide

Abstract

Severe infections and their attributable mortality are major complications in recipients of allogeneic hematopoietic stem cell transplantation (alloSCT). We herein report 236 adult patients who received haploSCT with PTCy. The median follow-up for survivors was 37 months. The overall incidence of bloodstream infections by gram-positive and gram-negative bacteria at 37 months was 51% and 46%, respectively. The incidence of cytomegalovirus infection was 69%, while Epstein Barr virus infections occurred in 10% of patients and hemorrhagic cystitis in 35% of cases. Invasive fungal infections occurred in 11% at 17 months. The 3-year incidence of infection-related mortality was 19%. The median interval from transplant to IRM was 3 months (range 1–30), 53% of IRM occurred >100 days post-haploSCT. Risk factors for IRM included age >50 years, lymphoid malignancy, and developing grade III-IV acute GvHD. Bacterial infections were the most common causes of IRM (51%), mainly due to gram-negative bacilli BSI. In conclusion, severe infections are the most common causes of NRM after haploSCT with PTCy, with a reemergence of gram-negative bacilli as the most lethal pathogens. More studies focusing on the severe infections after haploSCT with PTCy and differences with other types of alloSCT in adults are clearly warranted.

Distinct activities of Vδ1+ T‐cells upon different cytomegalovirus reactivation status after haematopoietic transplantation

“…Allogeneic haematopoietic cell transplantation (alloHCT) is now a well-established and standard treatment for malignant and non-malignant haematological diseases. However, infectious complications due to the general impairment of immune system remain the major cause of morbidity and mortality after alloHCT [1,2]. Cytomegalovirus (CMV) reactivation and related diseases are the most frequent viral infectious complications in this context.…”

Haploidentical Stem Cell Transplantation for Acute Myeloid Leukemia: Current Therapies, Challenges and Future Prospective

“…According to the CIBMTR data, relapse remains an important challenge in AML patients who undergo haploidentical allografts. Infection is another challenge following haplo-SCTbased immune tolerance induced either by G-CSF and ATG or by PTCy (57,58,103,104). Here, we discussed the recent emerging strategies for relapse or infection intervention or treatment for AML subjects.…”

“…In the past two decades, advances in the establishment of algorithms for best haploidentical donor selection (40)(41)(42), optimization of conditioning regimens (43)(44)(45), shifts from TCD grafts to unmanipulated bone marrow and/or peripheral blood harvests (3,5,21,46,47), enhancement of hematopoietic recovery through endothelial cell-directed N-acetyl-L-cysteine intervention and/or donor-specific antibody desensization (34,48,49), biomarker-directed graft-versus-host disease (GVHD) prophylaxis (50)(51)(52), minimal/measurable residual disease (MRD)-directed relapse intervention (7,53), and approaches for enhancing immunologic recovery (54)(55)(56) have successfully improved the outcomes of patients with hematological malignancies, especially those with AML receiving haplo-SCT. Unfortunately, for subjects with AML who underwent haploidentical allografts, relapse and infections remain the causes of death that restrict further improvement in clinical outcomes (57,58). In this review, we discussed the current therapies and challenges in haplo-SCT for AML treatment, mainly focusing on unmanipulated haploidentical transplant protocols.…”

CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update

“…PTCy is a method of in vivo T cell depletion that mainly acts on alloreactive T cells after haploSCT. CMV reactivation was noticed in 42%-69.2% of patients who underwent PTCy-haploSCT (51)(52)(53)(54)(55)(56)(57)(58). A total of 2.8%-4.5% of patients experienced CMV-associated disease (51,52).…”