Impact of Antifungal Prophylaxis Continuation or Discontinuation After Allogeneic Hematopoietic Cell Transplant on the Incidence of Invasive Mold Infection.

Background: Continuing antifungal prophylaxis (AFPx) to prevent invasive mold infections (IMIs) in recipients of allogeneic hematopoietic cell transplantation (alloHCT) after primary hospital discharge from alloHCT admission varies among transplant centers despite recommendations to continue prophylaxis through day +75. Characteristics driving AFPx prescribing at hospital discharge and outcomes are unknown. Methods: In this retrospective analysis, we reviewed patients continuing AFPx vs no AFPx at hospital discharge. We included patients with a hospital stay ≥7 days and ≤40 days. We excluded patients with a history of IMI prior to alloHCT, new IMI during admission, or death prior to discharge. Our primary objective was incidence of probable or proven IMI per the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Our secondary objectives were nonrelapse mortality at day +100, overall survival at day +100, and characteristics driving AFPx discontinuation at hospital discharge. Results: Of the 430 patients identified, 387 met inclusion criteria. At discharge, 56% (217/387) continued AFPx, and 44% (170/387) had no AFPx. At day +100, 3 probable IMI cases occurred in the group with continued AFPx vs 1 probable IMI case in the no-AFPx group (no proven IMI). Univariate analysis showed no difference in cumulative incidence of probable IMI (P = .440), nonrelapse mortality (P = .072), and overall survival (P = .855) between groups. Multivariable logistic regression demonstrated that patients were less likely to continue AFPx if they had a diagnosis other than acute myeloid leukemia, a length of stay ≤30 days, acute graft-vs-host disease grade 0 or 1, and corticosteroid use ≤5 days. Conclusions: There was no difference in probable IMI at day +100 after alloHCT based on continuing vs discontinuing AFPx at hospital discharge after alloHCT admission supporting a risk-adapted prophylaxis approach.

Functional SARS-CoV-2-specific T cells of donor origin in allogeneic stem cell transplant recipients of a T-cell-replete infusion: A prospective observational study.

In the current post-pandemic era, recipients of an allogeneic hematopoietic stem cell transplant (HCT) deserve special attention. In these vulnerable patients, vaccine effectiveness is reduced by post-transplant immune-suppressive therapy; consequently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is often associated with elevated morbidity and mortality. Characterizing SARS-CoV-2 adaptive immunity transfer from immune donors to HCT recipients in the context of immunosuppression will help identify optimal timing and vaccination strategies that can provide adequate protection to HCT recipients against infection with evolving SARS-CoV-2 variants. We performed a prospective observational study (NCT04666025 at ClinicalTrials.gov) to longitudinally monitor the transfer of SARS-CoV-2-specific antiviral immunity from HCT donors, who were either vaccinated or had a history of COVID-19, to their recipients via T-cell replete graft. Levels, function, and quality of SARS-CoV-2-specific immune responses were longitudinally analyzed up to 6 months post-HCT in 14 matched unrelated donor/recipients and four haploidentical donor/recipient pairs. A markedly skewed donor-derived SARS-CoV-2 CD4 T-cell response was measurable in 15 (83%) recipients. It showed a polarized Th1 functional profile, with the prevalence of central memory phenotype subsets. SARS-CoV-2-specific IFN-γ was detectable throughout the observation period, including early post-transplant (day +30). Functionally experienced SARS-CoV-2 Th1-type T cells promptly expanded in two recipients at the time of post-HCT vaccination and in two others who were infected and survived post-transplant COVID-19 infection. Our data suggest that donor-derived SARS-CoV-2 T-cell responses are functional in immunosuppressed recipients and may play a critical role in post-HCT vaccine response and protection from the fatal disease. Clinical trial registration: clinicaltrials.gov, identifier NCT04666025.

Successful outcome of pre-engraftment COVID-19 in an HCT patient: impact of targeted therapies and cellular immunity.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic that upended existing protocols and practices, including those for allogeneic hematopoietic stem cell transplantation (HCT). Here, we describe the successful clinical course and multiple key interventions administered to an acute lymphoblastic leukemia patient, who tested SARS-CoV-2 positive by reverse transcriptase polymerase chain reaction on day -1 of matched unrelated donor (SARS-CoV-2 immunoglobulin G negative) T-cell-replete HCT. This experience allowed for implementing a virologic and immunomonitoring panel to characterize the impact of SARS-CoV-2 on the recipient's nascent humoral and cellular immune response. The finding of robust, functional, and persistent levels of SARS-CoV-2-specific T cells, starting early after transplant was unexpected, and in combination with the clinical strategy, may have contributed to the favorable outcome. Additionally, it is plausible that preexisting cross-reactive endemic coronavirus immunity in the allogeneic graft reduced recipient susceptibility to COVID-19 disease. This case supports the critical role that T-cell responses may play in mitigating SARS-CoV-2 infection, even in the context of transplant immunosuppression, in which reconstitution of humoral response is commonly delayed. Interventional approaches to transfer SARS-CoV-2-specific cellular immunity such as HCT donor vaccination and adaptive cellular therapy could be of benefit.

Herpes Virus Infections Other than Cytomegalovirus in the Recipients of Hematopoietic Stem Cell Transplantation.

This review discusses the epidemiologic and clinical aspects of herpes viruses other than cytomegalovirus in patients who have undergone hematopoietic stem cell transplantation.