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1.
Blood and marrow transplant within 4 weeks of SARS-CoV-2 infection is associated with increased risk of mortality: a National COVID Cohort Collaborative (N3C) Study
Mohan, M., Kothari, A., Verhagen, N., Shreenivas, A., Radhakrishnan, S. V., Dhakal, B., Figueroa-Castro, C., Chhabra, S., Janz, S., Pasquini, M., et al
Bone marrow transplantation. 2023
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2.
SARS-CoV-2 vaccination in the first year after allogeneic hematopoietic cell transplant: a prospective, multicentre, observational study
Hill, J. A., Martens, M. J., Young, J. H., Bhavsar, K., Kou, J., Chen, M., Lee, L. W., Baluch, A., Dhodapkar, M. V., Nakamura, R., et al
EClinicalMedicine. 2023;59:101983
Abstract
BACKGROUND The optimal timing for SARS-CoV-2 vaccines within the first year after allogeneic hematopoietic cell transplant (HCT) is poorly understood. METHODS We conducted a prospective, multicentre, observational study of allogeneic HCT recipients who initiated SARS-CoV-2 vaccinations within 12 months of HCT. Participants were enrolled at 22 academic cancer centers across the United States. Participants of any age who were planning to receive a first post-HCT SARS-CoV-2 vaccine within 12 months of HCT were eligible. We obtained blood prior to and after each vaccine dose for up to four vaccine doses, with an end-of-study sample seven to nine months after enrollment. We tested for SARS-CoV-2 spike protein (anti-S) IgG; nucleocapsid protein (anti-N) IgG; neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains; and SARS-CoV-2-specific T-cell receptors (TCRs). The primary outcome was a comparison of anti-S IgG titers at the post-V2 time point in participants initiating vaccinations <4 months versus 4-12 months after HCT using a propensity-adjusted analysis. We also evaluated factors associated with high-level anti-S IgG titers (≥2403 U/mL) in logistic regression models. FINDINGS Between April 22, 2021 and November 17, 2021, 175 allogeneic HCT recipients were enrolled in the study, of whom all but one received mRNA SARS-CoV-2 vaccines. SARS-CoV-2 anti-S IgG titers, neutralizing antibody titers, and TCR breadth and depth did not significantly differ at all tested time points following the second vaccination among those initiating vaccinations <4 months versus 4-12 months after HCT. Anti-S IgG ≥2403 U/mL correlated with neutralizing antibody levels similar to those observed in a prior study of non-immunocompromised individuals, and 57% of participants achieved anti-S IgG ≥2403 U/mL at the end-of-study time point. In models adjusted for SARS-CoV-2 infection pre-enrollment, SARS-CoV-2 vaccination pre-HCT, CD19+ B-cell count, CD4+ T-cell count, and age (as applicable to the model), vaccine initiation timing was not associated with high-level anti-S IgG titers at the post-V2, post-V3, or end-of-study time points. Notably, prior graft-versus-host-disease (GVHD) or use of immunosuppressive medications were not associated with high-level anti-S IgG titers. Grade ≥3 vaccine-associated adverse events were infrequent. INTERPRETATION These data support starting mRNA SARS-CoV-2 vaccination three months after HCT, irrespective of concurrent GVHD or use of immunosuppressive medications. This is one of the largest prospective analyses of vaccination for any pathogen within the first year after allogeneic HCT and supports current guidelines for SARS-CoV-2 vaccination starting three months post-HCT. Additionally, there are few studies of mRNA vaccine formulations for other pathogens in HCT recipients, and these data provide encouraging proof-of-concept for the utility of early vaccination targeting additional pathogens with mRNA vaccine platforms. FUNDING National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health.
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3.
Efficacy of a third SARS-CoV-2 mRNA vaccine dose among hematopoietic cell transplantation, CAR T cell, and BiTE recipients
Abid, M. B., Rubin, M., Ledeboer, N., Szabo, A., Longo, W., Mohan, M., Shah, N. N., Fenske, T. S., Abedin, S., Runaas, L., et al
Cancer cell. 2022
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4.
Response to SARS-CoV-2 vaccination in patients after hematopoietic cell transplantation and CAR-T cell therapy
Dhakal, B., Abedin, S. M., Fenske, T. S., Chhabra, S., Ledeboer, N., Hari, P., Hamadani, M.
Blood. 2021
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5.
Graft cryopreservation does not impact overall survival allogeneic hematopoietic cell transplantation using post-transplant cyclophosphamide for GVHD prophylaxis
Hamadani, M., Zhang, M. J., Tang, X. Y., Fei, M., Brunstein, C., Chhabra, S., D'Souza, A., Milano, F., Phelan, R., Saber, W., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
INTRODUCTION The COVID-19 pandemic has created significant barriers to timely donor evaluation, cell collection and graft transport for allogeneic hematopoietic stem cell transplantation (allo-HCT). To ensure availability of donor cells on the scheduled date of infusion, many sites now collect cryopreserve grafts before the start of pretransplant conditioning. Post-transplant cyclophosphamide (ptCY), is an increasingly used approach for graft-versus-host disease (GVHD) prophylaxis but the impact of graft cryopreservation on the outcomes of allo-HCT using ptCY is not known. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared the outcomes of HCT using cryopreserved versus fresh grafts in patients undergoing HCT for hematologic malignancy with ptCY. METHODS We analyzed 274 patients with hematologic malignancy undergoing allo-HCT from 2013-2018 with cryopreserved grafts and ptCY. Eighteen received bone marrow and 256, peripheral blood grafts. These were matched for age, graft type, disease risk index (DRI) and propensity score to 1,080 patients that underwent allo-HCT with a fresh graft. The propensity score, which is an assessment of the likelihood of receiving a fresh versus cryopreserved graft, was calculated logistic regression to account for the following: disease histology, Karnofsky Performance Score (KPS), HCT-comorbidity index, conditioning regimen intensity, donor type and recipient race. The primary endpoint was overall survival (OS). Secondary endpoints included acute and chronic graft-versus-host disease GVHD, non-relapse mortality (NRM), relapse/progression and disease-free survival (DFS). Because of multiple comparisons, only p-values <0.01 were considered statistically significant. RESULTS The two cohorts (cryopreserved versus fresh) were similar in patient age, KPS, diagnosis, DRI, HCT-comorbidity index, donor/graft source, and conditioning intensity. One-year probabilities of OS were 71.1% (95% confidence interval, 68.3-73.8%) with fresh grafts and 70.3% (64.6-75.7%) with cryopreserved grafts (p=0.81). Corresponding probabilities of OS survival at two years were 60.6% (57.3-63.8%) and 58.7% (51.9-65.4%) (p=0.62). In matched pair regression analysis, graft cryopreservation was not associated with a significantly higher risk of mortality (Hazard Ratio for cryopreserved versus fresh [HR] =1.05, 95% confidence interval, 0.86-1.29, p=0.60). Similarly, rates neutrophil recovery (HR=0.91, 0.80-1.02, p=0.12), platelet recovery (HR=0.88, 0.78-1.00, p=0.05), grade 3-4 acute GVHD (HR=0.78, 0.50-1.22, p=0.27), NRM (HR=1.16, 0.86-1.55, p=0.32) and relapse/progression (HR=1.21, 0.97-1.50, p=0.09) were similar with cryopreserved versus fresh grafts. There were somewhat lower rates chronic GVHD (HR=0.78, 0.61-0.99, p=0.04) and DFS (HR for treatment failure=1.19, 95%CI=1.01-1.29, p=0.04) with graft cryopreservation that were of marginal statistical significance after adjusting for multiple comparisons. CONCLUSIONS Graft cryopreservation does not significantly delay hematopoietic recovery, increase acute GVHD risk or NRM, or decrease overall survival after all-HCT using ptCY.
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6.
Severity of cytokine release syndrome and its association with infections after T-cell replete haploidentical related donor transplantation
Abid, M. B., Hamadani, M., Szabo, A., Hari, P. N., Graham, M. B., Frank, M. O., Collier, W. S., Abedin, S., Jerkins, J. H., Pasquini, M. C., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
An increased risk of infections has been described after T-cell-replete haploidentical transplantation (haploHCT). Cytokine release syndrome (CRS) after haploHCT is a known phenomenon but the impact of CRS severity on the risk of infections remains unexplored. We retrospectively evaluated 78 consecutive adult haploHCT recipients from 2012 to 2018 for the development of CRS (graded by Lee et al. criteria) and examined the incidence and mortality due to infections in correlation with CRS severity. Eighty percent of patients developed infections within 180 days of HCT in our study cohort that was stratified by severity of CRS into 3 groups. A significantly higher proportion of patients with CRS grades 2 (89%) and ≥3 (90%) had at least one infection, compared to grade 0-1 (68%) in the first 100 days (p=0.04). Bloodstream infections (BSI) were seen more frequently in CRS grades 2 and ≥3 in the first 6 months. Multivariable analysis for time-to-infection showed that CRS grade ≥3 was independently associated with a higher risk of any infection, compared to grade 0-1 (HR 3.05, p=0.007). CRS grade ≥3 was also associated with a higher hazard of viral (HR 3.42, p=0.04) and bacterial infections (HR 2.83, p=0.03) compared to CRS grade 0-1. After adjusting for time-to-neutrophil engraftment as a time-dependent covariate, CRS grade ≥3 still had a significant effect on viral infections (HR 2.49, p=0.03), but not on bacterial infections (HR 1.32, p=0.57). CRS grade was also a significant predictor for infection density (overall, bacterial, and viral). The incidence of infection-related mortality by day+100 was higher in patients with severe CRS. Severe CRS developing after PTCy-based haploHCT is independently associated with viral infections and increased the risk of bacterial infections likely through delayed neutrophil engraftment.
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7.
Impact of haploidentical hematopoietic cell transplantation conditioning intensity on the incidence and severity of post-transplantation viral infections
Raj, R. V., Hari, P., Pasquini, M., Epperla, N., D'Souza, A., Fenske, T., Shaw, B. E., Rizzo, J. D., Drobyski, W., Hamadani, M.
Bone Marrow Transplantation. 2016;51(12):1602-1604