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A phase II randomized, placebo-controlled, multicenter trial to evaluate the efficacy of cytomegalovirus PepVax vaccine in preventing cytomegalovirus reactivation and disease after allogeneic hematopoietic stem cell transplant
Nakamura, R., La Rosa, C., Yang, D., Hill, J. A., Rashidi, A., Choe, H., Zhou, Q., Lingaraju, C. R., Kaltcheva, T., Longmate, J., et al
Haematologica. 2024
Abstract
Not available.
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The impact of SARS-CoV2 vaccines on the incidence of graft versus host disease in allogeneic hematopoietic stem cell transplant recipients: a single-center retrospective study
Ngo, D., Chen, J., Tinajero, J., Aribi, A., Arslan, S., Marcucci, G., Nakamura, R., Al Malki, M. M., Forman, S. J., Dadwal, S., et al
Stem cell research & therapy. 2023;14(1):95
Abstract
This study reports the incidence of chronic graft versus host disease (GvHD) in allogeneic hematopoietic stem cell transplant (alloHCT) recipients who received SARS-CoV2 vaccination. The overall rates of new and worsening chronic GvHD combined were 14%, with median time from vaccination to GVHD being approximately three to four weeks. A majority of the cases were of mild to moderate severity and primarily localized to either the skin, mouth, or joints. Prior chronic GVHD and recent transplant were associated with higher GVHD rates following COVID-19 vaccination. More prospective studies are needed to provide a definitive mechanism for the impact of SARS-CoV2 vaccination on alloHCT patients.
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Association of pre-transplant vancomycin resistant enterococcus colonization status on long-term outcomes of allogeneic-hematopoietic cell transplantation
Salhotra, A., Sandhu, K. S., Yang, D., Mokhtari, S., O'Hearn, J., Tegtmeier, B., Al Malki, M. M., Abella, J., Meguro, A., Dickter, J., et al
Bone marrow transplantation. 2022
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Financial Burden in Blood or Marrow Transplantation Survivors During the COVID-19 Pandemic: A BMTSS Report
Bhatia, S., Dai, C., Hageman, L., Wu, J., Schlichting, E., Siler, A., Funk, E., Hicks, J., Lim, S., Balas, N., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022;:Jco2200461
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Abstract
PURPOSE The financial burden experienced by blood or marrow transplant (BMT) survivors during the COVID-19 pandemic remains unstudied. We evaluated the risk for high out-of-pocket medical costs and associated financial burden experienced by BMT survivors and a sibling comparison group during the COVID-19 pandemic. METHODS This study included 2,370 BMT survivors and 750 siblings who completed the BMT Survivor Study survey during the pandemic. Participants reported employment status, out-of-pocket medical costs, and financial burden. Medical expenses ≥ 10% of the annual household income constituted high out-of-pocket medical costs. Logistic regression identified factors associated with high out-of-pocket medical costs and financial burden. RESULTS BMT survivors were more likely to incur high out-of-pocket medical costs (11.3% v 3.1%; adjusted odds ratio [aOR], 2.88; 95% CI, 1.84 to 4.50) than the siblings. Survivor characteristics associated with high out-of-pocket medical costs included younger age at study (aOR(per_year_younger_age), 1.02; 95% CI, 1.00 to 1.03), lower prepandemic annual household income and/or education (< $50,000 US dollars and/or < college graduate: aOR, 1.96; 95% CI, 1.42 to 2.69; reference: ≥ $50,000 in US dollars and ≥ college graduate), > 1 chronic health condition (aOR, 2.82; 95% CI, 2.00 to 3.98), ≥ 1 hospitalization during the pandemic (aOR, 2.11; 95% CI, 1.53 to 2.89), and being unemployed during the pandemic (aOR, 1.52; 95% CI, 1.06 to 2.17). Among BMT survivors, high out-of-pocket medical costs were significantly associated with problems in paying medical bills (aOR, 10.57; 95% CI, 7.39 to 15.11), deferring medical care (aOR, 4.93; 95% CI, 3.71 to 6.55), taking a smaller dose of medication than prescribed (aOR, 4.99; 95% CI, 3.23 to 7.70), and considering filing for bankruptcy (aOR, 3.80; 95% CI, 2.14 to 6.73). CONCLUSION BMT survivors report high out-of-pocket medical costs, which jeopardizes their health care and may affect health outcomes. Policies aimed at reducing financial burden in BMT survivors, such as expanding access to patient assistance programs, may mitigate the negative health consequences.
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Safety and Tolerability of SARS-CoV-2 Emergency-Use Authorized Vaccines Allogeneic Hematopoietic Stem Cell Transplant Recipients
Ali, H., Ngo, D., Aribi, A., Arslan, S., Dadwal, S., Marcucci, G., Nakamura, R., Forman, S. J., Chen, J., Malki, M. M. A.
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND The safety and efficacy of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emergency-use authorized (EUA) vaccines has been confirmed in general population. However, there is no data on its safety/tolerability or efficacy in recipients of allogeneic hematopoietic stem cell transplant (HCT). OBJECTIVES We performed this study to identify the incidence of adverse events following SARS-CoV2 EUA vaccines and the incidence of new onset GVHD or worsening of existing GVHD after EUA vaccine administration and the incidence SAR-CoV2 positivity in vaccinated HCT patients. STUDY DESIGN We retrospectively reviewed 113 HCT patients who received at least one dose of EUA vaccine to describe the safety/tolerability, any impact on graft-versus-host disease (GVHD), and incidence of SARS-CoV2 PCR positivity after vaccination. Patients received either Pfizer (BNT162b2) or Moderna (mRNA-1273) vaccines. Patients were included if they were 18 years or older and received at least one dose of vaccine in the post HCT setting. RESULTS Most patients presented with myalgias/arthralgias (first dose 7.7%, second dose 14.6%), fatigue (first dose 15.4%, second dose 29.2%), and injection site pain (first dose 40.4%, second dose 43.8%). Other side effects experienced by patients included: nausea, vomiting, diarrhea, headache, injection-site rash and swelling. Liver function abnormalities occurred in 18.6% of patients. The incidence of neutropenia, thrombocytopenia, and lymphopenia occurred at 13.3%, 11.5%, and 8.8% respectively. Forty percent of patients who had active chronic GVHD at the time of vaccination where worsening chronic GVHD occurred in 3.5% of patients. New chronic GVHD developed in 9.7% of patients after vaccination. CONCLUSION In conclusion, the SARS-CoV2 EUA vaccines were well-tolerated in allogeneic HCT recipients.
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Influence of donor KIR genotypes on reduced relapse risk in acute myelogenous leukemia after hematopoietic stem cell transplantation in patients with CMV reactivation
Nakamura, R., Gendzekhadze, K., Palmer, J., Tsai, N. C., Mokhtari, S., Forman, S. J., Zaia, J. A., Senitzer, D., Marcucci, G., Stein, A.
Leukemia research. 2019;87:106230
Abstract
Multiple retrospective studies have demonstrated an association between cytomegalovirus (CMV) reactivation and reduced risk of AML relapse. However, the potential mechanism explaining this association remains elusive. We investigated a homogeneous cohort of 288 adult patients with AML in remission who received allogeneic hematopoietic stem cell transplantation (HCT) from matched sibling/unrelated donors between 1995 and 2011. The 5-year cumulative incidence of relapse was greater in patients without CMV reactivation compared with those with reactivation (30.2% vs. 12.1%, p=0.001) in a landmark analysis. In multivariate analyses CMV reactivation was independently associated with reduced relapse risk (HR: 0.49 [0.25-0.95], p=0.036) and increased non-relapse mortality (26.5% vs. 13.1%, p=0.002) resulting in similar 5-year overall survival (64.5% vs. 59.1%, p=0.8). In further subgroup analyses the protective effect of CMV reactivation was significant in patients who received HCT from donors with KIR Bx compared to KIR AA (11.7% vs. 29.5%, p=0.01). Likewise, the protective effect of CMV reactivation was more significant when the donors had 2DS1 activating KIR (11.5% vs. 30.7%, p=0.05) compared with those without 2DS1 (14.3% vs. 27.5%, p=0.12). Our data independently confirmed the association between CMV reactivation and AML relapse, suggesting the involvement of donor KIR genotypes and NK cell-mediated graft-versus-leukemia effect.
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Efficacy of low-dose zoster prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation
Mascarenhas, K., Teh, J. B., Peng, K., Kim, H., Sy, A., Forman, S. J., Wong, F. L., Nakamura, R., Dadwal, S. S., Armenian, S. H.
Bone marrow transplantation. 2019
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Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial
Nakamura, R., La Rosa, C., Longmate, J., Drake, J., Slape, C., Zhou, Q., Lampa, M. G., O'Donnell, M., Cai, J. L., Farol, L., et al
The Lancet Haematology. 2016;3(2):e87-98
Abstract
BACKGROUND Patients seropositive for cytomegalovirus (CMV) and undergoing allogeneic haemopoietic stem-cell transplantation (HCT) are at risk for CMV reactivation. Stimulating viral immunity by vaccination might achieve CMV viraemia control without the need for antiviral agents. CMVPepVax is a chimeric peptide composed of a cytotoxic CD8 T-cell epitope from CMV pp65 and a tetanus T-helper epitope. It is formulated with the adjuvant PF03512676, a Toll-like receptor 9 agonist, which augments cellular immunity. We aimed to assess safety, immunogenicity, and possible clinical benefit of the CMVPepVax vaccine in patients undergoing HCT. METHODS We did a randomised, open-label, phase 1b trial at one transplant centre in the USA. Eligible patients were CMV-seropositive, positive for HLA-A*0201, aged 18-75 years, and undergoing HCT from a matched-related or matched-unrelated donor. Patients were reassessed for eligibility on day 28 after HCT. We randomly allocated patients to either the CMVPepVax vaccine or observation, in blocks stratified by CMV donor serostatus. CMVPepVax was administered subcutaneously on days 28 and 56. The primary outcome was safety, which consisted of secondary graft failure, grade III-IV acute GVHD, non-relapse mortality by day 100, serious adverse events related to the vaccine (judged by the data and safety monitoring committee [DSMC]) grade 3-4 adverse events related to the vaccine (judged by the DSMC) within 2 weeks of vaccination, and development of double-strand (ds) DNA autoantibodies. Statistical analyses included all randomised patients and were done per-protocol. This study is registered with ClinicalTrials.gov, number NCT01588015. This trial is closed to accrual and the final analysis is presented in this report. FINDINGS Between Oct 31, 2012, and Nov 5, 2014, 36 eligible patients were allocated to either CMVPepVax (n=18) or observation (n=18), with no adverse effect on HCT (no secondary graft failures in either group) or cases of acute GVHD (seven patients assigned vaccine and six under observation had acute GVHD of grade 2 or less), and no unexpected adverse events. Compared with observation, better relapse-free survival was recorded in patients allocated the vaccine (seven vs one; hazard ratio [HR] 0.12, 95% CI 0.01-0.94; p=0.015). No patients had non-relapse mortality by day 100. One serious adverse event (grade 1 fever) was attributed to CMVPepVax but resolved within 48 h. Four patients assigned the vaccine had a serious adverse event, which was unrelated to the vaccine (grade 3 thrombocytopenia, grade 3 device-related infection, grade 2 nausea, and grade 1 fever), compared with nine patients under observation (grade 4 maculopapular rash, grade 3 nausea, grade 3 infection, grade 3 thrombotic thrombocytopenic purpurea, grade 2 nausea, grade 2 generalised muscle weakness, grade 2 infection, grade 1 fever, and grade 1 fatigue; p=0.16). 54 grade 3-4 adverse events were reported in patients assigned the vaccine compared with 91 in patients who were under observation (p=0.2). No patients had grade III-IV acute GVHD or developed dsDNA autoantibodies. INTERPRETATION The results show safety and immunogenicity of the CMVPepVax vaccine. The prospect of substantial clinical benefits warrant testing in a phase 2 trial. FUNDING National Cancer Institute. Copyright © 2016 Elsevier Ltd. All rights reserved.