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Isolation of a novel intertypic recombinant human mastadenovirus B2 from two unrelated bone marrow transplant recipients.

ABSTRACT: Human adenoviruses (HAdV) are well-known opportunistic pathogens of immunocompromised adult and pediatric patients but specific associations between HAdV species or individual HAdV types and disease are poorly understood. In this study we report the isolation of a novel HAdV-B2 genotype from two unrelated immunocompromised patients, both recipients of a hematopoietic cell transplant. In both patients, the course of HAdV infection is consistent with a scenario of reactivation of a latent virus rather than a primary opportunistic infection. Archived HAdV PCR-positive plasma, urine, and stool specimens were processed for virus isolation and detailed molecular characterization. Virus isolates were recovered from patient 1 from PCR-positive urine specimens obtained at days 103 and 116 after transplant in association with gross hematuria, and from a stool specimen obtained 138 days after transplant in association with diarrhea. An isolate was recovered from patient 2 from a PCR-positive urine specimen. Hexon and fiber gene amplification and sequencing were carried out for initial molecular typing, identifying the isolates as an intertypic recombinant with a HAdV-11-like hexon gene and a HAdV-77-like fiber gene. Comprehensive restriction fragment length polymorphism (RFLP) analysis was performed on viral DNA purified from urine and stool isolates, and next generation whole genome sequencing was carried out on purified viral genomic DNA. The genomes of the two isolated strains are 99.5% identical and represent the same RFLP genomic variant. The identified virus is a novel HAdV-B2 genotype designated HAdV-78 exhibiting a HAdV-11-like penton base, a HAdV-11-like hexon and a HAdV-77-like fiber (P11H11F77).

SUBMITTER: Kajon AE

PROVIDER: S-EPMC7210458 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Isolation of a novel intertypic recombinant human mastadenovirus B2 from two unrelated bone marrow transplant recipients.

Kajon A E AE Lamson D M DM Spiridakis E E Cardenas A M AM Babady N E NE Fisher B T BT St George K K

New microbes and new infections 20200409

Human adenoviruses (HAdV) are well-known opportunistic pathogens of immunocompromised adult and pediatric patients but specific associations between HAdV species or individual HAdV types and disease are poorly understood. In this study we report the isolation of a novel HAdV-B2 genotype from two unrelated immunocompromised patients, both recipients of a hematopoietic cell transplant. In both patients, the course of HAdV infection is consistent with a scenario of reactivation of a latent virus ra ...[more]

PMID: 32405419

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Project description:PurposeHematopoietic cell transplantation (HCT) is curative for hematologic disorders, but outcomes are historically inferior when using HLA-mismatched donors. Despite unrelated donor registries listing > 38 million volunteers, 25%-80% of US patients lack an HLA-matched unrelated donor, with significant disparity across ethnic groups. We hypothesized that HCT with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCy), a novel strategy successful in overcoming genetic disparity using mismatched related donors, would be feasible and increase access to HCT.Patients and methodsWe performed a prospective phase II study of MMUD bone marrow HCT with PTCy for patients with hematologic malignancies. The primary end point was 1-year overall survival (OS), hypothesized to be 65% or better. 80 patients enrolled at 11 US transplant centers (December 2016-March 2019). Following myeloablative or reduced-intensity conditioning-based HCT, patients received PTCy on days +3, +4, with sirolimus and mycophenolate mofetil starting on day +5. We compared outcomes to Center for International Blood and Marrow Transplant Research contemporary controls receiving PTCy.ResultsNotably, 48% of patients enrolled were ethnic minorities. 39% of pairs were matched for 4-6 out of 8 HLA alleles. The primary end point was met, with 1-year OS of 76% (90% CI, 67.3 to 83.3) in the entire cohort, and 72% and 79% in the myeloablative and reduced-intensity conditioning strata, respectively. Secondary end points related to engraftment and graft-versus-host-disease were reached. Multivariate analysis comparing the study group with other mismatched HCT controls found no significant differences in OS.ConclusionOur prospective study demonstrates the feasibility and effectiveness of HCT with an MMUD in the setting of PTCy. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.

Project description:We report a comparison of time to recovery, side effects, and change in blood counts from baseline to after donation from unrelated donors who participated in the Blood and Marrow Transplant Clinical Trials Network phase III randomized, multicenter trial (0201) in which donor-recipient pairs were randomized to either peripheral blood stem cell (PBSC) or bone marrow (BM) donation. Of the entire cohort, 262 donated PBSC and 264 donated BM; 372 (71%) donors were from domestic and 154 (29%) were from international centers (145 German and 9 Canadian). PBSC donors recovered in less time, with a median time to recovery of 1 week compared with 2.3 weeks for BM donors. The number of donors reporting full recovery was significantly greater for donors of PBSC than of BM at 1, 2, and 3 weeks and 3 months after donation. Multivariate analysis showed that PBSC donors were more likely to recover at any time after donation compared with BM donors (hazard ratio, 2.08; 95% confidence interval [CI], 1.73 to 2.50; P < .001). Other characteristics that significantly increased the likelihood of complete recovery were being an international donor and donation in more recent years. Donors of BM were more likely to report grades 2 to 4 skeletal pain, body symptoms, and fatigue at 1 week after donation. In logistic regression analysis of domestic donors only in which toxicities at peri-collection time points (day 5 filgrastim for PBSC donors and day 2 after collection of BM donors) could be analyzed, no variable was significantly associated with grades 2 to 4 skeletal pain, including product donated (BM versus PBSC; odds ratio, 1.13; 95% CI, .74 to 1.74; P = .556). Blood counts were affected by product donated, with greater mean change from baseline to after donation for white blood cells, neutrophils, mononuclear cells, and platelets in PBSC donors whereas BM donors experienced a greater mean change in hemoglobin. This analysis provided an enhanced understanding of donor events as product donated was independent of physician bias or donor preference.

Project description:BackgroundRandomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.MethodsWe conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37).ResultsThe overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse.ConclusionsWe did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).

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Isolation of a novel intertypic recombinant human mastadenovirus B2 from two unrelated bone marrow transplant recipients.

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Isolation of a novel intertypic recombinant human mastadenovirus B2 from two unrelated bone marrow transplant recipients.

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