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SERIOUS STEM CELL DONATION EVENTS AND RECIPIENT ADVERSE REACTIONS RELATED TO SARS-CoV-2: REVIEW OF REPORTS TO THE WORLD MARROW DONOR ASSOCIATION
Pawson, R., Anthias, C., Cody, M., Fechter, M., Fournier, D., O'Flaherty, E., Oliviera, D., van Eerden, E., Mengling, T.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND The SARS-CoV-2 pandemic has deeply impacted hematopoietic stem cell (HSC) donations and transplants. Many changes in practice have been introduced and it is vital to monitor the impact of these on donations and transplants. As part of a global response to this pandemic, the World Marrow Donor Association (WMDA) asked that its member registries and cord blood banks submit SARS-CoV-2-related adverse events to the WMDA-operated Serious Product Events and Adverse Reactions (SPEAR) database. OBJECTIVE This article reviews SARS-CoV-2-related SPEARs that occurred in 2020. STUDY DESIGN The WMDA Serious Product Events and Adverse Reactions (SPEAR) Committee reviewed reports submitted via an online tool. The Committee reviewed each report following the EU definitions of a serious adverse event or reaction and determined the imputability and its impact. Reports submitted in 2020 were included in this analysis RESULTS 74 such reports were received and were classified as: donor-related 41 (55.4%); recipient-related 3 (4.1%); technical issues 31 (41.8%) transport-related issues 4 (5.4%). Five cases appeared in more than one category. The commonest adverse events reported were of cells being unused. Many of these cases were caused by the uncoupling of the donation and transplant consequent on the cryopreservation of products as well as technical issues related to cell viability. Experience in some registries suggests these issues have become less frequent as transplant centres have become used to the changes in practice. CONCLUSION Lessons learnt include the importance of confirming recipient eligibility before the donors starts mobilisation or collection and minimising the time from collection of cells to transplant. Transplant centres should familiarise themselves with the expected cell losses when PBSC and BM products are cryopreserved and have validated viability assays for quality assurance. Reassuringly there were no reports of donors becoming severely unwell because of G-CSF or of transmission of SARS-CoV-2 to recipients and only one report of complete failure of transport of a donation.
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Outcomes in human T-cell leukemia virus type I carriers after hematopoietic stem cell transplantation for diseases other than adult T cell leukemia/lymphoma: a Japanese national survey
Nakano, N., Nakasone, H., Fuji, S., Shinohara, A., Suzuki, R., Utsunomiya, A., Eto, T., Morishima, S., Ikegame, K., Kakinoki, Y., et al
The Lancet regional health. Western Pacific. 2023;40:100902
Abstract
BACKGROUND Human T-cell leukemia virus type I (HTLV-1) is a retrovirus known to cause adult T-cell leukemia/lymphoma (ATL). There are few reports on hematopoietic stem cell transplantation (HSCT) for HTLV-1 carriers with diseases other than ATL. METHODS A total of 25,839 patients (24,399 adults and 1440 children) with pre-transplant HTLV-1 serostatus information recorded in the Japanese National Survey Database who had undergone their first HSCT were analyzed. We investigated the overall survival (OS), transplant-related mortality (TRM), and disease-related mortality (DRM) after HSCT in relation to HTLV-1 serologic status. FINDINGS Three hundred and forty-eight patients were HTLV-1 antibody carriers. The number of HTLV-1 carriers and noncarriers among adult patients who received allogeneic HSCT (allo-HSCT) or autologous HSCT (auto-HSCT) was 237/15,777 and 95/8920, respectively, and was 16/1424 among pediatric patients who received allo-HSCT. No pediatric HTLV-1 carrier recipients undergoing auto-HSCT were identified. There were no significant differences between HTLV-1 carriers and non-carriers regarding stem cell source, disease risk, or HCT-CI score prior to allo-HSCT. Multivariate analysis of OS (P = 0.020) and TRM (P = 0.017) in adult patients showed that HTLV-1 positive status was a significant prognostic factor. In children, TRM was significantly higher (P = 0.019), but OS was not significantly different. In adult patients who underwent auto-HSCT, HTLV-1 positive status was not a significant prognostic factor. In adult allo-HSCT patients, cytomegalovirus reactivation was significantly more common in HTLV-1 carriers (P = 0.001). INTERPRETATION HTLV-1 antibody positivity was shown to have a poor prognosis in OS and TRM after allo-HSCT in adult patients and in TRM after allo-HSCT in pediatric patients. FUNDING This work was supported in part by the practical research programs of the Japan Agency for Medical Research and Development (AMED) under grant number 17ck0106342h0001.
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A 16-month-long experience of COVID-19 in allogeneic haematopoietic stem cell transplantation recipients: An SFGM-TC multicentre cohort study
Xhaard, A., Xhaard, C., Rubio, M. T., Berceanu, A., Botella-Garcia, C., Coman, T., Tavernier, E., Labussière-Wallet, H., Chevallier, P., Legrand, F., et al
British journal of haematology. 2023
Abstract
This 16-month-long multicentre retrospective study of 225 allogeneic haematopoietic stem cell transplantation (alloHSCT) recipients with COVID-19 examines risk factors for severity and mortality, describing the successive waves of infections (from March to June 2020 and from August 2020 to June 2021). We confirm the negative role of low respiratory tract disease and immunosuppressive treatment. We highlight significantly lower percentages of severe forms and COVID-19-related mortality during the second wave. Monthly comparative evolution of cases in alloHSCT recipients and in the French population shows a higher number of cases in alloHSCT recipients during the first wave and a decrease from February 2021.
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Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry
Busca, A., Salmanton-García, J., Marchesi, F., Farina, F., Seval, G. C., Van Doesum, J., De Jonge, N., Bahr, N. C., Maertens, J., Meletiadis, J., et al
Frontiers in Immunology. 2023;14:1125030
Abstract
BACKGROUND The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT. METHODS This multicenter retrospective study promoted by the European Hematology Association - Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022. RESULTS The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53). CONCLUSIONS Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.
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Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry
Ljungman, P., Tridello, G., Piñana, J. L., Ciceri, F., Sengeloev, H., Kulagin, A., Mielke, S., Yegin, Z. A., Collin, M., Einardottir, S., et al
Frontiers in immunology. 2023;14:1125824
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Editor's Choice
Abstract
INTRODUCTION COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. METHODS This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. RESULTS The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. DISCUSSION Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.
PICO Summary
Population
Adults and children who tested PCR positive to COVID-19 after previous allogeneic transplant, and were reported to the EBMT registry (n=986)
Intervention
Analysis of the outcome of COVID-19 during important phases of the COVID-19.
Comparison
Patients contracting COVID-19 at different time points of the pandemic were compared
Outcome
The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age, worse performance status, contracting COVID-19 within the first 30 days or 30 - 100 days after HCT, ongoing immunosuppression, pre-existing lung disease, and recipient CMV seropositivity had negative impact on overall survival while patients contracting COVID-19 in 2020 or 2021 had worse overall survival than patients with COVID-19 diagnosed in 2022.
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Reduced immunogenicity of a third COVID-19 vaccination among recipients of allogeneic haematopoietic stem cell transplantation
Einarsdottir, S., Martner, A., Nicklasson, M., Wiktorin, H. G., Arabpour, M., Törnell, A., Vaht, K., Waldenström, J., Ringlander, J., Bergström, T., et al
Haematologica. 2022
Abstract
Not available.
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Allogeneic haematopoietic cell transplant services in Australia and New Zealand in the first year of the COVID-19 pandemic: A report from Australia and New Zealand Transplant and Cellular Therapies
Othman, J., Aarons, D., Bajel, A., Butler, J., Doocey, R., O'Brien, T., Purtill, D., Smith, L., Wilcox, L., Hamad, N.
Internal medicine journal. 2022
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Abstract
BACKGROUND The COVID-19 pandemic has caused major disruption to health systems, with allogeneic haematopoietic cell transplant (alloHCT) services a particularly vulnerable area. Ongoing provision of alloHCT has required dynamic responses at national and local levels. In Australia and New Zealand (ANZ), a high reliance on unrelated donors from overseas registries has posed an additional challenge. AIMS To describe the impact of COVID-19 on alloHCT services in ANZ in the first year of the pandemic. METHODS Data from the national alloHCT recipient and unrelated donor registries was extracted for a 2-year time frame. Comparisons were made between a pre-pandemic period of 1st March 2019 to 29th February 2020 and the corresponding dates during the pandemic, 1st March 2020 to 28th February 2021. RESULTS There was a 13% decrease in the number of allogeneic transplants, a reversal of steady increases in previous years, with the largest decrease in unrelated donor transplants. Local donors supplied a greater proportion of unrelated stem cell products. With a switch to universal cryopreservation, the time from request of a product to infusion increased by a median of 25.5 days for overseas products and 14 days for local products. There was a significant increase in the number of products collected but not used. CONCLUSIONS A strong public health response and coordinated transplant community activities allowed for safe provision of alloHCT in ANZ, however our data suggests that the timely delivery of allogeneic transplants was affected by the COVID-19 pandemic. Continued dedicated efforts are required to minimise further impacts. This article is protected by copyright. All rights reserved.
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Adenovirus disease after hematopoietic cell transplantation: A Japanese transplant registry analysis
Inamoto, Y., Takeda, W., Hirakawa, T., Sakaguchi, H., Nakano, N., Uchida, N., Doki, N., Ikegame, K., Katayama, Y., Sawa, M., et al
American journal of hematology. 2022
Abstract
We analyzed a Japanese registry database to elucidate the incidence, risk factors, and outcomes of adenovirus (AdV) disease after autologous and allogeneic hematopoietic cell transplantation (HCT) in contemporary real-world patients. We evaluated the cumulative incidence of AdV disease, as well as risk factors and survival and treatment details, among 25233 patients who underwent autologous HCT and 48380 patients who underwent allogeneic HCT between 2005 and 2019. The 1-year cumulative incidences of AdV disease after autologous and allogeneic HCT were 0.18% and 1.52%, respectively, in children, and 0.49% and 2.99%, respectively, in adults. Among patients with AdV disease, renourinary infection was the most common manifestation, and viremia or disseminated disease occurred in 6% of those after autologous HCT and 19% of those after allogeneic HCT. In multivariate analysis, age ≥50 years and lymphoma were associated with AdV disease after autologous HCT, while patient age ≥50 years, male patients, lymphoma, HCT-specific comorbidity index ≥3, HLA-mismatched or haploidentical donors, cord blood, in vivo T-cell depletion, HCT from 2005-2009, acute graft-versus-host disease (GVHD), and chronic GVHD were associated with AdV disease after allogeneic HCT. The 1-year probabilities of survival after disease diagnosis were 65% in autologous HCT and 44% in allogeneic HCT. Regardless of AdV disease burden, there was an increased risk of mortality after both autologous and allogeneic HCT. The most commonly used antiviral agents were cidofovir and vidarabine. The probabilities of improvement and survival with currently available agents were suboptimal. AdV disease after HCT remains a challenge. Better antiviral modalities are necessary. This article is protected by copyright. All rights reserved.
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Neither COVID-19, nor cryopreservation, prevented allogeneic product infusion: A report from the National Marrow Donor Program
Farhadfar, N., Newman, J., Novakovich, J., Barten, J., Ndifon, E. T., Oakes, J., Cody, M., Pham, H. P., Auletta, J. J., Miller, J. P., et al
Frontiers in immunology. 2022;13:937900
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Editor's Choice
Abstract
BACKGROUND The Coronavirus Disease 2019 (COVID-19) pandemic in early 2020 has resulted in an unprecedented level of uncertainty and challenge for the stem cell donor registries. To address these challenges, rapid strategies were implemented by the National Marrow Donor Registry (NMDP) and its network partners. Herein, we aim to report the impact of the COVID-19 pandemic on the collection, utilization of grafts, and short-term outcomes of patients who received stem cell products from COVID-19-positive donors. METHODS NMDP data during the early phase (1 March 2020 through 1 May 2020) of the pandemic were compared to the later phase (1 March 2021 through 1 May 2021). Odds ratios were calculated to determine the impact of the pandemic on graft sources requested by transplant centers (TCs). The Kruskal-Wallis test was used to test the effect of the pandemic on the disease indication, volume of searches, and number of products not infused. RESULTS Although there was an initial decline in overall donor searches during the early phase of the pandemic, these numbers increased reaching pre-pandemic levels during the later phase. Urgent malignant diseases remained the most common indication for transplant in 2021. The pandemic necessitated cryopreservation of stem cell products due to transportation restrictions as well as clinical uncertainties in managing the virus. Cryopreserved grafts remained the most common requested grafts throughout the pandemic. In the later phase of the pandemic, the total numbers of requests for fresh grafts increased, mostly due to the increase in requests for fresh bone marrow (BM) grafts. As the pandemic continued, TCs became more accepting of cryopreservation, resulting in a reduction in the number of products not infused. Lastly, no short-term deleterious outcomes were noted among the patients who had stem cell products infused from a SARS-CoV-2-positive donor. CONCLUSION Throughout the pandemic, the NMDP and TCs worked tirelessly to ensure that patients would receive lifesaving grafts when needed. The data reported here, although limited by small numbers, illustrate that transplantation from donors with COVID-19 is feasible and safe.
PICO Summary
Population
Data on allogeneic transplants reported to the CIBMTR registry
Intervention
Donor collection and infusion dates for the period March 2020 – July 2020
Comparison
Donor collection and infusion dates for the period March 2021 – July 2021
Outcome
Although there was an initial decline in overall donor searches during the early phase of the pandemic, these numbers increased reaching pre-pandemic levels during the later phase. Urgent malignant diseases remained the most common indication for transplant in 2021. The pandemic necessitated cryopreservation of stem cell products due to transportation restrictions as well as clinical uncertainties in managing the virus. Cryopreserved grafts remained the most common requested grafts throughout the pandemic. In the later phase of the pandemic, the total numbers of requests for fresh grafts increased, mostly due to the increase in requests for fresh bone marrow grafts. As the pandemic continued, transplant centres became more accepting of cryopreservation, resulting in a reduction in the number of products not infused. Lastly, no short-term deleterious outcomes were noted among the patients who had stem cell products infused from a SARS-CoV-2-positive donor.
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Clinical Characteristics and Outcomes of COVID-19 in Pediatric and Early Adolescent and Young Adult Haematopoietic Stem Cell Transplant Recipients: A Cohort Study
Bhatt, N. S., Sharma, A., Martin, A. S., Abid, M. B., Brown, V. I., Diaz, M. A., Frangoul, H., Gadalla, S. M., Herr, M. M., Krem, M. M., et al
Transplantation and cellular therapy. 2022
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Editor's Choice
Abstract
BACKGROUND Adult hematopoietic stem cell transplantation (HSCT) recipients are at a high risk of adverse outcomes after COVID-19. While children have had better outcomes after COVID-19 compared to adults, data on risk factors and outcomes of COVID-19 among pediatric HSCT recipients are lacking. OBJECTIVES To describe the risk-factors and outcomes of COVID-19 among pediatric and early adolescent and young adult HSCT recipients STUDY DESIGN : We describe outcomes of HSCT recipients who were ≤21 years of age at COVID-19 diagnosis and were reported to the Center for International Blood and Marrow Transplant Research between March 27, 2020, and May 7, 2021. The primary outcome was overall survival after COVID-19 diagnosis. We determined risk factors of COVID-19 as a secondary outcome, in a subset of allogeneic HSCT recipients. RESULTS A total of 167 pediatric HSCT recipients (135 allogeneic; 32 autologous HSCT recipients) were included. Median time from HSCT to COVID-19 was 15 months (IQR 7-45) for allogeneic HSCT recipients and 16 months (6-59) for autologous HSCT recipients. Median follow-up from COVID-19 diagnosis was 53 days (range 1-270) and 37 days (1-179) for allogeneic and autologous HSCT recipients, respectively. While COVID-19 was mild in 87% (n=146/167), 10% (n=16/167) of patients required supplemental oxygen or mechanical ventilation. The 45-day overall survival was 95% (95% CI 90-99) and 90% (74-99) for allogeneic and autologous HSCT recipients, respectively. Cox regression analysis showed that patients with hematopoietic cell transplant comorbidity index (HCT-CI) score of 1-2 were more likely to be diagnosed with COVID-19 (HR 1.95; 95% CI 1.03-3.69, p=0.042) compared to those with HCT-CI of 0. CONCLUSIONS Pediatric and early adolescent and young adult HSCT recipients with pre-HSCT comorbidities were more likely to be diagnosed with COVID-19. Overall mortality, albeit higher than the reported general population estimates, was lower when compared with previously published data focusing on adult HSCT recipients.
PICO Summary
Population
Children and adolescents who were infected with COVID-19 after transplant, and reported to the CIBMTR database (n=167)
Intervention
Allogeneic transplant prior to COVID infection (n=135)
Comparison
Autologous transplant prior to COVID infection (n=32)
Outcome
Median time from HSCT to COVID-19 was 15 months (IQR 7-45) for allogeneic HSCT recipients and 16 months (6-59) for autologous HSCT recipients. Median follow-up from COVID-19 diagnosis was 53 days (range 1-270) and 37 days (1-179) for allogeneic and autologous HSCT recipients, respectively. While COVID-19 was mild in 87% (n=146/167), 10% (n=16/167) of patients required supplemental oxygen or mechanical ventilation. The 45-day overall survival was 95% (95% CI 90-99) and 90% (74-99) for allogeneic and autologous HSCT recipients, respectively. Cox regression analysis showed that patients with hematopoietic cell transplant comorbidity index (HCT-CI) score of 1-2 were more likely to be diagnosed with COVID-19 (HR 1.95; 95% CI 1.03-3.69) compared to those with HCT-CI of 0.