Case Report: Favorable outcome of allogeneic hematopoietic stem cell transplantation in SARSCoV2 positive recipient, risk-benefit balance between infection and leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in SARS-CoV-2 positive candidates is usually delayed until the clinical resolution of the infection's symptoms and a negative nasopharyngeal molecular test. However, prolonged SARS-CoV-2 positivity has been frequently observed in haematological malignancies, thus representing a challenge for the timing of transplant procedures. Here, we report on the case of a 34-year-old patient with recent pauci-symptomatic COVID-19 undergoing transplant for high-risk acute B-lymphoblastic leukemia before achieving viral clearance. Shortly before their scheduled allogeneic HSCT from a matched unrelated donor, the patient developed mild Omicron BA.5 infection receiving nirmatrelvir/ritonavir with fever resolution within 72 hours. Twenty-three days after COVID-19 diagnosis, because of increasing minimal residual disease values in the context of high-risk refractory leukemia and clinical resolution of SARS-2-CoV infection with reduction of viral load at surveillance nasopharyngeal swabs, it was decided not to delay further allo-HSCT. During myelo-ablative conditioning, the nasopharyngeal SARS-CoV-2 viral load increased while the patient remained asymptomatic. Consequently, two days before the transplant, intra-muscular tixagevimab/cilgavimab 300/300 mg and a 3-day course of intravenous remdesivir were administered. During the pre-engraftment phase, veno-occlusive disease (VOD) occurred at day +13, requiring defibrotide treatment to obtain a slow but complete recovery. The post-engraftment phase was characterized by mild COVID-19 at day +23 (cough, rhino-conjunctivitis, fever) that spontaneously resolved, achieving viral clearance at day +28. At day +32, she experienced grade I acute graft-versus host disease (a-GVHD, skin grade II) treated with steroids and photo-apheresis, without further complications during follow-up until day +180. Addressing the issue of allo-HSCT timing in patients recovering from SARS-CoV-2 infection with high-risk malignant diseases is challenging because of 1] the high risk of COVID-19 clinical progression, 2] the impact of transplant delay on leukemia prognosis and 3] the occurrence of endothelial complications such as VOD, a-GVHD, and transplant associated thrombotic micro-angiopathy. Our report describes the favourable outcome of allo-HSCT in a recipient with active SARS-CoV2 infection and high-risk leukemia thanks to timely anti-SARS-CoV-2 preventive therapies and prompt management of transplant-related complications.

Risk factors and characteristics influencing humoral response to COVID-19 vaccination in patients after allogeneic stem cell transplantation.

Introduction: Vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is approved and recommended for immunocompromised patients such as patients after allogeneic stem cell transplantation (allo-SCT). Since infections represent a relevant cause of transplant related mortality we analyzed the advent of immunization to SARS-CoV-2 vaccination in a bicentric population of allogeneic transplanted patients. Methods: We retrospectively analyzed data of allo-SCT recipients in two German transplantation centers for safety and serologic response after two and three SARS-CoV-2 vaccinations. Patients received mRNA vaccines or vector-based vaccines. All patients were monitored for antibodies against SARS-CoV2-spike protein (anti-S-IgG) with an IgG ELISA assay or an EIA Assay after two and three doses of vaccination. Results: A total of 243 allo-SCT patients underwent SARS-CoV-2 vaccination. The median age was 59 years (range 22-81). While 85% of patients received two doses of mRNA vaccines, 10% had vector-based vaccines and 5% received a mixed vaccination. The two vaccine doses were well tolerated with only 3% patients developing a reactivation of graft versus host disease (GvHD). Overall, 72% of patients showed a humoral response after two vaccinations. In the multivariate analysis age at time of allo-SCT (p=0.0065), ongoing immunosuppressive therapy (p= 0.029) and lack of immune reconstitution (CD4-T-cell counts <200/µl, p< 0.001) were associated with no response. Sex, intensity of conditioning and the use of ATG showed no influence on seroconversion. Finally, 44 out of 69 patients that did not respond after the second dose received a booster and 57% (25/44) showed a seroconversion. Discussion: We showed in our bicentric allo-SCT patient cohort, that a humoral response could be achieve after the regular approved schedule, especially for those patients who underwent immune reconstitution and were free from immunosuppressive drugs. In over 50% of the initial non-responders after 2-dose vaccination, a seroconversion can be achieved by boostering with a third dose.

How I prevent viral reactivation in high-risk patients.

Preventing viral infections at an early stage is a key strategy for successfully improving transplant outcomes. Preemptive therapy and prophylaxis with antiviral agents have been successfully used to prevent clinically significant viral infections in hematopoietic cell transplant recipients. Major progress has been made over the past decades in preventing viral infections through a better understanding of the biology and risk factors, as well as the introduction of novel antiviral agents and advances in immunotherapy. High-quality evidence exists for the effective prevention of herpes simplex virus, varicella-zoster virus, and cytomegalovirus infection and disease. Few data are available on the effective prevention of human herpesvirus 6, Epstein-Barr virus, adenovirus, and BK virus infections. To highlight the spectrum of clinical practice, here we review high-risk situations that we handle with a high degree of uniformity and cases that feature differences in approaches, reflecting distinct hematopoietic cell transplant practices, such as ex vivo T-cell depletion.

Emergency Department Utilization Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Longitudinal Analysis of 557 Patients.

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are at risk of various complications during post-transplantation follow-up. Some patients may refer to an emergency department (ED) for medical attention, but data on ED visits by HSCT recipients are lacking. In the present study, we aimed to assess ED utilization in HSCT recipients and associated risk factors during post-transplantation follow-up, identify subgroups of HSCT recipients presenting to the ED, analyze outcomes and prognostic factors for hospitalization and 30-day mortality after ED visits, and assess mortality hazard following an ED presentation. The study involved a retrospective single-center longitudinal analysis including 557 consecutive recipients of allogeneic HSCT at the Medical University of Vienna, Austria, between January 2010 and January 2020. Descriptive statistics, event estimates accounting for censored data with competing risks, latent class analysis, and multivariate regression models were used for data analysis. Out of 557 patients (median age at HSCT, 49 years [interquartile range (IQR), 39 to 58 years]; 233 females and 324 males), 137 (25%) presented to our center's ED at least once during post-HSCT follow-up (median individual follow-up, 2.66 years; IQR, .72 to 5.59 years). Cumulative incidence estimates of a first ED visit in the overall cohort were 19% at 2 years post-HSCT, 25% at 5 years post-HSCT, and 28% at 10 years post-HSCT. These estimates were increased to 34%, 41%, and 43%, respectively, in patients residing in Vienna. Chronic graft-versus-host disease (GVHD) was the sole risk factor showing a statistically significant association with ED presentation in multivariate analysis (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.63 to 3.35). Patients presented to the ED with various and often multiple symptoms. We identified 3 latent patient groups in the ED, characterized mainly by the time from HSCT, chronic GVHD, and documented pulmonary infection. Hospitalization was required in 132 of all 216 analyzed ED visits (61%); in-hospital mortality and 30-day mortality rates were 13% and 7%, respectively. Active acute GVHD, systemic steroids, documented infection, pulmonary infiltrates, and oxygen supplementation were statistically significant predictors of hospitalization; shorter time from HSCT, pulmonary infiltrates, and hemodynamic instability were independent risk factors for 30-day mortality. ED presentation during the last 30 days increased the mortality hazard in the overall cohort (HR, 4.56; 95% CI, 2.68 to 7.76) after adjustment for relevant confounders. One-quarter of the patients visited the ED for medical attention at least once during post-HSCT follow-up. Depending on the presence of identified risk factors, a significant proportion of patients may require hospitalization and be at risk for adverse outcomes. Screening for these risk factors and specialist consultation should be part of managing most HSCT recipients presenting to the ED.

Three doses of a recombinant conjugated SARS-CoV-2 vaccine early after allogeneic hematopoietic stem cell transplantation: predicting indicators of a high serologic response-a prospective, single-arm study.

Background: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients must be vaccinated against SARS-CoV-2 as quickly as possible after transplantation. The difficulty in obtaining recommended SARS-CoV-2 vaccines for allo-HSCT recipients motivated us to utilize an accessible and affordable SARS-CoV-2 vaccine with a recombinant receptor-binding domain (RBD)-tetanus toxoid (TT)-conjugated platform shortly after allo-HSCT in the developing country of Iran. Methods: This prospective, single-arm study aimed to investigate immunogenicity and its predictors following a three-dose SARS-CoV-2 RBD-TT-conjugated vaccine regimen administered at 4-week (± 1-week) intervals in patients within 3-12 months post allo-HSCT. An immune status ratio (ISR) was measured at baseline and 4 weeks (± 1 week) after each vaccine dose using a semiquantitative immunoassay. Using the median ISR as a cut-off point for immune response intensity, we performed a logistic regression analysis to determine the predictive impact of several baseline factors on the intensity of the serologic response following the third vaccination dose. Results: Thirty-six allo-HSCT recipients, with a mean age of 42.42 years and a median time of 133 days between hematopoietic stem cell transplant (allo-HSCT) and the start of vaccination, were analyzed. Our findings, using the generalized estimating equation (GEE) model, indicated that, compared with the baseline ISR of 1.55 [95% confidence interval (CI) 0.94 to 2.17], the ISR increased significantly during the three-dose SARS-CoV-2 vaccination regimen. The ISR reached 2.32 (95% CI 1.84 to 2.79; p = 0.010) after the second dose and 3.87 (95% CI 3.25 to 4.48; p = 0.001) after the third dose of vaccine, reflecting 69.44% and 91.66% seropositivity, respectively. In a multivariate logistic regression analysis, the female sex of the donor [odds ratio (OR) 8.67; p = 0.028] and a higher level donor ISR at allo-HSCT (OR 3.56; p = 0.050) were the two positive predictors of strong immune response following the third vaccine dose. No serious adverse events (i.e., grades 3 and 4) were observed following the vaccination regimen. Conclusions: We concluded that early vaccination of allo-HSCT recipients with a three-dose RBD-TT-conjugated SARS-CoV-2 vaccine is safe and could improve the early post-allo-HSCT immune response. We further believe that the pre-allo-HSCT SARS-CoV-2 immunization of donors may enhance post-allo-HSCT seroconversion in allo-HSCT recipients who receive the entire course of the SARS-CoV-2 vaccine during the first year after allo-HSCT.

Applications of virus-specific T cell therapies post-BMT.

Hematopoietic stem cell transplantation (HSCT) has been used as a curative standard of care for moderate to severe primary immunodeficiency disorders as well as relapsed hematologic malignancies for over 50 years [1,2]. However, chronic and refractory viral infections remain a leading cause of morbidity and mortality in the immune deficient period following HSCT, where use of available antiviral pharmacotherapies is limited by toxicity and emerging resistance [3]. Adoptive immunotherapy using virus-specific T cells (VSTs) has been explored for over 2 decades [4,5] in patients post-HSCT and has been shown prior phase I-II studies to be safe and effective for treatment or preventions of viral infections including cytomegalovirus, Epstein-Barr virus, BK virus, and adenovirus with minimal toxicity and low risk of graft vs host disease [6-9]. This review summarizes methodologies to generate VSTs the clinical results utilizing VST therapeutics and the challenges and future directions for the field.

Specific immune response to mRNA vaccines against COVID-19 in patients receiving allogeneic stem cell transplantation for myeloid malignancy was altered by immunosuppressive therapy.

BACKGROUND: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are at high risk of complications associated with COVID-19 infection due to dysfunction of their immune system. Vaccination can protect from the adverse consequences of COVID-19. However, studies on the efficacy of COVID-19 vaccines in HSCT recipients with insufficient post-HSCT immune reconstitution are still scarce. In our study, we determined how immunosuppressive medication and the reconstitution of the cellular immune system influenced T cell responses specific for the surface glycoprotein of SARS-CoV-2 virus (S antigen) after two doses of mRNA vaccine against COVID-19 in patients with myeloid malignancies treated with HSCT. METHODS: Vaccination outcomes were followed in 18 (allo-HSCT) recipients and 8 healthy volunteers. The IgG antibodies against SARS-CoV-2 spike (S) and nucleocapsid (NCP) protein were determined in ELISA and S-specific T cells were detected using a sensitive ELISPOT-IFNγ based on in vitro expansion and restimulation of T cells in pre- and post-vaccination blood samples. Multiparametric flow cytometry analysis of peripheral blood leukocyte differentiation markers was employed for determination of reconstitution of the main subpopulations of T cells and NK cells at month 6 after HSCT. RESULTS: S- specific IgG antibody response detected in 72% of the patients was lower than in healthy vaccinees (100%). Vaccine-induced T-cell responses to S1 or S2 antigen were significantly reduced in HSCT recipients, which were treated with corticosteroids in dose 5 mg of prednisone- equivalents or higher during the vaccination period or in preceeding 100 days in comparison with recipients un-affected with corticosteroids. A significant positive correlation was found between the level of anti-SARS-Cov-2 spike protein IgG antibodies and the number of functional S antigen-specific T cells. Further analysis also showed that the specific response to vaccination was significantly influenced by the interval between administration of vaccine and transplantation. Vaccination outcomes were not related to age, sex, type of mRNA vaccine used, basic diagnosis, HLA match between HSC donor and recipient, and blood counts of lymphocytes, neutrophils, and monocytes at the time of vaccination. Multiparametric flow cytometry analysis of peripheral blood leukocyte differentiation markers showed that good humoral and cellular S-specific immune responses induced by vaccination were associated with well-reconstituted CD4+ T cells, mainly CD4+ effector memory subpopulation at six months after HSCT. CONCLUSIONS: The results showed that both humoral and cellular adaptive immune responses of HSCT recipients to the SARS-CoV-2 vaccine were significantly suppressed by corticosteroid therapy. Specific response to the vaccine was significantly affected by the length of the interval between HSCT and vaccination. Vaccination as early as 5 months after HSCT can lead to a good response. Immune response to the vaccine is not related to age, gender, HLA match between HSC donor and recipient, or type of myeloid malignancy. Vaccine efficacy was dependent on well-reconstituted CD4+ T cells, at six months after HSCT.

A French single-center experience on allogeneic stem cell transplant cryopreservation during severe acute respiratory syndrome coronavirus 2 pandemic.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for chemo-resistant hematological malignancies. Because of transport restriction imposed by the coronavirus disease 2019 pandemic, regulatory bodies and societies recommended graft cryopreservation before recipient conditioning. However, the freezing and thawing processes, including washing steps, might impair CD34+ cell recovery and viability, thereby impacting the recipient engraftment. Over 1 year (between March 2020 and May 2021), we aimed to analyze the results of frozen/thawed peripheral blood stem cell allografts in terms of stem cell quality and clinical outcomes. METHODS: Transplant quality was evaluated by comparing total nucleated cells (TNCs), CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM)/kg numbers as well as TNC and CD34+ cell viabilities before and after thawing. Intrinsic biological parameters such as granulocyte, platelet and CD34+ cell concentrations were analyzed, as they might be responsible for a quality loss. The impact of the CD34+ cell richness of the graft on TNC and CD34 yields was evaluated by designing three groups of transplants based on their CD34 /kg value at collection: >8 × 10 6/kg, between 6 and 8 × 106/kg and <6 × 106/kg. The consequences of cryopreservation were compared in the fresh and thawed group by evaluating the main transplant outcomes. RESULTS: Over 1 year, 76 recipients were included in the study; 57 patients received a thawed and 19 patients a fresh allo-SCT. None received allo-SCT from a severe acute respiratory syndrome coronavirus 2-positive donor. The freezing of 57 transplants led to the storage of 309 bags, for a mean storage time (between freezing and thawing) of 14 days. For the fresh transplant group, only 41 bags were stored for potential future donor lymphocyte infusions. Regarding the graft characteristics at collection, median number of cryopreserved TNC and CD34+ cells/kg were greater than those for fresh infusions. After thawing, median yields were 74.0%, 69.0% and 48.0% for TNC, CD34+ cells and CFU-GM, respectively. The median TNC dose/kg obtained after thawing was 5.8 × 108, with a median viability of 76%. The median CD34+ cells/kg was 5 × 106, with a median viability of 87%. In the fresh transplant group, the median TNC/kg was 5.9 × 108/kg, and the median CD34+ cells/kg and CFU-GM/kg were 6 × 106/kg and 276.5 × 104/kg, respectively. Sixty-one percent of the thawed transplants were out of specifications regarding the CD34+ cells/ kg requested cell dose (6 × 106/kg) and 85% of them would have had this dose if their hematopoietic stem cell transplant had been infused fresh. Regarding fresh grafts, 15.8% contained less than 6 × 106 CD34+ cells /kg and came from peripheral blood stem cells that did not reach 6 × 106 CD34+ cells /kg at collection. Regarding the factor that impaired CD34 and TNC yield after thawing, no significant impact of the granulocyte count, the platelet count or the CD34+ cells concentration/µL was observed. However, grafts containing more than 8 × 10 6/kg at collection showed a significantly lower TNC and CD34 yield. CONCLUSIONS: Transplant outcomes (engraftment, graft-versus-host disease, infections, relapse or death) were not significantly different between the two groups.

Managing Survivorship after Hematopoietic Cell Transplantation.

PURPOSE OF REVIEW: With improvement in survival after hematopoietic cell transplantation (HCT), it has become important to focus on the late complications experienced by the survivors that may lead to late mortality and morbidity to be able to provide patient-centered care across the transplant continuum. The goals of this article are to describe the status of literature on late complications in HCT survivors; offer a brief overview of the status of the screening, prevention, and management of these complications; and identify opportunities for future practice and research. RECENT FINDINGS: This is an exciting time for the field with increasing awareness about survivorship issues. Studies are moving beyond description to examining pathogenesis of these late complications and identifying biomarkers. The eventual goal is to promote changes in our transplant techniques to decrease the incidence of these complications as well as help develop interventions targeting these late effects. There is also an emphasis on improving health care delivery models to provide optimal post-HCT management for medical and psychosocial complications through close coordination between multiple stakeholders and leveraging technology to help address the barriers in delivery of care to fulfill the unmet needs in this area. The increasing population of HCT survivors with their burden of late effects underscores the need for concerted efforts to improve long-term medical and psychosocial outcomes for this group.

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.

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.

SARS-CoV-2 vaccine antibody response and breakthrough infections in transplant recipients.

Rates and modulators of SARS-CoV-2 vaccine nonresponse and breakthrough infections remain unclear in serially vaccinated transplant recipients. In a prospective, mono-centric, observational study, 1878 adult solid organ and hematopoietic cell transplant recipients, with prior SARS-CoV-2 vaccination, were included between March 2021 and February 2022. SARS-CoV-2 anti-spike IgG antibodies were measured at inclusion and details on SARS-CoV-2 vaccine doses and infection were collected. No life-threatening adverse events were reported after a total of 4039 vaccine doses. In transplant recipients without prior SARS-CoV-2 infection (n = 1636), antibody response rates ranged widely, from 47% in lung transplant to 90% in liver transplant and 91% in hematopoietic cell transplant recipients after third vaccine dose. Antibody positivity rate and levels increased after each vaccine dose in all types of transplant recipients. In multivariable analysis, older age, chronic kidney disease and daily dose of mycophenolate and corticosteroids were negatively associated with antibody response rate. Overall rate of breakthrough infections was 25.2% and mainly (90.2%) occurred after third and fourth vaccine dose. Lung transplant recipients had the highest rates of severe breakthrough infection (10.5%) and death (2.5%). In multivariable analysis, older age, daily dose of mycophenolate and corticosteroids were associated with severe breakthrough infection. Transplant recipients with infection before first vaccine dose (n = 160) had higher antibody response rates and levels after each vaccine dose, and a significantly lower overall rate of breakthrough infections compared to those without prior infection. Antibody response after SARS-CoV-2 vaccination and rate of severe breakthrough infections vary largely between different transplant types and are modulated by specific risk factors. The observed heterogeneity supports a tailored approach against COVID-19 in transplant recipients.

Prolonged SARS-CoV-2 infection during autologous hematopoietic stem cell transplantation from Hodgkin's lymphoma: a case report.

Autologous hematopoietic stem cell transplantation (HSCT) for relapsed Hodgkin's lymphoma increases the risk of infection by using intensive chemotherapy. This risk is obviously ongoing given the increased virulence of severe COVID-19. We report a case of a young man with Hodgkin's lymphoma who received conditioning chemotherapy followed by autologous HSCT and tested positive for SARS-CoV-2 by polymerase chain reaction (PCR) during the early phase of aplasia with persistence of COVID-19 beyond 30 days with favorable follow-up and clinical improvement on treatment. For this type of patient with hematologic malignancy, viral infection can be fatal and strict medical precautions with isolation rules must be maintained, especially for SARS-CoV-2.

A secondary CD34+ acute lymphoblastic leukemia unmasked and mobilized by G-CSF in an autologous stem cell donor with testicular cancer.

BACKGROUND: Late complications of chemotherapy include treatment-related secondary leukemias. We describe an unusual case of a new treatment-related acute lymphoblastic leukemia (t-ALL) that was unmasked and mobilized by G-CSF during autologous hematopoietic progenitor cell collection (HPCC) in a young man with testicular cancer. METHODS: Electronic chart review of the patient medical history and pertinent laboratory findings. Patient CD34 and blast results were compared to 4249 autologous and 437 allogeneic HPCC performed between 2004 and 2022. In autologous donors, the %blast and %CD34 were compared by linear regression and paired t-test using commercial software. RESULTS: The patient was a 21-year-old male with relapsed testicular cancer referred for G-CSF cytokine-only mobilization and autologous HPCC. His pre-mobilization WBC count and differential were normal. On the day of HPCC, his WBC = 37.9 K/mcL with 12% blasts and 9.75% circulating CD34+ cells. The patient was admitted 9 days after HPCC with a normal WBC count and 15% blasts. He was diagnosed with a pro-B t-ALL bearing an t(4:11)(q21:q23) translocation and KMT2A-AF4 rearrangement. Upon review, this patient had the highest %CD34 among 4686 HPCC and was the only donor with %CD34 > 1% after a cytokine-only mobilization. CONCLUSION: We report a case of t-ALL that mimicked CD34+ HPC and was mobilized by high-dose G-CSF. Up to 70% of secondary leukemias bear 11q23/KMT2A rearrangements, which occur at the multipotent stem cell stage and can result in myeloid and lymphoid leukemias. Donors who have received past chemotherapy, especially with topoisomerase II inhibitors, are at increased risk for 11q23/KMT2A leukemias.

Coronavirus disease 2019 vaccination in transplant recipients.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) vaccination is considered one of the most promising and socioeconomically sustainable strategy to help control the pandemic and several vaccines are currently being distributed in nationwide mass immunization campaigns. Very limited data are available on benefits and risks of COVID-19 vaccination in immunocompromised patients and in particular in solid organ or hematopoietic stem cell transplant recipients as they were excluded from phase III trials. This review summarizes current knowledge, international guidelines and controversies regarding COVID-19 vaccination in these vulnerable populations. RECENT FINDINGS: Various COVID-19 vaccine platforms showed good efficacy in phase III trials in the immunocompetent and there are data arising on the safety and immunogenicity of these vaccines in the immunocompromised population. SUMMARY: Transplant recipients could benefit significantly from COVID-19 vaccination, both through active immunization provided they elicit protective vaccine responses, and probably through cocooning by immunization of caregivers and healthcare personnel and thus reducing the risk of SARS-coronavirus-2 exposure. Although awaiting more data on the safety and efficacy of COVID-19 vaccines to inform potential adaptations of vaccine regimens, we strongly recommend prioritizing COVID-19 vaccination of solid and hematopoietic stem cell transplant recipients to decrease COVID-19-related morbidity and mortality.

COVID-19 in hematopoietic cell transplant recipients.

In this study, we aim to report the outcome of COVID-19 in hematopoietic cell transplant (HCT) recipients. HCT recipients (n = 32) with hematological disease and hospitalized for COVID-19 were included in the study. A cohort of age and comorbid disease-matched hospitalized COVID-19 patients with hematological malignancy but not underwent HCT (n = 465), and another cohort of age and comorbid disease-matched hospitalized COVID-19 patients without cancer (n = 497) were also included in the study for comparison. Case fatality rate (CFR) was 5.6% in patients without cancer, 11.8 in patients with hematological malignancy and 15.6% in HCT recipients. The CFR in HCT recipients who were not receiving immunosuppressive agents at the time of COVID-19 diagnosis was 11.5%, whereas it was 33% in HCT recipients who were receiving an immunosuppressive agent at the time of COVID-19 diagnosis. In conclusion, our study reveals that for the current pandemic, HCT recipients, especially those receiving immunosuppressive drugs, constitute a special population of cancer patients.

A 16-month-long experience of COVID-19 in allogeneic haematopoietic stem cell transplantation recipients: An SFGM-TC multicentre cohort study.

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.

Impact of COVID-19 Related Restrictions on Infections in Children with Cancer or after Hematopoietic SCT.

BACKGROUND: Infections are a major concern for immunocompromised children. We investigated whether non-pharmaceutical interventions (NPIs) implemented in the general population during the coronavirus disease 2019 (COVID-19) pandemic in Germany had an impact on frequency, type and severity of infections in these patients. PATIENTS AND METHODS: We analyzed all admissions to the clinic of pediatric hematology, oncology and stem cell transplantation (SCT) with (suspected) infection or fever of unknown origin (FUO) from 2018 to 2021. RESULTS: We compared a 27-month period before NPIs (Pre-COVID: 01/2018-03/2020; 1041 cases) with a 12-month period with underlying NPIs (COVID: 04/2020-03/2021; 420 cases). During the COVID period the number of in-patient stays with FUO or infections decreased (38,6 cases/month vs. 35,0 cases/month), the median duration of hospital stays was longer (8 d (CI95: 7-8 d) vs. 9 d (CI95: 8-10 d) P=0,02)), the mean number of antibiotics per case increased (2,1 (CI95: 2,0-2,2) vs. 2,5 (CI95: 2,3-2,7); P=0,003)) and a substantial reduction of viral respiratory and gastrointestinal infections per case was seen (0,24 vs. 0,13; P<0,001). Notably, there was no detection of respiratory syncytial virus, influenza and norovirus, between May 2020 and March 2021. Based on need of intensive care measures and further parameters we conclude that severe (bacterial) infections were not significantly reduced by NPIs. CONCLUSIONS: Introduction of NPIs in the general population during the COVID-pandemic substantially reduced viral respiratory and gastrointestinal infections in immunocompromised patients, while severe (bacterial) infections were not prevented.

Outcome of SARS-CoV2 infection in hematopoietic stem cell transplant recipients for autoimmune diseases.

Hematopoietic stem cell transplant (HSCT) recipients may be at high risk of mortality from coronavirus disease 2019 (COVID-19). However, specific data on COVID-19 after treatment with HSCT in patients affected by autoimmune diseases (ADs) are still lacking. In this multicenter observational study of the European Society for Blood and Marrow Transplantation (EBMT), clinical data on COVID-19 in 11 patients affected by severe ADs treated with HSCT (n = 3 allogeneic transplant; n = 8 autologous transplant) are reported. All patients were symptomatic during the initial phase of the SARS-CoV-2 infection. At screening, 5 patients reported upper respiratory symptoms, 3 patients had cough without oxygen requirement, and 6 patients exhibited extra-pulmonary symptoms. Four cases developed a lower respiratory tract disease (LRTD). Hospitalization was required in 6 cases, without necessity of intensive care unit (ICU) admission and/or ventilation/supplemental oxygen. Different interventions were adopted: remdesivir (n = 1), nirmatrelvir/ritonavir (n = 1), sotrovimab (n = 1), immunoglobulins (n = 1). At last follow-up, all patients are alive and had resolution of the infection. The current analysis describing the mild-moderate course of COVID-19 in transplant recipients affected by ADs, similar to the course observed in ADs under standard treatments, provides useful information to support the delivery of HSCT programs in this field. Vaccination and new treatments available for SARS-CoV-2 may be useful to further minimize the risk of infection.