Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 113
Filter
2.
Front Immunol ; 14: 1184956, 2023.
Article in English | MEDLINE | ID: covidwho-20240799

ABSTRACT

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.


Subject(s)
COVID-19 , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia , Female , Humans , Adult , RNA, Viral , COVID-19 Testing , COVID-19/complications , SARS-CoV-2 , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Leukemia/therapy , Graft vs Host Disease/etiology
3.
Semin Hematol ; 60(1): 10-19, 2023 01.
Article in English | MEDLINE | ID: covidwho-2317424

ABSTRACT

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.


Subject(s)
Epstein-Barr Virus Infections , Hematopoietic Stem Cell Transplantation , Virus Diseases , Humans , T-Lymphocytes/transplantation , Herpesvirus 4, Human , Neoplasm Recurrence, Local , Virus Diseases/therapy , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods
4.
Leuk Res ; 130: 107314, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-2316820

ABSTRACT

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.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Neoplasms , Humans , COVID-19 Vaccines , COVID-19/prevention & control , SARS-CoV-2 , Hematopoietic Stem Cell Transplantation/adverse effects , Immunoglobulin G , Immunosuppression Therapy , mRNA Vaccines , Immunity
5.
Curr Hematol Malig Rep ; 18(3): 75-82, 2023 06.
Article in English | MEDLINE | ID: covidwho-2316044

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Survivorship , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Survivors , Delivery of Health Care , Biomarkers , Disease Progression
6.
Transplant Cell Ther ; 29(5): 321.e1-321.e9, 2023 05.
Article in English | MEDLINE | ID: covidwho-2313869

ABSTRACT

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.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Male , Female , Humans , Middle Aged , Retrospective Studies , Transplantation, Homologous/adverse effects , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Risk Factors , Hematopoietic Stem Cell Transplantation/adverse effects
7.
Blood ; 141(17): 2062-2074, 2023 04 27.
Article in English | MEDLINE | ID: covidwho-2313904

ABSTRACT

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.


Subject(s)
Epstein-Barr Virus Infections , Hematopoietic Stem Cell Transplantation , Virus Diseases , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/prevention & control , Herpesvirus 4, Human , Virus Diseases/prevention & control , Virus Diseases/etiology , Antiviral Agents/therapeutic use
8.
Transfusion ; 63(4): 684-689, 2023 04.
Article in English | MEDLINE | ID: covidwho-2293628

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Testicular Neoplasms , Humans , Male , Young Adult , Antigens, CD34 , Granulocyte Colony-Stimulating Factor/adverse effects , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cells , Leukapheresis/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/chemically induced , Testicular Neoplasms/therapy , Testicular Neoplasms/chemically induced
9.
Curr Opin Infect Dis ; 34(4): 275-287, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-2257881

ABSTRACT

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.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Transplant Recipients , COVID-19/etiology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/classification , Clinical Decision-Making , Disease Management , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunocompromised Host , Immunogenicity, Vaccine , Organ Transplantation/adverse effects , Organ Transplantation/methods , Outcome Assessment, Health Care , Vaccination
10.
Front Immunol ; 14: 1125824, 2023.
Article in English | MEDLINE | ID: covidwho-2269481

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.


Subject(s)
COVID-19 , Communicable Diseases , Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Humans , Middle Aged , Bone Marrow , Transplantation, Homologous , COVID-19/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Communicable Diseases/complications , Cytomegalovirus Infections/complications , Registries
11.
JAMA ; 329(11): 918-932, 2023 03 21.
Article in English | MEDLINE | ID: covidwho-2280685

ABSTRACT

Importance: Chronic lymphocytic leukemia (CLL), defined by a minimum of 5 × 109/L monoclonal B cells in the blood, affects more than 200 000 people and is associated with approximately 4410 deaths in the US annually. CLL is associated with an immunocompromised state and an increased rate of complications from infections. Observations: At the time of diagnosis, the median age of patients with CLL is 70 years, and an estimated 95% of patients have at least 1 medical comorbidity. Approximately 70% to 80% of patients with CLL are asymptomatic at the time of diagnosis, and one-third will never require treatment for CLL. Prognostic models have been developed to estimate the time to first treatment and the overall survival, but for patients who are asymptomatic, irrespective of disease risk category, clinical observation is the standard of care. Patients with symptomatic disease who have bulky or progressive lymphadenopathy or hepatosplenomegaly and those with a low neutrophil count, anemia, or thrombocytopenia and/or symptoms of fever, drenching night sweats, and weight loss (B symptoms) should be offered treatment. For these patients, first-line treatment consists of a regimen containing either a covalent Bruton tyrosine kinase (BTK) inhibitor (acalabrutinib, zanubrutinib, or ibrutinib) or a B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax). There is no evidence that starting either class before the other improves outcomes. The covalent BTK inhibitors are typically used indefinitely. Survival rates are approximately 88% at 4 years for acalabrutinib, 94% at 2 years for zanubrutinib, and 78% at 7 years for ibrutinib. Venetoclax is prescribed in combination with obinutuzumab, a monoclonal anti-CD20 antibody, in first-line treatment for 1 year (overall survival, 82% at 5-year follow-up). A noncovalent BTK inhibitor, pitobrutinib, has shown an overall response rate of more than 70% after failure of covalent BTK inhibitors and venetoclax. Phosphoinositide 3'-kinase (PI3K) inhibitors (idelalisib and duvelisib) can be prescribed for disease that progresses with BTK inhibitors and venetoclax, but patients require close monitoring for adverse events such as autoimmune conditions and infections. In patients with multiple relapses, chimeric antigen receptor T-cell (CAR-T) therapy with lisocabtagene maraleucel was associated with a 45% complete response rate. The only potential cure for CLL is allogeneic hematopoietic cell transplant, which remains an option after use of targeted agents. Conclusions and Relevance: More than 200 000 people in the US are living with a CLL diagnosis, and CLL causes approximately 4410 deaths each year in the US. Approximately two-thirds of patients eventually need treatment. Highly effective novel targeted agents include BTK inhibitors such as acalabrutinib, zanubrutinib, ibrutinib, and pirtobrutinib or BCL2 inhibitors such as venetoclax.


Subject(s)
Antineoplastic Agents , Leukemia, Lymphocytic, Chronic, B-Cell , Tyrosine Protein Kinase Inhibitors , Aged , Humans , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Immunotherapy, Adoptive , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effects , Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors , Receptors, Chimeric Antigen , Tyrosine Protein Kinase Inhibitors/adverse effects , Tyrosine Protein Kinase Inhibitors/therapeutic use , United States/epidemiology
12.
Br J Haematol ; 201(6): 1066-1071, 2023 06.
Article in English | MEDLINE | ID: covidwho-2287135

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.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Humans , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , COVID-19/etiology , Immunosuppressive Agents/adverse effects , Risk Factors
13.
Front Immunol ; 14: 1125030, 2023.
Article in English | MEDLINE | ID: covidwho-2253359

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.


Subject(s)
COVID-19 , Hematologic Diseases , Hematopoietic Stem Cell Transplantation , Adult , Humans , Middle Aged , Retrospective Studies , COVID-19/etiology , Hematologic Diseases/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Stem Cell Transplantation
14.
Am J Transplant ; 23(6): 844-847, 2023 06.
Article in English | MEDLINE | ID: covidwho-2252571

ABSTRACT

Peripheral allogeneic hematopoietic stem cell transplant recipients are the most vulnerable patients to community-acquired respiratory viruses such as respiratory syncytial virus, influenza virus, or others. These patients are likely to develop severe acute viral infections; community-acquired respiratory viruses have also been identified as triggers of bronchiolitis obliterans (BO). BO is a manifestation of pulmonary graft-versus-host disease, most often leading to irreversible ventilatory impairment. To date, there are no data on whether Severe acute respiratory syndrome â€‹coronavirus 2 (SARS-CoV-2) could be a trigger for BO. Here, we report the first report of a case of bronchiolitis obliterans syndrome following SARS-CoV-2 infection occurring 10 months after allogeneic hematopoietic stem cell transplant with a flare of underlying extra thoracic graft-versus-host disease. This observation provides a new perspective and should be of particular interest to clinicians, suggesting the need for close monitoring of pulmonary function test (PFTs) after SARS-CoV-2 infection. The mechanisms leading to bronchiolitis obliterans syndrome after SARS-CoV-2 infection require further investigation.


Subject(s)
Bronchiolitis Obliterans Syndrome , Bronchiolitis Obliterans , COVID-19 , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , SARS-CoV-2 , Bronchiolitis Obliterans/etiology , Hematopoietic Stem Cell Transplantation/adverse effects
15.
Bone Marrow Transplant ; 58(5): 558-566, 2023 05.
Article in English | MEDLINE | ID: covidwho-2250581

ABSTRACT

Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.


Subject(s)
COVID-19 , Communicable Diseases , Hematopoietic Stem Cell Transplantation , Humans , Male , Child , Female , Transplantation, Homologous , Prospective Studies , Bone Marrow , COVID-19 Testing , Cough/etiology , COVID-19/etiology , SARS-CoV-2 , Hematopoietic Stem Cell Transplantation/adverse effects , Risk Factors , Disease Progression , Communicable Diseases/etiology
16.
Transplant Proc ; 55(3): 543-546, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2249441

ABSTRACT

BACKGROUND: Patients with hematologic malignancies are considered at high risk for COVID-19 infection either from the disease or the treatment. Hematopoietic stem cell transplantation, one of the approved therapies for hematologic malignancies, was performed worldwide during the COVID-19 era with some regulations, such as COVID-19 testing, before proceeding with transplantation or cellular therapy. To the authors' knowledge, none have reported the result of autologous hematopoietic stem cell transplantation in an active COVID-19 patient. CASE PRESENTATION: We describe a successful clinical course of autologous bone marrow transplantation for 2 lymphoma patients who tested positive for COVID-19. A thorough discussion was conducted between multidisciplinary hemato-oncology, intensive care, and infectious diseases teams. The decision was to proceed toward bone marrow transplantation with some modifications in the transplantation protocol and close patient monitoring. CONCLUSION: Our cases lend credence that successful autologous bone marrow transplantation is possible among active COVID-19 patients. The obstacles we faced could be overcome with collaboration between a highly qualified multidisciplinary team. Despite the potential complications, the benefits of bone marrow transplantation among patients with a high risk of relapse and who are still COVID-19-positive outweigh the risks. However, further studies are still recommended to support our inference.


Subject(s)
COVID-19 , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Humans , Bone Marrow Transplantation/adverse effects , COVID-19 Testing , Neoplasm Recurrence, Local/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Transplantation, Autologous
17.
J Autoimmun ; 136: 103024, 2023 04.
Article in English | MEDLINE | ID: covidwho-2261228

ABSTRACT

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.


Subject(s)
Autoimmune Diseases , COVID-19 , Hematopoietic Stem Cell Transplantation , Humans , SARS-CoV-2 , RNA, Viral , Transplant Recipients , Hematopoietic Stem Cell Transplantation/adverse effects , Autoimmune Diseases/epidemiology , Autoimmune Diseases/therapy
18.
Int J Environ Res Public Health ; 20(3)2023 01 17.
Article in English | MEDLINE | ID: covidwho-2240873

ABSTRACT

INTRODUCTION: The SARS-CoV-2 pandemic generated the need to keep immunosuppressed patients away from hospital institutions for as long as possible. This in turn stimulated the implementation of a home hospitalization model for autologous hematopoietic stem-cell transplantation (HSCT). PURPOSE: To analyze whether there are significant differences in post-transplantation complications related to catheters observed in patients treated in the home-transplant care modality compared to patients treated in the hospital. METHODOLOGY: Observational, analytical, longitudinal, and retrospective study of cases and controls. A convenience sample was chosen, in which the cases comprised 20 patients included in the home HSCT care model. For each patient, it was considered suitable to propose two controls among those who received autologous transplantation in the last five years with a baseline demographic and pathological profile similar to the case for whom they were control. RESULTS: The home patients achieved an average of 22.4 ± 2.6 days of evolution with an average of 16.4 ± 2.08 days post-transplant, compared to the hospital process with an average of 21.21 ± 4.18 days of evolution and 15.51 ± 3.96 days post-transplant (evolution days p = 0.022; post-transplant days p = 0.002). A higher percentage of use of parenteral nutrition (p = 0.036) and transfusions (p = 0.003) was observed during the post-transplant phase in the hospital. The rest of the therapeutic measures did not show significant differences. When analyzing the frequency of adverse effects in the post-transplant phase, a significant increase in neutropenic fever (OR = 8.55) and positive blood cultures (OR = 6.65) was observed in hospital patients. Any other significant differences in other variables related to PICC were found (presence and days of neutropenic fever, catheter infection, complications, pathogens, admission to the ICU, or death). Concerning local complications (pain, DVT, Medical adhesive-related Skin Injury, and erythema), there was more erythema in the hospital (p = 0.056). CONCLUSIONS: The results obtained indicate that regarding the appearance of complications associated with PICCs in home hospitalization HSCT patients, there are no significant differences compared to hospitalization, so that home care can be a safe context for people with these lines.


Subject(s)
COVID-19 , Catheterization, Central Venous , Hematopoietic Stem Cell Transplantation , Humans , Catheterization, Central Venous/methods , Catheters , COVID-19/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Hospitalization , Retrospective Studies , Risk Factors , SARS-CoV-2 , Transplantation, Autologous/adverse effects
19.
Transpl Infect Dis ; 25(2): e14003, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2234450

ABSTRACT

BACKGROUND: Patients undergoing allogeneic stem-cell transplantation (allo-SCT) have reduced responses to vaccines due to immunosuppressive status linked to GvHD prophylaxis and treatment. In our study, we compared humoral responses to anti-SARS-CoV-2 mRNA vaccine, and infection onset, according to patients and transplant features; we also evaluated cellular response in patients without seroconversion. METHODS: We tested antibodies titer after second and third vaccine doses. Antibodies were detected through an immune-enzymatic assay. In a patients' subgroup without seroconversion, we tested cell-mediated responses evaluating interferon-gamma release by T-lymphocytes exposed to virus spike protein. RESULTS: Seroconversion rate increased from 66% at 30 days to 81% at 90 days after the second dose; it was 97% at 150 days after the third dose. We found a significant association between seroconversion after the second dose and two variables: shorter interval between allo-SCT and vaccination; ongoing immunosuppression. Twelve of 19 patients (63%) without antibodies after the second dose did not show cellular responses. Nineteen percent of patients developed SARS-CoV-2 infection after the third dose, with favorable outcome in all cases. Patients within 12 months after allo-SCT showed a significantly higher infection risk. CONCLUSIONS: Our study suggests that an interval shorter than 12 months between allo-SCT and first vaccine dose and/or ongoing immunosuppression were associated with humoral and cellular response deficiency after two doses. Third dose induced an increased and sustained humoral response in the majority of patients. However, patients within 1 year after allo-SCT remained at higher infection risk and may be candidate for prophylaxis with anti-SARS-CoV-2 monoclonal antibodies.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Humans , COVID-19/prevention & control , SARS-CoV-2 , Vaccination , Antibodies, Viral , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cells , RNA, Messenger
20.
Transpl Infect Dis ; 25(3): e14024, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2223540

ABSTRACT

INTRODUCTION: A high incidence of mortality and severe COVID-19 infection was reported in hematopoietic stem cell transplant (HSCT) recipients during the early phases of the COVID-19 pandemic; however, outcomes with subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as the omicron variant, have yet to be reported. Additionally, rollout of COVID-19 vaccinations in subsequent pandemic waves may modify COVID-19 disease severity and mortality in this immunocompromised population. We describe COVID-19 outcomes among a highly vaccinated population of HSCT recipients at a single center during successive waves of community transmission arising from the SARS-CoV-2 delta and omicron variants. METHODS: We retrospectively reviewed medical records of all HSCT recipients at our institution who tested positive for SARS-CoV-2 from May 2021 to May 2022. Descriptive statistics were reported; the chi-square test was utilized to identify factors associated with 90-day all-cause mortality and severity of COVID-19 infection. RESULTS: Over the 1-year study period, 77 HSCT recipients at our center contracted COVID-19 (43 allogenic; 34 autologous). Twenty-six (33.8%) patients were infected with the SARS-CoV-2 delta variant, while 51 (66.2%) had the SARS-CoV-2 omicron variant. Thirty-nine (50.6%) patients required hospitalization. More than 80% had received prior COVID-19 vaccination (57.1% with two doses, 27.3% with three doses). The majority (90.9%) had mild disease; only one (1.3%) patient required mechanical ventilation. Active hematological disease at time of COVID-19 infection was associated with increased odds of mortality [odds ratio (OR) = 6.90, 95% confidence interval (CI) = 1.20-40]. The 90-day all-cause mortality was 7.8% (six patients). Infection with the omicron variant (vs. delta) was associated with less severe illness (OR = 0.05, 95% CI = 0.01-0.47) and decreased odds of mortality (OR = 0.08, 95% CI = 0.01-0.76). Being on immunosuppression (OR = 5.10, 95% CI = 1.10-23.60) and being unvaccinated at disease onset (OR = 14.76, 95% CI = 2.89-75.4) were associated with greater severity of COVID-19 infection. CONCLUSION: We observed favorable outcomes with COVID-19 infection in a cohort of vaccinated HSCT patients. The SARS-CoV-2 omicron variant was associated with both less severe illness and decreased odds of mortality. As COVID-19 moves toward endemicity, early access to treatment and encouraging vaccination uptake is crucial in mitigating the challenge of COVID-19 management among HSCT recipients. Surveillance and assessment of clinical outcomes with new SARS-CoV-2 variants also remains important in this immunocompromised population.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Humans , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , COVID-19 Vaccines , Pandemics , Retrospective Studies , Transplant Recipients , Hematopoietic Stem Cell Transplantation/adverse effects
SELECTION OF CITATIONS
SEARCH DETAIL