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1.
Cochrane Database Syst Rev ; 5: CD013070, 2022 05 13.
Article in English | MEDLINE | ID: covidwho-1843835

ABSTRACT

BACKGROUND: Crohn's disease (CD) is an inflammatory bowel disease that causes inflammation and stricture, of any part of the mucosa and the gut wall. It forms skip lesions, sparing the areas in between the affected parts of the gastrointestinal tract. Crohn's disease could have one of three complications; fistula, intestinal obstruction due to stricture, or gastrointestinal inflammation presenting as severe diarrhoea. Stem cell therapy (SCT) is an innovative treatment that has been recently used in CD. The exact role of SCT in CD is still unclear. Stem cells modify the immunity of the patients or act as a "reset tool" for the immune system as in the case of systemically-injected stem cells, or regenerate the affected area of necrotic and inflammatory tissue as in the case of local injection into the lesion. Stem cells are a wide variety of cells including pluripotent stem cells or differentiated stem cells. The hazards range from rejection to symptomatic manifestations as fever or increase infection.  OBJECTIVES: The objective of this Cochrane systematic review is to assess the effects of stem cell transplantation compared to standard of care alone or with placebo on efficacy and safety outcomes in patients with refractory CD. SEARCH METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and clinical trial registries (Clinicaltrials.gov, World Health Organization-International Clinical Trials Registry Platform WHO ICTRP) from inception to 19 March 2021, without any language, publication year, or publication status restrictions. In addition, we searched references of included studies and review articles for further references. An update of the published studies was done during the writing of the review. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) that assessed the effectiveness and safety of SCT in refractory CD versus standard care alone (control) or with placebo. DATA COLLECTION AND ANALYSIS: Two review authors (SEN and SFA) independently screened the studies retrieved from the search results for inclusion, extracted data and assessed the risk of bias. Any disagreement was resolved through a consensus between the authors. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We conducted our search on 19 March 2021 and identified 639 records. We added two records by a manual search of the published reviews on the topic to a total of 641 records. The Covidence program removed 125 duplicates making a total of 516 reports. Two review authors (SEN and SFA) screened titles and abstracts and excluded 451 records with the remaining 65 for full-text records screened independently by the two authors; only 18 studies were considered for inclusion.  We included seven RCTs with a total of 442 participants for the meta-analysis. The intervention group included 234 patients, and the control group included 208 patients. Nine trials are ongoing and, two abstracts are awaiting classification. All patients in the control and intervention groups received the standard therapy for CD. Only three studies used blinding methods for the control group in the form of a placebo, with one study of the three stated that the blinding method was inefficient. The patients and personnel were aware of the intervention in the rest of the four studies as they were open-label trials. However, the effect of unblinding was balanced by the low risk of detection bias in five of the included studies. The evidence is uncertain about the effect of SCT on achieving clinical remission as compared to control/placebo (risk ratio (RR) 1.88, 95% Confidence Interval (CI) 0.80 to 4.41; 3 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT on achieving Crohn's Disease Activity Index (CDAI) <150 at 24 weeks compared to control (RR1.02 95% CI 0.67 to 1.56; 4 studies; very-low certainty evidence). SCT is likely to achieve fistula closure as compared to the control/placebo both in the short term (RR 1.48, 95% CI 1.12 to 1.96); low-certainty evidence) and in the long term (RR 1.42, 95% CI 1.09 to 1.87; 4 studies; low-certainty evidence) follow-up. The evidence is very uncertain about the effect of SCT to cause no difference in the number of total adverse events as compared to the control/placebo (RR 0.99, 95% CI [0.88 to  1.13); 4 studies; very-low-certainty evidence). However, SCT is likely to increase the number of serious adverse events as compared to the control/placebo (RR 1.22, 95% CI 0.88 to 1.67; 7 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT to decrease the withdrawal due to adverse events as compared to the control/placebo (RR 0.78, 95% CI 0.32 to 1.89; 3 studies; very-low certainty evidence). Funding by pharmaceutical companies was found in three studies, with one including more than 50% of our studied population. AUTHORS' CONCLUSIONS: SCT shows an uncertain effect on clinical remission with low certainty of evidence. SCT shows an uncertain effect on CDAI score to reach <150 after 24 weeks of treatment, with very low certainty evidence. SCT shows beneficial effects on fistula-closure during short and long-term follow-up with low-certainty evidence in both outcomes. There was no change in the total number of adverse events with SCT as compared to control, with very low certainty evidence. While there was a moderate effect on increasing the number of serious adverse events in the SCT group, as compared to the control with low-certainty evidence. Withdrawal due to adverse events was slightly higher in the control group with very low certainty evidence. All the participants were refractory to standard medical treatment, but the number of participants was small, this may limit the generalizability of the results. Further research is needed for validation. More objective outcomes are needed in the assessment of stem cell effectiveness in the treatment of Crohn's disease, especially the intestinal CD subtype; with standardization of the dose, methods of stem cell preparation, route of administration, and inclusion criteria to the studies to achieve clear results.


Subject(s)
Crohn Disease , Hematopoietic Stem Cell Transplantation , Constriction, Pathologic , Crohn Disease/drug therapy , Humans , Inflammation , Remission Induction
3.
Int J Hematol ; 115(5): 611-615, 2022 May.
Article in English | MEDLINE | ID: covidwho-1797499

ABSTRACT

We evaluated anti-spike protein antibody (anti-S) production in 130 hematopoietic stem cell transplant (HSCT) recipients who received the coronavirus disease-2019 vaccine. Sixty-five received allo-HSCT and 65 received auto-HSCT. Disease-specific treatments were being administered to 43.1% of allo-HSCT and 69.2% of auto-HSCT patients. Seropositivity was observed in 87.7% of allo-HSCT and 89.2% in auto-HSCT patients. Anti-S antibody production was significantly impaired in auto-HSCT patients compared with controls (178U/mL [0.4-4990.0] vs. 669 U/mL [40.3-4377.0], p < 0.001), but not in allo-HSCT patients (900 U/mL [0.4-12,893.0] vs. 860 U/mL [40.3-8988.0], P = 0.659). Clinically relevant anti-S antibody levels (> 264 U/mL) were achieved in 59.2% of patients (76.9% in allo-HSCT and 41.5% in auto-HSCT). The main factors influencing the protective level of the antibody response were the CD19 + cell count and serum immunoglobulin G levels, and these were significant in both allo-HSCT and auto-HSCT patients. Other factors included time since HSCT, complete remission status, use of immunosuppressive drugs, and levels of lymphocyte subsets including CD4, CD8 and CD56 positive cells, but these were only significant in allo-HSCT patients. Allo-HSCT patients had a relatively favorable antibody response, while auto-HSCT patients had poorer results.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Retrospective Studies , Transplantation, Autologous , Transplantation, Homologous
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 645-648, 2022 Apr.
Article in Chinese | MEDLINE | ID: covidwho-1786420

ABSTRACT

Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide since outbreak in December 2019, and become a global public health crisis. Patients with hematological malignancy concurrently infected with COVID-19 are often associated with severe even fatal complications, due to low basic immune function, high intensity of chemotherapy and radiotherapy, and slow immune reconstruction post hematopoietic stem cell transplantation, and their treatment strategies, such as anti-infective therapy, blood transfusion, and the use of granulocyte colony stimulating factor need to be adjusted. The characteristics of patients, chemotherapy, hematopoietic stem cell transplantation, and other clinical factors may affect the prognosis of patients with hematological malignancy concurrently infected with COVID-19. Herein, the latest research progress is reviewed.


Subject(s)
COVID-19 , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematologic Neoplasms/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Prognosis
5.
BMJ Open ; 12(4): e059516, 2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1784838

ABSTRACT

INTRODUCTION AND OBJECTIVE: Research activity was impacted by the novel COVID-19 pandemic, the PERCEPT myeloma trial was no exception. This pilot randomised trial delivered a face-to-face exercise intervention prior to and during autologous stem cell transplantation (ASCT) in myeloma patients, as a consequence of COVID-19 it required significant adaptions to continue. This brief communication describes how the previously published study protocol was adapted for virtual delivery. In addition, we highlight the challenge of continuing the study which was embedded within a clinical pathway also impacted by the pandemic. SUMMARY: The original trial protocol was amended and continued to recruit and deliver an exercise prehabilitation intervention virtually. Continued delivery of the intervention was deemed important to participants already enrolled within the trial and the adapted virtual version of the trial was acceptable to the research ethics committee as well as participants. Development of effective, remotely delivered rehabilitation and physical activity programmes are likely to benefit people living with myeloma. The COVID-19 pandemic provided an opportunity to explore the feasibility of a virtual programme for ASCT recipients, however, continued changes to the clinical pathway within which the study was embedded posed the greatest challenge and ultimately led to early termination of recruitment. TRIAL REGISTRATION NUMBER: ISRCTN15875290; pre-results.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , COVID-19/prevention & control , Hematopoietic Stem Cell Transplantation/methods , Humans , Multiple Myeloma/rehabilitation , Pandemics/prevention & control , Preoperative Exercise , Randomized Controlled Trials as Topic , Transplantation, Autologous
6.
Front Immunol ; 13: 839844, 2022.
Article in English | MEDLINE | ID: covidwho-1775672

ABSTRACT

Mesenchymal stromal cells (MSCs) possess profound immunomodulatory and regenerative properties that are of clinical use in numerous clinical indications with unmet medical need. Common sources of MSCs include among others, bone marrow (BM), fat, umbilical cord, and placenta-derived decidua stromal cells (DSCs). We here summarize our more than 20-years of scientific experience in the clinical use of MSCs and DSCs in different clinical settings. BM-MSCs were first explored to enhance the engraftment of autografts in hematopoietic cell transplantation (HCT) and osteogenesis imperfecta around 30 years ago. In 2004, our group reported the first anti-inflammatory use of BM-MSCs in a child with grade IV acute graft-versus-host disease (GvHD). Subsequent studies have shown that MSCs appear to be more effective in acute than chronic GvHD. Today BM-MSC-therapy is registered for acute GvHD in Japan and for GvHD in children in Canada and New Zeeland. MSCs first home to the lung following intravenous injection and exert strong local and systemic immunomodulatory effects on the host immune system. Thus, they were studied for ameliorating the cytokine storm in acute respiratory distress syndrome (ARDS). Both, MSCs and DSCs were used to treat SARS-CoV-2 coronavirus-induced disease 2019 (COVID-19)-induced ARDS. In addition, they were also used for other novel indications, such as pneumomediastinum, colon perforation, and radiculomyelopathy. MSC and DSCs trigger coagulation and were thus explored to stop hemorrhages. DSCs appear to be more effective for acute GvHD, ARDS, and hemorrhages, but randomized studies are needed to prove superiority. Stromal cell infusion is safe, well tolerated, and only gives rise to a slight fever in a limited number of patients, but no major side effects have been reported in multiple safety studies and metaanalysis. In this review we summarize current evidence from in vitro studies, animal models, and importantly our clinical experience, to support stromal cell therapy in multiple clinical indications. This encloses MSC's effects on the immune system, coagulation, and their safety and efficacy, which are discussed in relation to prominent clinical trials within the field.


Subject(s)
COVID-19 , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Animals , COVID-19/therapy , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hemorrhage/etiology , Humans , Mesenchymal Stem Cell Transplantation/adverse effects , Pregnancy , SARS-CoV-2
8.
Transplant Cell Ther ; 28(5): 279.e1-279.e4, 2022 May.
Article in English | MEDLINE | ID: covidwho-1763866

ABSTRACT

Little is known about the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, several studies have reported that adequate protection could be provided to this population. The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. Specific anti-Spike (S) antibody responses were assessed in a cohort of 117 allo-HSCT recipients after 2 injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment, and levels of CD4+and CD8+ T cells, B cells, and natural killer cells at the time of V1. Overall, the S-antibody response rate, evaluated at a median of 35 days after V2, was 82.9% for the entire cohort, with 71 patients (61%) reaching the highest titer. In univariate analysis, a lower pre-V1 median total lymphocyte count, lower CD4+ T cell and B cell counts, ongoing I/C treatment, and a haploidentical donor were characteristic of nonhumoral responders. However, multiparameter analysis showed that B cell aplasia was the sole factor predicting the absence of a specific immune response (odds ratio, 0.01; 95% confidence interval, 0.00 to 0.10; P < 10-3). Indeed, the rate of humoral response was 9.1% in patients with B cell aplasia versus 95.9% in patients with a B cell count >0 (P < 10-9). These results advocate for the administration of anti-SARS-CoV-2 vaccination in allo-HSCT recipients as early as peripheral B cell levels can be detected, and also suggest the need for close monitoring of B-cell reconstitution after Allo-HSCT.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Biomarkers , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines , Hematopoietic Stem Cell Transplantation/methods , Humans , RNA, Messenger , SARS-CoV-2 , Vaccination
9.
J Hematol Oncol ; 15(1): 27, 2022 03 18.
Article in English | MEDLINE | ID: covidwho-1745434

ABSTRACT

Hematopoietic stem cell transplant (HSCT) recipients are at high-risk for severe COVID-19 and have altered immune responses to vaccination. We sought to evaluate the dynamics of immune response to BNT162b2 mRNA vaccine in HSCT recipients. We systematically proposed vaccination with BNT162b2 to HSCT recipients and gave a third vaccine dose to those showing titers of IgG(S-RBD) below 4160 AU/mL 1 month following the second dose. We then quantified anti-SARS-CoV-2 antibodies dynamics in 133 of these HSCT recipients (88 after two and 45 after three vaccine doses) 6 months after the first vaccine dose. Mean IgG(S-RBD) titer at 6 months was significantly lower than the peak value measured 1 month after a second (p < 0.001) or third (p < 0.01) vaccine dose. IgG(S-RBD) titers at 6 months were strongly correlated to peak values (p < 0.001) and a peak titer above 10,370 AU/mL predicted persistent protection at 6 months. Seventy-two percent (96/133) of patients retained protective antibody levels at 6 months. Immunosuppressive drugs and low lymphocyte counts in peripheral blood correlated with lower IgG(S-RBD) titers at 6 months. Four patients (3%) developed PCR-documented SARS-CoV-2 infection and one died.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , SARS-CoV-2 , Vaccines, Synthetic
10.
Blood Adv ; 6(9): 2723-2730, 2022 May 10.
Article in English | MEDLINE | ID: covidwho-1741922

ABSTRACT

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti-RBD-S1 IgG) and for SARS-CoV-2-specific T-cell immunity, reflected by induction of T-cell-derived interferon-γ in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlap S1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P = .009, Fisher's exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P = .02, Fisher's exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (<100 BAU/mL) of anti-RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P = .007, Fisher's exact test). We conclude that although allo-HSCT recipients achieve serum anti-RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2-specific T-cell immunity may subsequently translate into insufficient humoral responses.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunity, Humoral , Immunoglobulin G , SARS-CoV-2 , Survivors , T-Lymphocytes , Vaccination
11.
Hematol Oncol Clin North Am ; 36(2): 353-363, 2022 04.
Article in English | MEDLINE | ID: covidwho-1734426

ABSTRACT

Autoimmune hemolytic anemia (AHIA) is the group of acquired autoimmune conditions resulting from the development of autologous antibodies directed against autologous red blood cell antigens resulting in red cell lysis. Beyond the presence, severity, and duration of hemolysis which can lead to symptomatic anemia, additional complications at presentation and during treatment require a high degree of clinical vigilance. These include among others cutaneous, thrombotic, renal disorders, and infectious disorders. Complications can be due to the presence of the pathologic antibody itself, the process of hemolysis, or attributed to treatment. Comprehensive management of AIHA requires awareness and assessment of complications at diagnosis, during, and following treatment.


Subject(s)
Anemia, Hemolytic, Autoimmune , Hematopoietic Stem Cell Transplantation , Thrombosis , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/etiology , Anemia, Hemolytic, Autoimmune/therapy , Erythrocytes , Hematopoietic Stem Cell Transplantation/adverse effects , Hemolysis , Humans
12.
Stem Cell Res Ther ; 13(1): 96, 2022 03 07.
Article in English | MEDLINE | ID: covidwho-1731542

ABSTRACT

BACKGROUND: Cell-free Mesenchymal stromal cells (MSCs) have been considered due to their capacity to modulate the immune system and suppress cytokine storms caused by SARS-CoV-2. This prospective randomized double-blind placebo-controlled clinical trial aimed to assess the safety and efficacy of secretome derived from allogeneic menstrual blood stromal cells (MenSCs) as a treatment in patients with severe COVID-19. METHODS: Patients with severe COVID-19 were randomized (1:1) to either MenSC-derived secretome treatment or the control group. Subjects received five intravenous infusions of 5 mL secretome or the same volume of placebo for five days and were monitored for safety and efficacy for 28 days after treatment. Adverse events, laboratory parameters, duration of hospitalization, clinical symptom improvement, dynamic of O2 saturation, lymphocyte number, and serial chest imaging were analyzed. RESULTS: All safety endpoints were observed without adverse events after 72 h of secretome injection. Within 28 days after enrollment, 7 patients (50%) were intubated in the treated group versus 12 patients (80%) in the control group. Overall, 64% of patients had improved oxygen levels within 5 days of starting treatment (P < 0.0001) and there was a survival rate of 57% in the treatment group compared to 28% in the control group was (P < 0.0001). Laboratory values revealed that significant acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. Significant improvement in lymphopenia was associated with an increase in mean CD4+ and CD8+ lymphocyte counts of 20% (P = 0.06) and 15% (P < 0.05), respectively. Following treatment, percentage of pulmonary involvement showed a significant improvement in the secretome group (P < 0.0001). This improvement differed significantly between survivors and those who were dying (P < 0.005). CONCLUSIONS: For the first time, this study demonstrated that in hospitalized patients with severe COVID-19, therapy with MenSCs-derived secretome leads to reversal of hypoxia, immune reconstitution, and downregulation of cytokine storm, with no adverse effects attributable to the treatment. Given these outcomes, it may be possible to use this type of treatment for serious inflammatory lung disease with a mechanism similar to COVID-19 in the future. However, it is necessary to evaluate the safety and efficacy of MenSCs-derived secretome therapy in clinical trials on a larger population of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05019287. Registered 24AGUEST 2021, retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05019287 . IRCT, IRCT20180619040147N6. Registered 04/01/2021.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cells , COVID-19/therapy , Double-Blind Method , Humans , Prospective Studies , SARS-CoV-2 , Treatment Outcome
13.
J Pediatr Health Care ; 36(3): 280-285, 2022.
Article in English | MEDLINE | ID: covidwho-1730025

ABSTRACT

The COVID-19 pandemic has impacted the care of countless individuals, including pediatric oncology patients. The initial lack of knowledge about the disease course and implications of infection led to delays in treatment to minimize additional harm. In pediatric oncology, unnecessary delays in chemotherapy or hematopoietic stem cell transplantation may increase the risk of disease relapse. This case report describes one high-risk pediatric oncology patient's clinical course through hematopoietic stem cell transplantation immediately following COVID-19 infection complicated by multisystem inflammatory syndrome in children. The disease course, monitoring, long-term outcome, and recommendations for future research are reviewed.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , COVID-19/complications , COVID-19/therapy , Child , Humans , Pandemics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Systemic Inflammatory Response Syndrome , Transplantation, Homologous
14.
Eur J Cancer ; 159: 78-86, 2021 12.
Article in English | MEDLINE | ID: covidwho-1719646

ABSTRACT

PURPOSE: There are limited data on SARS-CoV-2 (COVID-19) infection in children with cancer or after haematopoietic stem cell transplant (HSCT). We describe the severity and outcomes of SARS-COV-2 in these patients and identify factors associated with severe disease. METHODS: This was a multinational, observational study of children (aged <19 years) with cancer or HSCT and SARS-CoV-2 confirmed by polymerase chain reaction. COVID-19 was classified as asymptomatic, mild, moderate, severe or critical (≥1 organ support). Exact polytomous regression was used to determine the relationship between clinical variables and disease severity. RESULTS: One hundred and thirty-one patients with COVID-19 across 10 countries were identified (median age 8 years). Seventy-eight (60%) had leukaemia/lymphoma, 48 (37%) had solid tumour and five had primary immunodeficiency and HSCT. Fever (71%), cough (47%) and coryza (29%) were the most frequent symptoms. The median duration of detectable virus was 16 days (range, 1-79 days). Forty-nine patients (37%) were hospitalised for COVID-19 symptoms, and 15 (11%) required intensive care unit-level care. Chemotherapy was delayed/modified in 35% of patients. COVID-19 was asymptomatic in 32% of patients, mild in 47%, moderate in 8%, severe in 4% and critical in 9%. In 124 patients (95%), a full recovery was documented, and four (3%) died due to COVID-19. Any comorbidity (odds ratio, 2.94; 95% confidence interval [CI], 1.81-5.21), any coinfection (1.74; 95% CI 1.03-3.03) and severe baseline neutropenia (1.82; 95% CI 1.13-3.09) were independently and significantly associated with increasing disease severity. CONCLUSION: Although most children with cancer had asymptomatic/mild disease, 13% had severe COVID-19 and 3% died. Comorbidity, coinfection and neutropenia may increase the risk of severe disease. Our data may help management decisions in this vulnerable population.


Subject(s)
COVID-19/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasms/epidemiology , Adolescent , Age Factors , COVID-19/diagnosis , COVID-19/mortality , Child , Child, Preschool , Coinfection , Comorbidity , Female , Humans , Male , Neoplasms/diagnosis , Neoplasms/mortality , Neutropenia/epidemiology , Prognosis , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors
17.
Transplantation ; 105(7): 1405-1422, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1706459

ABSTRACT

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has raised concerns for programs overseeing donation and transplantation of cells, tissues, and organs (CTO) that this virus might be transmissible by transfusion or transplantation. Transplant recipients are considered particularly vulnerable to pathogens because of immunosuppression, and SARS-CoV-2 is likely to generate complications if contracted. Several signs and symptoms observed in COVID-19 positive patients reflect damage to multiple organs and tissues, raising the possibility of extrapulmonary SARS-CoV-2 infections and risk of transmission. At the beginning of the pandemic, a consensus has emerged not to consider COVID-19 positive patients as potential living or deceased donors, resulting in a global decrease in transplantation procedures. Medical decision-making at the time of organ allocation must consider safely alongside the survival advantages offered by transplantation. To address the risk of transmission by transplantation, this review summarizes the published cases of transplantation of cells or organs from donors infected with SARS-CoV-2 until January 2021 and assesses the current state of knowledge for the detection of this virus in different biologic specimens, cells, tissues, and organs. Evidence collected to date raises the possibility of SARS-CoV-2 infection and replication in some CTO, which makes it impossible to exclude transmission through transplantation. However, most studies focused on evaluating transmission under laboratory conditions with inconsistent findings, rendering the comparison of results difficult. Improved standardization of donors and CTO screening practices, along with a systematic follow-up of transplant recipients could facilitate the assessment of SARS-CoV-2 transmission risk by transplantation.


Subject(s)
COVID-19/transmission , Donor Selection/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Organ Transplantation/adverse effects , Postoperative Complications/etiology , SARS-CoV-2/isolation & purification , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19/virology , Humans , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Risk
18.
Transplant Cell Ther ; 28(4): 214.e1-214.e11, 2022 04.
Article in English | MEDLINE | ID: covidwho-1705633

ABSTRACT

Vaccines against SARS-CoV-2 have been rapidly approved. Although pivotal studies were conducted in healthy volunteers, little information is available on the safety and efficacy of mRNA vaccines in immunocompromised patients, including recipients of allogeneic hematopoietic cell transplantation (allo-HCT). Here we used a novel assay to analyze patient- and transplantation-related factors and their influence on immune responses to SARS-CoV-2 vaccination over an extended period (up to 6 months) in a large and homogenous group of allo-HCT recipients at a single center in Switzerland. We examined longitudinal antibody responses to SARS-CoV-2 vaccination with BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) in 110 allo-HCT recipients and 86 healthy controls. Seroprofiling recording IgG, IgA, and IgM reactivity against SARS-CoV-2 antigens (receptor-binding domain, spike glycoprotein subunits S1 and S2, and nucleocapsid protein) was performed before vaccination, before the second dose, and at 1, 3, and 6 months after the second dose. Patients were stratified to 3 groups: 3 to 6 months post-allo-HCT, 6 to 12 months post-allo-HCT, and >12 months post-allo-HCT. Patients in the 3 to 6 months and 6 to 12 months post-allo-HCT groups developed significantly lower antibody titers after vaccination compared with patients in the >12 months post-allo-HCT group and healthy controls (P < .001). Within the cohort of allo-HCT recipients, patients age >65 years (P = .030), those receiving immunosuppression for prevention or treatment of graft-versus-host disease (GVHD) (P = .033), and patients with relapsed disease (P = .014) displayed low humoral immune responses to the vaccine. In contrast, the intensity of the conditioning regimen, underlying disease (myeloid/lymphoid/other), and presence of chronic GVHD had no impact on antibody levels. Antibody titers achieved the highest levels at 1 month after the second dose of the vaccine but waned substantially in all transplantation groups and healthy controls over time. This analysis of long-term vaccine antibody response is of critical importance to allo-HCT recipients and transplant physicians to guide treatment decisions regarding revaccination and social behavior during the SARS-CoV-2 pandemic.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Aged , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , SARS-CoV-2 , Vaccination
19.
Bone Marrow Transplant ; 57(5): 742-752, 2022 May.
Article in English | MEDLINE | ID: covidwho-1702554

ABSTRACT

In 2020, 45,364 HCT in 41,016 patients, 18,796 (41%) allogeneic and 26,568 (59%) autologous in 690 centers were reported. Changes observed were as follows: total number of HCT -6.5%, allogeneic HCT -5.1%, autologous HCT -7.5%, and were more pronounced in non-malignant disorders for allogeneic HCT and in autoimmune disease for autologous HCT. Main indications were myeloid malignancies 10,441 (25%), lymphoid malignancies 26,120 (64%) and non-malignant disorders 2532 (6%). A continued growth in CAR-T cellular therapies to 1874 (+65%) patients in 2020 was observed. In allogeneic HCT, the use of haploidentical donors increased while use of unrelated and sibling donors decreased. Cord blood HCT increased by 11.7% for the first time since 2012. There was a significant increase in the use of non-myeloablative but a drop in myeloablative conditioning and in use of marrow as stem cell source. We interpreted these changes as being due to the SARS-CoV-2 pandemic starting early in 2020 in Europe and provided additional data reflecting the varying impact of the pandemic across selected countries and larger cities. The transplant community confronted with the pandemic challenge, continued in providing patients access to treatment. This annual report of the EBMT reflects current activities useful for health care planning.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Neoplasms , Europe/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Neoplasms/etiology , Pandemics , SARS-CoV-2 , Transplantation, Homologous
20.
Transplant Cell Ther ; 28(4): 215.e1-215.e10, 2022 04.
Article in English | MEDLINE | ID: covidwho-1693202

ABSTRACT

In response to the widespread COVID-19 pandemic, cryopreservation of allogeneic donor apheresis products was implemented to mitigate the challenges of donor availability and product transport. Although logistically beneficial, the impact of cryopreservation on clinical outcomes and graft composition remains unclear. In this study, we compared outcomes and graft composition with cryopreserved versus fresh allografts in the setting of allogeneic hematopoietic cell transplantation (allo-HCT). We retrospectively analyzed the clinical outcomes of 30 consecutive patients who received cryopreserved allografts between March and August 2020 and 60 consecutive patients who received fresh allografts before the COVID-19 pandemic. Primary endpoints were hematopoietic engraftment and graft failure (GF), and secondary outcomes were overall survival (OS), relapse-free survival (RFS) and nonrelapse mortality (NRM). In addition, extended immunophenotype analysis was performed on cryopreserved and prospectively collected fresh apheresis samples. Compared with recipients of fresh allografts, both neutrophil and platelet recovery were delayed in recipients of cryopreserved reduced-intensity conditioning (RIC) allo-HCT, with a median time to engraftment of 24 days versus 18 days (P = .01) for neutrophils and 27 days versus 18 days (P = .069) for platelets. We observed primary GF in 4 of 30 patients in the cryopreserved cohort (13.3%) versus only 1 of 60 patients (1.7 %) in the fresh cohort (P = .03). Cryopreserved RIC allo-HCT was associated with significantly lower median total, myeloid, and T cell donor chimerism at 1 month. OS and RFS were inferior for cryopreserved graft recipients (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.00 to 4.67) and HR, 1.90; 95% CI, 0.95 to 3.79, respectively. Using an extended immunophenotype analysis, we compared 14 samples from the cryopreserved cohort to 6 prospectively collected fresh apheresis donor samples. These analyses showed both a decrease in total cell viability and a significantly reduced absolute number of natural killer cells (CD3-CD56+) in the cryopreserved apheresis samples. In this single-institution study, we found delayed engraftment and a trend toward clinical inferiority of cryopreserved allografts compared with fresh allografts. Further evaluation of the use of cryopreserved allografts and their impact on clinical and laboratory outcomes is warranted.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , COVID-19/epidemiology , Cryopreservation , Humans , Neoplasm Recurrence, Local , Pandemics , Retrospective Studies
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