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2.
Blood Cancer J ; 12(1): 8, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1630561

ABSTRACT

Understanding antibody-based SARS-CoV-2 immunity in hematologic malignancy (HM) patients following infection is crucial to inform vaccination strategies for this highly vulnerable population. This cross-sectional study documents the anti-SARS-CoV-2 humoral response and serum neutralizing activity in 189 HM patients recovering from a PCR-confirmed infection. The overall seroconversion rate was 85.7%, with the lowest values in patients with lymphoid malignancies or undergoing chemotherapy. Therapy-naive patients in the "watch and wait" status were more likely to seroconvert and display increased anti-s IgG titers. Enhanced serum neutralizing activity was observed in the following SARS-CoV-2-infected HM patient groups: (i) males; (ii) severe COVID-19; and (iii) "watch and wait" or "complete/partial response". The geometric mean (GeoMean) ID50 neutralization titers in patients analyzed before or after 6 months post-infection were 299.1 and 306.3, respectively, indicating that >50% of the patients in either group had a neutralization titer sufficient to provide 50% protection from symptomatic COVID-19. Altogether, our findings suggest that therapy-naive HM patients mount a far more robust immune response to SARS-CoV-2 infection vs. patients receiving anti-cancer treatment, raising the important question as to whether HM patients should be vaccinated before therapy and/or receive vaccine formats capable of better recapitulating the natural infection.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antineoplastic Agents/administration & dosage , COVID-19/immunology , Hematologic Neoplasms , Immunity, Humoral , SARS-CoV-2/immunology , Aged , Female , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/immunology , Humans , Male , Middle Aged
3.
Br J Cancer ; 126(5): 691-692, 2022 03.
Article in English | MEDLINE | ID: covidwho-1623449

ABSTRACT

Cancer patients with COVID-19 have reduced survival. While most cancer patients, like the general population, have an almost 100% rate of seroconversion after COVID-19 infection or vaccination, patients with haematological malignancies have lower seroconversion rates and are far less likely to gain adequate protection. This raises the concern that patients with haematological malignancies, especially those receiving immunosuppressive therapies, may still develop the fatal disease when infected with COVID-19 after vaccination. There is an urgent need to develop Guidelines to help direct vaccination schedules and protective measures in oncology patients, differentiating those with haematological malignancies and those in an immunocompromised state.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/immunology , Hematologic Neoplasms/drug therapy , Immunosuppressive Agents/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Humans , Immunocompromised Host/drug effects , Practice Guidelines as Topic , Seroconversion , Vaccination
4.
Cancer Discov ; 12(1): 62-73, 2022 01.
Article in English | MEDLINE | ID: covidwho-1595223

ABSTRACT

Coronavirus disease 2019 (COVID-19) infection results in both acute mortality and persistent and/or recurrent disease in patients with hematologic malignancies, but the drivers of persistent infection in this population are unknown. We found that B-cell lymphomas were at particularly high risk for persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity. Further analysis of these patients identified discrete risk factors for initial disease severity compared with disease chronicity. Active therapy and diminished T-cell counts were drivers of acute mortality in COVID-19-infected patients with lymphoma. Conversely, B cell-depleting therapy was the primary driver of rehospitalization for COVID-19. In patients with persistent SARS-CoV-2 positivity, we observed high levels of viral entropy consistent with intrahost viral evolution, particularly in patients with impaired CD8+ T-cell immunity. These results suggest that persistent COVID-19 infection is likely to remain a risk in patients with impaired adaptive immunity and that additional therapeutic strategies are needed to enable viral clearance in this high-risk population. SIGNIFICANCE: We describe the largest cohort of persistent symptomatic COVID-19 infection in patients with lymphoid malignancies and identify B-cell depletion as the key immunologic driver of persistent infection. Furthermore, we demonstrate ongoing intrahost viral evolution in patients with persistent COVID-19 infection, particularly in patients with impaired CD8+ T-cell immunity.This article is highlighted in the In This Issue feature, p. 1.


Subject(s)
COVID-19/immunology , COVID-19/virology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/virology , /virology , Adult , Aged , Aged, 80 and over , B-Lymphocytes/immunology , Female , Humans , Male , Middle Aged , Risk Factors , SARS-CoV-2/immunology , T-Lymphocytes/immunology
5.
Cancer Cell ; 40(2): 114-116, 2022 02 14.
Article in English | MEDLINE | ID: covidwho-1588171
7.
Br J Haematol ; 196(4): 892-901, 2022 02.
Article in English | MEDLINE | ID: covidwho-1511287

ABSTRACT

Patients with haematological malignancies have a high risk of severe infection and death from SARS-CoV-2. In this prospective observational study, we investigated the impact of cancer type, disease activity, and treatment in 877 unvaccinated UK patients with SARS-CoV-2 infection and active haematological cancer. The primary end-point was all-cause mortality. In a multivariate analysis adjusted for age, sex and comorbidities, the highest mortality was in patients with acute leukaemia [odds ratio (OR) = 1·73, 95% confidence interval (CI) 1·1-2·72, P = 0·017] and myeloma (OR 1·3, 95% CI 0·96-1·76, P = 0·08). Having uncontrolled cancer (newly diagnosed awaiting treatment as well as relapsed or progressive disease) was associated with increased mortality risk (OR = 2·45, 95% CI 1·09-5·5, P = 0·03), as was receiving second or beyond line of treatment (OR = 1·7, 95% CI 1·08-2·67, P = 0·023). We found no association between recent cytotoxic chemotherapy or anti-CD19/anti-CD20 treatment and increased risk of death within the limitations of the cohort size. Therefore, disease control is an important factor predicting mortality in the context of SARS-CoV-2 infection alongside the possible risks of therapies such as cytotoxic treatment or anti-CD19/anti-CD20 treatments.


Subject(s)
Antigens, CD20/immunology , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/complications , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Adult , Antineoplastic Agents, Immunological/adverse effects , COVID-19/etiology , COVID-19/immunology , Female , Hematologic Neoplasms/immunology , Humans , Leukemia/complications , Leukemia/drug therapy , Leukemia/immunology , Male , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Prospective Studies , Risk Factors
9.
Eur J Haematol ; 108(2): 91-98, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1488195

ABSTRACT

People with hematologic malignancies are at a high risk of morbidity and mortality from COVID-19. The response to vaccination is highly limited in patients with chronic lymphocytic leukemia. Less than half of the patients develop antibody response, suggesting that they remain at risk of SARS-CoV-2 infection even after the vaccination. Reasons for inadequate response to COVID-19 vaccination in chronic lymphocytic leukemia are multifactorial and attributed to disease-related immune dysregulation and patient- and therapy-related factors. The negative predictors of response to vaccination include hypogammaglobulinemia, advanced age, current active treatment, and past treatment anti-CD20 monoclonal antibodies. Despite using booster doses and heterologous immunization to improve humoral and cellular immunity, some patients with chronic lymphocytic leukemia will fail to respond. Active treatment at the time of vaccination and a recent history of anti-CD20 monoclonal antibodies use are the strongest predictors of the non-response. Current data support informing patients with chronic lymphocytic leukemia and other hematologic malignancies about the risk of infection regardless of vaccination. These individuals and members of their households should continue extreme preventive actions despite relaxed local regulations. Other emerging non-vaccine preventive strategies include passive and post-exposure prevention with monoclonal antibodies.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , SARS-CoV-2/immunology , COVID-19 Vaccines/administration & dosage , Hematologic Neoplasms/complications , Hematologic Neoplasms/immunology , Humans , Immunization, Passive/methods , Immunocompromised Host , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Pandemics , Post-Exposure Prophylaxis/methods , Risk Factors , Treatment Failure
10.
Blood ; 139(10): 1439-1451, 2022 03 10.
Article in English | MEDLINE | ID: covidwho-1472341

ABSTRACT

Evidence regarding the effectiveness of COVID-19 vaccine in patients with impaired immunity is limited. Initial observations suggest a lower humoral response in these patients. We evaluated the relative effectiveness of the mRNA BNT162b2 vaccine in patients with hematological neoplasms compared with matched controls. Data on patients with hematological neoplasms after 2 vaccine doses were extracted and matched 1:1 with vaccinated controls. Subpopulation analyses focused on patients receiving therapy for hematological neoplasm, patients without treatment who were only followed, and recipients of specific treatments. The analysis focused on COVID-19 outcomes from days 7 through 43 after the second vaccine dose in these areas: documented COVID-19 infection by polymerase chain reaction; symptomatic infection; hospitalizations; severe COVID-19 disease; and COVID-19-related death. In a population of 4.7 million insured people, 32 516 patients with hematological neoplasms were identified, of whom 5017 were receiving therapy for an active disease. Vaccinated patients with hematological neoplasms, compared with vaccinated matched controls, had an increased risk of documented infections (relative risk [RR] 1.60, 95% CI 1.12-2.37); symptomatic COVID-19 (RR 1.72, 95% CI 1.05-2.85); COVID-19-related hospitalizations (RR 3.13, 95% CI 1.68-7.08); severe COVID-19 (RR 2.27, 95% CI 1.18-5.19); and COVID-19-related death (RR 1.66, 95% CI 0.72-4.47). Limiting the analysis to patients on hematological treatments showed a higher increased risk. This analysis shows that vaccinated patients with hematological neoplasms, in particular patients receiving treatment, suffer from COVID-19 outcomes more than vaccinated individuals with intact immune system. Ways to enhance COVID-19 immunity in this patient population, such as additional doses, should be explored.


Subject(s)
COVID-19 , Hematologic Neoplasms , SARS-CoV-2/immunology , Aged , /immunology , COVID-19/immunology , COVID-19/mortality , COVID-19/prevention & control , Female , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Humans , Male , Middle Aged
11.
Br J Haematol ; 196(3): 548-558, 2022 02.
Article in English | MEDLINE | ID: covidwho-1467542

ABSTRACT

Patients affected by lymphoid malignancies (LM) are frequently immune-compromised, suffering increased mortality from COVID-19. This prospective study evaluated serological and T-cell responses after complete mRNA vaccination in 263 patients affected by chronic lymphocytic leukaemia, B- and T-cell lymphomas and multiple myeloma. Results were compared with those of 167 healthy subjects matched for age and sex. Overall, patient seroconversion rate was 64·6%: serological response was lower in those receiving anti-cancer treatments in the 12 months before vaccination: 55% vs 81·9% (P < 0·001). Anti-CD20 antibody plus chemotherapy treatment was associated with the lowest seroconversion rate: 17·6% vs. 71·2% (P < 0·001). In the multivariate analysis conducted in the subgroup of patients on active treatment, independent predictors for seroconversion were: anti-CD20 treatment (P < 0·001), aggressive B-cell lymphoma diagnosis (P = 0·002), and immunoglobulin M levels <40 mg/dl (P = 0·030). The T-cell response was evaluated in 99 patients and detected in 85 of them (86%). Of note, 74% of seronegative patients had a T-cell response, but both cellular and humoral responses were absent in 13·1% of cases. Our findings raise some concerns about the protection that patients with LM, particularly those receiving anti-CD20 antibodies, may gain from vaccination. These patients should strictly maintain all the protective measures.


Subject(s)
/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , COVID-19 , Hematologic Neoplasms , Immunity, Cellular/drug effects , Lymphoproliferative Disorders , SARS-CoV-2/immunology , T-Lymphocytes/immunology , /immunology , Aged , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , Female , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/immunology , Humans , Immunoglobulin M/immunology , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/immunology , Male , Middle Aged , Prospective Studies , Seroconversion
12.
Blood Cancer J ; 11(9): 151, 2021 09 14.
Article in English | MEDLINE | ID: covidwho-1408475

ABSTRACT

The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.


Subject(s)
COVID-19/immunology , Hematologic Neoplasms/immunology , Immunity, Humoral/drug effects , Rituximab/pharmacology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/drug effects , Antibodies, Viral/metabolism , Antibody Formation/drug effects , Antibody Formation/physiology , Antibody Specificity/drug effects , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Case-Control Studies , Female , Follow-Up Studies , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/epidemiology , Hospitalization , Humans , Italy/epidemiology , Longitudinal Studies , Male , Middle Aged , Rituximab/therapeutic use
15.
Blood Cancer J ; 11(8): 142, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1351934

ABSTRACT

This study evaluated the safety and immunogenicity of BNT162b2 vaccine in patients with hematological malignancies. Antibodies blocking spike binding to immobilized ACE-2 (NAb) correlated with anti-Spike (S) IgG d42 titers (Spearman r = 0.865, p < 0.0001), and an anti-S IgG d42 level ≥3100 UA/mL was predictive of NAb ≥ 30%, the positivity cutoff for NAb (p < 0.0001). Only 47% of the patients achieved an anti-S IgG d42 level ≥3100 UA/mL after the two BNT162b2 inocula, compared to 87% of healthy controls. In multivariable analysis, male patients, use of B-cell targeting treatment within the last 12 months prior to vaccination, and CD19+ B-cell level <120/uL, were associated with a significantly decreased probability of achieving a protective anti-S IgG level after the second BNT162b2 inoculum. Finally, using the IFN-γ ELISPOT assay, we found a significant increase in T-cell response against the S protein, with 53% of patients having an anti-S IgG-positive ELISPOT after the second BNT162b2 inoculum. There was a correlation between the anti-S ELISPOT response and IgG d42 level (Spearman r = 0.3026, p = 0.012). These findings suggest that vaccination with two BNT162b2 inocula translates into a significant increase in humoral and cellular response in patients with hematological malignancies, but only around half of the patients can likely achieve effective immune protection against COVID-19.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/complications , COVID-19/immunology , Hematologic Neoplasms/complications , Hematologic Neoplasms/immunology , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Adaptive Immunity , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/administration & dosage , Comorbidity , Female , Host-Pathogen Interactions/immunology , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Risk Factors , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Young Adult
17.
Br J Haematol ; 195(4): 523-531, 2021 11.
Article in English | MEDLINE | ID: covidwho-1341248

ABSTRACT

Haemato-oncological patients are at risk in case of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Currently, vaccination is the best-evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato-oncological patients. A total of 259 haemato-oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS® Anti-SARS-CoV-2-S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P < 0·001). Haematological patients receiving systemic treatment had a 14·2-fold increased risk of non-responding (95% confidence interval 3·2-63·3, P = 0·001). Subgroups of patients with lymphoma or chronic lymphocytic leukaemia were at highest risk of serological non-response. Low immunoglobulin G (IgG) level, lymphocyte- and natural killer (NK)-cell counts were significantly associated with poor serological response (P < 0·05). Vaccination was well tolerated with only 2·7% of patients reporting severe side-effects. Patients with side-effects developed a higher S/RBD-antibody titre compared to patients without side-effects (P = 0·038). Haematological patients under treatment were at highest risk of serological non-response. Low lymphocytes, NK cells and IgG levels were found to be associated with serological non-response. Serological response in oncological patients was encouraging. The use of BNT162b2 is safe in haemato-oncological patients.


Subject(s)
Antibody Formation/drug effects , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Hematologic Neoplasms/immunology , SARS-CoV-2/immunology , Aged , Antibodies, Viral/immunology , Antibody Formation/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Female , Humans , Immunoassay/methods , Immunoglobulin G/blood , Killer Cells, Natural/cytology , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Lymphocytes/cytology , Lymphoma/immunology , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , SARS-CoV-2/genetics , Safety
18.
Lancet Haematol ; 8(8): e583-e592, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1337052

ABSTRACT

BACKGROUND: Haematological malignancies and their treatments are likely to affect SARS-CoV-2 vaccine efficacy. We aimed to evaluate serological response to BNT162b2 vaccine in patients with haematological malignancies by type of treatment. METHODS: Our national prospective cohort study was done in Lithuania and assessed serological response to one and two BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine doses in healthy health-care workers and in patients with haematological malignancies. Eligible participants were aged 18 years or older, had received both vaccine doses, and had available biobanked blood samples from before vaccination and after the second dose. Biobanked samples and health data were obtained from Vilnius University Hospital Santaros Klinikos Biobank. Abbott Architect SARS-CoV-2 IgG Quant II chemiluminescent microparticle assay was used to quantify serum anti-SARS-CoV-2-S1 IgG antibody (anti-S1 IgG antibody) concentrations 0-10 days before the first BNT162b2 vaccine, on the day of second immunisation (around day 21), and 7 to 21 days after the second immunisation. Adverse events were assessed by a standardised questionnaire. Breakthrough infections were characterised clinically and by SARS-CoV-2 genotyping whenever possible. This study is registered with ClinicalTrials.gov, NCT04871165. FINDINGS: Between Jan 8 and April 21, 2021, 885 participants with haematological malignancies were included in the study. 857 patients were anti-S1 IgG seronegative at timepoint 0 and constituted the main analysis cohort. The age-matched comparison was made between 315 patients with haematological malignancies who were aged 18-60 years and 67 healthy health-care workers in the same age group. Patients aged 18-60 years with haematological malignancies had lower median anti-S1 IgG antibody responses after two BNT162b2 vaccine doses than did health-care workers of the same age group (median 6961 AU/mL [IQR 1292-20 672] vs 21 395 AU/mL [14 831-33 553]; p<0·0001). Compared with untreated patients with haematological malignancies (n=53; median 5761 AU/mL [629-16 141]), patients actively treated with Bruton tyrosine kinase inhibitors (BTKIs; n=44; 0 AU/mL [0-7]; p<0·0001), ruxolitinib (n=16; 10 AU/mL [0-45]; p<0·0001), venetoclax (n=10; 4 AU/mL [0-1218]; p=0·0005), or anti-CD20 antibody therapy (n=87; 17 AU/mL [1-2319]; p<0·0001) showed particularly poor anti-S1 IgG antibody responses following two BNT162b2 doses. Patients being treated with tyrosine kinase inhibitors (n=41; 10 537 AU/mL [IQR 2335-19 388]) or patients who received autologous haematopoietic stem-cell transplantation (HSCT; n=192; 6203 AU/mL [1451-16 834]) or allogeneic HSCT (n=122; 6304 AU/mL [1120-16 913]) were among the subgroups with the highest numerical responses. Nine SARS-CoV-2 infections and three COVID-19 deaths were observed among fully vaccinated patients with haematological malignancies. INTERPRETATION: Patients with haematological malignancies mount blunted and heterogeneous antibody responses to the full course of BNT162b2 mRNA vaccination. Patients who are actively treated with BTKIs, ruxolitinib, venetoclax, or anti-CD20 antibody therapies seem to be the most negatively affected and might be left unprotected from SARS-CoV-2 infection. Breakthrough severe SARS-CoV-2 infections in fully vaccinated patients with haematological malignancies emphasise the importance of ongoing strict adherence to non-pharmacological interventions and household vaccination while SARS-CoV-2 is circulating in the community. FUNDING: Vilnius University Hospital Santaros Klinikos. TRANSLATION: For the Lithuanian translation of the abstract see Supplementary Materials section.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Hematologic Neoplasms/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Female , Hematologic Neoplasms/blood , Hematologic Neoplasms/complications , Hematologic Neoplasms/virology , Humans , Lithuania/epidemiology , Male , Middle Aged , Prospective Studies
19.
Int J Mol Sci ; 22(14)2021 Jul 17.
Article in English | MEDLINE | ID: covidwho-1323267

ABSTRACT

Cytokines are a broad group of small regulatory proteins with many biological functions involved in regulating the hematopoietic and immune systems. However, in pathological conditions, hyperactivation of the cytokine network constitutes the fundamental event in cytokine release syndrome (CRS). During the last few decades, the development of therapeutic monoclonal antibodies and T-cell therapies has rapidly evolved, and CRS can be a serious adverse event related to these treatments. CRS is a set of toxic adverse events that can be observed during infection or following the administration of antibodies for therapeutic purposes and, more recently, during T-cell-engaging therapies. CRS is triggered by on-target effects induced by binding of chimeric antigen receptor (CAR) T cells or bispecific antibody to its antigen and by subsequent activation of bystander immune and non-immune cells. CRS is associated with high circulating concentrations of several pro-inflammatory cytokines, including interleukins, interferons, tumor necrosis factors, colony-stimulating factors, and transforming growth factors. Recently, considerable developments have been achieved with regard to preventing and controlling CRS, but it remains an unmet clinical need. This review comprehensively summarizes the pathophysiology, clinical presentation, and treatment of CRS caused by T-cell-engaging therapies utilized in the treatment of hematological malignancies.


Subject(s)
Cytokine Release Syndrome/etiology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Immunotherapy, Adoptive/adverse effects , T-Lymphocytes/immunology , T-Lymphocytes/transplantation , Animals , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/therapy , Humans
20.
Arch Dis Child ; 107(2): 186-188, 2022 02.
Article in English | MEDLINE | ID: covidwho-1322772

ABSTRACT

BACKGROUND: Children with cancer are not at increased risk of severe SARS-CoV-2 infection; however, adults with haematological malignancies have increased risk of severe infections compared with non-haematological malignancies. METHODS: We compared patients with haematological and non-haematological malignancies enrolled in the UK Paediatric Coronavirus Cancer Monitoring Project between 12 March 2020 and 16 February 2021. Children who received stem cell transplantation were excluded. RESULTS: Only 2/62 patients with haematological malignancy had severe/critical infections, with an OR of 0.5 for patients with haematological compared with non-haematological malignancies. INTERPRETATION: Children with haematological malignancies are at no greater risk of severe SARS-CoV-2 infection than those with non-haematological malignancies.


Subject(s)
COVID-19/epidemiology , Hematologic Neoplasms/epidemiology , Severity of Illness Index , Adolescent , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Child , Child, Preschool , Cohort Studies , Female , Hematologic Neoplasms/immunology , Humans , Infant , Male , Risk Assessment/statistics & numerical data , Risk Factors , SARS-CoV-2/immunology
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