COVID ‐19 vaccine response in patients with hematologic malignancy: a systematic review and meta‐analysis

Abstract Introduction: Emerging data suggests that seroresponse (SR) in patients with hematologic malignancy following COVID-19 vaccination is likely lower than in patients without blood cancer. The objective of this study was to perform a systematic review and meta-analysis on SR in patients with hematologic malignancy who received COVID-19 vaccination (submitted to PROSPERO for registration). Methods: We searched PubMed and EMBASE from December 1, 2020, to July 22, 2021, to identify studies of SR following COVID-19 vaccine in adult patients with hematologic malignancy (including studies in which patients with hematologic malignancy represented a subset of a broader population). Patients with positive serologic response at baseline (prior to vaccination) or known COVID-19 infection were excluded. The primary outcomes were pooled SR estimates following COVID-19 vaccination in patients with hematologic malignancy, and pooled SR estimates of subgroups based on hematologic malignancy type. Secondary outcomes were pooled relative risk ratio (RR; compared to non-cancer controls) based on dichotomous-effect SR in all patients, and subgroups based on hematologic malignancy type, treatment status, and use of anti-CD20 therapy. Pooled estimates and RR with its associated 95% confidence intervals (CIs) were calculated using MetaXL (EpiGear), and Reference Manager (Cochrane) using random effects model. Results A total of 17 studies comprising 2834 patients with hematologic malignancy from Europe, United Kingdom and North America were included (Figure 1). The pooled estimate for SR was 58% (95% CI 48-67%, I 2 95%), with a RR of 0.53 (95% 0.42-0.66, I 2 94%) when compared to controls (10 studies with comparison group, 1092 hematologic malignancy patients, 830 controls; Figure 2). The pooled estimate for SR varied by type of hematologic malignancy: lymphomas SR 52% (95% CI 36-68%, 7 studies, 832 patients, I 2 94%); chronic lymphocytic leukemia (CLL) SR 42% (95% CI 25-60%, 6 studies, 921 patients, I 2 93%); plasma cell dyscrasias SR 66% (95% CI 47-83%, 8 studies, 611 patients, I 2 95%); myeloproliferative neoplasms (MPNs, including chronic myelogenous leukemia) SR 83% (95% CI 68-95%, 6 studies, 227 patients, I 2 58%); acute leukemia SR 86% (95% CI 77-94%, 2 studies, 67 patients, 46 acute myelogenous leukemia [AML] and 15 acute lymphocytic leukemia], I 2 0%). The RR for SR also varied by type of hematologic malignancy: lymphomas (excluding CLL) RR 0.48 (95% CI 0.34-0.68, 4 studies, 337 patients, I 2 89%); CLL RR 0.37 (95% CI 0.25-0.53, 3 studies, 194 patients, I 2 54%); plasma cell dyscrasias RR 0.73 (95% CI 0.62-0.86, 5 studies, 323 patients, I 2 70%); RR MPN 0.78 (95% CI 0.62-0.99, 3 studies, 199 patients, I 2 90%). The pooled estimate for SR in those receiving treatment was 42% (95% CI 26-58%, 9 studies, 683 patients, I 2 94%). The pooled estimates for SR for those receiving anti-CD20, bruton tyrosine kinase inhibitor (BTKi), or venetoclax were 13% (95% CI 1-32%, 6 studies, 367 patients, I 2 88%), 42% (95% CI 17-71%, 3 studies, 319 patients, I 2 75%), and 20% (95% CI 0-54%, 3 studies, 39 patients, I 2 66%), respectively. The RR for those receiving treatment for their hematologic malignancy compared to those who were not receiving treatment was 0.51 (95% CI 0.37-0.71, 8 studies, 579 patients, I 2 89%; Figure 3). . The RR of patients receiving anti-CD20 therapy compared to non-cancer controls was 0.13 (95% CI 0.02-0.93, 102 patients, I 2 73%). For patients treated with anti-CD20 therapy, the RR of those receiving vaccination within 9-12 months compared to beyond 9-12 months was 0.12 (95% CI 0.06-0.25, 2 studies, 74 patients, I 2 0%; Figure 4). Conclusion: Our systematic review and meta-analysis suggests that patients with hematologic malignancy have a lower SR rate following vaccination compared to controls. Furthermore, SR is variable across different types of hematologic malignancy, with very good response rates seen in patients with myeloid diseases (MPN and AML) and poor response rates seen in lymphoma and CLL. Active treatment, particularly anti-CD20 therapy within 12 months of vaccination, is associated with a particularly low SR following vaccination. Additional studies are needed to understand non-humoral responses to vaccination, and to guide decisions regarding how to optimize vaccine response in patients with blood cancer. We plan to update the systematic review and meta-analysis as more data become available. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Vaccine response following anti-CD20 therapy: a systematic review and meta-analysis of 905 patients

Blood Advances ◽

10.1182/bloodadvances.2021004629 ◽

2021 ◽

Vol 5 (12) ◽

pp. 2624-2643

Author(s):

Abi Vijenthira ◽

Inna Gong ◽

Stephen D. Betschel ◽

Matthew Cheung ◽

Lisa K. Hicks

Keyword(s):

Systematic Review ◽

Influenza Vaccine ◽

Pandemic Influenza ◽

Hematologic Malignancy ◽

Meta Analysis ◽

Vaccine Dose ◽

Hematologic Malignancies ◽

Healthy Controls ◽

Vaccine Response ◽

Anti Cd20

Abstract The objective of this study was to perform a systematic review of the literature on vaccine responsiveness in patients who have received anti-CD20 therapy. PubMed and EMBASE were searched up to 4 January 2021 to identify studies of vaccine immunogenicity in patients treated with anti-CD20 therapy, including patients with hematologic malignancy or autoimmune disease. The primary outcomes were seroprotection (SP), seroconversion (SC), and/or seroresponse rates for each type of vaccine reported. As the pandemic influenza vaccine (2009 H1N1) has standardized definitions for SP and SC, and represented a novel primary antigen similar to the COVID-19 vaccine, meta-analysis was conducted for SC of studies of this vaccine. Pooled estimates, relative benefit ratios (RBs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-eight studies (905 patients treated with anti-CD20 therapy) were included (19 studies of patients with hematologic malignancies). Patients on active (<3 months since last dose) anti-CD20 therapy had poor responses to all types of vaccines. The pooled estimate for SC after 1 pandemic influenza vaccine dose in these patients was 3% (95% CI, 0% to 9%), with an RB of 0.05 (95% CI, 0-0.73) compared with healthy controls and 0.22 (95% CI, 0.09-0.56) compared with disease controls. SC compared with controls seems abrogated for at least 6 months following treatment (3-6 months post anti-CD20 therapy with an RB of 0.50 [95% CI, 0.24-1.06] compared with healthy and of 0.44 [95% CI, 0.23-0.84] compared with disease controls). For all vaccine types, response to vaccination improves incrementally over time, but may not reach the level of healthy controls even 12 months after therapy.

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Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients

Blood ◽

10.1182/blood.2020008824 ◽

2020 ◽

Vol 136 (25) ◽

pp. 2881-2892

Author(s):

Abi Vijenthira ◽

Inna Y. Gong ◽

Thomas A. Fox ◽

Stephen Booth ◽

Gordon Cook ◽

...

Keyword(s):

Systematic Review ◽

Pediatric Patients ◽

Hematologic Malignancy ◽

Meta Analysis ◽

Hematologic Malignancies ◽

Hospitalized Patients ◽

Adult Patients ◽

Risk Of Death ◽

Dying Patients ◽

Pooled Prevalence

Abstract Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

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Impact of Influenza Infection Among Adult and Pediatric Populations With Hematologic Malignancy and hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis

Clinical Therapeutics ◽

10.1016/j.clinthera.2021.03.002 ◽

2021 ◽

Author(s):

Eleftheria Atalla ◽

Markos Kalligeros ◽

Evangelia K. Mylona ◽

Maria Tsikala-Vafea ◽

Fadi Shehadeh ◽

...

Keyword(s):

Systematic Review ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Hematologic Malignancy ◽

Influenza Infection ◽

Meta Analysis ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Pediatric Populations

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Corrigendum to: Hepatitis-B Vaccine Response in Inflammatory Bowel Disease Patients: A Systematic Review and Meta-analysis

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab077 ◽

2021 ◽

Keyword(s):

Systematic Review ◽

Inflammatory Bowel Disease ◽

Hepatitis B ◽

Bowel Disease ◽

Meta Analysis ◽

Hepatitis B Vaccine ◽

Vaccine Response ◽

Inflammatory Bowel

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Effectiveness of influenza vaccines in adults with chronic liver disease: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2019-031070 ◽

2019 ◽

Vol 9 (9) ◽

pp. e031070

Author(s):

Suvi Härmälä ◽

Constantinos A Parisinos ◽

Laura Shallcross ◽

Alastair O'Brien ◽

Andrew Hayward

Keyword(s):

Systematic Review ◽

Liver Disease ◽

Influenza Vaccination ◽

Low Cost ◽

Influenza Infection ◽

Meta Analysis ◽

Serological Response ◽

Vaccine Response ◽

Eligibility Criteria

ObjectivesPatients with liver disease frequently require hospitalisation with infection often the trigger. Influenza vaccination is an effective infection prevention strategy in healthy and elderly but is often perceived less beneficial in patients with liver disease. We investigated whether influenza vaccination triggered serological response and prevented hospitalisation and death in liver disease.DesignSystematic review and meta-analysis.Data sourcesMEDLINE, EMBASE, PubMed and CENTRAL up to January 2019.Eligibility criteriaRandomised or observational studies of the effects of influenza vaccine in adults with liver disease.Data extraction and synthesisTwo reviewers screened studies, extracted data and assessed risk of bias and quality of evidence. Primary outcomes were all-cause hospitalisation and mortality. Secondary outcomes were cause-specific hospitalisation and mortality, and serological vaccine response. Random-effects meta-analysis was used to estimate pooled effects of vaccination.ResultsWe found 10 041 unique records, 286 were eligible for full-text review and 12 were included. Most patients had viral liver disease. All studies were of very low quality. Liver patients both with and without cirrhosis mounted an antibody response to influenza vaccination, and vaccination was associated with a reduction in risk of hospital admission from 205/1000 to 149/1000 (risk difference −0.06, 95% CI −0.07 to 0.04) in patients with viral liver disease. Vaccinated patients were 27% less likely to be admitted to hospital compared with unvaccinated patients (risk ratio 0.73, 95% CI 0.66 to 0.80). No effect against all-cause or cause-specific mortality or cause-specific hospitalisation was found.ConclusionsThe low quantity and quality of the evidence means that the protective vaccine effect may be uncertain. Considering the high risk of serious health outcomes from influenza infection in patients with liver disease and the safety and low cost of vaccination, overall, the potential benefits of seasonal vaccination both to patients and the healthcare systems are likely to outweigh the costs and risks associated with vaccination.PROSPERO registration numberCRD42017067277.

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Effects of exercise in patients treated with stem cell transplantation for a hematologic malignancy: A systematic review and meta-analysis

Cancer Treatment Reviews ◽

10.1016/j.ctrv.2013.01.001 ◽

2013 ◽

Vol 39 (6) ◽

pp. 682-690 ◽

Cited By ~ 82

Author(s):

Saskia Persoon ◽

Marie José Kersten ◽

Karen van der Weiden ◽

Laurien M. Buffart ◽

Frans Nollet ◽

...

Keyword(s):

Systematic Review ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematologic Malignancy ◽

Meta Analysis

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Mortality in Cancer Patients With COVID-19 Who Are Admitted to an ICU or Who Have Severe COVID-19: A Systematic Review and Meta-Analysis

JCO Global Oncology ◽

10.1200/go.21.00072 ◽

2021 ◽

pp. 1286-1305

Author(s):

Amogh Rajeev Nadkarni ◽

Swapna C. Vijayakumaran ◽

Sudeep Gupta ◽

Jigeeshu V. Divatia

Keyword(s):

Systematic Review ◽

Cancer Patients ◽

Critically Ill ◽

Odds Ratio ◽

Hematologic Malignancy ◽

Meta Analysis ◽

Risk Of Bias ◽

Cancer Subtypes ◽

Newcastle Ottawa Scale ◽

Random Effects Modeling

PURPOSE There are scarce data to aid in prognostication of the outcome of critically ill cancer patients with COVID-19. In this systematic review and meta-analysis, we investigated the mortality of critically ill cancer patients with COVID-19. METHODS We searched online databases and manually searched for studies in English that reported on outcomes of adult cancer patients with COVID-19 admitted to an intensive care unit (ICU) or those with severe COVID-19 between December 2019 and October 2020. Risk of bias was assessed by the Modified Newcastle-Ottawa Scale. The primary outcome was all-cause mortality. We also determined the odds of death for cancer patients versus noncancer patients, as also outcomes by cancer subtypes, presence of recent anticancer therapy, and presence of one or more comorbidities. Random-effects modeling was used. RESULTS In 28 studies (1,276 patients), pooled mortality in cancer patients with COVID-19 admitted to an ICU was 60.2% (95% CI, 53.6 to 6.7; I2 = 80.27%), with four studies (7,259 patients) showing higher odds of dying in cancer versus noncancer patients (odds ratio 1.924; 95% CI, 1.596 to 2.320). In four studies (106 patients) of patients with cancer and severe COVID-19, pooled mortality was 59.4% (95% CI, –39.4 to 77.5; I2 = 72.28%); in one study, presence of hematologic malignancy was associated with significantly higher mortality compared with nonhematologic cancers (odds ratio 1.878; 95% CI, 1.171 to 3.012). Risk of bias was low. CONCLUSION Most studies were reported before the results of trials suggesting the benefit of dexamethasone and tocilizumab, potentially overestimating mortality. The observed mortality of 60% in cancer patients with COVID-19 admitted to the ICU is not prohibitively high, and admission to the ICU should be considered for selected patients (registered with PROSPERO, CRD42020207209).

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Circulating miRNAs as Auxiliary Diagnostic Biomarkers for Multiple Myeloma: A Systematic Review, Meta-Analysis, and Recommendations

Frontiers in Oncology ◽

10.3389/fonc.2021.698197 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yunhui Xiang ◽

Liuyun Zhang ◽

Pinpin Xiang ◽

Juan Zhang

Keyword(s):

Systematic Review ◽

Multiple Myeloma ◽

Likelihood Ratio ◽

Hematologic Malignancy ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Considerable Proportion ◽

Mirna Cluster ◽

Circulating Mirnas

Multiple myeloma (MM) is a hematologic malignancy characterized by aberrant expansion of monoclonal plasma cells with high mortality and severe complications due to the lack of early diagnosis and timely treatment. Circulating miRNAs have shown potential in the diagnosis of MM with inconsistent results, which remains to be fully assessed. Here we updated a meta-analysis with relative studies and essays published in English before Jan 31, 2021. After steps of screening, 32 studies from 11 articles that included a total of 627 MM patients and 314 healthy controls were collected. All data were analyzed by REVMAN 5.3 and Stata MP 16, and the quality of included literatures was estimated by Diagnostic Accuracy Study 2 (QUADAS-2). The pooled area under the curve (AUC) shown in summary receiver operating characteristic (SROC) analyses of circulating miRNAs was 0.87 (95%CI, 0.81–0.89), and the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.79, 0.86, 5, 0.27, 22, respectively. Meta-regression and subgroup analysis exhibited that “miRNA cluster”, patient “detailed stage or Ig isotype” accounted for a considerable proportion of heterogeneity, revealing the importance of study design and patient inclusion in diagnostic trials; thus standardized recommendations were proposed for further studies. In addition, the performance of the circulating miRNAs included in MM prognosis and treatment response prediction was summarized, indicating that they could serve as valuable biomarkers, which would expand their clinical application greatly.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=234297, PROSPERO, identifier (CRD42021234297).

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