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Therapeutic Advances in Hematology 2024Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient... (Review)
Review
BACKGROUND
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological cancer. Due to its low incidence, researchers struggle to gather sufficient prospective data to inform clinical treatment.
OBJECTIVES
We sought to summarize the clinical characteristics and current treatment methods of BPDCN and provide more specific guidance on treatment options.
DESIGN
A systematic literature review using data from 74 Chinese BPDCN patients.
DATE RESOURCES AND METHODS
We retrospectively analyzed the clinical manifestations, treatment response, survival outcomes, and prognostic factors of six BPDCN patients treated at the First Affiliated Hospital of Zhengzhou University and 68 patients described in 28 articles published in the China Knowledge Network database since 2019.
RESULTS
In Chinese patients, the disease occurred with a male-to-female ratio of 2.52 and a median age of onset of 50 years in adults and 10 years in pediatric patients. Immunohistochemical analysis revealed distinctive immune phenotypes of BPDCN cells, characterized by high expression levels of CD4, CD56, CD123, and HLA-DR, while showing minimal to no expression of myeloperoxidase (MPO), CD20, and CD79a. There was no significant difference in the initial complete remission (CR) rate, relapse rate, and the overall survival (OS) time of patients receiving acute myeloid leukemia-like, acute lymphocytic leukemia-like, or non-Hodgkin's lymphoma-like chemotherapy regimens. Univariate analysis identified CD3 expression, male gender, and central nervous system infiltration as hazardous factors. In multivariate analysis, age proved to be an independent prognostic indicator, indicating better prognosis and longer OS time in younger patients. Notably, hematopoietic stem cell transplantation (HSCT) emerged as a significant factor in improving the survival outcomes for individuals diagnosed with BPDCN. However, further investigation is needed to explore the role of HSCT and the best timing for its implementation in pediatric BPDCN patients.
CONCLUSION
Administering HSCT during the initial CR state following inductive chemotherapy might extend the OS and improve the prognosis of patients with BPDCN.
PubMed: 38832237
DOI: 10.1177/20406207241251602 -
Annals of Medicine Dec 2024Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an... (Meta-Analysis)
Meta-Analysis
Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
BACKGROUND
Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.
METHODS
The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.
CONCLUSION
Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
Topics: Humans; Immunotherapy, Adoptive; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; Sialic Acid Binding Ig-like Lectin 2; Receptors, Chimeric Antigen; Child; Treatment Outcome; Neoplasm, Residual; Cytokine Release Syndrome; Recurrence; Neurotoxicity Syndromes
PubMed: 38738799
DOI: 10.1080/07853890.2024.2349796 -
JMA Journal Apr 2024The possibility of developing a severe coronavirus infectious (COVID-19) disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased,... (Review)
Review
BACKGROUND
The possibility of developing a severe coronavirus infectious (COVID-19) disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased, particularly in patients with hematological malignancies. These patients are more likely to produce less antibody protection due to the immunocompromised nature of the disease and the anticancer treatments. Therefore, the present systematic review intended to evaluate the seroconversion rate of COVID-19 vaccines in patients with hematological malignancies compared with healthy controls.
METHODS
A comprehensive systematic search was conducted in Medline via PubMed, EMBASE, and the World Health Organization COVID-19 Research Database, as well as other searches (i.e., reference list from article search and manual searches), from December 2020 to May 2022. The outcome of interest included estimating the seroconversion rates following COVID-19 vaccination in patients with hematological malignancies and comparing them with those in healthy controls. After two-step screening, the data were extracted and the summary measures were calculated using a random-effects model.
RESULTS
A total of 39 articles regarding patients with hematological malignancies were included in the present review. After the first vaccine dose, these patients had considerably lower antibody response rates (37.0%) compared with healthy controls (74.5%). Following the second vaccine dose, the seroconversion rate in patients reached 66.8%, whereas it peaked at 97.9% in the healthy controls following complete immunization. Notably, the BNT162b2 and ChAdOx1 vaccine combination achieved the highest seropositivity rate of approximately 70%. Multiple myeloma, chronic lymphocytic leukemia, and lymphoma were the cancers of interest in most of the studies.
CONCLUSIONS
The results of the present study highlighted the comparatively low seropositivity rates in patients with hematological malignancies, with substantial variations in rates across disease groups. The findings emphasize the possibility of additional booster doses for these individuals to enhance their immunity against SARS-CoV-2.
PubMed: 38721084
DOI: 10.31662/jmaj.2023-0171 -
Critical Reviews in Oncology/hematology May 2024Asparaginase is essential in the initial management of acute lymphoblastic leukemia (ALL) but frequently leads to venous thromboembolism (VTE). Using anticoagulants for... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of the effectiveness of primary thromboprophylaxis in acute lymphoblastic leukemia during early-phase therapy including asparaginase or its prolonged form.
Asparaginase is essential in the initial management of acute lymphoblastic leukemia (ALL) but frequently leads to venous thromboembolism (VTE). Using anticoagulants for primary VTE prevention has been studied with no consensus. We conducted a systematic literature search in PubMed, Scopus, and Web of science and performed random-effect meta-analysis using Mantel-Haenszel method in RevMan 5.4 to analyze primary pharmacological thromboprophylaxis during asparaginase treatment in early-phase (induction, consolidation, or intensification phase) therapy in patients with ALL with all ages and followed with subgroup analysis by age. Meta-analysis of 13 articles describing the effect of antithrombin supplementation in 1375 patients showed that antithrombin prophylaxis decreases the risk of VTE by 43% (RR, 0.57; 95% CI, 0.38 - 0.83; p=0.004), with mild heterogeneity (I=35%, p=0.10) and moderate certainty by GRADE. 8 articles included for meta-analysis of low-molecular weight heparin (LMWH) treatment in 612 patients showed that it decreased the risk of VTE by nearly 40% (RR, 0.61; 95% CI, 0.45 - 0.81; p=0.00081), with minimal heterogeneity (I=14%, p=0.31) but low certainty. Subgroup analysis showed that only prophylaxis with antithrombin supplementation significantly decreased the VTE rate in adult patients with moderate certainty. In pediatric patients, one nonrandomized prospective study showed that LMWH combined with antithrombin has a better thromboprophylaxis effect than antithrombin alone. In the PREVAPIX-ALL trial, prophylaxis with direct factor Xa inhibitor Apixaban did not benefit children younger than 18 years except for cases of obesity. We concluded that thromboprophylaxis with antithrombin is effective in ALL patients older than 18 years during the early phase of therapy, and LMWH combined with antithrombin supplementation might be effective for pediatric patients with ALL. Apixaban is effective in pediatric ALL patients with obesity and needs further study in other high-risk patients.
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Asparaginase; Venous Thromboembolism; Anticoagulants; Heparin, Low-Molecular-Weight; Antithrombins
PubMed: 38583546
DOI: 10.1016/j.critrevonc.2024.104347 -
Frontiers in Oncology 2024Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side... (Review)
Review
Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.
PubMed: 38450195
DOI: 10.3389/fonc.2024.1324859 -
International Journal of Environmental... Feb 2024Lung cancer is a leading cause of death with nearly 1.8 million deaths estimated worldwide in 2020. Although benzene is classified as a human carcinogen (Group 1) on the... (Meta-Analysis)
Meta-Analysis Review
Lung cancer is a leading cause of death with nearly 1.8 million deaths estimated worldwide in 2020. Although benzene is classified as a human carcinogen (Group 1) on the basis of its association with acute myeloid/non-lymphocytic leukaemia, there is still limited evidence that it may influence lung cancer risk. This study examined the potential link between benzene exposure and risk of lung cancer using a systematic review of epidemiological studies and meta-analysis. We searched through PubMed, Web of Science and Scopus databases up to 10 February 2023 to identify all articles on the association between benzene exposure and lung cancer (incidence or prevalence) and/or mortality. We extracted the risk estimates of the highest and the lowest reported categories of benzene exposure and conducted a meta-analysis using a random-effects model. Heterogeneity and publication bias were analysed using an I test and funnel plots asymmetry, respectively. Twenty-one studies were included in the final analysis, with a total of 10,750 lung cancer cases and 2899 lung cancer deaths. Overall, risk estimates of lung cancer prevalence and mortality in association with benzene exposure were 1.20 ( = 14; 95% CI 1.05-1.37) and 1.15 ( = 13; 95% CI 1.02-1.30), respectively. In all cases, heterogeneity was quite large, while no significant publication bias was observed. When only studies that adjusted for smoking habit were selected, the risk for lung cancer increased by up to 34% ( = 9; 95% CI 1.10-1.64). Our data, which show a strong association between benzene exposure and lung cancer risk, may have important public health implications. However, further studies are needed to identify the lung cancer risk associated with benzene exposure considering different smoking conditions.
Topics: Humans; Benzene; Lung Neoplasms; Occupational Exposure; Risk; Leukemia, Myeloid, Acute
PubMed: 38397694
DOI: 10.3390/ijerph21020205 -
Supportive Care in Cancer : Official... Feb 2024To systematically evaluate the impact of physical exercise intervention on children with acute lymphoblastic leukemia (ALL) during the treatment and rehabilitation... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the impact of physical exercise intervention on children with acute lymphoblastic leukemia (ALL) during the treatment and rehabilitation consolidation periods.
METHOD
Randomized controlled trials (RCTs) were retrieved from PubMed, Scopus, Web of Science, CNKI, and Cochrane databases, with a search time range from database establishment to September 1, 2023. The quality of the included RCTs was evaluated using the Cochrane risk assessment tool, and a systematic evaluation was conducted using RevMan 5.4. The study has been registered with INPLASY (registration number: 202390100).
RESULT
A total of 12 RCTs including 423 subjects was included. The meta-analysis results showed that long-term exercise intervention can effectively improve the endurance performance (SMD = 1.37, 95% CI 0.45 to 2.29, p = 0.004), functional mobility (MD = - 1.17, 95% CI - 1.85 to - 0.49, p = 0.0008), cancer-related fatigue (CRF) (MD = - 1.25, 95% CI - 1.69 to - 0.80, p < 0.00001), and quality of life (QOL) (MD = 4.93, 95% CI 1.80 to 8.05, p = 0.002) of ALL children during the treatment and rehabilitation consolidation periods. Its promoting effect on the muscle strength (SMD = 0.53, 95% CI - 0.33 to 1.39, p = 0.23) and bone mineral density (BMD) (SMD = 0.48, 95% CI 0.20 to 0.77, p = 0.05) of the subjects was not significant. Further meta-analysis showed that exercise intervention with a duration of less than 1 year (SMD = 0.91, 95% CI 0.55 to 1.28, p < 0.00001) rather than more than 1 year (SMD = - 0.16, 95% CI - 0.61 to 0.29, p = 0.49) can effectively reduce subject BMD, while in terms of strength, exercise intervention can effectively improve strength during the treatment period (SMD = 0.97, 95% CI 0.40 to 1.54, p = 0.0008) rather than the consolidation period (SMD = - 0.27, 95% CI - 1.08 to 0.53, p = 0.51).
CONCLUSION
Long-term regular exercise can effectively improve the endurance, functional mobility, CRF, and QOL of children with ALL in the rehabilitation and treatment consolidation stages. Their strength and BMD may be influenced by the timing of treatment and the intervention cycle, respectively. Considering the limited number of included literature and the instability of some outcome indicators, it is necessary to design more comprehensive and rigorous high-quality RCTs in the future to test the exercise efficacy of ALL children.
Topics: Child; Humans; Bone Density; Databases, Factual; Exercise Therapy; Fatigue; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Muscle Strength; Randomized Controlled Trials as Topic
PubMed: 38381189
DOI: 10.1007/s00520-024-08355-z -
Critical Reviews in Oncology/hematology Apr 2024Long noncoding RNAs (lncRNAs), as gene expression modulators, are potential players in Acute Lymphoblastic Leukemia (ALL) pathogenesis. We systematically explored... (Review)
Review
Long noncoding RNAs (lncRNAs), as gene expression modulators, are potential players in Acute Lymphoblastic Leukemia (ALL) pathogenesis. We systematically explored current literature on lncRNA expression in ALL to identify lncRNAs consistently reported as differentially expressed (DE) either in ALL versus controls or between ALL subtypes. By comparing articles that provided global expression data for DE lncRNAs in the ETV6::RUNX1-positive ALL subtype, we identified four DE lncRNAs in three independent studies (two versus other subtypes and one versus controls), showing concordant expression of LINC01013, CRNDE and lnc-KLF7-1. Additionally, LINC01503 was consistently downregulated on ALL versus controls. Within RT-qPCR studies, twelve lncRNA were DE in more than one source. Thus, several lncRNAs were supported as DE in ALL by multiple sources, highlighting their potential role as candidate biomarkers or therapeutic targets. Finally, as lncRNA annotation is rapidly expanding, standardization of reporting and nomenclature is urgently needed to improve data verifiability and compilation.
Topics: Humans; RNA, Long Noncoding; Biomarkers; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Gene Expression Profiling; Kruppel-Like Transcription Factors
PubMed: 38341118
DOI: 10.1016/j.critrevonc.2024.104290 -
Pediatric Blood & Cancer Apr 2024Corticosteroids are essential to curative acute lymphoblastic leukemia (ALL) treatment, yet have significant neuropsychiatric side effects that decrease quality of life... (Review)
Review
Corticosteroids are essential to curative acute lymphoblastic leukemia (ALL) treatment, yet have significant neuropsychiatric side effects that decrease quality of life for patients and families. We conducted a scoping review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to describe the existing measurement tools used to evaluate neurobehavioral side effects of corticosteroids in pediatric ALL. From various databases and registers, 4047 studies were identified. Twenty-four articles met inclusion criteria. Clinical assessment was most used to evaluate these symptoms. Twelve validated measures were identified. Existing data about neuropsychiatric side effects of corticosteroids in pediatric ALL are extremely heterogeneous, creating challenges for standardized assessment and management.
Topics: Child; Humans; Quality of Life; Adrenal Cortex Hormones; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38263506
DOI: 10.1002/pbc.30881 -
Blood Advances Feb 2024Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Recent postmarketing... (Meta-Analysis)
Meta-Analysis
Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL). Recent postmarketing studies of ibrutinib, another small molecule inhibitor, suggested that these agents may predispose to opportunistic infections. We sought to systematically review the randomized controlled trial (RCT) evidence of venetoclax to assess whether it predisposes patients to infectious adverse events (IAEs) and neutropenia. We systematically reviewed RCTs comparing venetoclax therapy with active or placebo controls for patients with hematologic malignancies. Data on IAEs and neutropenia were pooled by Bayesian meta-analysis, and we computed the probability of any increased risk (P[risk ratio (RR) > 1]) of IAEs or neutropenic complications. Seven RCTs were included, comprising 2067 patients. In CLL (n = 1032), there was a low probability of increased risk of high-grade (P[RR > 1] = 71.2%) and fatal IAEs (P[RR > 1] = 64.5%) and high-grade neutropenia (P[RR > 1] = 63.4%). There were insufficient data to perform a meta-analysis of IAEs in AML; however, 1 trial suggested an increased risk of IAEs with venetoclax. Furthermore, in AML (n = 642), venetoclax was associated with a high probability of increased risk of high-grade neutropenia (P[RR > 1] = 94.6%) and febrile neutropenia (P[RR > 1] = 90.6%). Our results suggest that venetoclax has a low probability of increased risk of IAEs or neutropenia in CLL. By contrast, there is likely increased risk of high-grade neutropenia and febrile neutropenia in AML. Importantly, our analyses did not identify any specific IAEs that would benefit from routine antimicrobial prophylaxis or pre-emptive testing.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Hematologic Neoplasms; Leukemia, Myeloid, Acute; Communicable Diseases; Febrile Neutropenia; Sulfonamides; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 38154071
DOI: 10.1182/bloodadvances.2023011964