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Expert Review of Hematology 2024This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and blinatumomab.
METHODS
PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies.
RESULTS
The pooled complete remission (CR) rate and minimal residual disease (MRD) negative rate were 48%, 31% for blinatumomab, and 86% and 80% for CAR T-cell therapy.
CONCLUSIONS
The CAR T-cell therapy group exhibited a higher likelihood of CR rate than the blinatumomab group in every analysis regardless of adjustment subgroups. CAR T-cell therapy was associated with a significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with blinatumomab (2-year OS 55% vs 25%; 2-year RFS 40% vs 22%). CAR T-cell therapy was more effective for achieving CR and bridging to allogeneic hematopoietic stem cell transplantation (allo-SCT) than blinatumomab (2-year OS 75% vs. 57%). An emerging role for blinatumomab is as a bridging agent pre-SCT, and for patients who achieve an MRD-negative state pre-SCT, post-SCT outcomes are expected to be the same as CAR-T. For adverse effects (AEs), blinatumomab was associated with a lower rate of grade ≥3 hematological toxicity, CRS, and neurological events.
Topics: Humans; Immunotherapy, Adoptive; Hematopoietic Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antibodies, Bispecific; Recurrence; Antigens, CD19
PubMed: 38135295
DOI: 10.1080/17474086.2023.2298732 -
BMC Cancer Nov 2023Children with acute lymphoblastic leukaemia (ALL) experience multiple symptoms that occur in complicated patterns and negatively affect patient outcomes. To date, no... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Children with acute lymphoblastic leukaemia (ALL) experience multiple symptoms that occur in complicated patterns and negatively affect patient outcomes. To date, no systematic review has been performed on the prevalence of symptoms in children with ALL.
OBJECTIVE
The study aimed to report and analyse the prevalence of symptoms in children with ALL during treatment.
METHODS
A systematic search was conducted in eight databases (PubMed, Ovid Embase, Web of Science, CINAHL, PsycINFO, China WanFang Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure) for studies published between January 1, 2000, and August 12, 2023. The methodological quality of the included studies was evaluated and a meta-analysis was performed to pool the prevalence of symptoms.
RESULTS
In total, 17 studies were included, from which 34 symptoms were identified. The symptom prevalence ranged between 1.5 and 91.0% and the most frequent symptoms observed were fatigue, lack of energy, dry mouth, lack of appetite, sweating, and feeling irritable, which occurred in at least 60% of the patients.
CONCLUSIONS
Symptoms remain highly prevalent in paediatric patients with ALL, which provides support for the need for symptom assessment in the clinical setting. Specific intervention is urgently needed to mitigate the symptoms in children with ALL and help them cope with the symptom burden.
Topics: Humans; Child; Prevalence; Emotions; China; Fatigue; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37968600
DOI: 10.1186/s12885-023-11581-z -
Leukemia Research Dec 2023We aimed to evaluate the efficacy, safety, and latent toxicity of total body irradiation (TBI)-based conditioning regimens compared to non-TBI regimens for pediatric... (Meta-Analysis)
Meta-Analysis Review
A comprehensive comparison between TBI vs non-TBI-based conditioning regimen in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis.
INTRODUCTION
We aimed to evaluate the efficacy, safety, and latent toxicity of total body irradiation (TBI)-based conditioning regimens compared to non-TBI regimens for pediatric patients (under 18 years old) with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT).
METHODS
A systematic search was performed on MEDLINE, Scopus, WOS, and PMC. Also, a search for grey literature was performed on Google Scholar and relevant articles' references were included. Relevant articles which met the inclusion criteria were retrieved up to October 31th, 2022. CMA version 2 was used for the quantitative synthesis of the data.
RESULTS
Eight studies on efficacy and safety of TBI and non-TBI as a conditioning regimen were analyzed and six comparative studies on late toxicity were investigated. The meta-analysis revealed a hazard ratio (HR) of 1.508 (95% CI 0.96-2.35) for overall survival (OS) in instances of non-TBI conditioning. Also, an HR of 1.503 (95% CI 1.006-2.25) for disease-free- survival (DFS) favoring TBI-based conditioning. Late complications were reported to be significantly higher in the TBI conditioning regimen group than in the non-TBI group.
CONCLUSION
It appears that non-TBI regimens are as effective as TBI regimens in pediatrics with ALL regarding OS. Occurrence of latent toxicity is higher with TBI conditioning regimen. Conversely, TBI-based regimens are superior to non-TBI conditioning regimens regarding DFS. Considering all aspects, non-TBI conditioning regimens can be an alternative treatment option for pediatric ALL undergoing HSCT.
Topics: Humans; Child; Adolescent; Whole-Body Irradiation; Retrospective Studies; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Disease-Free Survival; Progression-Free Survival; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Graft vs Host Disease; Cyclophosphamide
PubMed: 37918224
DOI: 10.1016/j.leukres.2023.107416 -
Annals of Hematology Aug 2023IKZF1 (IKAROS family Zinc Finger 1) alteration is an essential regulator of both T- and B-cell lineage specification with leukemogenic potential. IKZF1 deletion have... (Meta-Analysis)
Meta-Analysis
IKZF1 (IKAROS family Zinc Finger 1) alteration is an essential regulator of both T- and B-cell lineage specification with leukemogenic potential. IKZF1 deletion have been described in childhood acute lymphoblastic leukemia (ALL) with varying prevalence often influenced by underlying cytogenetics and also shown to have diverse prognostic significance. We aimed to evaluate the prevalence and prognostic significance of IKZF1 deletion among childhood ALL. Electronic databases of MEDLINE, EMBASE and SCOPUS were searched and 32 studies found eligible. Estimated prevalence of IKZF1 deletion among BCR::ABL1 negative and BCR::ABL1 positive ALL patients was 14% (95%CI:13-16%, I = 79%; 26 studies) and 63% (95%CI:59-68% I = 42%; 10 studies) respectively. Most common site of IKZF1 deletion was whole chromosome (exon1-8) deletion in 32.3% (95%CI: 23.8-40.7%) followed by exon 4-7 deletion in 28.6% (95%CI: 19.7-37.5%). A positive minimal residual disease at the end of induction was more common among patients with IKZF1 deletion, odds ratio: 3.09 (95%CI:2.3-4.16, I = 54%; 15 studies). Event-free survival and overall survival were significantly worse for IKZF1 deletion, hazard ratio (HR): 2.10 (95%CI:1.90-2.32, I = 28%; 31 studies) and HR: 2.38 (95%CI:1.93-2.93, I = 40; 15 studies) respectively. In summary, the current meta-analysis highlights the frequency of IKZF1 deletion and its negative impact on survival in childhood ALL. Further studies exploring the influence of IKZF1 deletion in the presence of classical cytogenetic and other copy number alterations would further help in characterising its prognostic role.
Topics: Child; Humans; Prognosis; Prevalence; Ikaros Transcription Factor; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Progression-Free Survival; Gene Deletion; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37154889
DOI: 10.1007/s00277-023-05250-1 -
Cytotherapy Sep 2023The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults...
A systematic review on the cost-effectiveness assessment of tisagenlecleucel for refractory or relapsing B-cell acute lymphoblastic leukemia (R/R B-ALL) treatment in children and young adults.
BACKGROUND AIMS
The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We sought to evaluate the cost-effectiveness of tisagenlecleucel compared with conventional salvage therapies in pediatric and young adult patients with R/R B-ALL.
METHODS
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses parameters as registered in International Prospective Register of Systematic Reviews (CRD42021266998). Literature was searched using the MEDLINE databases via PubMed, EMBASE, Lilacs, the Cochrane Central Register of Controlled Trials and Web of Science in January 2022. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts were reviewed.
RESULTS
In total, 5627 publications were identified, from which six eligible studies were selected. The conventional therapies identified were blinatumomab (Blina), clofarabine monotherapy (Clo-M), clofarabine combined with cyclophosphamide and etoposide (Clo-C) and the combination of fludarabine, cytarabine and idarubicin (FLA-IDA). The discounted incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for tisagenlecleucel compared with Clo-C and Blina averages was $38 837 and $25 569, respectively. In relation to the cost of the drug, the average of tisagenlecleucel was approximately 4.3 times, 10.8 times or 4.7 times greater than the Clo-M, Clo-C and Blina, respectively.
CONCLUSIONS
This systematic review highlighted that tisagenlecleucel is a much more expensive therapy than conventional alternatives. However, tisagenlecleucel performed well on the ICER, not exceeding $100 000/QALY. It was also found that the advanced therapy product was more effective than the conventional small molecule and biological drugs, in terms of life years and QALY gained.
Topics: Humans; Young Adult; Child; Clofarabine; Cost-Benefit Analysis; Receptors, Antigen, T-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence
PubMed: 37341664
DOI: 10.1016/j.jcyt.2023.05.011 -
Advances in Therapy Dec 2023Clofarabine monotherapy at a dose of 52 mg/m per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL)... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Clofarabine monotherapy at a dose of 52 mg/m per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL) in patients aged 1-21 years after at least two prior regimens. To address a post-marketing requirement for additional evidence of the clinical benefit of clofarabine in its approved indication, a meta-analysis of patient-level data was conducted.
METHODS
A systematic literature review was conducted, using the Dr.Evidence software platform, DOC Search, and Embase, to identify clinical trials with patients with R/R ALL who received clofarabine monotherapy at 52 mg/m. The primary endpoint was complete remission (CR). Secondary endpoints were overall remission (OR, defined by CR or CR with either incomplete platelet recovery or incomplete neutrophil and platelet recovery), duration of response, overall survival (OS), and safety.
RESULTS
A total of 754 patients in 12 clinical studies were analyzed including 682 patients with R/R ALL treated with clofarabine monotherapy at 52 mg/m; of them, 374 were aged < 22 years (pediatric population). Rates of CR and OR were 16% (95% confidence interval [CI] 7, 26) and 28% (95% CI 20, 37), respectively, in the pediatric population and 12% (95% CI 5, 21) and 21% (95% CI 13, 31) in the overall population. Median OS (evaluable in three studies in pediatric patients) was 3.7 months (95% CI 0.1, 31.4), reaching 10.1 months (95% CI 0.3, 68.9) for those achieving OR. Sensitivity analyses supported these findings. The most frequent grade 3-4 adverse events were liver abnormalities, anemia, diarrhea, and febrile neutropenia.
CONCLUSION
In this meta-analysis, CR duration and median OS in pediatric patients with R/R ALL appeared to be slightly longer than in the phase II study. No new safety signals were identified. Results support the use of clofarabine monotherapy in its approved indication.
Topics: Child; Humans; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Clofarabine; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Clinical Trials as Topic
PubMed: 37819554
DOI: 10.1007/s12325-023-02696-7 -
Pathology, Research and Practice Sep 2023Highly supported microRNAs (miRNAs) are key players in cancer development. Each of these miRNAs may act as an oncomir, a tumor-suppressor, or both in various cancers.... (Review)
Review
BACKGROUND
Highly supported microRNAs (miRNAs) are key players in cancer development. Each of these miRNAs may act as an oncomir, a tumor-suppressor, or both in various cancers. Mir-151a-5p is believed to be one of these miRNAs with diverse roles. We have conducted this systematic review to clarify the role of mir-151a-5p in formation of various cancers.
METHODS AND MATERIALS
We searched for existing articles in PubMed, Web of Science, Cochrane, Scopus, and RNAcentral databases up to November 2022. A total of 23 articles were qualified and included in the present systematic review. This review is registered on JBI at https://jbi.global/systematic-review-register. Expression levels, diagnostic and prognostic values, biological processes, and targeted downstream genes are included.
RESULTS
Assembled data indicate the expression levels of mir-151a-5p vary from down- to up-regulated based on the type of the cancer. Its functional role depends on the genetic profile of cancerous tissue. Results mostly point to the oncogenic role of this miRNA in Pituitary adenomas, Acute Myeloid Leukemia (AML), Endometrial, Lung, Barrett's carcinogenesis, Colorectal, Myelodysplastic syndromes, Hepatocellular carcinoma and Breast cancers, as its inhibited targets seem to be controlling several signaling pathways, cell adhesion, and cell cycle. At the same time, tumor-suppressing role has also been observed only in Malignant Pleural Mesothelioma, Central Nerve System (CNS) lymphoma, Chronic Myeloid and Acute Lymphocytic Leukemia. Two types of cancers, prostate and colon, show contradictory results as there are studies supporting both up- and down-regulation in these cancers. Pituitary adenomas, Barrett's carcinogenesis and CNS lymphomas are top cancers diagnosed with mir-151-5p. However, prognostic feature is only applicable to Lung adenocarcinoma.
DISCUSSION
Based on the present findings and further studies in the future, mir-151a-5p may be used as diagnostic and prognostic biomarkers or even a therapeutic target in cancer studies.
DATA AVAILABILITY STATEMENT
The articles used in this study can be found with the defined search phrase in mentioned databases. A list of selected articles will be available on reasonable requests.
Topics: Male; Humans; Pituitary Neoplasms; MicroRNAs; Carcinogenesis; Cell Transformation, Neoplastic; Genes, Tumor Suppressor; Gene Expression Regulation, Neoplastic
PubMed: 37562284
DOI: 10.1016/j.prp.2023.154576 -
Leukemia & Lymphoma 2023Relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) is a challenging disease with low rates of remission and survival in adult patients. Anti-CD19... (Meta-Analysis)
Meta-Analysis
Differences in efficacy and safety among CAR-Ts anti-CD19/CD22, anti-CD19, and anti-CD22, in adult patients with relapse/refractory B-cell acute lymphoblastic leukemia: a meta-analysis and systematic review.
Relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) is a challenging disease with low rates of remission and survival in adult patients. Anti-CD19 Chimeric Antigen Receptor T-cells (CAR-Ts) therapies have been approved for these patients. Dual-target CAR-Ts against CD19 and CD22 have recently been developed to improve the efficacy of the single-target therapy; however, extent of the improvement using this dual-target therapy has yet to be determined. We performed a meta-analysis of the outcome and safety of CAR-Ts, comparing anti-CD19 vs anti-CD22 vs dual-target anti-CD19/CD22 CAR-Ts, to elucidate the differences and limitations of these therapies in adult patients with R/R B-ALL. our results suggest that anti-CD19/CD22 CAR-Ts generate lower incidence of relapse and neurotoxicity, but similar results were obtained regarding complete remission, minimal residual disease, overall survival, and cytokine release syndrome compared with single-target anti-CD19 and anti-CD22 CAR-Ts.
Topics: Humans; Adult; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Lymphoma, B-Cell; Antigens, CD19; Acute Disease; Sialic Acid Binding Ig-like Lectin 2
PubMed: 37548560
DOI: 10.1080/10428194.2023.2243357 -
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 -
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