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Current Oncology (Toronto, Ont.) Jan 2023Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and young adults. Treatment is long and involves 2-3 years of a prolonged maintenance phase... (Review)
Review
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and young adults. Treatment is long and involves 2-3 years of a prolonged maintenance phase composed of oral chemotherapies. Adherence to these medications is critical to achieving good outcomes. However, adherence is difficult to determine, as there is currently no consensus on measures of adherence or criteria to determine nonadherence. Furthermore, there have been few studies in pediatric B-ALL describing factors associated with nonadherence. Thus, we performed a systematic review of literature on oral chemotherapy adherence during maintenance therapy in ALL following PRISMA guidelines. Published studies demonstrated various objective and subjective methods of assessing adherence without generalizable definitions of nonadherence. However, the results of these studies suggested that nonadherence to oral maintenance chemotherapy was associated with increased risk of relapse. Future studies of B-ALL therapy should utilize a uniform assessment of adherence and definitions of nonadherence to better determine the impact of nonadherence on B-ALL outcomes and identify predictors of nonadherence that could yield targets for adherence improving interventions.
Topics: Child; Humans; Adolescent; Young Adult; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Administration, Oral; Recurrence
PubMed: 36661705
DOI: 10.3390/curroncol30010056 -
Frontiers in Pediatrics 2022Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that has proven efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL)....
BACKGROUND
Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that has proven efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Despite its efficacy, it has also been associated with the development of potentially serious adverse events such as the cytokine release syndrome (CRS) and neurologic events. The present meta-analysis aimed to assess the safety profile of blinatumomab in terms of serious adverse events, CRS, and neurologic events (such as seizure and encephalopathy) in pediatric patients with B-cell ALL.
METHODS AND FINDINGS
A systematic review was conducted in Pubmed up to December 10, 2021 to retain pediatric clinical trials on blinatumomab. A random effect meta-analysis approach was used. This study followed the PRISMA statement. Four out of the 255 initial references were selected, of which 2 were phase 1/2 clinical trials and 2 phase 3 clinical trials. Blinatumomab was associated with a lower risk of serious adverse events (Risk ratio RR, 0.56; 95% CI, 0.32-0.99), febrile neutropenia (RR, 0.13; 95% CI, 0.06-0.26), infection (RR, 0.40; 95% CI, 0.29-0.56), and grade ≥ 3 adverse events (RR, 0.79; 95% CI, 0.67-0.93) compared to chemotherapy. No difference in the risk of CRS (RR, 8.37; 95% CI, 0.27-260.97) and seizure (RR, 6.43; 95% CI, 0.79-53.08) was observed between groups, while for encephalopathy a higher risk was associated with blinatumomab compared to chemotherapy (RR, 8.90; 95% CI, 1.08-73.29).
CONCLUSION
Our data support the good safety profile of bliantumomab in treating pediatric patients with B-ALL.
PubMed: 35935358
DOI: 10.3389/fped.2022.929122 -
Clinical Epigenetics 2016Aberrant DNA methylation has been identified as a key molecular event regulating the pathogenesis of myelodysplastic syndromes (MDS); myeloid neoplasms with an inherent... (Comparative Study)
Comparative Study Review
BACKGROUND
Aberrant DNA methylation has been identified as a key molecular event regulating the pathogenesis of myelodysplastic syndromes (MDS); myeloid neoplasms with an inherent risk of transformation to acute myeloid leukemia (AML). Based on the above findings, DNA hypomethylating agents (HMA) have been widely used to treat AML and MDS, especially in elderly patients and in those who are not eligible for allogeneic stem cell transplantation (SCT). Our goal was to determine if there is any therapeutic advantage of HMA vs. conventional care regimens (CCR) and indirectly compare the efficacy of azacitidine and decitabine in this patient population.
METHODS
Eligible studies were limited to randomized controlled trials comparing HMA to CCR in adult patients with AML or MDS.
RESULTS
Overall survival (OS) rate was 33.2 vs. 21.4 % (RR 0.83, 95 % CI 0.71-0.98) and overall response rate (ORR) 23.7 vs. 13.4 % (RR 0.87, 95 % CI 0.81-0.93) for HMA and CCR, respectively. In subgroup analyses, only azacitidine treatment showed OS improvement (RR 0.75, 95 % CI 0.64-0.98) and not decitabine. Cytogenetic risk or bone marrow blast count did not have independent prognostic impact.
CONCLUSION
Collectively, these results demonstrate that HMA have superior outcomes compared to CCR and suggest that azacitidine in comparison to decitabine, may be more effective.
Topics: Aged; Antimetabolites, Antineoplastic; Azacitidine; DNA Methylation; Decitabine; Epigenesis, Genetic; Female; Humans; Leukemia, Myeloid, Acute; Male; Myelodysplastic Syndromes; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome
PubMed: 27307795
DOI: 10.1186/s13148-016-0233-2 -
Pharmaceuticals (Basel, Switzerland) Mar 20226-Mercaptopurine (6-MP) is a cornerstone of the maintenance regimen for pediatric acute lymphoblastic leukemia (ALL). Inosine triphosphate pyrophosphatase (ITPA) is... (Review)
Review
6-Mercaptopurine (6-MP) is a cornerstone of the maintenance regimen for pediatric acute lymphoblastic leukemia (ALL). Inosine triphosphate pyrophosphatase (ITPA) is considered a candidate pharmacogenetic marker that may affect metabolism and 6-MP-induced toxicities; however, the findings are inconsistent. Therefore, we attempted to evaluate the effect of ITPA 94C>A polymorphism on 6-MP-induced hematological toxicity and hepatotoxicity through a systematic review and meta-analysis. A literature search for qualifying studies was conducted using the PubMed, Web of Science, and Embase databases until October 2021. Overall, 10 eligible studies with 1072 pediatric ALL patients were included in this meta-analysis. The results indicated that ITPA 94C>A was significantly associated with 6-MP-induced neutropenia (OR 2.38, 95% CI: 1.56−3.62; p = 0.005) and hepatotoxicity (OR 1.98, 95% CI: 1.32−2.95; p = 0.0009); however, no significant association was found between the ITPA 94C>A variant and 6-MP-induced leukopenia (OR 1.75, 95% CI: 0.74−4.12; p = 0.20). This meta-analysis demonstrated that ITPA 94C>A polymorphism could affect 6-MP-induced toxicities. Our findings suggested that ITPA genotyping might help predict 6-MP-induced myelosuppression and hepatotoxicity.
PubMed: 35455413
DOI: 10.3390/ph15040416 -
Journal of Environmental Health Science... Jun 2023Heavy metals and metalloids are recognized as environmental threats, which are considered highly toxic and carcinogenic. Epidemiologically, their association with...
PURPOSE
Heavy metals and metalloids are recognized as environmental threats, which are considered highly toxic and carcinogenic. Epidemiologically, their association with leukemia is under debate. We aim to clarify the association between the heavy metal(loid)s in serum and leukemia via a systematic review and meta-analysis.
METHODS
We searched PubMed, Embase, Google Scholar, and CNKI (China National Knowledge Infrastructure) databases for all related articles. The standardized mean difference and its 95% confidence interval was used to evaluate the association of leukemia with heavy metal(loid)s in serum. The statistical heterogeneity among studies was assessed with the Q-test and statistics.
RESULTS
Among 4,119 articles related to metal(loid)s and leukemia, 21 studies met our inclusion criteria, which are all cross-sectional studies. These 21 studies involved 1,316 cases and 1,310 controls, based on which we evaluate the association of heavy metals/metalloids in serum with leukemia. Our results indicated positive differences for serum chromium, nickel, and mercury in leukemia patients, while a negative difference for serum manganese in acute lymphocytic leukemia (ALL).
CONCLUSION
Our results suggested an elevated trend of serum chromium, nickel, and mercury concentrations in leukemia patients while descending trend of serum manganese concentration in ALL patients. The result of sensitivity analysis between lead, cadmium, and leukemia and publication bias of association between chromium and leukemia also needed attention. Future research work may focus on the dose-response relationship between any of these elements and the leukemia risks, and further elucidation of how these elements are related to leukemia may shed light on the prevention and treatment of leukemia.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40201-023-00853-2.
PubMed: 37159736
DOI: 10.1007/s40201-023-00853-2 -
Frontiers in Pharmacology 2022Several clinical trials have been conducted to evaluate the effects of blinatumomab in childhood B cell acute lymphoblastic leukemia (B-ALL). We conducted this...
Several clinical trials have been conducted to evaluate the effects of blinatumomab in childhood B cell acute lymphoblastic leukemia (B-ALL). We conducted this meta-analysis to validate the efficacy and safety of blinatumomab in pediatric patients with relapsed/refractory B-ALL (R/R B-ALL). We searched and investigated all relevant studies in the PubMed, Web of Science, Embase, and Cochrane Library databases. The primary outcomes were complete response (CR), overall survival (OS), event free survival (EFS), minimal residual disease (MRD) response, allogeneic hematopoietic stem cell transplantation (allo-HSCT) and were calculated separately for randomized controlled trials (RCTs) and single-arm studies. The secondary end points were adverse effects (AEs) and the relapse rate. The Cochrane, bias assessment tool, was used to assess the risk of bias in RCTs. The methodological quality of single-arm studies was assessed using the methodological index for non-randomized studies (MINORS) tool. The meta-analysis included two RCTs and 10 single-arm studies, including 652 patients in total. Our study showed that in the single-arm studies, the combined CR rate was 0.56 (95% confidence interval (CI): 0.45 -0.68), the odds ratios (ORs) of OS was 0.43 (95% CI 0.32 -0.54), the EFS rate was 0.30 (95% CI: 0.20 -0.40), the MRD response was 0.51 (95% CI: 0.34 -0.68), allo-HSCT rate was 0.62 (95% CI: 0.50 -.74), the AE rate was 0.65 (95% CI: 0.54 -0.76) and the relapse rate was 0.32 (95% CI: 0.27 -0.38). In the RCTs, the blinatumomab-treated group compared with the chemotherapy group had a combined OS rate of 0.12 (95% CI: 0.05 -0.19) and an EFS rate of 2.16 (95% CI: 1.54 -3.03). The pooled MRD response rate was 4.71 (95% CI:2.84 -7.81), allo-HSCT was 3.24 (95% CI: 1.96 -5.35), the AE rate was 0.31 (95% CI: 0.16 -0.60), and the relapse rate was 0 .69 (95% CI: 0.43 -1.09). According to this meta-analysis, blinatumomab shows potent therapeutic efficacy and limited AEs in children with R/R B- ALL. https://www.crd.york.ac.uk/prospero/, identifier CRD42022361914.
PubMed: 36703737
DOI: 10.3389/fphar.2022.1032664 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2020The presence of Philadelphia (Ph)-like ALL among patients with acute lymphoblastic leukemia (ALL) may indicate a poor prognosis similar to Ph ALL, although the data are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The presence of Philadelphia (Ph)-like ALL among patients with acute lymphoblastic leukemia (ALL) may indicate a poor prognosis similar to Ph ALL, although the data are still inconclusive and the prevalence of Ph-like ALL varied considerably across studies.
PATIENTS AND METHODS
We performed a systematic review and meta-analysis in order to identify all cohort studies of patients with ALL that reported the prevalence of Ph-like ALL and to summarize their results together. The pooled prevalence and rate were calculated by the DerSimonian-Laird random-effect model with double arcsine transformation.
RESULTS
Across the 15 included studies describing 11,040 ALL patients, the peak prevalence of the presence of Ph-like ALL among patients with ALL was between ages 11 and 40 years, where the pooled prevalence was 25.8% to 26.2%. The pooled 5-year overall survival rate of Ph-like ALL was 42.8% (95% confidence interval, 23.9-64.1; I 93%). Comparative analysis with B-other ALL patients was conducted by the Mantel-Haenszel method; it found that Ph-like ALL patients had a significantly lower chance of being alive at 5 years (pooled odds ratio, 0.35; 95% confidence interval, 0.25-0.50; P < .00001, I = 40%). The chance of Ph-like ALL patients surviving at 5 years was similar to Ph-positive ALL patients (pooled odds ratio, 0.72; 95% confidence interval, 0.26-2.02; P = .53, I = 77%).
CONCLUSION
Ph-like ALL is not uncommon among ALL patients, and its presence is associated with an unfavorable outcome. More investigations are needed for better therapeutic options.
Topics: Child; Female; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prevalence; Treatment Outcome
PubMed: 31699654
DOI: 10.1016/j.clml.2019.08.003 -
Asian Pacific Journal of Cancer... Apr 2022we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk. (Meta-Analysis)
Meta-Analysis
Association of Somatic Gene Mutations with Risk of Transformation into Acute Myeloid Leukemia in Patients with Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis.
OBJECTIVES
we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk.
MATERIALS AND METHODS
The protocol for this systematic review and meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) with ID number of CRD42020218581. Systematic literature search was conducted by all authors up to October 2021 on: (1) PubMed, (2) EBSCOhost, (3) Scopus, (4) JSTOR, and (5) grey literatures. Hand-searching for relevant articles was also conducted. The following keywords with their synonyms and combinations using Boolean operators were applied to all database: "myelodysplastic syndrome", SRSF2", "SF3B1", "U2AF1", "ASXL1", "DNMT3A", "TET2", "IDH1", "IDH2", "RUNX1", "acute myeloid leukemia progression", and "leukemia free survival". Outcome was measured using hazard ratio (HR).
RESULTS
We identified 14 articles to be used for this systematic review and meta-analysis. There was no statistically significant difference in AML transformation risk between U2AF1 mutant and U2AF1 wildtype MDS patients (HR: 1.41; 95% CI: 0.95-2.07, p=0.08, I2=0%). Pooled HR showed that patients with SRSF2 mutation had higher risk of AML transformation (HR 2.62; 95% CI: 1.54-4.45; p= .0004; I2= 55%). The pooled HR for SF3B1 was 0.48 (95% CI: 0.22-1.06, p=0.07, I2=55%). Mutations of TET2, ASXL1, and EZH2 were not associated with AML transformation. Meanwhile, DNMT3A mutations were associated with AML transformation with pooled HR of 2.73 (95% CI: 1.43-5.21; p= 0.08; I2: 67%). The pooled HR for IDH genes was smaller (HR: 2.92; 95%CI: 1.21-7.06; p=0.02; I2:65%). Patients with RUNX1 mutation were associated with AML transformation (HR: 1.85; 95%CI: 1.11-3.09; p=0.02; I2:38%).
CONCLUSION
Based from our analyses, MDS patients with mutations of SRSF2, DNMT3A, IDH, and RUNX1 have higher hazard ratio for AML transformation.
Topics: Adult; Core Binding Factor Alpha 2 Subunit; Humans; Leukemia, Myeloid, Acute; Mutation; Myelodysplastic Syndromes; Splicing Factor U2AF
PubMed: 35485665
DOI: 10.31557/APJCP.2022.23.4.1107 -
Frontiers in Medicine 2022Hypomethylating agents (HMAs) seem to have a range of properties favorable to post-allogeneic hematopoietic stem cell transplantation (allo-SCT) maintenance in acute...
Maintenance With Hypomethylating Agents After Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis.
INTRODUCTION
Hypomethylating agents (HMAs) seem to have a range of properties favorable to post-allogeneic hematopoietic stem cell transplantation (allo-SCT) maintenance in acute myeloid leukemia (AML) patients.
MATERIALS AND METHODS
The Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases were independently searched by two investigators to identify relevant studies published inception to 18 November 2021. These trials compared HMA maintenance to observation following allo-SCT for AML or myelodysplastic syndrome.
RESULTS
The meta-analysis eligibility criteria were fulfilled by 14 studies. The overall survival and relapse-free survival of the HMA maintenance group were superior to the observation group, with a pooled risk ratio (RR) of 1.38 and 1.46, respectively. Moreover, the cumulative incidence of relapse was significantly lower in those who received HMAs. The HMA group also had lower non-relapse mortality compared with the observation group. Overall, the incidences of grades III-IV acute graft-vs.-host disease (GVHD) and chronic GVHD did not differ in both groups. However, when looking specifically at those receiving decitabine maintenance, the rate of chronic GVHD seemed to be lower compared with observation alone.
CONCLUSIONS
The current systematic review and meta-analysis illustrated that AML and MDS patients receiving HMA maintenance after allo-SCT had better outcomes in regards to OS, RFS, NRM, CIR as well as a reduced incidence of chronic GVHD.
PubMed: 35242779
DOI: 10.3389/fmed.2022.801632