-
Current Oncology (Toronto, Ont.) Sep 2023Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have significantly worse outcomes than their younger counterparts. Current treatment... (Review)
Review
Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have significantly worse outcomes than their younger counterparts. Current treatment guidelines rely mostly on non-randomized retrospective studies. We performed a systematic review of studies published within the last 15 years comparing pediatric-inspired regimens (PIR) versus adult-type regimens or performing an age-stratified analysis of outcomes in the AYA population. Due to the heterogeneity of data, a meta-analysis was not possible. However, the gathered data show a trend toward improvement in outcomes and an acceptable toxicity profile in patients treated with PIRs compared to conventional adult-type regimens. There is still room for further improvement, as older patients within the AYA population tend to perform poorly with PIR or conventional adult-type chemotherapy. Further randomized studies are needed to develop an optimal treatment strategy for AYA with ALL.
PubMed: 37754540
DOI: 10.3390/curroncol30090625 -
Cancer Gene Therapy Jun 2023Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL).... (Meta-Analysis)
Meta-Analysis
Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis.
Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL). However, identifying the factors that influence long-term response to this therapy is necessary to optimize patient selection and treatment allocation. We conducted a literature review and meta-analysis to investigate the use of autologous anti-CD19 CAR T cell therapy in both pediatric and adult patients with R/R B-ALL, using several databases including MEDLINE, Cochrane Central, ScienceDirect, Web of Science, Journals@Ovid, Embase, and clinicaltrial.gov. A total of 38 reports were analyzed, which enrolled 2134 patients. Time-to-event endpoints were estimated using reconstructed patient survival data. The study explored key modulators of response, including costimulatory domains, disease status, age, and lymphodepletion. The median overall survival and event-free survival were 36.2 months [95% CI 28.9, NR] and 13.3 months [95% CI 12.2, 17], respectively. The overall response rate was 76% [95% CI 71, 81]. The use of 4-1BB costimulatory domain in the CAR construct, administration of low-dose cyclophosphamide lymphodepletion, and pretreatment morphologic remission were associated with better overall survival, with hazard ratios of 0.72, 0.56, and 0.66, respectively. Morphologic remission and 4-1BB domain were associated with better event-free survival, with hazard ratios of 0.66 and 0.72, respectively. These findings suggest that CAR T cell therapy may offer long-term benefits to patients with R/R B-ALL. However, further research is needed to optimize patient selection and better understand the impact of various factors on the outcome of CAR T cell therapy.
Topics: Adult; Humans; Child; Receptors, Chimeric Antigen; Receptors, Antigen, T-Cell; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; T-Lymphocytes
PubMed: 36750666
DOI: 10.1038/s41417-023-00593-3 -
Annals of Palliative Medicine Jul 2021A meta-analysis was performed to examine the clinical efficacy of drugs in the treatment of acute myelogenous leukemia (AML). (Meta-Analysis)
Meta-Analysis
BACKGROUND
A meta-analysis was performed to examine the clinical efficacy of drugs in the treatment of acute myelogenous leukemia (AML).
METHODS
combinations of terms of "acute myeloid leukemia", "fludara", "cytarabine", "cladribine", "aclacinomycin", "granulocyte colony-stimulating factor (G-CSF)", and "hyaluronic acid" were searched in Chinese databases. "acute myelogenous leukemia", "fludara", "cytarabine", "cladribine", "aclacinomycin", "granulocyte colony-stimulating factor", and "hyaluronic acid" were searched in English databases. Review Manager 5.3 was employed for the meta-analysis.
RESULTS
Ultimately, 12 articles were included. Most of the articles had a low-risk bias, and were of medium or high quality. The complete remission rates were tested for heterogeneity [chi-square test (Chi2) =4.10, degrees of freedom (df)=10, I2=0%; P=0.94]. The fixed effect model analysis showed that the difference between experimental participants and controls was considerable [Z=13.15, odds ratio (OR) =12.82, 95% confidence interval (CI): (8.77, 18.76); P<0.01]. The overall effective rates were tested for heterogeneity (Chi2=1.58, df=7, I2=0%; P=0.98), and difference between experimental participants and controls was considerable [Z=10.70, OR =1.32, 95% CI: (7.32,17.89); P<0.01]. The overall adverse reaction rates were tested for heterogeneity (Chi2=0.42, df=5, I2=0%; P=0.99), and the difference between experimental participants and controls was considerable [Z=5.00, OR =0.38, 95% CI: (0.26, 0.55); P<0.01]. The circles of some studies in the funnel diagrams were symmetrical with the midline, the accuracy of included trials was high, the publications were not biased, and the final conclusions were reliable.
CONCLUSIONS
This meta-analysis showed that drug treatments of AML can improve complete remission and total effective rates and reduce adverse reaction rates, and thus are worthy of clinical promotion.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Treatment Outcome
PubMed: 34353076
DOI: 10.21037/apm-21-1390 -
Oncology Nursing Forum Mar 2015Systematically summarize findings from research conducted on adult acute leukemia survivors as they relate to symptoms and quality of life (QOL). (Review)
Review
PURPOSE/OBJECTIVES
Systematically summarize findings from research conducted on adult acute leukemia survivors as they relate to symptoms and quality of life (QOL).
DATA SOURCES
Systematic review of the literature from 1990–2013 found in the PubMed, PsycINFO®, EMBASE, and CINAHL® databases, as well as manual searches.
DATA SYNTHESIS
The review identified 16 quantitative studies and 1 qualitative study published from 1990–2013 that used a self-reported QOL or symptom questionnaire. Fatigue was the most commonly assessed and reported symptom, followed by depression.
CONCLUSIONS
Acute leukemia and its treatment have a significant impact in all QOL domains. Future studies should include longitudinal research, more than one recruitment site, increased minority representation, and home-based exercise interventions as ways to improve all domains of QOL.
IMPLICATIONS FOR NURSING
This review increases awareness of commonly reported symptoms faced by adults with acute leukemia. Oncology nurses are central in monitoring and reporting symptoms to the interdisciplinary team that may contribute to changes in function, with the overall goal of optimizing QOL over time.
Topics: Adult; Aged; Epidemiologic Studies; Humans; Leukemia, Myeloid, Acute; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Qualitative Research; Quality of Life; Research Design; Spirituality; Survivors; Symptom Assessment
PubMed: 25806895
DOI: 10.1188/15.ONF.E91-E101 -
Cadernos de Saude Publica 2009Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure... (Review)
Review
Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure to non-ionizing radiation generated by low frequency magnetic fields with childhood leukemia. The current article reviews the case-control studies published on this subject. Of 152 articles tracked in different databases, ten studies from North America, Asia, and Europe met the defined selection criteria, with patients diagnosed from 1960 to 2004. Methodological limitations were observed in these articles, including difficulties with the procedures for assessing exposure. An association may exist between exposure to low frequency magnetic fields and acute lymphoblastic leukemia in children, but this association is weak, preventing the observation of consistency in the findings. Future studies from a wider range of geographic regions should focus on the analysis of acute lymphoblastic leukemia, which is the subtype with the greatest impact on the increasing overall incidence of childhood leukemia.
Topics: Case-Control Studies; Child; Electromagnetic Fields; Environmental Exposure; Humans; Incidence; Leukemia, Radiation-Induced; Odds Ratio; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Radiation Dosage; Risk Factors
PubMed: 20027391
DOI: 10.1590/s0102-311x2009001500009 -
The Cochrane Database of Systematic... Sep 2022This review is the third update of a previously published Cochrane Review. The original review, looking at all possible cardioprotective agents, was split and this part... (Review)
Review
BACKGROUND
This review is the third update of a previously published Cochrane Review. The original review, looking at all possible cardioprotective agents, was split and this part now focuses on dexrazoxane only. Anthracyclines are effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent or reduce this cardiotoxicity, different cardioprotective agents have been studied, including dexrazoxane.
OBJECTIVES
To assess the efficacy of dexrazoxane to prevent or reduce cardiotoxicity and determine possible effects of dexrazoxane on antitumour efficacy, quality of life and toxicities other than cardiac damage in adults and children with cancer receiving anthracyclines when compared to placebo or no additional treatment.
SEARCH METHODS
We searched CENTRAL, MEDLINE and Embase to May 2021. We also handsearched reference lists, the proceedings of relevant conferences and ongoing trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which dexrazoxane was compared to no additional therapy or placebo in adults and children with cancer receiving anthracyclines.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data extraction, risk of bias and GRADE assessment of included studies. We analysed results in adults and children separately. We performed analyses according to the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
For this update, we identified 548 unique records. We included three additional RCTs: two paediatric and one adult. Therefore, we included a total of 13 eligible RCTs (five paediatric and eight adult). The studies enrolled 1252 children with leukaemia, lymphoma or a solid tumour and 1269 participants, who were mostly diagnosed with breast cancer. In adults, moderate-quality evidence showed that there was less clinical heart failure with the use of dexrazoxane (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.11 to 0.43; 7 studies, 1221 adults). In children, we identified no difference in clinical heart failure risk between treatment groups (RR 0.20, 95% CI 0.01 to 4.19; 3 studies, 885 children; low-quality evidence). In three paediatric studies assessing cardiomyopathy/heart failure as the primary cause of death, none of the children had this outcome (1008 children, low-quality evidence). In the adult studies, different definitions for subclinical myocardial dysfunction and clinical heart failure combined were used, but pooled analyses were possible: there was a benefit in favour of the use of dexrazoxane (RR 0.37, 95% CI 0.24 to 0.56; 3 studies, 417 adults and RR 0.46, 95% CI 0.33 to 0.66; 2 studies, 534 adults, respectively, moderate-quality evidence). In the paediatric studies, definitions of subclinical myocardial dysfunction and clinical heart failure combined were incomparable, making pooling impossible. One paediatric study showed a benefit in favour of dexrazoxane (RR 0.33, 95% CI 0.13 to 0.85; 33 children; low-quality evidence), whereas another study showed no difference between treatment groups (Fischer exact P = 0.12; 537 children; very low-quality evidence). Overall survival (OS) was reported in adults and overall mortality in children. The meta-analyses of both outcomes showed no difference between treatment groups (hazard ratio (HR) 1.04, 95% 0.88 to 1.23; 4 studies; moderate-quality evidence; and HR 1.01, 95% CI 0.72 to 1.42; 3 studies, 1008 children; low-quality evidence, respectively). Progression-free survival (PFS) was only reported in adults. We subdivided PFS into three analyses based on the comparability of definitions, and identified a longer PFS in favour of dexrazoxane in one study (HR 0.62, 95% CI 0.43 to 0.90; 164 adults; low-quality evidence). There was no difference between treatment groups in the other two analyses (HR 0.95, 95% CI 0.64 to 1.40; 1 study; low-quality evidence; and HR 1.18, 95% CI 0.97 to 1.43; 2 studies; moderate-quality evidence, respectively). In adults, there was no difference in tumour response rate between treatment groups (RR 0.91, 95% CI 0.79 to 1.04; 6 studies, 956 adults; moderate-quality evidence). We subdivided tumour response rate in children into two analyses based on the comparability of definitions, and identified no difference between treatment groups (RR 1.01, 95% CI 0.95 to 1.07; 1 study, 206 children; very low-quality evidence; and RR 0.92, 95% CI 0.84 to 1.01; 1 study, 200 children; low-quality evidence, respectively). The occurrence of secondary malignant neoplasms (SMN) was only assessed in children. The available and worst-case analyses were identical and showed a difference in favour of the control group (RR 3.08, 95% CI 1.13 to 8.38; 3 studies, 1015 children; low-quality evidence). In the best-case analysis, the direction of effect was the same, but there was no difference between treatment groups (RR 2.51, 95% CI 0.96 to 6.53; 4 studies, 1220 children; low-quality evidence). For other adverse effects, results also varied. None of the studies evaluated quality of life. If not reported, the number of participants for an analysis was unclear.
AUTHORS' CONCLUSIONS
Our meta-analyses showed the efficacy of dexrazoxane in preventing or reducing cardiotoxicity in adults treated with anthracyclines. In children, there was a difference between treatment groups for one cardiac outcome (i.e. for one of the definitions used for clinical heart failure and subclinical myocardial dysfunction combined) in favour of dexrazoxane. In adults, no evidence of a negative effect on tumour response rate, OS and PFS was identified; and in children, no evidence of a negative effect on tumour response rate and overall mortality was identified. The results for adverse effects varied. In children, dexrazoxane may be associated with a higher risk of SMN; in adults this was not addressed. In adults, the quality of the evidence ranged between moderate and low; in children, it ranged between low and very low. Before definitive conclusions on the use of dexrazoxane can be made, especially in children, more high-quality research is needed. We conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in children and adults with cancer who are treated with anthracyclines. However, clinicians and patients should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects, including SMN, for each individual. For children, the International Late Effects of Childhood Cancer Guideline Harmonization Group has developed a clinical practice guideline.
Topics: Adult; Anthracyclines; Antibiotics, Antineoplastic; Cardiotonic Agents; Cardiotoxicity; Child; Dexrazoxane; Heart Failure; Humans; Leukemia, Myeloid, Acute; Polyketides; Systematic Reviews as Topic
PubMed: 36162822
DOI: 10.1002/14651858.CD014638.pub2 -
Pharmaceutics Mar 2022Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic... (Review)
Review
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by remarkable toxicity and great variability in response to treatment. Plenteous pharmacogenetic studies have already been published for classical therapies, such as cytarabine or anthracyclines, but such studies remain scarce for newer drugs. There is evidence of the relevance of polymorphisms in response to treatment, although most studies have limitations in terms of cohort size or standardization of results. The different responses associated with genetic variability include both increased drug efficacy and toxicity and decreased response or resistance to treatment. A broad pharmacogenetic understanding may be useful in the design of dosing strategies and treatment guidelines. The aim of this study is to perform a review of the available publications and evidence related to the pharmacogenetics of AML, compiling those studies that may be useful in optimizing drug administration.
PubMed: 35335935
DOI: 10.3390/pharmaceutics14030559 -
Cancers Oct 2022The association between hepcidin and acute leukemia (AL) or hematopoietic cell transplantation (HCT) in children and adults remains obscure. We aimed to assess this... (Review)
Review
OBJECTIVES
The association between hepcidin and acute leukemia (AL) or hematopoietic cell transplantation (HCT) in children and adults remains obscure. We aimed to assess this potential relationship through a systematic review of observational studies.
METHODS
An electronic search of three databases, including PubMed, Scopus, and Web of Science Core Collection, was performed up to 31 March 2022. Two independent reviewers assessed the search results according to predetermined inclusion and exclusion criteria, following PRISMA guidelines.
RESULTS
Of the 3607 titles identified, 13 studies published between 2008 and 2021 met the inclusion criteria. Most studies included a moderate number of participants and controls and used enzyme-linked immunosorbent assay (ELISA) to determine serum hepcidin levels. The principal findings: (1) serum hepcidin levels in patients with AL or undergoing HCT are increased compared to controls, regardless of the patient's age and the phase of disease treatment; (2) AL therapy and HCT significantly influence serum hepcidin levels; (3) serum hepcidin may predict a worse outcome in patients with AL and post-HCT.
CONCLUSIONS
This systematic review provides an overview of observational studies that deal with the association of hepcidin with AL and HCT. Although disturbances in iron metabolism are common in AL and HCT, and hepcidin seems to play a cardinal role in their modulation, more extensive research is needed.
PubMed: 36230859
DOI: 10.3390/cancers14194936 -
American Journal of Translational... 2023To systematically assess the efficacy of hematopoietic stem cell transplantation (HSCT) and bone marrow transplantation (BMT) in treating acute myeloid leukemia (AML). (Review)
Review
OBJECTIVE
To systematically assess the efficacy of hematopoietic stem cell transplantation (HSCT) and bone marrow transplantation (BMT) in treating acute myeloid leukemia (AML).
METHODS
PubMed, EMBASE, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure (CNKI), China VIP database, Wanfang database and China Biomedical Literature Database (CBM) were searched for case-control trials of bone marrow HSCT and peripheral HSCT (PHSCT) for treating AML. Two independent researchers extracted the data between January 2000 and May 2022. Each retrieved article was assessed according to the bias risk defined in Cochrane Handbook 5.3, and data were analyzed by meta-analysis using RevMan5.3.
RESULTS
Through computer database retrieval, 7 clinical controlled studies were included, with 1280 samples. A meta-analysis was conducted on the survival rates. The PHSCT and the BMT groups showed no noticeable difference in overall survival (OS) and disease-free survival (DFS) rates (P>0.05). The incidence of acute graft-versus-host disease (GVHD) and chronic GVHD in the BMT group was noticeably lower (P<0.05). The disease recurrence rate in tthe BMT group was lower (P<0.05), but no noticeable differences were found in recurrence-related mortality (P>0.05). Furthermore, there was also no noticeable difference in non-relapse-related mortality (P>0.05). Funnel charts were drawn on the basis of OS rate, DFS rate, incidences of acute GVHD and chronic GVHD, and recurrence. Afterwards publication bias analysis was carried out. Symmetry presented in the majority of the funnel charts and asymmetry was seen in a few, suggesting possible publication bias in the selected literature because of the small sample and the heterogeneity.
CONCLUSION
BMT can be used as an effective treatment for patients with AML, because it can reduce the recurrence rate and the incidence of complications while ensuring a curative effect, suggesting that BMT is worth popularizing in the clinic. Longer follow-up studies are needed to provide more support for the clinical application of BMT in AML patients.
PubMed: 36777836
DOI: No ID Found -
Cancers Aug 2022MicroRNAs (miRNAs) have been implicated in childhood acute lymphoblastic leukemia (ALL) pathogenesis. We performed a systematic review and meta-analysis of miRNA... (Review)
Review
MicroRNAs (miRNAs) have been implicated in childhood acute lymphoblastic leukemia (ALL) pathogenesis. We performed a systematic review and meta-analysis of miRNA single-nucleotide polymorphisms (SNPs) in childhood ALL compared with healthy children, which revealed (i) that the CC genotype of rs4938723 in pri-miR-34b/c and the TT genotype of rs543412 in miR-100 confer protection against ALL occurrence in children; (ii) no significant association between rs2910164 genotypes in miR-146a and childhood ALL; and (iii) SNPs in DROSHA, miR-449b, miR-938, miR-3117 and miR-3689d-2 genes seem to be associated with susceptibility to B-ALL in childhood. A review of published literature on differential expression of miRNAs in children with ALL compared with controls revealed a significant upregulation of the miR-128 family, miR-130b, miR-155, miR-181 family, miR-210, miR-222, miR-363 and miR-708, along with significant downregulation of miR-143 and miR-148a, seem to have a definite role in childhood ALL development. MicroRNA signatures among childhood ALL subtypes, along with differential miRNA expression patterns between B-ALL and T-ALL cases, were scrutinized. With respect to T-ALL pediatric cases, we reanalyzed RNA-seq datasets with a robust and sensitive pipeline and confirmed the significant differential expression of hsa-miR-16-5p, hsa-miR-19b-3p, hsa-miR-92a-2-5p, hsa-miR-128-3p (ranked first), hsa-miR-130b-3p and -5p, hsa-miR-181a-5p, -2-3p and -3p, hsa-miR-181b-5p and -3p, hsa-miR-145-5p and hsa-miR-574-3p, as described in the literature, along with novel identified miRNAs.
PubMed: 36010971
DOI: 10.3390/cancers14163976