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Pharmacological Research Apr 2023Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell... (Meta-Analysis)
Meta-Analysis Review
Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.
Topics: Humans; Adult; Receptors, Chimeric Antigen; T-Lymphocytes; Hematologic Neoplasms; Chronic Disease; Multiple Myeloma; Recurrence; Cell- and Tissue-Based Therapy
PubMed: 36963592
DOI: 10.1016/j.phrs.2023.106742 -
Journal of Hematology & Oncology Mar 2023TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line... (Meta-Analysis)
Meta-Analysis
BACKGROUND
TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA).
METHODS
We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies were included that reported on complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), event-free survival (EFS), duration of response (DoR), and overall response rate (ORR) among patients with TP53m AML receiving first-line treatment with IC, HMA, or VEN + HMA.
RESULTS
Searches of EMBASE and MEDLINE identified 3006 abstracts, and 17 publications describing 12 studies met the inclusion criteria. Random-effects models were used to pool response rates, and time-related outcomes were analyzed with the median of medians method. IC was associated with the greatest CR rate of 43%, and CR rates were 33% for VEN + HMA and 13% for HMA. Rates of CR/CRi were comparable for IC (46%) and VEN + HMA (49%) but were lower for HMA (13%). Median OS was uniformly poor across treatments: IC, 6.5 months; VEN + HMA, 6.2 months; and HMA, 6.1 months. For IC, the EFS estimate was 3.7 months; EFS was not reported for VEN + HMA or HMA. The ORR was 41% for IC, 65% for VEN + HMA, and 47% for HMA. DoR was 3.5 months for IC, 5.0 months for VEN + HMA, and was not reported for HMA.
CONCLUSIONS
Despite improved responses seen with IC and VEN + HMA compared to HMA, survival was uniformly poor, and clinical benefits were limited across all treatments for patients with newly diagnosed, treatment-naïve TP53m AML, demonstrating a significant need for improved treatment for this difficult-to-treat population.
Topics: Humans; Retrospective Studies; Treatment Outcome; Leukemia, Myeloid, Acute; Progression-Free Survival; Mutation; Tumor Suppressor Protein p53; Observational Studies as Topic
PubMed: 36879351
DOI: 10.1186/s13045-023-01417-5 -
Frontiers in Oncology 2023Fms-like tyrosine kinase 3 (FLT3) gene mutations occur in approximately 30% of all patients with acute myeloid leukemia (AML). Internal tandem duplication (ITD) in the...
BACKGROUND
Fms-like tyrosine kinase 3 (FLT3) gene mutations occur in approximately 30% of all patients with acute myeloid leukemia (AML). Internal tandem duplication (ITD) in the juxtamembrane domain and point mutations within the tyrosine kinase domain (TKD) are two distinct types of FLT3 mutations. FLT3-ITD has been determined as an independent poor prognostic factor, but the prognostic impact of potentially metabolically related FLT3-TKD remains controversial. Hence, we performed a meta-analysis to investigate the prognostic significance of FLT3-TKD in patients with AML.
METHODS
A systematic retrieval of studies on FLT3-TKD in patients with AML was performed in PubMed, Embase, and Chinese National Knowledge Infrastructure databases on 30 September 2020. Hazard ratio (HR) and its 95% confidence intervals (95% CIs) were used to determine the effect size. Meta-regression model and subgroup analysis were used for heterogeneity analysis. Begg's and Egger's tests were performed to detect potential publication bias. The sensitivity analysis was performed to evaluate the stability of findings in meta-analysis.
RESULTS
Twenty prospective cohort studies (n = 10,970) on the prognostic effect of FLT3-TKD in AML were included: 9,744 subjects with FLT3-WT and 1,226 subjects with FLT3-TKD. We found that FLT3-TKD revealed no significant effect on disease-free survival (DFS) (HR = 1.12, 95% CI: 0.90-1.41) and overall survival (OS) (HR = 0.98, 95% CI: 0.76-1.27) in general. However, meta-regressions demonstrated that patient source contributed to the high heterogeneity observed in the prognosis of FLT3-TKD in AML. To be specific, FLT3-TKD represented a beneficial prognosis of DFS (HR = 0.56, 95% CI: 0.37-0.85) and OS (HR = 0.63, 95% CI: 0.42-0.95) for Asians, whereas it represented an adverse prognosis of DFS for Caucasians with AML (HR = 1.34, 95% CI: 1.07-1.67).
CONCLUSION
FLT3-TKD revealed no significant effects on DFS and OS of patients with AML, which is consistent with the controversial status nowadays. Patient source (Asians or Caucasians) can be partially explained the different effects of FLT3-TKD in the prognosis of patients with AML.
PubMed: 36874106
DOI: 10.3389/fonc.2023.1086846 -
Farmacia Hospitalaria : Organo Oficial... 2023Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative... (Review)
Review
OBJECTIVE
Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative studies that focus their results on how to accompany patients in the course of the disease over time. The objective of this review is to find out what are the expectations, information needs and experiences that determine adherence to treatment with tyrosine kinase inhibitors in patients with Chronic Myeloid Leukemia in qualitative research articles published in the scientific literature.
METHODS
A systematic review of qualitative research articles published between 2003-2021 was carried out in PubMed/Medline, Web of Science and Embase databases. Main keywords used were: "Leukemia, Myeloid" and "Qualitative Research". Articles on the acute phase or blast phase were excluded.
RESULTS
184 publications were located. After elimination of duplicates, 6 (3%) were included and 176 (97%) publications were excluded. Studies show that the illness is a turning point in patients' lives, and they develop their own strategies for managing the adverse effects. The factors that determine medication experiences with tyrosine kinase inhibitors should be addressed by implementing personalized strategies: this would result in early detection of problems, reinforce education at each stage and promote open discussion about complex causes underlying the treatment failure.
CONCLUSIONS
This systematic review provides evidence that implementation personalized strategies must be done to adress the factors that determine the illness experience with Chronic Myeloid Leukemia and receiving treatment with tyrosine kinase inhibitors.
Topics: Humans; Antineoplastic Agents; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Drug-Related Side Effects and Adverse Reactions; Fusion Proteins, bcr-abl
PubMed: 36870818
DOI: 10.1016/j.farma.2023.02.002 -
Blood Jun 2023The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear,... (Meta-Analysis)
Meta-Analysis
The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear, particularly in the context of modern intensive therapy. This systematic review and meta-analysis examined the impact of reducing the frequency of vincristine-steroid pulses during maintenance for pediatric patients newly diagnosed with B-cell ALL. Two authors reviewed all eligible studies identified through a comprehensive search, extracted data from 25 publications (12 513 patients), and assessed the risk of bias. We created historical and contemporary subgroups; the latter included trials providing both a version of Protocol III from the early Berlin-Frankfurt-Munster trials and eliminating routine prophylactic cranial radiation. Meta-analysis of event-free survival data suggested no benefit between more frequent or less frequent pulses in contemporary trials (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.85-1.09), which differed significantly from historical trials (HR, 0.79; 95% CI, 0.68-0.91; P = .04). We found no significant impact of reduced pulse frequency on overall survival or relapse risk. There was however increased odds of grade 3+ nonhepatic toxicity in the high-pulse frequency group (odds ratio, 1.31; 95% CI, 1.12-1.52). This systematic review suggests that the previous benefit conferred by frequent pulses of vincristine-steroids in maintenance therapy for pediatric B-cell ALL in historical trials no longer applies in contemporary trials but is associated with toxicity. These results will help guide the development of the next phase of clinical trials in the field of pediatric ALL and question the continued use of pulses in maintenance among patients not in clinical trials, particularly those experiencing toxicity.
Topics: Humans; Child; Vincristine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Adrenal Cortex Hormones; Steroids; Progression-Free Survival; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 36821772
DOI: 10.1182/blood.2022018899 -
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 -
Nanoscale Advances Jan 2023: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and... (Review)
Review
: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and release drugs selectively at desired sites using targeting or sensing strategies. As drug carriers, they could improve therapeutic outcomes while reducing systemic toxicity. They have also shown promise in improving leukemia detection and diagnosis. The study aimed to assess the potential of nanotechnology-based diagnostics and therapeutics in preclinical human acute lymphoblastic leukemia (h-ALL). : We performed a systematic search through April 2022. Articles written in English reporting the toxicity, efficacy, and safety of nanotechnology-based drugs (in the aspect of treatment) and specificity, limit of detection (LOD), or sensitivity (in the aspect of the detection field) in preclinical h-ALL were included. The study was performed according to PRISMA instructions. The methodological quality was assessed using the QualSyst tool. : A total of 63 original articles evaluating nanotechnology-based therapeutics and 35 original studies evaluating nanotechnology-based diagnostics were included in this review. As therapeutics in ALL, nanomaterials offer controlled release, targeting or sensing ligands, targeted gene therapy, photodynamic therapy and photothermic therapy, and reversal of multidrug-resistant ALL. A narrative synthesis of studies revealed that nanoparticles improve the ratio of efficacy to the toxicity of anti-leukemic drugs. They have also been developed as a vehicle for biomolecules (such as antibodies) that can help detect and monitor leukemic biomarkers. Therefore, nanomaterials can help with early diagnostics and personalized treatment of ALL. : This review discussed nanotechnology-based preclinical strategies to achieve ALL diagnosis and therapy advancement. This involves modern drug delivery apparatuses and detection devices for prompt and targeted disease diagnostics. Nonetheless, we are yet in the experimental phase and investigational stage in the field of nanomedicine, with many features remained to be discovered as well as numerous problems to be solved.
PubMed: 36756502
DOI: 10.1039/d2na00483f -
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 -
The Cochrane Database of Systematic... Feb 2023Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019... (Review)
Review
BACKGROUND
Convalescent plasma may reduce mortality in patients with viral respiratory diseases, and is being investigated as a potential therapy for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of this intervention is required.
OBJECTIVES
To assess the effectiveness and safety of convalescent plasma transfusion in the treatment of people with COVID-19; and to maintain the currency of the evidence using a living systematic review approach.
SEARCH METHODS
To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, Cochrane COVID-19 Study Register, and the Epistemonikos COVID-19 L*OVE Platform. We searched monthly until 03 March 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating convalescent plasma for COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess bias in included studies we used RoB 2. We used the GRADE approach to rate the certainty of evidence for the following outcomes: all-cause mortality at up to day 28, worsening and improvement of clinical status (for individuals with moderate to severe disease), hospital admission or death, COVID-19 symptoms resolution (for individuals with mild disease), quality of life, grade 3 or 4 adverse events, and serious adverse events.
MAIN RESULTS
In this fourth review update version, we included 33 RCTs with 24,861 participants, of whom 11,432 received convalescent plasma. Of these, nine studies are single-centre studies and 24 are multi-centre studies. Fourteen studies took place in America, eight in Europe, three in South-East Asia, two in Africa, two in western Pacific and three in eastern Mediterranean regions and one in multiple regions. We identified a further 49 ongoing studies evaluating convalescent plasma, and 33 studies reporting as being completed. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease 29 RCTs investigated the use of convalescent plasma for 22,728 participants with moderate to severe disease. 23 RCTs with 22,020 participants compared convalescent plasma to placebo or standard care alone, five compared to standard plasma and one compared to human immunoglobulin. We evaluate subgroups on detection of antibodies detection, symptom onset, country income groups and several co-morbidities in the full text. Convalescent plasma versus placebo or standard care alone Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.03; 220 per 1000; 21 RCTs, 19,021 participants; high-certainty evidence). It has little to no impact on need for invasive mechanical ventilation, or death (RR 1.03, 95% CI 0.97 to 1.11; 296 per 1000; 6 RCTs, 14,477 participants; high-certainty evidence) and has no impact on whether participants are discharged from hospital (RR 1.00, 95% CI 0.97 to 1.02; 665 per 1000; 6 RCTs, 12,721 participants; high-certainty evidence). Convalescent plasma may have little to no impact on quality of life (MD 1.00, 95% CI -2.14 to 4.14; 1 RCT, 483 participants; low-certainty evidence). Convalescent plasma may have little to no impact on the risk of grades 3 and 4 adverse events (RR 1.17, 95% CI 0.96 to 1.42; 212 per 1000; 6 RCTs, 2392 participants; low-certainty evidence). It has probably little to no effect on the risk of serious adverse events (RR 1.14, 95% CI 0.91 to 1.44; 135 per 1000; 6 RCTs, 3901 participants; moderate-certainty evidence). Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces or increases all-cause mortality at up to day 28 (RR 0.73, 95% CI 0.45 to 1.19; 129 per 1000; 4 RCTs, 484 participants; very low-certainty evidence). We are uncertain whether convalescent plasma reduces or increases the need for invasive mechanical ventilation, or death (RR 5.59, 95% CI 0.29 to 108.38; 311 per 1000; 1 study, 34 participants; very low-certainty evidence) and whether it reduces or increases the risk of serious adverse events (RR 0.80, 95% CI 0.55 to 1.15; 236 per 1000; 3 RCTs, 327 participants; very low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus human immunoglobulin Convalescent plasma may have little to no effect on all-cause mortality at up to day 28 (RR 1.07, 95% CI 0.76 to 1.50; 464 per 1000; 1 study, 190 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and mild disease We identified two RCTs reporting on 536 participants, comparing convalescent plasma to placebo or standard care alone, and two RCTs reporting on 1597 participants with mild disease, comparing convalescent plasma to standard plasma. Convalescent plasma versus placebo or standard care alone We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (odds ratio (OR) 0.36, 95% CI 0.09 to 1.46; 8 per 1000; 2 RCTs, 536 participants; very low-certainty evidence). It may have little to no effect on admission to hospital or death within 28 days (RR 1.05, 95% CI 0.60 to 1.84; 117 per 1000; 1 RCT, 376 participants; low-certainty evidence), on time to COVID-19 symptom resolution (hazard ratio (HR) 1.05, 95% CI 0.85 to 1.30; 483 per 1000; 1 RCT, 376 participants; low-certainty evidence), on the risk of grades 3 and 4 adverse events (RR 1.29, 95% CI 0.75 to 2.19; 144 per 1000; 1 RCT, 376 participants; low-certainty evidence) and the risk of serious adverse events (RR 1.14, 95% CI 0.66 to 1.94; 133 per 1000; 1 RCT, 376 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. Convalescent plasma versus standard plasma We are uncertain whether convalescent plasma reduces all-cause mortality at up to day 28 (OR 0.30, 95% CI 0.05 to 1.75; 2 per 1000; 2 RCTs, 1597 participants; very low-certainty evidence). It probably reduces admission to hospital or death within 28 days (RR 0.49, 95% CI 0.31 to 0.75; 36 per 1000; 2 RCTs, 1595 participants; moderate-certainty evidence). Convalescent plasma may have little to no effect on initial symptom resolution at up to day 28 (RR 1.12, 95% CI 0.98 to 1.27; 1 RCT, 416 participants; low-certainty evidence). We did not identify any study reporting other key outcomes. This is a living systematic review. We search monthly for new evidence and update the review when we identify relevant new evidence.
AUTHORS' CONCLUSIONS
For the comparison of convalescent plasma versus placebo or standard care alone, our certainty in the evidence that convalescent plasma for individuals with moderate to severe disease does not reduce mortality and has little to no impact on clinical improvement or worsening is high. It probably has little to no effect on SAEs. For individuals with mild disease, we have low certainty evidence for our primary outcomes. There are 49 ongoing studies, and 33 studies reported as complete in a trials registry. Publication of ongoing studies might resolve some of the uncertainties around convalescent plasma therapy for people with asymptomatic or mild disease.
Topics: Humans; COVID-19; COVID-19 Serotherapy; Immunoglobulins; SARS-CoV-2; Virus Diseases
PubMed: 36734509
DOI: 10.1002/14651858.CD013600.pub5 -
BMJ Open Feb 2023Whether -PTD has a prognostic impact on patients with acute myeloid leukaemia (AML) is controversial. Therefore, we conducted a meta-analysis to assess the prognostic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Whether -PTD has a prognostic impact on patients with acute myeloid leukaemia (AML) is controversial. Therefore, we conducted a meta-analysis to assess the prognostic value of -PTD in patients with AML.
METHODS
Eligibility criteria: we included studies concerning the prognostic value of -PTD in patients with AML.
INFORMATION SOURCES
Eligible studies were identified from PubMed, Embase, Medline, Web of Science, Cochrane Library and Chinese Biomedical Database. The systematic search date was 19 December 2020.Risk of bias: Sensitivity analysis was used to evaluate the stability and reliability of the combined results. Begg's and Egger's tests were used to assess the publication biases of studies.
SYNTHESIS OF RESULTS
We calculated the pooled HRs and their 95% CIs for overall survival (OS) and event-free survival (EFS) by Stata V.12 software.
RESULTS
Included studies: 18 studies covering 6499 patients were included.
SYNTHESIS OF RESULTS
-PTD conferred shorter OS in total population (HR=1.30, 95% CI 1.09 to 1.51). In the subgroup analysis, -PTD also resulted in shorter OS in karyotypically normal AML patients (HR=2.72, 95% CI 1.83 to 3.61) and old AML patients (HR=1.93, 95% CI 1.44 to 2.42). -PTD indicated no prognostic impact on EFS in total population (HR=1.26, 95% CI 0.86 to 1.66). However, in the sensitivity analysis, -PTD resulted in poor EFS (HR=1.34, 95% CI 1.04 to 1.64) when deleting the study with a relatively obvious effect on the combined HR. In the subgroup analysis, -PTD was associated with poor EFS in old AML patients (HR=1.64, 95% CI 1.25 to 2.03).
CONCLUSION
The findings indicated that -PTD had an adverse impact on the prognosis of patients with AML in the total population, and the conclusion can also be applied to some subgroups including karyotypically normal AML and old AML patients. -PTD may be a promising genetic biomarker in patients with AML in the future.
TRIAL REGISTRATION NUMBER
CRD42021227185.
Topics: Humans; Reproducibility of Results; Prognosis; Leukemia, Myeloid, Acute; Progression-Free Survival; Publication Bias
PubMed: 36725100
DOI: 10.1136/bmjopen-2022-062376