-
Experimental Hematology & Oncology 2020The DNA hypomethylating agents (HMAs) decitabine and azacitidine have been widely used in the management of elderly patients with acute myeloid leukemia (AML). However,... (Review)
Review
BACKGROUND
The DNA hypomethylating agents (HMAs) decitabine and azacitidine have been widely used in the management of elderly patients with acute myeloid leukemia (AML). However, no direct clinical trials have been carried out to compare the two agents. A systematic review and network meta-analysis were performed to indirectly compare the efficacy and safety of decitabine and azacitidine in elderly AML patients.
METHODS
We systematically searched PubMed, Medline, Web of Science, Embase and Cochrane Library through May 14, 2019. Randomized controlled trials on elderly AML patients comparing the efficacy and safety between decitabine and azacitidine, or comparing one of HMAs to standard supportive care or placebo were selected. The major outcomes of interest were performed with methods of adjusted indirect comparison and the fixed effect model.
RESULTS
Only three RCTs including a total number of 1086 patients were identified. Direct comparisons showed that azacitidine significantly reduced mortality (RR = 0.90, 95% CI 0.83-0.97) while decitabine was not significantly associated with lower mortality (RR = 0.97, 95% CI 0.92-1.02) compared to the conventional care regimen (CCR). In addition, for the indirect method, azacitidine significantly reduced mortality compared to decitabine (RR = 0.83 95% CI 0.77-0.90) and was more likely to improve complete response (CR) (RR = 1.66, 95% CI 1.17-2.35, low-certainty evidence). No statistical significance was found for the other studied outcomes.
CONCLUSIONS
Compared to CCR, decitabine and azacitidine can promote studied outcomes in elderly AML patients. Indirect evidence with low certainty was used to compare these two agents. The superiority of either agent cannot be confirmed, and head-to-head clinical trials are still required.
PubMed: 32190414
DOI: 10.1186/s40164-020-00160-8 -
Cureus Jun 2020Chronic myeloid leukemia (CML) represents a common condition in the spectrum of myeloproliferative disorders (MPD). It classically exhibits leukocytosis, but rarely... (Review)
Review
Chronic myeloid leukemia (CML) represents a common condition in the spectrum of myeloproliferative disorders (MPD). It classically exhibits leukocytosis, but rarely presents with isolated thrombocytosis. This paper is designed to review the clinicopathologic features, treatment, and outcomes of patients with CML who present with isolated thrombocytosis. We searched PubMed, MEDLINE®, ScienceDirect, and Scopus for English-language articles about case series and case reports for the period 2000-2020 with the terms "chronic myeloid leukemia" and "thrombocytosis" and pooled them with a case from our institution. Cases were also incorporated from the reference list and screened for inclusion. A total of 20 cases were included in the final cohort. The male-to-female ratio was 1:1.86. The mean age of the patients at the time of initial diagnosis was 40.5 years (range: 9-77 years). Out of 17 cases with available data, seven (41%) were asymptomatic and found to have thrombocytosis incidentally upon routine blood work. Five cases (29.4%) either had a history of thrombotic events or presented with severe thrombotic complications, including ischemic cerebrovascular accidents (CVA), myocardial infarction (MI), pulmonary embolism (PE), and/or miscarriages. Four cases (23.5%) had more than one symptom at presentation, including headache, syncope, and bruising. The average platelet count was 1,923 × 10/L (range: 584-8,688 × 10/L), and one case (5%) had anemia. The bone marrow (BM) examination showed normal cellularity and normal myeloid to erythroid (M/E) ratio in seven (50%) and 11 (84.6%) out of the 14 and 13 cases with reported data, respectively. Moreover, megakaryocytes in the BM were small in 10 cases (71.4%), pleomorphic in three cases (21.4%), and dysplastic in one case (7.1%). Accurate differentiation among MPD subtypes and the exclusion of CML is critical in reaching a proper diagnosis to decide on proper therapy and eventually modify outcomes. Prompt evaluation for the precise diagnosis of patients presenting with isolated marked thrombocytosis will help expedite their diagnosis and initiation of a specific tyrosine kinase inhibitor (TKI) therapy, thereby promptly inducing remission, preventing thrombotic complications, and avoiding adverse drug events, which would eventually improve outcomes.
PubMed: 32596094
DOI: 10.7759/cureus.8788 -
BMC Cancer Jun 2023Whether isocitrate dehydrogenase 2 (IDH2) R140 and R172 gene mutations affect the prognosis of patients with acute myeloid leukemia (AML) is controversial. Here, we... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whether isocitrate dehydrogenase 2 (IDH2) R140 and R172 gene mutations affect the prognosis of patients with acute myeloid leukemia (AML) is controversial. Here, we performed a meta-analysis to assess their prognostic value.
METHODS
Eligible studies were systematically searched from PubMed, Embase, the Cochrane Library and Chinese databases up to June 1, 2022. We extracted the hazard ratios (HRs) and their 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) to carry out a meta-analysis by a fixed effect model or random effect model according to the heterogeneity between studies.
RESULTS
A total of 12725 AML patients from 11 studies were included in this meta-analysis, of which 1111 (8.7%) and 305 (2.4%) had IDH2R140 and IDH2R172 mutations, respectively. The results revealed that both IDH2R140 and IDH2R172 mutations had no significant effect on OS (IDH2R140: HR = 0.92, 95% CI: 0.77-1.10, P = 0.365; IDH2R172: HR = 0.91, 95% CI: 0.65-1.28, P = 0.590) or PFS (IDH2R140: HR = 1.02, 95% CI: 0.75-1.40, P = 0.881; IDH2R172: HR = 1.31, 95% CI: 0.78-2.22, P = 0.306) in AML patients. Subgroup analysis of AML patients with IDH2R140 mutation revealed that studies from the USA (HR = 0.60, 95% CI: 0.41-0.89, P = 0.010) and ≤ 50 years old (HR = 0.63, 95% CI: 0.50-0.80, P = 0.000) had longer OS. However, studies from Sweden (HR = 1.94, 95% CI: 1.07-3.53, P = 0.030) had shorter OS. Meanwhile, subgroup analysis of AML patients with IDH2R172 mutation showed that studies from Germany/Austria (HR = 0.76, 95% CI: 0.61-0.94, P = 0.012) and from Sweden (HR = 0.22, 95% CI: 0.07-0.74, P = 0.014) had longer OS, whereas studies from the UK (HR = 1.49, 95% CI: 1.13-1.96, P = 0.005) and studies with nonmultivariate analysis of data type (HR = 1.35, 95% CI: 1.06-1.73, P = 0.014) had shorter OS. In addition, our study also found that patients with IDH2R140 mutation had significantly longer OS (HR = 0.61, 95% CI: 0.39-0.96, P = 0.032) and PFS (HR = 0.31, 95% CI: 0.18-0.52, P = 0.021) than patients with IDH2R172 mutation, despite some degree of heterogeneity.
CONCLUSIONS
This meta-analysis demonstrates that IDH2R140 mutation improves OS in younger AML patients and that the prognostic value of IDH2R172 mutation is significantly heterogeneous. Differences in region and data type have a significant impact on the prognosis of AML patients with IDH2R140 and/or IDH2R172 mutations. Additionally, AML patients with IDH2R140 mutation have a better prognosis than those with IDH2R172 mutations, albeit with some degree of heterogeneity.
Topics: Humans; Middle Aged; Prognosis; Disease-Free Survival; Leukemia, Myeloid, Acute; Mutation; Progression-Free Survival
PubMed: 37291515
DOI: 10.1186/s12885-023-11034-7 -
Transplantation and Cellular Therapy Nov 2022Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only known treatment modality that can offer the possibility of cure for acute myeloid leukemia... (Meta-Analysis)
Meta-Analysis
Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only known treatment modality that can offer the possibility of cure for acute myeloid leukemia (AML). Unfortunately, relapse and disease progression still occur in more than one third of cases even when patients are allografted in complete hematologic remission (CR). Treatment of AML relapsing after a first allo-HCT is particularly challenging. A second allo-HCT is offered to patients considered fit for the procedure, but reported outcomes have been conflicting. To perform a systematic review and meta-analysis to assess the totality of evidence on the role of a second allo-HCT in patients with AML, we performed a comprehensive literature search using PUBMED/MEDLINE and EMBASE on August 25, 2021, and extracted clinical outcome data relating to benefits (CR, overall survival [OS], and progression-free/disease-free survival [PFS/DFS]) and harms (acute and chronic graft-versus-host disease, non-relapse mortality [NRM], and relapse). The search identified 821 studies. Only 20 studies (n = 2772 patients) met our inclusion criteria. A second allo-HCT resulted in pooled CR, OS, PFS/DFS, NRM and relapse rates of 67%, 34%, 30%, 27%, and 51%, respectively. OS was 2-fold higher when the second allo-HCT was performed in CR (38% versus 17%) and 3-fold higher in patients who had a later relapse from the first allo-HCT (34% versus 10%). There was no apparent difference in pooled OS (hazard ratio = 1.01; 95% confidence interval, 0.78-1.31; P = .94) whether the same original donor or a different one was used. Notwithstanding several limitations apart from the high heterogeneity among included studies, this analysis shows that a second allo-HCT is a reasonable treatment option for relapsed AML. The procedure appears to be more effective when performed in CR and in patients who had a later relapse from the first allo-HCT. The high pooled relapse rates exceeding 50%, even when receiving the second allo-HCT in CR is worrisome and emphasizes the need to incorporate new therapies whether as post-transplantation maintenance or consolidation to mitigate relapse risk. This analysis was limited to patients receiving a second allo-HCT for the sole purpose of treating AML relapse. Accordingly, we caution against extrapolating these findings to other indications such as treatment of graft failure, poor graft function, or mixed donor chimerism.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Leukemia, Myeloid, Acute; Transplantation, Homologous; Graft vs Host Disease; Remission Induction; Recurrence
PubMed: 35970301
DOI: 10.1016/j.jtct.2022.08.008 -
American Journal of Blood Research 2021Acute myeloid leukemia (AML) is a rapidly progressive hematological malignancy that is difficult to cure. The prognosis is poor and treatment options are limited in case... (Review)
Review
Acute myeloid leukemia (AML) is a rapidly progressive hematological malignancy that is difficult to cure. The prognosis is poor and treatment options are limited in case of relapse. A comprehensive assessment of current disease burden and the clinical efficacy of non-intensive therapies in this population are lacking. We conducted two systematic literature reviews (SLRs). The first SLR (disease burden) included observational studies reporting the incidence and economic and humanistic burden of relapsed/refractory (RR) AML. The second SLR (clinical efficacy) included clinical trials (phase II or later) reporting remission rates (complete remission [CR] or CR with incomplete hematologic recovery [CRi]) and median overall survival (mOS) in patients with RR AML or patients with AML who are ineligible for intensive chemotherapy. For both SLRs, MEDLINE/Embase were searched from January 1, 2008 to January 31, 2020. Clinical trial registries were also searched for the clinical efficacy SLR. After screening, two independent reviewers determined the eligibility for inclusion in the SLRs based on full-text articles. The disease burden SLR identified 130 observational studies. The median cumulative incidence of relapse was 29.4% after stem cell transplant and 46.8% after induction chemotherapy. Total per-patient-per-month costs were $28,148-$29,322; costs and health care resource use were typically higher for RR versus non-RR patients. Patients with RR AML had worse health-related quality of life (HRQoL) scores than patients with AML across multiple instruments, and lower health utility values versus other AML health states (i.e. newly diagnosed, remission, consolidation, and maintenance therapy). The clinical efficacy SLR identified 50 trials (66 total trial arms). CR/CRi rates and mOS have remained relatively stable and low over the last 2 decades. Across all arms, the median rate of CR/CRi was 18.3% and mOS was 6.2 months. In conclusion, a substantial proportion of patients with AML will develop RR AML, which is associated with significant humanistic and economic burden. Existing treatments offer limited efficacy, highlighting the need for more effective non-intensive treatment options.
PubMed: 34540343
DOI: No ID Found -
Hematology (Amsterdam, Netherlands) Dec 2022Compared with the 3 + 7 regimen, the addition of gemtuzumab ozogamicin (GO) has improved survival in patients with acute myeloid leukemia (AML). We conducted a... (Meta-Analysis)
Meta-Analysis
Compared with the 3 + 7 regimen, the addition of gemtuzumab ozogamicin (GO) has improved survival in patients with acute myeloid leukemia (AML). We conducted a systematic review and meta-analysis to examine the overall efficacy and safety of GO in combination with conventional chemotherapy regimens in patients with AML. We searched several databases (MEDLINE, Embase, Web of Science and Cochrane Library). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS); odds ratios (ORs) with 95% CIs were calculated for the other outcomes. Ten records involving 11 randomized controlled trials (RCTs) met the inclusion criteria. GO plus induction chemotherapy significantly increased RFS (HR: 0.84, 95% CI: 0.73-0.98), decreased the incidence of relapse (OR: 0.78, 95% CI: 0.68-0.91) and resistant disease (OR: 0.72, 95% CI: 0.61-0.84), and had no significant effect on the rate of complete remission (CR) with or without incomplete platelet recovery (OR: 1.21, 95% CI: 0.94-1.55), 30-day mortality (OR: 1.25, 95% CI: 0.99-1.57). Subgroup analysis showed significant OS benefits for patients with favorable cytogenetic (HR: 0.50, 95% CI: 0.28-0.89) or given GO at induction stage (HR: 0.91, 95% CI: 0.84-1.00). Compared with other dosing schedule groups, 3 mg/m fractionated schedule had a greater RFS benefit (HR: 0.52, 95% CI: 0.36-0.76) and lower relapse risk (OR: 0.48, 95% CI: 0.28-0.84). Adding low-dose GO to induction or both induction and post-remission chemotherapy has considerable efficacy and unequivocal safety for newly diagnosed adult AML.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Disease Management; Drug Resistance, Neoplasm; Gemtuzumab; Humans; Leukemia, Myeloid, Acute; Prognosis; Proportional Hazards Models; Recurrence; Treatment Outcome
PubMed: 34957930
DOI: 10.1080/16078454.2021.2013410 -
Medicine Sep 2022This analysis aimed to assess the effect of decitabine combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treating recurrent and refractory... (Meta-Analysis)
Meta-Analysis
Efficacy of decitabine combined with allogeneic hematopoietic stem cell transplantation in the treatment of recurrent and refractory acute myeloid leukemia (AML): A systematic review and meta-analysis.
BACKGROUND
This analysis aimed to assess the effect of decitabine combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treating recurrent and refractory acute myeloid leukemia.
METHOD
The present analysis was carried out according to the principles of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline statement. Web of Science, Embase, PubMed, The Cochrane Library, CNKI, VIP, and WanFang Data databases were searched for trials published from their corresponding inception to September 13, 2021. Retrospective research or published randomized controlled trials in Chinese or English were ruled out. The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database scale. Mean differences with 95% confidence intervals were used to analyze continuous data. The I2 test was used to determine heterogeneity, and the meta-analysis was conducted using Revman 5.4.
RESULTS
Eight studies including 795 participants in total were identified. Decitabine and allo-HSCT showed significant reductions in recurrence after transplantation (odds ratio [OR] = 0.29, 95% confidence interval [CI] (0.17, 0.50), P < .00001), leukemia-free survival (OR = 2.17, 95% CI (1.47, 3.21), P < .0001), graft related death (OR = 0.50, 95% CI (0.25, 0.98), P = .04), and significant improvements in complete remission (OR = 0.39, 95% CI = 0.23-0.68, P = .0007) and partial remission (OR = 0.46, 95%CI = 0.27-0.78, P = .004). The median follow-up time, acute graft-versus-host disease, and no remission had no significant difference between treatment and control groups (the median follow-up time: OR = -1.76, 95% CI (-6.28, 2.76), P = .45; acute graft-versus-host disease: OR = 0.72, 95% CI (0.50, 1.03), P = .08; no remission: OR = 3.19, 95%CI = 2.06-4.94, P = .05). Overall, the magnitude of the effect was found to be in the small to moderate range.
CONCLUSION
Decitabine combined with allo-HSCT can obtain lower recurrence risk and longer disease-free survival time, and improve the prognosis of patients. The safety is relatively stable. Due to the varying quality level of the included studies, the validation of multiple high-quality studies still needs improvement.
Topics: Decitabine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Retrospective Studies
PubMed: 36123842
DOI: 10.1097/MD.0000000000030644 -
Cancer Epidemiology Aug 2014The association between alcohol and leukemia risk has been addressed in several studies in the past two decades, but results have been inconsistent. Therefore, we... (Meta-Analysis)
Meta-Analysis Review
The association between alcohol and leukemia risk has been addressed in several studies in the past two decades, but results have been inconsistent. Therefore, we conducted a systematic review and meta-analysis to quantify the dose-risk relation. Through the literature search up to August 2013, we identified 18 studies, 10 case-control and 8 cohorts, carried out in a total of 7142 leukemia cases. We derived pooled meta-analytic estimates using random-effects models, taking into account the correlation between estimates, and we performed a dose-risk analysis using a class of nonlinear random-effects meta-regression models. Stratified analyses were carried out on leukemia subtypes and groups, in order to identify possible etiologic differences. Compared with nondrinkers, the relative risks (RRs) for all leukemia were 0.94 [95% confidence interval (CI), 0.85-1.03], 0.90 (95% CI, 0.80-1.01) and 0.91 (95% CI, 0.81-1.02) for any, light (≤ 1 drink/day) and moderate to heavy (>1 drink/day) alcohol drinking, respectively. The summary RRs for any alcohol drinking were 1.47 (95% CI, 0.47-4.62) for acute lymphoblastic leukemia, 0.94 (95% CI 0.77-1.15) for chronic lymphocytic leukemia, 1.02 (95% CI, 0.86-1.21) for acute myeloid leukemia and 0.93 (95% CI 0.75-1.14) for chronic myeloid leukemia. The subgroup analysis on geographical area for all leukemia combined showed RRs of 0.84 (95% CI, 0.76-0.93), 0.92 (95% CI, 0.83-1.01) and 1.32 (95% CI, 1.02-1.70) for studies conducted in America, Europe and Asia, respectively. We did not find an increased risk of leukemia among alcohol drinkers. If any, a modest favorable effect emerged for light alcohol drinking, with a model-based risk reduction of approximately 10% in regular drinkers.
Topics: Alcohol Drinking; Humans; Leukemia; Risk Factors
PubMed: 24986108
DOI: 10.1016/j.canep.2014.06.001 -
Clinical Infectious Diseases : An... Jun 2020Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic...
BACKGROUND
Bacteremia and other invasive bacterial infections are common among children with cancer receiving intensive chemotherapy and in pediatric recipients of hematopoietic stem cell transplantation (HSCT). Systemic antibacterial prophylaxis is one approach that can be used to reduce the risk of these infections. Our purpose was to develop a clinical practice guideline (CPG) for systemic antibacterial prophylaxis administration in pediatric patients with cancer and those undergoing HSCT.
METHODS
An international and multidisciplinary panel was convened with representation from pediatric hematology/oncology and HSCT, pediatric infectious diseases (including antibiotic stewardship), nursing, pharmacy, a patient advocate, and a CPG methodologist. The panel used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to generate recommendations based on the results of a systematic review of the literature.
RESULTS
The systematic review identified 114 eligible randomized trials of antibiotic prophylaxis. The panel made a weak recommendation for systemic antibacterial prophylaxis for children receiving intensive chemotherapy for acute myeloid leukemia and relapsed acute lymphoblastic leukemia (ALL). Weak recommendations against the routine use of systemic antibacterial prophylaxis were made for children undergoing induction chemotherapy for ALL, autologous HSCT and allogeneic HSCT. A strong recommendation against its routine use was made for children whose therapy is not expected to result in prolonged severe neutropenia. If used, prophylaxis with levofloxacin was recommended during severe neutropenia.
CONCLUSIONS
We present a CPG for systemic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. Future research should evaluate the long-term effectiveness and adverse effects of prophylaxis.
Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Child; Hematopoietic Stem Cell Transplantation; Humans; Levofloxacin; Neoplasms
PubMed: 31676904
DOI: 10.1093/cid/ciz1082 -
Journal of Clinical Medicine Sep 2019Reduced-intensity conditioning (RIC) regimens are established options for hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML)... (Review)
Review
Reduced-intensity conditioning (RIC) regimens are established options for hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the efficacy of RIC regimens for patients with high-risk disease is limited. The addition of a fludarabine, amsacrine, and cytarabine (FLAMSA)-sequential conditioning regimen was introduced for patients with high-risk MDS and AML to combine a high anti-leukemic activity with the advantages of RIC. The current systematic literature review and meta-analysis was conducted with the aim of identifying all cohort studies of patients with AML and/or MDS who received FLAMSA-RIC to determine its efficacy and toxicity. Out of 3044 retrieved articles, 12 published studies with 2395 overall patients (18.1-76.0 years; 96.8% AML and 3.2% MDS; follow-up duration of 0.7-145 months; 50.3% had active AML disease before HSCT) met the eligibility criteria and were included in the meta-analysis. In the pooled analysis, the 1- and 3-year overall survival (OS) rates were 59.6% (95% confidence interval (CI), 47.9-70.2%) and 40.2% (95% CI, 28.0-53.7%), respectively. The pooled 3-year OS rate of the patients who achieved CR1 or CR2 prior to HSCT was 60.1% (95% CI, 55.1-64.8%) and the percentage of those with relapse or refractory disease was 27.8% (95% CI, 23.3-32.8%). The pooled 3-year leukemia-free survival (LFS) rate was 39.3% (95% CI, 26.4-53.9%). Approximately 29% of the patients suffered from grades 2-4 acute graft-versus-host disease (GVHD), while 35.6% had chronic GVHD. The pooled 1- and 3-year non-relapse mortality (NRM) rates were 17.9% (95% CI, 16.1-19.8%) and 21.1% (95% CI, 18.8-23.7%), respectively. Our data indicates that the FLAMSA-RIC regimen is an effective and well-tolerated regimen for HSCT in patients with high-risk AML and MDS.
PubMed: 31514339
DOI: 10.3390/jcm8091437