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Frontiers in Medicine 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing the coronavirus disease of 2019. The disease has caused millions of deaths since the...
INTRODUCTION
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing the coronavirus disease of 2019. The disease has caused millions of deaths since the first pandemic at the end of 2019. Immunocompromised individuals are more likely to develop severe infections. Numerous mutations had developed in SARS-CoV-2, resulting in strains (Alfa Beta Delta Omicron) with varying degrees of virulence disease severity. In CML (chronic myeloid leukemia) patients, there is a lot of controversy regarding the effect of the treatment on the patient outcome. Some reports suggested potential better outcomes among patients with CML, likely due to the use of TKI; other reports showed no significant effects. Additionally, it is unknown how much protection immunization provides for cancer patients.
METHOD
In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, we conducted a systematic review. Retrospective, prospective studies, reviews, case series, and case reports of chronic myeloid leukemia patients aged above 18 years who had SARS-CoV-2 infection were included. English literature was screened using PubMed, SCOPUS, and Google Scholar. Search terms include chronic myeloid leukemia, chronic myelogenous leukemia, and SARS-CoV-2 and Coronavirus disease 2019 (COVID-19). We searched the reference lists of the included studies for any new articles. The search included all articles published up to April 20, 2023. The review is registered in PROSPERO (registration number CRD42022326674).
RESULTS
We reviewed 33 articles of available published literature up to April 2023 and collected data from a total of 682 CML patients with COVID-19. Most patients were in the chronic phase, seven were in the accelerated phase, and eight were in the blast phase. Disease severity was classified according to WHO criteria. Mortality was seen in 45 patients, and there were no reports of thrombotic events. Two hundred seventy-seven patients were in the era before vaccination; among them, eight were in the intensive care unit (ICU), and mortality was 30 (11%). There were 405 patients after the era of vaccination; among them, death was reported in 15 (4%) patients and ICU in 13 patients.
LIMITATIONS AND CONCLUSION
The major limitation of this review is the lack of details about the use or hold of TKIs during SARS-CoV-2 infection. Additionally, after the appearance of the different variants of the SARS-CoV-2 virus, few studies mentioned the variant of the virus, which makes it difficult to compare the outcome of the other variants of the SARS-CoV-2 virus in patients with CML. Despite the limitations of the study, CML patients with COVID-19 have no significant increase in mortality compared to other hematological malignancy. Hematological cancers are associated with an increased risk of thrombosis, which is expected to increase in patients with COVID-19. However, patient with CML has not been reported to have a significant increase in thrombosis risk. The available data indicates that COVID-19's effect on patients with chronic myeloid leukemia (CML) still needs to be better understood due to the limited data.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php? RecordID:326674.
PubMed: 38327268
DOI: 10.3389/fmed.2023.1280271 -
Translational Cancer Research Apr 2022Acute myeloid leukemia (AML) is one of the main types of leukemia that threatens the life and health of patients. A large number of clinical studies have been conducted...
BACKGROUND
Acute myeloid leukemia (AML) is one of the main types of leukemia that threatens the life and health of patients. A large number of clinical studies have been conducted on the etiology of the disease. However, there are few evidence-based medical studies and no definitive treatment guidelines.
METHODS
Related articles were searched from Medline, Excerpta Medica Database (EMBASE), EBSCO, OVID, Chinese Biology Medicine Disc (CBMDISC), and Wanfang databases. The search time limit was from the establishment of the database to September 2021. The search terms were as follows: acute myeloid leukemia, AML, electromagnetic field, case-control study, cohort study, and risk factors. All literatures were included according to PICOS standards, and the risk of deviation and literature quality were assessed. RevMan 5.3 software was used for meta-analysis.
RESULTS
The 10 articles included were of high quality and low bias risk. The research results showed that compared with healthy people, among the risk factors for AML, family tumor history [risk ratio (RR) =0.98; 95% confidence interval (CI): (0.57, 1.69); Z=0.08; P=0.94] and the hepatitis B virus (HBV) infection rate [odds ratio (OR) =1.34; 95% CI: (0.57, 3.13); Z=0.68; P=0.50] showed no significant differences, but the hepatitis C virus (HCV) infection rate [OR =1.60; 95% CI: (1.17, 2.19); Z=2.92; P=0.003] and environmental exposure rate [OR =1.49; 95% CI: (1.01, 2.21); Z=2.02; P=0.04] increased significantly.
CONCLUSIONS
A total of 10 articles were included to analyze AML risk factors and related content. The results suggested that HCV infection and environmental exposure history such as home decoration were risk factors for AML.
PubMed: 35571664
DOI: 10.21037/tcr-22-27 -
Frontiers in Immunology 2023We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML).
METHODS
We performed a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.
RESULTS
We analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I=65%) and 65.2% (95% CI 0.36-0.91, I=57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I=77%), 3.9% (95% CI 0.00-0.19, I=22%), and 1.6% (95%CI 0.00-0.21, I=33%), respectively.
CONCLUSION
CAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.
Topics: Humans; Receptors, Chimeric Antigen; Antigens, CD19; Immunotherapy, Adoptive; Leukemia, Myeloid, Acute; Cell- and Tissue-Based Therapy
PubMed: 37168849
DOI: 10.3389/fimmu.2023.1152457 -
Clinical Epigenetics Jul 2023To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically evaluate the efficacy and safety of FDA-approved isocitrate dehydrogenase (IDH) inhibitors in the treatment of IDH-mutated acute myeloid leukemia (AML).
METHODS
We used R software to conduct a meta-analysis of prospective clinical trials of IDH inhibitors in the treatment of IDH-mutated AML published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to November 15th, 2022.
RESULTS
A total of 1109 IDH-mutated AML patients from 10 articles (11 cohorts) were included in our meta-analysis. The CR rate, ORR rate, 2-year survival (OS) rate and 2-year event-free survival (EFS) rate of newly diagnosed IDH-mutated AML (715 patients) were 47%, 65%, 45% and 29%, respectively. The CR rate, ORR rate, 2-year OS rate, median OS and median EFS of relapsed or refractory (R/R) IDH-mutated AML (394 patients) were 21%, 40%, 15%, 8.21 months and 4.73 months, respectively. Gastrointestinal adverse events were the most frequently occurring all-grade adverse events and hematologic adverse events were the most frequently occurring ≥ grade 3 adverse events.
CONCLUSION
IDH inhibitor is a promising treatment for R/R AML patients with IDH mutations. For patients with newly diagnosed IDH-mutated AML, IDH inhibitors may not be optimal therapeutic agents due to low CR rates. The safety of IDH inhibitors is controllable, but physicians should always pay attention to and manage the differentiation syndrome adverse events caused by IDH inhibitors. The above conclusions need more large samples and high-quality RCTs in the future to verify.
Topics: Humans; Prospective Studies; DNA Methylation; Leukemia, Myeloid, Acute; Enzyme Inhibitors; Mutation
PubMed: 37434249
DOI: 10.1186/s13148-023-01529-2 -
Pharmaceutics Apr 2022Antineoplastic uptake by blast cells in acute myeloid leukemia (AML) could be influenced by influx and efflux transporters, especially solute carriers (SLCs) and... (Review)
Review
Antineoplastic uptake by blast cells in acute myeloid leukemia (AML) could be influenced by influx and efflux transporters, especially solute carriers (SLCs) and ATP-binding cassette family (ABC) pumps. Genetic variability in and could produce interindividual differences in clinical outcomes. A systematic review was performed to evaluate the influence of and polymorphisms and their combinations on efficacy and safety in AML cohorts. Anthracycline intake was especially influenced by polymorphisms, associated with lower hepatic uptake, showing higher survival rates and toxicity in AML studies. The variant alleles of were related to anthracycline intracellular accumulation, increasing complete remission, survival and toxicity. Similar findings have been suggested with and polymorphisms. Polymorphisms of , responsible for cytarabine uptake, demonstrated significant associations with survival and response in Asian populations. Promising results were observed with and combinations regarding anthracycline toxicities. Knowledge of the role of transporter pharmacogenetics could explain the differences observed in drug disposition in the blast. Further studies including novel targeted therapies should be performed to determine the influence of genetic variability to individualize chemotherapy schemes.
PubMed: 35456712
DOI: 10.3390/pharmaceutics14040878 -
Oncology 2023Therapy-related leukemia is a term that describes the occurrence of leukemia following exposure to hematotoxins and radiation to emphasize the difference from leukemia... (Review)
Review
BACKGROUND
Therapy-related leukemia is a term that describes the occurrence of leukemia following exposure to hematotoxins and radiation to emphasize the difference from leukemia that arises de novo. Many agents and host factors contribute to this entity of leukemias. Therapy-related acute myeloid leukemia has an extensive literature review in contrast to therapy-related chronic myeloid leukemia (t-CML). Radioactive iodine (RAI), an established agent in the management of differentiated thyroid carcinomas, has raised concern due to its possible carcinogenic effects.
SUMMARY
In this article, we reviewed all the reports from the 1960s to date related to t-CML following RAI on Google Scholar and PubMed. We have identified 14 reports and found that most reports were for men under the age of 60 years with primary papillary thyroid carcinoma and mixed follicular-papillary thyroid carcinoma who developed t-CML mainly between 4 and 7 years after exposure to varying doses of I131. However, the mean dose was 287.78 millicuries (mCi). It was reported that a statistically significant increase in leukemia following RAI therapy (relative risk of 2.5 for I131 vs. no I131). Also, there was a linear relationship between the cumulative dose of I131 and the risk of leukemia. Doses higher than 100 mCi were associated with a greater risk of developing secondary leukemia, and most of the leukemias developed within the initial 10 years of exposure. The precise mechanism through which RAI provokes leukemia is largely unclear. A few mechanisms have been proposed.
KEY MESSAGES
Although the risk for t-CML appears to be low based on current reports and does not represent a contraindication to RAI therapy, it should not be disregarded. We suggest including it in the risk-benefit discussion before initiating this therapy. Long-term follow-up for patients is advisable for those who received doses over 100 mCi with a complete blood count, possibly yearly, for the first 10 years. The new onset of significant leukocytosis post RAI exposure should raise the suspicion for t-CML. Further studies are needed to establish or refute a causal relationship.
Topics: Male; Humans; Middle Aged; Thyroid Neoplasms; Iodine Radioisotopes; Thyroid Cancer, Papillary; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Risk Assessment
PubMed: 37231874
DOI: 10.1159/000530463 -
Cancers Sep 2023In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid... (Review)
Review
In recent years, the association of venetoclax (VEN) with hypomethylating agents (HMAs) significantly improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) who were unfit for intensive chemotherapy and became the standard of care after the publication of the pivotal RCT VIALE-A. However, it is still not clear to what extent the results observed in the VIALE-A apply to a real-world setting. For this reason, we carried out a systematic review and meta-analysis of real-world studies on newly diagnosed patients with AML, ineligible for intensive induction chemotherapy, receiving first-line VEN+HMA. We then compared their results in term of survival with those from the VIALE-A. Kaplan-Meier curves were extracted from all included studies and individual survival data was reconstructed. We then estimated a pooled survival curve and compared it with the results of the VIALE-A using the log-rank test. We also conducted a secondary analysis including only studies considering VEN plus azacytidine (AZA) as treatment, as this was the schedule originally used in the VIALE-A. Nineteen real-world studies met the inclusion criteria and were included in the systematic review. Most of them reported a worse survival than the VIALE-A. The pooled survival curve was similar to that reported in the VIALE-A during the first three months of treatment but diverged thereafter (-value = 0.0001). The pooled median survival among the real-world studies was 9.37 months (95%CI 8.81-10.5), substantially lower than that reported in the VIALE-A (14.7 months; 95%CI 11.9-18.7). Results slightly increased when the analysis was restricted to the studies using VEN+AZA as treatment (median survival: 11.5 months; 95%CI 10.2-14.8). Survival of newly diagnosed AML patients treated with VEN+HMAs in a real-world setting seems to be lower than previously reported in the VIALE-A, while the effect of VEN+AZA is more in line with expected results. Future studies are needed to evaluate whether this apparent discrepancy is due to the different characteristics of enrolled patients or to a non-optimal adherence to therapy, and whether alternative regimens can provide better results in terms of safety and effectiveness.
PubMed: 37760587
DOI: 10.3390/cancers15184618 -
Leukemia & Lymphoma Mar 2018Data regarding clinical characteristics, therapy, maternal and fetal outcomes of pregnancy-associated acute myeloid leukemia (PA-AML) are limited. This study (including... (Meta-Analysis)
Meta-Analysis
Data regarding clinical characteristics, therapy, maternal and fetal outcomes of pregnancy-associated acute myeloid leukemia (PA-AML) are limited. This study (including 138 cases published between 1955 and 2013) provides comprehensive assessment of these clinical parameters and may serve as a platform for developing management recommendations. Most patients (58%) received anthracycline-cytarabine-based regimens (ACBRs), which were associated with significantly increased complete remission (CR: 91%). Yet, the maternal overall survival (OS: ∼30%) was relatively low, probably reflecting reduced application of risk-adapted consolidation and allogeneic stem cell transplantation (allo-SCT). Fetal exposure to ACBRs resulted in a live birth rate of 87%, with complications (16%) diagnosed only in chemotherapy-subjected neonates. This study demonstrates safety and efficacy of ACBRs during pregnancy. Therapy and delivery schedule should allow early referral of high-risk patients to allo-SCT. Generation of a pool of high-quality data on PA-AML could contribute to providing evidence-based therapy and lead to improved maternal and fetal survival.
Topics: Female; Fetal Diseases; Humans; Leukemia, Myeloid, Acute; Pregnancy; Pregnancy Complications, Hematologic; Prognosis; Survival Rate
PubMed: 28703077
DOI: 10.1080/10428194.2017.1347651 -
Cancer Oct 2023Acute myeloid leukemia (AML) has been considered an oncologic emergency that requires initiation of chemotherapy immediately after diagnosis. With the introduction of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute myeloid leukemia (AML) has been considered an oncologic emergency that requires initiation of chemotherapy immediately after diagnosis. With the introduction of novel targeted therapies, there is a potential benefit associated with delaying definitive treatment for identification of actionable therapeutic targets. Unfortunately, cytogenetic/molecular testing can take >7 days to return, and there is not a consensus regarding the prognostic impact of time from diagnosis to treatment (TDT) in AML.
METHODS
A literature review and meta-analysis of studies done to date that evaluate TDT was conducted. Studies that reported baseline characteristics, TDT, and outcomes for patients with AML were selected. Outcomes included overall survival (OS), complete remission (CR), and mortality. Studies that measured CR rates within each TDT range and data to calculate odds ratios were included in the meta-analysis. The remaining outcomes were synthesized descriptively for literature review.
RESULTS
Thirteen studies were identified, which comprised a total of 14,946 patients. Median TDT values were between 1 and 8 days. Several studies found a significant association between prolonged TDT and older age and lower proliferation burden. Four of 11 studies did not detect a significant relationship between TDT and OS. No studies found a significant association between TDT and early death. Six of eight studies did not find a significant association between TDT and CR rate. The meta-analysis found a significant association between prolonged TDT and decreased achievement of CR (p < .05).
CONCLUSIONS
Results were highly variable but suggest it may be feasible to pursue cytogenetic/molecular testing in patients who are clinically stable, particularly in those aged 60 years and older.
Topics: Humans; Middle Aged; Aged; Prognosis; Leukemia, Myeloid, Acute; Remission Induction
PubMed: 37254580
DOI: 10.1002/cncr.34894 -
Blood Advances Jun 2020Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer... (Meta-Analysis)
Meta-Analysis
Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer TKIs requires the definition of the optimal first-line TKI for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase (CP) CML. This systematic review of randomized controlled trials (RCTs) compares the efficacy and safety of imatinib vs second-generation (dasatinib, nilotinib, bosutinib) and third-generation TKIs (ponatinib) in adults with newly diagnosed Ph+ CP CML, concentrating on OS, progression-free survival (PFS), and hematological and nonhematological adverse events. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. Seven RCTs published between 1990 and 2019 (involving 3262 participants) satisfied the eligibility criteria. Two RCTs (imatinib vs nilotinib and imatinib vs dasatinib) found no difference in 5-year OS or PFS. Second- and third-generation TKIs improved 3-month major molecular responses (relative risk [RR], 4.28; 95% confidence interval [CI], 2.20-8.32) and other efficacy outcomes, decreased accelerated/blastic-phase transformations (RR, 0.44; 95% CI, 0.26-0.74), but were associated with more cases of thrombocytopenia (RR, 1.57; 95% CI, 1.20-2.05), cardiovascular events (RR, 2.54; 95% CI, 1.49-4.33), and pancreatic (RR, 2.29; 95% CI, 1.32-3.96) and hepatic effects (RR, 3.51; 95% CI 1.55-7.92). GRADE showed that the certainty of the evidence ranged from high to moderate. This study shows that, in comparison with imatinib, second- and third-generation TKIs improve clinical responses, but the safer toxicity profile of imatinib may make it a better option for patients with comorbidities.
Topics: Adult; Antineoplastic Agents; Dasatinib; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
PubMed: 32559295
DOI: 10.1182/bloodadvances.2019001329