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British Journal of Haematology Jan 2019Many patients with lower-risk myelodysplastic syndrome (MDS) experience anaemia, which has negative consequences. Erythropoiesis-stimulating agents (ESAs) and their... (Review)
Review
Clinical effectiveness and safety of erythropoietin-stimulating agents for the treatment of low- and intermediate-1-risk myelodysplastic syndrome: a systematic literature review.
Many patients with lower-risk myelodysplastic syndrome (MDS) experience anaemia, which has negative consequences. Erythropoiesis-stimulating agents (ESAs) and their biosimilars are used to treat anaemia in MDS and, currently, epoetin alfa and darbepoetin alfa are commonly used and recommended by clinical guidelines. To better understand the evidence available on the use of ESAs for anaemia in lower-risk MDS, we conducted a systematic literature review to identify randomized and nonrandomized prospective studies reporting on clinical efficacy/effectiveness, patient-reported quality of life (QoL), and safety. We extended our review to include retrospective studies for darbepoetin alfa specifically and to ascertain the feasibility of completing an indirect network meta-analysis comparing epoetin and darbepoetin alfa. Overall, 53 articles reporting on 35 studies were included. The studies indicated a clinical benefit of ESAs, with benefits observed across key clinical outcomes. ESAs showed consistent improvement in erythroid response rates (ESA-naïve, 45-73%; previous ESA exposure, 25-75%) and duration of response. Comparative studies demonstrated similar progression to acute myeloid leukaemia and several showed improved overall survival and QoL. Limited safety concerns were identified. This analysis confirmed ESA therapy should be the foremost first-line treatment of anaemia in most patients with lower-risk MDS who lack the 5q deletion.
Topics: Biosimilar Pharmaceuticals; Darbepoetin alfa; Epoetin Alfa; Hematinics; Humans; Myelodysplastic Syndromes; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 30549002
DOI: 10.1111/bjh.15707 -
Clinical Lymphoma, Myeloma & Leukemia Feb 2023The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The global incidence of myelodysplastic syndromes (MDS) has been estimated as 0.06 to 0.26/100,000. Since their introduction, hypomethylating agents have played a central role in the treatment of MDS, with heterogeneous real-world outcomes.
MATERIALS AND METHODS
We assessed and synthesized clinical outcomes of azacitidine (AZA) monotherapy in treatment-naïve patients with higher-risk MDS. A systematic literature review was conducted by searching MEDLINE, Embase, and CENTRAL to identify randomized clinical trials (RCTs) and observational studies, both prospective and retrospective, reporting complete remission (CR), partial remission (PR), overall survival (OS), duration of response (DOR), time-to-response (TTR), and myelosuppressive adverse events (AEs) for patients treated with AZA monotherapy. Noncomparative meta-analyses were used to summarize effects.
RESULTS
The search identified 3250 abstracts, of which 34 publications describing 16 studies (5 RCTs, 3 prospective, and 8 retrospective observational) were included. Across all studies, pooled CR was 16%; PR was 6%; Median OS was 16.4 months; median DOR was 10.1 months; median TTR was 4.6 months. Proportions of grade 3/4 anemia and thrombocytopenia AEs were 10% and 30%.
CONCLUSIONS
The effectiveness and efficacy of AZA monotherapy-as measured by CR and median OS-was limited. These findings highlight a significant unmet medical need for effective treatments for patients with higher-risk MDS.
Topics: Humans; Azacitidine; Antimetabolites, Antineoplastic; Myelodysplastic Syndromes; Treatment Outcome; Remission Induction
PubMed: 36428152
DOI: 10.1016/j.clml.2022.11.002 -
Journal of Clinical Medicine Feb 2022Anemia is the most common form of cytopenia in patients with myelodysplastic syndromes (MDS), who require chronic red blood cell transfusions and may present high serum...
Anemia is the most common form of cytopenia in patients with myelodysplastic syndromes (MDS), who require chronic red blood cell transfusions and may present high serum ferritin (SF) levels as a result of iron overload. To better understand the potential effects of high SF levels, we conducted a systematic literature review (SLR) to identify evidence on the relationship between SF levels and clinical, economic, or humanistic outcomes in adult patients with MDS. Of 267 references identified, 21 were included. No studies assessing SF levels and their relationship with humanistic or economic outcomes were identified. Increased SF levels were an indicator of worse overall survival and other worsened outcomes; however, the association was not consistently significant. SF levels were a significant prognostic factor for relapse incidence of MDS and showed a significant positive correlation with number of blood units transfused but were not associated with progression to acute myeloid leukemia or the time to transformation. Higher SF levels were also an indicator of a lower likelihood of leukemia-free survival, relapse-free survival, and event-free survival. The SLR suggests that SF levels are associated with clinical outcomes in MDS, with higher levels correlated with number of blood units transfused, frequently indicating worse outcomes.
PubMed: 35160344
DOI: 10.3390/jcm11030895 -
Medicine Nov 2022Systemic inflammatory and autoimmune manifestations (SIAMs) are frequently reported in Myelodysplastic syndromes (MDS). Studies focused on the impact of SIMAs on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systemic inflammatory and autoimmune manifestations (SIAMs) are frequently reported in Myelodysplastic syndromes (MDS). Studies focused on the impact of SIMAs on survival outcomes of MDS remains controversial. We performed this systematic review and meta-analysis to determine the association of SIAMs with overall survival, median survival, rate of acute myeloid leukemia transformation and mortality of MDS.
MATERIALS AND METHODS
An electronic search was conducted in 4 databases without any language restrictions, including PubMed, EMBASE, Medicine and Cochrane library up to April 30, 2021.
RESULTS
The 18 studies included a total of 4603 MDS patients, of which 1175 (25.5%) patients had SIAMs. MDS patients with SIAMs had a statistically shorter overall survival compared with patient without SIAMs (Hazard ratio, 2.43; 95% confidence interval [CI], 1.34-4.41; P < .01). Our results were most compatible with no effect of SIAMs on median survival, rate of acute myeloid leukemia transformation and mortality (Median survival ratio, 1.16; 95% CI, 0.91-1.47; Odds ratio, 0.96; 95% CI, 0.63-1.45 and 1.2; 95% CI, 0.84-1.7, respectively).
CONCLUSION
In this systematic review and meta-analysis, SIAMs appeared to have an adverse effect on overall survival of MDS patients. This finding suggested that SIAMs may be a potential independent prognostic factor for MDS.
Topics: Humans; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
PubMed: 36401363
DOI: 10.1097/MD.0000000000031427 -
Frontiers in Oncology 2021Circulating tumor DNA (ctDNA) has offered a minimally invasive approach for the detection and measurement of cancer. However, its diagnostic and prognostic value in...
Circulating tumor DNA (ctDNA) has offered a minimally invasive approach for the detection and measurement of cancer. However, its diagnostic and prognostic value in hematological malignancies remains unclear. Pubmed, Embase, and Cochrane Library were searched for relating literature. Diagnostic accuracy variables and disease progression prediction data were pooled by the Meta-Disc version 1.4 software. Review Manager version 5.4 software was applied for prognostic data analysis. A total of 11 studies met our inclusion criteria. In terms of diagnosis, the pooled sensitivity and specificity were 0.51 (95% confidence intervals (CI) 0.38-0.64) and 0.96 (95% CI 0.88-1.00), respectively. The AUSROC (area under the SROC) curve was 0.89 (95%CI 0.75-1.03). When it comes to the prediction of disease progression, the overall sensitivity and specificity was 0.83 (95% CI 0.67-0.94) and 0.98 (95% CI 0.93-1.00), respectively. Moreover, a significant association also existed between the presence of ctDNA and worse progression-free survival (HR 2.63, 95% CI 1.27-5.43, = 0.009), as well as overall survival (HR 2.92, 95% CI 1.53-5.57, = 0.001). The use of ctDNA in clinical practice for hematological malignancies is promising, as it may not only contribute to diagnosis, but could also predict the prognosis of patients so as to guide treatment. In the future, more studies are needed to realize the standardization of sequencing techniques and improve the detection sensitivity of exploration methods.
PubMed: 33747954
DOI: 10.3389/fonc.2021.632910 -
Asia-Pacific Journal of Oncology Nursing 2021Hematological malignancies require intensive and long-term treatment, which brings a significant burden on patients, leading to unmet supportive care needs. The purpose... (Review)
Review
Hematological malignancies require intensive and long-term treatment, which brings a significant burden on patients, leading to unmet supportive care needs. The purpose of this review was to investigate the unmet supportive care needs of patients with hematological malignancies during and after active treatment as well as the factors that affect them. A systematic bibliographic search was carried out in the PubMed database for English articles published between 2009 and 2020 according to the Preferred Reporting Items for Systematic Reviews guidelines and under the terms: "unmet needs", "supportive care", "hematological malignancy" and "hematological cancer." Twenty studies were evaluated and reviewed. Hierarchical frequently reported unmet supportive care needs were informational, emotional, physical, daily living/practical (accessibility, transportation, and financial problems), and family life/relational needs. In particular, patients with multiple myeloma most frequently reported unmet needs at the informational, physical, emotional, and daily living/practical domain. Patients with myelodysplastic syndromes reported physical, emotional, practical, and relational needs. Patients with leukemia and lymphoma rated their needs as informational, physical, psychological, daily living, and sexual. Sexual and spiritual unmet needs were reported at a low level. Predictive indicators for increased unmet supportive care needs were the type of the hematological malignancy, younger age, marital status, female gender, monthly income, coexistence of anxiety and depression, and altered quality of life. To conclude with, the literature reports a significant number of unmet supportive care needs in patients with hematological malignancies, whose frequency and intensity were influenced by a variety of factors. However, the large heterogeneity of studies (design, sample, and needs assessment tools) makes the generalization of the results difficult.
PubMed: 33426184
DOI: 10.4103/apjon.apjon_41_20 -
Medicine Aug 2018Hypomethylating agents (HMAs) are believed to have reliable efficacy in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Meanwhile, the adverse... (Meta-Analysis)
Meta-Analysis Review
Incidence and risk of hematologic toxicities with hypomethylating agents in the treatment of myelodysplastic syndromes and acute myeloid leukopenia: A systematic review and meta-analysis.
BACKGROUND
Hypomethylating agents (HMAs) are believed to have reliable efficacy in treating myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Meanwhile, the adverse events of HMAs have become an increasing concern. There is, however, no systematic meta-analysis available to evaluate overall hematologic toxicities for HMAs. In this meta-analysis, we aim to determine the risk of hematologic toxicities in patients treated with HMAs.
METHODS
Relevant studies were identified from PubMed, Embase, Cochrane Library, and the Clinical Trials. gov databases incepted to February 2018. All phase II and III trials meeting the inclusion criteria included adequate safety data. We calculated the relative risk (RR) of high-grade hematologic toxicities (HTEs) with corresponding 95% CI using Review Manager. The incidences of HTEs were also evaluated by R. Heterogeneity was calculated and reported mainly via I analyses.
RESULTS
A total of 2337 MDS or AML patients from 14 studies were identified in this meta-analysis. The overall incidences of high-grade hematologic toxicities in patients who received HMAs were: 27% of the patients with anemia, 45% with neutropenia, 38% with thrombocytopenia, and 25% with febrile neutropenia, respectively. There was a significantly increased RR of neutropenia and thrombocytopenia using HMAs, in comparison with conventional care regimens (CCR) based on the drug type (decitabine vs azacitidine).
CONCLUSIONS
We conclude that the use of HMAs are associated with an increased risk of neutropenia and thrombocytopenia in MDS or AML patients, and our results also demonstrate that HMAs exposure does not significantly increase the risk of high-grade anemia, leukopenia, or febrile neutropenia compared with CCR.
Topics: Antimetabolites, Antineoplastic; Hematologic Diseases; Humans; Incidence; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Risk
PubMed: 30142779
DOI: 10.1097/MD.0000000000011860 -
Asian Pacific Journal of Cancer... Apr 2022we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk. (Meta-Analysis)
Meta-Analysis
Association of Somatic Gene Mutations with Risk of Transformation into Acute Myeloid Leukemia in Patients with Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis.
OBJECTIVES
we aim to conduct a systematic review and meta-analysis in population of adult MDS patients to elucidate the role of these genes in AML transformation risk.
MATERIALS AND METHODS
The protocol for this systematic review and meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) with ID number of CRD42020218581. Systematic literature search was conducted by all authors up to October 2021 on: (1) PubMed, (2) EBSCOhost, (3) Scopus, (4) JSTOR, and (5) grey literatures. Hand-searching for relevant articles was also conducted. The following keywords with their synonyms and combinations using Boolean operators were applied to all database: "myelodysplastic syndrome", SRSF2", "SF3B1", "U2AF1", "ASXL1", "DNMT3A", "TET2", "IDH1", "IDH2", "RUNX1", "acute myeloid leukemia progression", and "leukemia free survival". Outcome was measured using hazard ratio (HR).
RESULTS
We identified 14 articles to be used for this systematic review and meta-analysis. There was no statistically significant difference in AML transformation risk between U2AF1 mutant and U2AF1 wildtype MDS patients (HR: 1.41; 95% CI: 0.95-2.07, p=0.08, I2=0%). Pooled HR showed that patients with SRSF2 mutation had higher risk of AML transformation (HR 2.62; 95% CI: 1.54-4.45; p= .0004; I2= 55%). The pooled HR for SF3B1 was 0.48 (95% CI: 0.22-1.06, p=0.07, I2=55%). Mutations of TET2, ASXL1, and EZH2 were not associated with AML transformation. Meanwhile, DNMT3A mutations were associated with AML transformation with pooled HR of 2.73 (95% CI: 1.43-5.21; p= 0.08; I2: 67%). The pooled HR for IDH genes was smaller (HR: 2.92; 95%CI: 1.21-7.06; p=0.02; I2:65%). Patients with RUNX1 mutation were associated with AML transformation (HR: 1.85; 95%CI: 1.11-3.09; p=0.02; I2:38%).
CONCLUSION
Based from our analyses, MDS patients with mutations of SRSF2, DNMT3A, IDH, and RUNX1 have higher hazard ratio for AML transformation.
Topics: Adult; Core Binding Factor Alpha 2 Subunit; Humans; Leukemia, Myeloid, Acute; Mutation; Myelodysplastic Syndromes; Splicing Factor U2AF
PubMed: 35485665
DOI: 10.31557/APJCP.2022.23.4.1107 -
Cureus May 2022Somatic () mutations are the most common mutations in various hematological malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).... (Review)
Review
A Systematic Review of the Role of Runt-Related Transcription Factor 1 (RUNX1) in the Pathogenesis of Hematological Malignancies in Patients With Inherited Bone Marrow Failure Syndromes.
Somatic () mutations are the most common mutations in various hematological malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Mono-allelic mutations in germline cells may cause familial platelet disorder (FPD), an inherited bone marrow failure syndrome (IBMFS) associated with an increased lifetime risk of AML. It is suspected that additional mutations may play a role in the pathogenesis of hematological malignancies in IBMFS. This review aims to study the role of mutations in the pathogenesis of hematological malignancies in patients with IBMFS. A PubMed database search was conducted using the following medical subject heading (MeSH) terms: "inherited bone marrow failure syndromes," "hematological neoplasms," "gene expression regulation, leukemic," "RUNX1 protein, human," "RUNX1 protein, mouse," and "Neutropenia, Severe Congenital, Autosomal recessive." Three studies published in 2020 were identified as meeting our inclusion and exclusion criteria. Leukemic progression in severe congenital neutropenia was used as a disease model to evaluate the clinical, molecular, and mechanistic basis of mutations identified in hematological malignancies. Studies in mice and genetically reprogrammed or induced pluripotent stem cells (iPSCs) have shown that isolated mutations are weakly leukemogenic and only initiate hyperproduction of immature hematopoietic cells when in combination with () mutations. Despite this, whole-exome sequencing (WES) performed on leukemogenic transformed cells revealed that all AML cells had an additional mutation in the () gene that caused hyperproduction of the ten-eleven translocation (TET2) protein. This protein causes inflammation in cells with mutations. This process is thought to be critical for clonal myeloid malignant transformation (CMMT) of leukemogenic cells. In conclusion, the combinations of and mutations have a prominent effect on myeloid differentiation resulting in the hyperproduction of myeloblasts. In other studies, it has been noted that the mutations in and genes are not sufficient for the full transformation of leukemogenic cells to AML, and an additional clonal mutation in the gene is essential for full transformation to occur. These data have implicitly demonstrated that mutations are critical in the pathogenesis of various hematological malignancies, and further investigations into the role of are paramount for the development of new cancer treatments.
PubMed: 35765406
DOI: 10.7759/cureus.25372 -
Medicina (Kaunas, Lithuania) Jun 2021Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a... (Review)
Review
Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. : A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. : To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. : Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic "neutropenic enterocolitis and sepsis" appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.
Topics: Adult; Child; Enterocolitis, Neutropenic; Humans; Lymphoma; Neoplasms; Prognosis; Sepsis
PubMed: 34203105
DOI: 10.3390/medicina57060638