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Leukemia Research Nov 2021The value of pre-transplant cytoreductive therapy for patients with myelodysplastic syndromes (MDS) is controversial. Here, we conducted a meta-analysis to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The value of pre-transplant cytoreductive therapy for patients with myelodysplastic syndromes (MDS) is controversial. Here, we conducted a meta-analysis to explore the effects of cytoreduction before transplantation.
METHODS
PubMed, Embase, Cochrane, and Chinese databases were searched to identify studies comparing post-transplant outcomes in MDS patients receiving different pre-transplant therapy. Pooled hazard ratios (HRs) and 95 % confidence intervals (CI) were calculated.
RESULTS
Eighteen reports were included. Post-transplant outcomes were similar for MDS patients receiving pre-transplant cytoreductive therapy and upfront transplantation in terms of overall survival (OS: HR, 0.92; 95 % CI, 0.79-1.07), relapse-free survival (RFS: HR, 1.18; 95 % CI, 0.94-1.47), cumulative incidence of relapse (CIR: HR, 1.08; 95 % CI, 0.88-1.33), and non-relapse mortality (NRM: HR, 0.93; 95 % CI, 0.74-1.18). Pre-transplant hypomethylating agents (HMAs) and chemotherapy were not different regarding post-transplant OS, RFS, CIR, and NRM. Achieving complete remission (CR) before transplantation was associated with increased RFS (HR, 0.80; 95 %CI, 0.63-1.00) and decreased NRM (HR, 0.53; 95 % CI, 0.32-0.90) when compared with upfront transplantation.
CONCLUSIONS
Timely transplantation is of great value for MDS patients. Suitable pre-transplant cytoreduction could be used during the search for donors.
Topics: Cytoreduction Surgical Procedures; Hematopoietic Stem Cell Transplantation; Humans; Myelodysplastic Syndromes; Prognosis
PubMed: 34217112
DOI: 10.1016/j.leukres.2021.106645 -
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 -
Leukemia Research Sep 2021Non-Hodgkin's lymphoma continues to be a highly prevalent entity in the general population. Currently, there are multiple treatment schemes based on chemotherapeutic... (Review)
Review Meta-Analysis
Non-Hodgkin's lymphoma continues to be a highly prevalent entity in the general population. Currently, there are multiple treatment schemes based on chemotherapeutic agents with a great success rate. However, there is a non-negligible percentage of patients who may relapse or be refractory. In this sense, new therapeutic options have emerged in the search for adequate responses, such as monoclonal antibodies that target the CD20 molecule. Another valid option is radioimmunotherapy (RIT), which combines using monoclonal antibodies for the specific targeting of malignant cells and radiation to destroy these cells. Despite the promising results that favor RIT in several clinical studies in different target populations and types of NHL, one situation to consider is the association of this therapy and second neoplasms (acute myeloid leukemia (AML) or myelodysplastic syndrome (MSD)). In this sense, we have proposed this meta-analysis to analyze the published information and determine the incidence of this association and determine this therapy's safety.
Topics: Humans; Lymphoma, Non-Hodgkin; Radiation Tolerance; Radioimmunotherapy; Treatment Outcome
PubMed: 34052662
DOI: 10.1016/j.leukres.2021.106615 -
Journal of Pediatric Hematology/oncology Aug 2021Eculizumab is indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). This study aimed to evaluate the efficacy and safety of eculizumab in patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Eculizumab is indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). This study aimed to evaluate the efficacy and safety of eculizumab in patients with PNH.
METHODS
PubMed, EMBASE, The Cochrane Library, and ClinicalTrials.gov were searched for prospective interventional studies treating PNH with eculizumab. The primary outcome was the change in lactate dehydrogenase (LDH) levels, whereas secondary outcomes included the change in hemoglobin (Hb) levels, transfusion rates, and adverse drug events.
RESULTS
Patients (n=235) from 6 studies were included in this meta-analysis. LDH and Hb levels and transfusion rates decreased significantly at 12, 26 weeks, 12, 15, and >15 months. The most frequent adverse events included nasopharyngitis (effect size [ES]: 0.53; 95% confidence intervals [CI]: 0.47 to 0.60; P=0.00), headache (ES: 0.47; 95% CI: 0.25 to 0.69; P=0.00), upper respiratory tract infection (ES: 0.37; 95% CI: 0.27 to 0.46; P=0.00), nausea (ES: 0.31; 95% CI: 0.24 to 0.38; P=0.00), fatigue, diarrhea, cough, pyrexia, abdominal pain, pain in extremities, and contusion.
CONCLUSION
Eculizumab is an effective and well-tolerated treatment for patients with PNH. It is effective at decreasing LDH levels and transfusion rates while increasing Hb levels. Further studies are needed to explore the safety of eculizumab.
Topics: Antibodies, Monoclonal, Humanized; Complement Inactivating Agents; Hemoglobinuria, Paroxysmal; Humans; L-Lactate Dehydrogenase; Treatment Outcome
PubMed: 33902068
DOI: 10.1097/MPH.0000000000002178 -
Leukemia Research Jun 2021
Corrigendum to "A systematic review of higher-risk myelodysplastic syndromes clinical trials to determine the benchmark of azacitidine and explore alternative endpoints for overall survival" [Leukemia Res. 104 March (2021)].
PubMed: 33896620
DOI: 10.1016/j.leukres.2021.106581 -
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 -
European Journal of Haematology Jul 2021Myelodysplastic syndromes (MDS) are a group of malignant hematologic diseases characterized by ineffective hematopoiesis, which may lead to chronic anemia and... (Meta-Analysis)
Meta-Analysis
Myelodysplastic syndromes (MDS) are a group of malignant hematologic diseases characterized by ineffective hematopoiesis, which may lead to chronic anemia and transfusion dependency, with up to 30% of patients progressing to acute myeloid leukemia (AML). Studies suggest transfusion dependency may impact overall survival (OS); however, there is a lack of evidence concerning the association between transfusion status (TS) and OS in patients with MDS who become transfusion independent (TI) after treatment. In addition, the holistic impact of TS on other clinical, economic, and humanistic outcomes has not been well understood. We conducted a systematic literature review (SLR) to understand this impact. Ten studies were included and showed consistent decrease in OS in transfusion dependent (TD) compared with TI patients. These findings were confirmed by a meta-analysis (MA) reporting better OS prognosis for TI patients. A second SLR was conducted to understand the association between TS and other clinical, economic, and humanistic outcomes. Twenty-eight studies were included and showed better prognosis for other outcomes, including AML progression and leukemia-free survival for TI patients. Risk of AML progression and cumulative non-leukemic death assessed by the MA showed a trend toward worse prognosis and higher risk of AML progression for TD patients. Lower healthcare resource utilization, better quality of life, and reduced non-leukemic death for TI patients were observed. Studies not eligible for MA also showed better clinical, economic, and humanistic outcomes for TI patients. These findings contribute to understanding the association between transfusion dependence and OS among other outcomes in patients with MDS.
Topics: Anemia; Bayes Theorem; Disease Progression; Disease-Free Survival; Erythrocyte Transfusion; Erythrocytes; Female; Humans; Leukemia, Myeloid, Acute; Male; Monte Carlo Method; Myelodysplastic Syndromes; Phenotype; Prognosis; Quality of Life; Risk; Treatment Outcome
PubMed: 33715214
DOI: 10.1111/ejh.13619 -
Leukemia Research May 2021The hypomethylating agent azacitidine can prolong overall survival (OS) in patients with higher risk-myelodysplastic syndromes (HR-MDS) compared to conventional... (Meta-Analysis)
Meta-Analysis
A systematic review of higher-risk myelodysplastic syndromes clinical trials to determine the benchmark of azacitidine and explore alternative endpoints for overall survival.
The hypomethylating agent azacitidine can prolong overall survival (OS) in patients with higher risk-myelodysplastic syndromes (HR-MDS) compared to conventional regimens. However, outcomes differ largely between studies, making it challenging to determine the contribution of novel therapies added to azacitidine. Further, a discrepancy is seen between complete (CR) or partial (PR) response rates and OS improvement with azacitidine, making it challenging to rely on earlier endpoints than OS. We conducted a systematic literature search and study-level systematic review of 237 clinical studies to better understand outcomes for HR-MDS patients treated with azacitidine. Pooled marrow CR was 9% (N = 2654; 95% CI: 6-13 %), CR rate was 17 % (N = 6943; 95% CI: 15-20 %), and median OS (mOS) was 18.6 months (N = 2820; 95% CI: 15.3-21.9). A weak correlation to mOS was detected with CR rate (207 patient cohorts, Pearson's r = 0.315; P < 0.0005), and a much stronger correlation with median progression-free survival (mPFS) (r=0.88, P = 3 × 10). Six-months progression-free survival rates correlated with 1-year OS rates but were only infrequently reported (N = 41 patient cohorts) therefore not allowing a robust recommendation for a surrogate to the established OS endpoint. Larger patient numbers and patient-level data appear necessary, especially for designing future clinical trials using azacitidine combinations.
Topics: Antimetabolites, Antineoplastic; Azacitidine; Clinical Trials as Topic; Disease-Free Survival; Humans; Myelodysplastic Syndromes; Survival Rate
PubMed: 33705966
DOI: 10.1016/j.leukres.2021.106555 -
BMC Cancer Mar 2021Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies.
METHODS
We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis.
RESULTS
Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML.
CONCLUSIONS
Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.
Topics: Carcinogens, Environmental; Causality; Epidemiologic Studies; Humans; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders
PubMed: 33676443
DOI: 10.1186/s12885-021-07908-3 -
Current Cancer Drug Targets 2021Redox dysregulation originating from metabolic alterations in cancer cells contributes to their proliferation, invasion, and resistance to therapy. Conversely, these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Redox dysregulation originating from metabolic alterations in cancer cells contributes to their proliferation, invasion, and resistance to therapy. Conversely, these features represent a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics. Amongst them, Vitamin K (VitK) carries the potential against cancer stem cells, in addition to the rest of tumor mass.
OBJECTIVES
To assess the possible benefits and safety of VitK for cancer treatment using a systematic review and meta-analysis with a mixed-methods approach.
METHODS
We performed a systematic search on several electronic databases for studies comparing VitK treatment with and without combination to the control groups. For quantitative studies, fully or partially reported clinical outcomes such as recurrence rates, survival, overall response and adverse reactions were assessed. For qualitative studies, a narrative synthesis was accomplished.
RESULTS
Our analysis suggested that the clinical outcome of efficacy, the pooled hazard ratio for progression-free survival, and the pooled relative risk for overall survival, and overall response were significantly higher in the VitK therapy group compared to the placebo group (p<0.05). We did not observe any significant difference in the occurrence of adverse events between groups. Among qualitative studies, VitK treatment targeting myelodysplastic syndrome and advanced solid tumors resulted in 24.1% and 10% of clinical response, respectively.
CONCLUSION
VitK not only exerts antitumor effects against a wide range of tumor types, but it also has excellent synergism with other therapeutic agents.
Topics: Humans; Neoplasms; Vitamin K
PubMed: 33475062
DOI: 10.2174/1568009621999210120182834