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Leukemia Research Oct 2023Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a...
Safety and efficacy of FLAG-Ida-based therapy combined with venetoclax for the treatment for newly diagnosed and relapsed/refractory patients with AML - A systematic review.
Venetoclax (VEN) in combination with intensive chemotherapy (IC) is increasingly used to treat patients with high-risk acute myeloid leukemia (AML). We conducted a systematic review to assess the safety and efficacy outcomes of FLAG-IDA in combination with VEN. The primary safety outcome was infection rate; the primary efficacy outcome was response to treatment (composite complete remission (CRc) and overall response rate (ORR). Risk of bias was assessed according to the ROBINS-I tool. Six studies including 221 patients with newly-diagnosed (ND AML (n = 120)) and R/R AML (n = 101) disease, were included in this systematic review. Pooling of results was not conducted due to major differences between studies. The reported rates of neutropenic fever, bacteremia, pneumonia and invasive fungal infections were at 44-55 %, 24-48 %, 12-30 % and 11-36 % of assessed patients, respectively. Time to ANC and platelet recovery ranged between 23 and 29 and 23-31 days, respectively. Early death rate was 8.7 % (14/160) patients: four patients at 30 days, additional ten in 60 days. CRc rates ranged between 53 % and 78 % for R/R AML. CRc for ND was reported by one study only (89 %). ORR were reported in 60-78 % of patients with R/R AML. Only one study reported an ORR for ND patients of 98 %. In our systematic review, FLAG-Ida plus VEN proved to be a potentially tolerable and effective regimen in ND and R/R AML patients. We suggest further evaluation and confirmation for the safety and efficacy of this new protocol in future RCTs.
Topics: Humans; Idarubicin; Leukemia, Myeloid, Acute; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 37598660
DOI: 10.1016/j.leukres.2023.107368 -
European Archives of... Aug 2023This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on... (Review)
Review
PURPOSE
This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on treatment efficacy but also on possible treatment-related adverse events, and treatment combinations with other techniques.
METHODS
Search criteria were applied to MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases and included all studies published up to March 2022 reporting paediatric lymphatic malformations treated with sirolimus. We selected all original studies that included treatment outcomes. After the removal of duplicates, selection of abstracts and full-text articles, and quality assessment, we reviewed eligible articles for patient demographics, lymphatic malformation type, size or stage, site, clinical response rates, sirolimus administration route and dose, related adverse events, follow-up time, and concurrent treatments.
RESULTS
Among 153 unique citations, 19 studies were considered eligible, with reported treatment data for 97 paediatric patients. Most studies (n = 9) were case reports. Clinical response was described for 89 patients, in whom 94 mild-to-moderate adverse events were reported. The most frequently administered treatment regimen was oral sirolimus 0.8 mg/m twice a day, with the aim of achieving a blood concentration of 10-15 ng/mL.
CONCLUSION
Despite promising results for sirolimus treatment in lymphatic malformation, the efficacy and safety profile of remains unclear due to the lack of high-quality studies. Systematic reporting of known side effects, especially in younger children, should assist clinicians in minimising treatment-associated risks. At the same time, we advocate for prospective multicentre studies with minimum reporting standards to facilitate improved candidate selection.
Topics: Humans; Child; Sirolimus; Prospective Studies; Treatment Outcome; Neck; Head; Lymphatic Abnormalities; Vascular Malformations
PubMed: 37115326
DOI: 10.1007/s00405-023-07991-1 -
Clinical Rheumatology Feb 2024Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may resist several lines of treatment. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of mycophenolate mofetil (MMF) in treating patients with ITP.
METHODS
We systematically searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) from inception until 10 October 2022. We included all clinical trials, either controlled or single arm, and prospective and retrospective observational studies that evaluate the efficacy and safety of MMF in patients with ITP. We assessed the risk of bias using three tools (ROBINS-I, Cochrane ROB-2, and NIH), each for eligible study design.
RESULTS
Nine studies were included in this meta-analysis, with a total of 411 patients with ITP. We found that MMF demonstrated an overall response rate of (62.09%; 95% CI = [43.29 to 77.84]) and the complete response rate was (46.75%; 95% CI = [24.84 to 69.99]). The overall proportion of adverse events was (12%; 95% CI = [6 to 24]). After the sensitivity analysis, the overall response rate became 50%; 95% CI = [38 to 63]) and the complete response rate became (32%; 95% CI = [24 to 42]). However, MMF did not appear to affect white blood cell counts or hemoglobin levels significantly.
CONCLUSION
This systematic review and meta-analysis demonstrate that MMF appears to be an effective and relatively safe treatment option for patients with ITP when combined with steroids and even in those who have not responded to standard therapies (steroid-resistant cases). Further research with well-designed studies is warranted to better understand the factors influencing treatment response and to refine the use of MMF in the management of ITP. An interactive version of our analysis can be accessed from here: https://databoard.shinyapps.io/mycophenolate_meta/.
Topics: Humans; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies; Prospective Studies; Steroids; Immunosuppressive Agents
PubMed: 37981614
DOI: 10.1007/s10067-023-06820-4 -
Frontiers in Immunology 2023IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue. The aim of this study was to conduct a systematic review and meta-analysis to assess risk factors and outcomes for IgA nephropathy recurrence.
METHODS
We used PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, CNKI, WanFang, VIP and CBM to search for relevant studies published in English and Chinese. Cohort or case-control studies reporting risk factors or outcomes for IgA nephropathy recurrence were included.
RESULTS
Fifty-eight studies were included. Compare to no recurrence group, those with IgAN recurrence had younger age (mean difference [MD]=-4.27 years; risk ratio [RR]=0.96), younger donor age (MD=-2.19 years), shorter time from IgA nephropathy diagnosis to end stage renal disease (MD=-1.84 years; RR=0.94), shorter time on dialysis (MD=-3.14 months), lower human leukocyte-antigen (HLA) mismatches (MD=-0.11) and HLA-DR mismatches (MD=-0.13). HLA-B46 antigen (RR=0.39), anti-IL-2-R antibodies induction (RR=0.68), mycophenolate mofetil (RR=0.69), and pretransplant tonsillectomy (RR=0.43) were associated with less IgAN recurrence. Of note, male recipient gender (RR=1.17), related donor (RR=1.53), retransplantation (RR=1.43), hemodialysis (RR=1.68), no induction therapy (RR=1.73), mTOR inhibitor (RR=1.51), angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (RR=1.63) were risk factors for IgAN recurrence. Recurrence increased the risk of graft loss (RR=2.19).
CONCLUSIONS
This study summarized the risk factors for recurrence of IgA nephropathy after kidney transplantation. Well-designed prospective studies are warranted for validation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=377480, identifier CRD42022377480.
Topics: Humans; Male; Glomerulonephritis, IGA; Kidney Transplantation; Risk Factors; Kidney Failure, Chronic; Mycophenolic Acid
PubMed: 38090563
DOI: 10.3389/fimmu.2023.1277017 -
Journal of Cancer Research and Clinical... Nov 2023The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway regulates proliferation, survival and metabolism, and its dysregulation... (Review)
Review
The phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway regulates proliferation, survival and metabolism, and its dysregulation is one of the most frequent oncogenic events across human malignancies. Over the last two decades, there has been significant focus on the clinical development of PI3K pathway inhibitors. More than 40 different inhibitors of this axis have reached various stages of clinical trials, but only a few of them have been approved by the Food and Drug Administration (FDA) for cancer treatment. These clinical results, however, could be improved given the importance of PI3K signaling in cancer and its role in linking cancer growth with metabolism. In this systematic review, after a glance at PI3K/AKT/mTOR pathway and its different inhibitors, we retrieved registered clinical trials evaluating the efficacy and safety of PI3K/AKT/mTOR inhibitors on Clinicaltrials.gov. Following the extraction of the data, finally we analyzed 2250 included studies in multiple steps, beginning with an overview and moving on to the details about type of malignancies, inhibitors, and treatment strategies. We also took a closer look at more than 100 phase III-IV clinical trials to pinpoint promising therapies, hoping that presenting a comprehensive picture of current clinical trials casts a flash of light on what remains to be done in future clinical trials of PI3K/AKT/mTOR inhibitors in human malignancies.
Topics: Humans; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Sirolimus; MTOR Inhibitors; Neoplasms; TOR Serine-Threonine Kinases; Phosphoinositide-3 Kinase Inhibitors
PubMed: 37594532
DOI: 10.1007/s00432-023-05277-x -
Drug Development Research Aug 2023This study aims to assess studies on circular RNAs (circRNAs) in the chemoresistance of triple-negative breast cancer (TNBC) and provide relevant references for the... (Review)
Review
This study aims to assess studies on circular RNAs (circRNAs) in the chemoresistance of triple-negative breast cancer (TNBC) and provide relevant references for the development of new TNBC chemotherapy sensitivity biomarkers and therapeutic targets. The PubMed, Embase, Web of Knowledge, Cochrane Library, and four Chinese databases were searched up to January 27, 2023, and studies related to TNBC chemoresistance were included. The basic characteristics of the studies and the mechanisms of circRNAs in regulating TNBC chemoresistance were analyzed. A total of 28 studies published between 2018 and 2023 were included, and the chemotherapeutics included adriamycin, paclitaxel, docetaxel, 5-fluorouracil, lapatinib, and so forth. A total of 30 circRNAs were identified, 86.67% (n = 26) of these circRNAs were reported to act as microRNA (miRNA) sponges to regulate chemotherapy sensitivity, while only two circRNAs (circRNA-MTO1 and circRNA-CREIT) interacted with proteins. A total of 14, 12, and 2 circRNAs were reported to be associated with chemoresistance to adriamycin, taxanes, and 5-fluorouracil, respectively. Six circRNAs were found to act as miRNA sponges that promote chemotherapy resistance by regulating the PI3K/Akt signalling pathway. CircRNAs participate in the regulation of TNBC chemoresistance and can be used as biomarkers and therapeutic targets for improving chemotherapy sensitivity. However, further studies are needed to confirm the role of circRNAs in TNBC chemoresistance.
Topics: Humans; RNA, Circular; Triple Negative Breast Neoplasms; Drug Resistance, Neoplasm; Phosphatidylinositol 3-Kinases; MicroRNAs; Biomarkers; Doxorubicin; Fluorouracil; Gene Expression Regulation, Neoplastic
PubMed: 37114737
DOI: 10.1002/ddr.22069 -
Medicina (Kaunas, Lithuania) Sep 2023Oxidative stress is involved in the alterations at the level of salivary glands, being the cause of oral pathologies like xerostomia, periodontitis, gingivitis,... (Review)
Review
Oxidative stress is involved in the alterations at the level of salivary glands, being the cause of oral pathologies like xerostomia, periodontitis, gingivitis, leucoplakia, and cancer. It is known that antioxidants can reverse changes induced by drugs or other chemicals in some organs, but the question is whether these substances can reduce or revert the effects of oxidative stress at the salivary gland level. Our aim was to find histopathological data at the level of salivary glands supporting the hypothesis of the reversal of oxidative stress-induced changes after the treatment with substances with antioxidant effect. : A systematic search was conducted in PubMed, Science Direct, and Springer databases, including research articles on oxidative stress histological aspects and oxidative stress biomarkers induced by drugs or other chemicals on salivary glands. : Out of 1756 articles, 25 articles were selected with data on tissue homogenate used for biochemical analysis of oxidative and antioxidative markers, along with routine hematoxylin eosin (HE) and immunohistochemical analysis used for histopathological and immunohistochemical diagnosis. Drugs (antineoplastic drugs, antibiotics, and analgesics), alcohol, heavy metals, and fluoride can cause oxidative stress, resulting in morphological changes in different tissues, including in salivary glands. There are many antioxidants but only a few were evaluated regarding the effects on salivary glands in animal studies, such as hesperidin and selenium, which can reverse the damage induced by cyclophosphamide; 10-dehydrogingerdione (10-DHGD), a compound extracted from ginger, which has a protective effect against the oxidative stress and apoptosis induced by tramadol; and glycyrrhizic acid, which may repair the injuries incurred after the administration of sodium nitrite. : Substances such as hesperidin, selenium, 10-dehydrogingerdione, and glycyrrhizic acid are antioxidants with proven restorative effects on salivary glands for the damage induced by oxidative stress after exposure to drugs and other chemical substances; however, demonstrating their similar effects in human salivary glands is challenging.
PubMed: 37763811
DOI: 10.3390/medicina59091692 -
Annals of Medicine Dec 2023We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy.
MATERIALS AND METHODS
We systematically searched three databases (PubMed, Web of Science and Embase) up to 20 February 2023. Extracting the effect size and 95% confidence intervals for overall survival (OS), progression-free survival (PFS) and the objective response rate (ORR).
RESULTS
A total of 65 articles were included. We identified the following factors that benefit ICI therapy: smoking status (PFS: 0.72 [0.62, 0.84], < .001), chemotherapy (PFS: 0.68 [0.58, 0.79], < .001), expression of programmed cell death ligand 1(PD-L1) (≥1%, ≥5%, or ≥10%) (≥1%: 0.76 [0.71,0.82], < .001; ≥5%: 0.62 [0.52, 0.74], < .001; ≥10%: 0.42 [0.30, 0.59], < .001). We also identified three adverse factors: epidermal growth factor receptor mutations (OS: 1.57 [1.06, 2.32], = .02), with liver metastases (OS: 1.16 [1.02,1.32], = .02) and antibiotics (OS: 3.13 [1.25,7.84], < .001; PFS: 2.54 [1.38, 4.68], = .003).
CONCLUSION
The results of this umbrella meta-analysis first supported pre-existing understandings of the relationship between beneficial and adverse factors with the efficacy of ICI therapy. In addition, the overexpression of PD-L1 may adversely affect patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; B7-H1 Antigen; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Randomized Controlled Trials as Topic
PubMed: 37212453
DOI: 10.1080/07853890.2023.2215543 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
JAMA Dermatology Aug 2023Chemotherapy-induced pseudocellulitis is an ill-defined term for a poorly understood phenomenon. Encompassing a myriad of cellulitis-mimicking oncologic adverse...
IMPORTANCE
Chemotherapy-induced pseudocellulitis is an ill-defined term for a poorly understood phenomenon. Encompassing a myriad of cellulitis-mimicking oncologic adverse cutaneous drug reactions (ACDRs), pseudocellulitis may be difficult to diagnosis, and the lack of treatment guidance may mean unnecessary antibiotic exposure and interruptions to oncologic care.
OBJECTIVES
To use case reports to characterize the various cellulitis-mimicking reactions caused by chemotherapeutic medications, to understand how these reactions affect patient care (ie, antibiotic exposure and interruptions to oncologic treatment), and to make recommendations for improved diagnosis and care of patients with chemotherapy-induced pseudocellulitis.
EVIDENCE REVIEW
A systematic review of case reports of patients with pseudocellulitis was performed. Reports were identified through database searches using PubMed and Embase, with subsequent reference searches. Included publications described at least 1 case of chemotherapy-induced ACDR and used the term pseudocellulitis or showed evidence of cellulitis mimicry. Cases of radiation recall dermatitis were excluded. Data were extracted from a total of 32 publications representing 81 patients diagnosed with pseudocellulitis.
FINDINGS
Of the 81 cases (median [range] age, 67 [36-80] years; 44 [54%] male patients), most were associated with gemcitabine use; pemetrexed use was reported less frequently. Only 39 were considered to be true chemotherapy-induced pseudocellulitis. These cases resembled infectious cellulitis and did not meet diagnostic criteria for any known diagnoses; therefore, these were described solely as pseudocellulitis. Of this group, 26 patients (67%) had been administered antibiotics before the correct diagnosis was made, and 14 patients (36%) experienced interruptions to their oncologic treatment plans.
CONCLUSIONS AND RELEVANCE
This systematic review found a variety of chemotherapy-induced ACDRs that mimic infectious cellulitis, including a group of reactions termed pseudocellulitis that do not meet criteria for other diagnoses. A more universally accepted definition and clinical research on chemotherapy-induced pseudocellulitis would allow for more accurate diagnosis, effective treatment, antibiotic stewardship, and continuation of oncologic treatment.
Topics: Humans; Male; Aged; Female; Deoxycytidine; Cellulitis; Antimetabolites, Antineoplastic; Gemcitabine; Drug-Related Side Effects and Adverse Reactions; Anti-Bacterial Agents
PubMed: 37379014
DOI: 10.1001/jamadermatol.2023.1735