-
Efficacy and safety of ruxolitinib in steroid-refractory graft-versus-host disease: A meta-analysis.Frontiers in Immunology 2022Ruxolitinib is an important treatment for steroid refractory graft-versus-host disease (SR-GVHD). Therefore, we reported the updated results of a systematic review and... (Meta-Analysis)
Meta-Analysis
Ruxolitinib is an important treatment for steroid refractory graft-versus-host disease (SR-GVHD). Therefore, we reported the updated results of a systematic review and meta-analysis of ruxolitinib as treatment for SR-GVHD. In addition, we wanted to compare the efficacy and safety between children and adults with SR-GVHD. Overall response rate (ORR) after ruxolitinib treatment was chosen as the primary end point. Complete response rate (CRR), infection, myelosuppression, and overall survival (OS) were chosen as secondary end points. A total of 37 studies were included in this meta-analysis, and 1,580 patients were enrolled. ORR at any time after ruxolitinib treatment was 0.77 [95% confidence interval (CI): 0.68-0.84] and 0.78 (95% CI: 0.74-0.81), respectively, for SR-aGVHD and SR-cGVHD. CRR at any time after ruxolitinib treatment was 0.49 (95% CI: 0.40-0.57) and 0.15 (95% CI: 0.10-0.23), respectively, for SR-aGVHD and SR-cGVHD. The ORRs at any time after treatment was highest in mouth SR-cGVHD, followed by skin, gut, joints and fascia, liver, eyes, esophagus, and lung SR-cGVHD. The incidence rate of infections after ruxolitinib treatment was 0.61 (95% CI: 0.45-0.76) and 0.47 (95% CI: 0.31-0.63), respectively, for SR-aGVHD and SR-cGVHD. The incidence rates of overall (grades I-IV) and severe (grades III-IV) cytopenia were 53.2% (95% CI: 16.0%-90.4%) and 31.0% (95% CI: 0.0-100.0%), respectively, for SR-aGVHD, and were 28.8% (95% CI:13.0%-44.6%) and 10.4% (95% CI: 0.0-27.9%), respectively, for SR-cGVHD. The probability rate of OS at 6 months after treatment was 63.9% (95% CI: 52.5%-75.2%) for SR-aGVHD. The probability rates of OS at 6 months, 1 year, and 2 years after treatment were 95% (95% CI: 79.5%-100.0%), 78.7% (95% CI: 67.2%-90.1%), and 75.3% (95% CI: 68.0%-82.7%), respectively, for SR-cGVHD. The ORR, CRR, infection events, and myelosuppression were all comparable between children and adults with SR-GVHD. In summary, this study suggests that ruxolitinib is an effective and safe treatment for SR-GVHD, and both children and adults with SR-GVHD could benefit from ruxolitinib treatment.
Topics: Adult; Child; Graft vs Host Disease; Humans; Nitriles; Pyrazoles; Pyrimidines; Steroids
PubMed: 35990629
DOI: 10.3389/fimmu.2022.954268 -
Health Science Reports May 2022Bendamustine, a bifunctional mechlorethamine alkylating agent, is used in the treatment of patients with hematologic malignancies. Myelosuppression and cytotoxic effect... (Review)
Review
BACKGROUND
Bendamustine, a bifunctional mechlorethamine alkylating agent, is used in the treatment of patients with hematologic malignancies. Myelosuppression and cytotoxic effect arises quite often after bendamustine treatment. To date, there have been no recommendations for routine chemoprophylaxis for pneumonia (PCP) in patients under treatment with this agent. The present systematic review aimed to evaluate the existing data on bendamustine effects on pneumocystis pneumonia.
METHOD
English papers were systematically reviewed using Web of Science, Embase, Google Scholar, PubMed, and Cochrane library. There was no time constraint for the paper search. The used keywords included "Pneumonia, Pneumocystis"or "Pneumocystis Pneumonia"or "Pneumocystis jirovecii" and "Bendamustine hydrochloride or Bendamustine. "Through our search, 113 papers were found, 26 of which were chosen following a review of the titles and abstracts; ultimately, 10 were included in the research.
RESULT
A total of 10 studies (out of 113 studies) were retrieved. The papers were classified into seven case reports, two clinical trials, and one retrospective analysis study. The case reports included 14 patients diagnosed with PCP after bendamustine administration between 2003 and 2019. The patients' mean age was with a range of 66.8. Non-Hodgkin's lymphoma (including diffuse large B-cell lymphoma and mantle cell lymphoma) ( = 9, 60%), chronic lymphocytic leukemia ( = 4, 26.6%), and breast cancer ( = 2, 13.4%) were the most prevalent types of malignancy. Bendamustine, along with rituximab, were the most commonly prescribed chemotherapy regimens during the treatments. Finally, the mortality rate among the patients whose results were reported ( = 9) was 44.44% ( = 4).
CONCLUSION
The present review described PCP infection in patients with malignancies after the treatment with bendamustine, a chemotherapeutic agent associated with lymphopenia. Further research is required to determine the PCP risk in patients with bendamustine treatment and identify individuals who may benefit from prophylaxis.
PubMed: 35509412
DOI: 10.1002/hsr2.610 -
Frontiers in Immunology 2023Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.
RESULTS
Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).
DISCUSSION
This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.
Topics: Humans; Adult; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Treatment Outcome; Cyclophosphamide; Tacrolimus; Azathioprine; Mycophenolic Acid; Glucocorticoids; Bone Marrow Diseases; Kidney Failure, Chronic; Recurrence; Herpes Zoster; Neoplasms
PubMed: 37901212
DOI: 10.3389/fimmu.2023.1232244 -
Frontiers in Pharmacology 2023This study aims to assess the clinical efficacy and safety of Trilaciclib in preventing chemotherapy-induced myelosuppression in adult patients through meta-analysis....
This study aims to assess the clinical efficacy and safety of Trilaciclib in preventing chemotherapy-induced myelosuppression in adult patients through meta-analysis. The PubMed, Embase, Cochrane Library, Clinical Trials, EU Clinical Trials Register, and International Clinical Trials Registry Platform were searched up to 25 October 2022. Only randomized controlled trials (RCTs) comparing the clinical outcomes of Trilaciclib and Trilaciclib plus chemotherapy for treating malignant cancers in adult patients were included. The primary outcome included the incidence of SN, FN, the DSN, and administration of ESAs, G-CSFs, and RBC or platelet transfusions, while the secondary outcomes included the risk of adverse events (AEs) and severe adverse events (SAEs). In total, four randomized controlled trials (RCTs) involving 345 patients with SCLC or breast cancer were included in this meta-analysis. Results showed that administration of Trilaciclib significantly reduced the occurrence of SN (19.3% vs. 42.2%, OR = 0.31), FN (3.22% vs. 6.72%, OR = 0.47), anemia (20.5% vs. 38.2%, OR = 0.38) and shortened the DSN during treatment. The proportion of patients receiving therapeutic use of ESAs (4.03% vs. 11.8%, OR = 0.31), G-CSF (37.0% vs. 53.5%, OR = 0.52), RBC transfusions (19.8% vs. 29.9%, OR = 0.56) was also statistically lower in the experimental group than in the control group. Meanwhile, the ORR, overall survival, and progress-free survival of the two groups were identical, and no negative impact of Trilaciclib on the clinical outcomes of chemotherapy treatments was found. Other chemotherapy-induced adverse events (AEs) and severe adverse events (SAEs) like diarrhea, fatigue, nausea, and vomiting were identical regardless of Trilaciclib usage. Trilaciclib demonstrated its efficacy in reducing the occurrence of chemotherapy-induced myelosuppression and utilization of supportive care interventions without undermining the clinical benefits of chemotherapy regimens during treatment with an acceptable safety profile.
PubMed: 37305548
DOI: 10.3389/fphar.2023.1157251 -
Transplant Infectious Disease : An... Aug 2023Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a...
Epidemiology, management, and burden of cytomegalovirus in solid organ transplant recipients in selected countries outside of Europe and North America: A systematic review.
BACKGROUND
Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a systematic review was conducted to describe the epidemiology, management, and burden of CMV post-SOT in selected countries outside of Europe and North America.
METHODS
MEDLINE, Embase, and Cochrane databases were searched for observational studies in SOT recipients across 15 countries in the regions of Asia, Pacific, and Latin America (search period: January 1, 2011 to September 17, 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatment patterns and guidelines, refractory and/or resistant CMV, patient-reported outcomes, and economic burden.
RESULTS
Of 2708 studies identified, 49 were eligible (n = 43/49; 87.8% in adults; n = 34/49, 69.4% in kidney recipients). Across studies, selection of CMV preventive strategy was based on CMV serostatus. Overall, rates of CMV infection (within 1 year) and CMV disease post-SOT were respectively, 10.3%-63.2% (9 studies) and 0%-19.0% (17 studies). Recurrence occurred in 35.4%-41.0% cases (3 studies) and up to 5.3% recipients died of CMV-associated causes (11 studies). Conventional treatments for CMV infection/disease included ganciclovir (GCV) or valganciclovir. Up to 4.4% patients were resistant to treatment (3 studies); no studies reported on refractory CMV. Treatment-related adverse events with GCV included neutropenia (2%-29%), anemia (13%-48%), leukopenia (11%-37%), and thrombocytopenia (13%-24%). Data on economic burden were scarce.
CONCLUSION
Outside of North America and Europe, rates of CMV infection/disease post-SOT are highly variable and CMV recurrence is frequent. CMV resistance and treatment-associated adverse events, including myelosuppression, highlight unmet needs with conventional therapy.
Topics: Adult; Humans; Cytomegalovirus; Cytomegalovirus Infections; Europe; North America; Ganciclovir; Organ Transplantation; Leukopenia
PubMed: 37254966
DOI: 10.1111/tid.14070 -
Clinical and Experimental Medicine Nov 2022Hyperthermia is a generic term for different techniques using heat in cancer therapies. Temperatures of about 42° Celsius in combination with chemo- or radiotherapy may... (Review)
Review
Hyperthermia is a generic term for different techniques using heat in cancer therapies. Temperatures of about 42° Celsius in combination with chemo- or radiotherapy may improve the effectiveness of those treatments. Clinical benefit is shown in "standard hyperthermia" with tumour temperatures assessed during treatment. This systematic review thoroughly assesses the state of evidence concerning the benefits and side effects of electro hyperthermia or whole-body hyperthermia ("alternative hyperthermia") in oncology. From 26 April 2021 to 09 May 2021, a systematic search was conducted searching five electronic databases (Embase, Cochrane, PsycINFO, CINAHL and Medline) to find studies concerning the use, effectiveness and potential harm of alternative medical hyperthermia therapy on cancer patients. From all 47,388 search results, 53 publications concerning 53 studies with 2006 patients were included in this systematic review. The patients were diagnosed with different types of cancer. The hyperthermic methods included whole-body hyperthermia (WBH) with different methods and electro hyperthermia (EH). The majority of the included studies were single-arm studies, counting in total 32 studies. Six studies were randomized controlled trials (RCT). In addition, one systematic review (SR) was found. The most critical endpoints were tumour response, survival data, pain relief, myelosuppression and toxicities. Outcome was heterogeneous, and considering the methodological limitations, clinical evidence for the benefit of alternative hyperthermia in cancer patients is lacking. Neither for whole-body hyperthermia nor for electro hyperthermia there is any evidence with respect to improvement of survival or quality of life in cancer patients.
Topics: Humans; Neoplasms; Hyperthermia, Induced; Quality of Life
PubMed: 35767077
DOI: 10.1007/s10238-022-00846-9 -
Frontiers in Pharmacology 2020Patients with advanced cancer often undergo myelosuppression after receiving chemotherapy. However, severe myelosuppression results in treatment delay, and some can even...
Patients with advanced cancer often undergo myelosuppression after receiving chemotherapy. However, severe myelosuppression results in treatment delay, and some can even be life-threatening. At present, cancer patients undergoing chemotherapy urgently need effective intervention strategies to prevent myelosuppression. Fortunately, ginsenoside Rg3 has shown promise as an anti-myelosuppression agent. Therefore, this study was conducted to evaluate the effectiveness of ginsenoside Rg3 in preventing chemotherapy-induced myelosuppression in cancer patients. The PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Weipu (VIP), and Wanfang databases were searched in this study. A total of 18 trials which reported on 2,222 subjects were identified. All trials concerning the use of ginsenoside Rg3 for the prevention of chemotherapy-induced myelosuppression (the decline of leukocyte, hemoglobin, platelet, and neutrophil counts) were randomized-controlled trials. Dichotomous data were expressed as odds ratio (OR) with their respective 95% confidence intervals (CI). The Cochrane evidence-based medicine systematic evaluation was used to evaluate the methodological quality of the included trials. The Review Manager 5.3 and Stata 12.0 software were used to perform the statistical analyses. The trial sequential analysis (TSA) was used to evaluate information size and prevention benefits. The results revealed obvious ginsenoside Rg3-induced improvement in the leukocyte (OR, 0.46; 95% CI, 0.37-0.55), hemoglobin (OR, 0.64; 95% CI, 0.53-0.77), platelet (OR, 0.60; 95% CI, 0.48-0.75) and neutrophil (OR, 0.62; 95% CI, 0.43-0.90) counts at toxic grades I-IV, and leukocyte (OR, 0.39; 95% CI, 0.28-0.54) counts at toxic grades III-IV. The sensitivity analysis revealed that the results were robust. The Egger's test indicated that there was no publication bias in the results. Overall, this study suggested that ginsenoside Rg3 is beneficial for alleviating the chemotherapy-induced decrease in leukocyte, hemoglobin, platelet, and neutrophil counts. However, the confirmation of the ginsenoside Rg3 can be recommended for myelosuppression patients was limited due to poor methodological quality. Thus, more rigorously designed randomized-controlled trials (RCTs) are required to assess the efficacy of ginsenoside Rg3 for myelosuppression.
PubMed: 32477128
DOI: 10.3389/fphar.2020.00649 -
Chinese Journal of Integrative Medicine Mar 2016To review the anticancer effects of Radix astragali (RA), one of the most commonly used herbs to manage cancer in East Asia, and its constituents and to provide evidence... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To review the anticancer effects of Radix astragali (RA), one of the most commonly used herbs to manage cancer in East Asia, and its constituents and to provide evidence of clinical usage through previously performed clinical studies.
METHODS
Preclinical and clinical studies related to the anticancer effects of RA were searched from inception to November 2013 in electronic databases. Two reviewers independently investigated 92 eligible studies, extracted all the data of studies and appraised methodological quality of clinical trials. The studies were categorized into in vitro and in vivo experimental studies and clinical studies, and analyzed by saponins, polysaccharides, and flavonoids of RA constituents, RA fraction, and whole extract.
RESULTS
In preclinical studies, RA was reported to have tumor growth inhibitory effects, immunomodulatory effects, and attenuating adverse effects by cytotoxic agents as well as chemopreventive effects. Saponins seemed to be the main constituents, which directly contributed to suppression of tumor growth through the activation of both intrinsic and extrinsic apoptotic pathway, modulation of intracellular signaling pathway, and inhibition of invasion and angiogenesis. Flavonoids suppressed tumor growth through the similar mechanisms with saponins. Polysaccharides showed immunomodulatory effects, contributing tumor shrinkages in animal models, despite the low cytotoxicity to cancer cells. Most of the clinical studies were performed with low evidence level of study designs because of various limitations. RA whole extracts and polysaccharides of RA were reported to improve the quality of life and ameliorate myelosuppression and other adverse events induced by cytotoxic therapies.
CONCLUSION
The polysaccharides, saponins, and flavonoids of RA, and the whole extract of RA have been widely reported with their anticancer effects in preclinical studies and showed a potential application as a adjunctive cancer therapeutics with the activities of immunomodulation, anti-proliferation and attenuation of adverse effects induced by cytotoxic therapy.
Topics: Animals; Antineoplastic Agents; Astragalus propinquus; Clinical Trials as Topic; Drugs, Chinese Herbal; Humans
PubMed: 26643507
DOI: 10.1007/s11655-015-2324-x -
Journal of Infection and Chemotherapy :... Aug 2021The incidence of linezolid-induced myelosuppression in pediatric patients was reported at large difference among prospective studies, with a range of 0-24%.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence of linezolid-induced myelosuppression in pediatric patients was reported at large difference among prospective studies, with a range of 0-24%. Additionally, there is little study which evaluated the impact of linezolid administration period on myelosuppression in pediatric patients, while it is one of the most frequent reason that linezolid therapy has to be discontinued in adult patients. Here, we performed a systematic review and meta-analysis to reveal the incidence of linezolid-induced thrombocytopenia and anemia, and impact of the administration period of linezolid on myelosuppression based on individual data analysis of pediatric patients.
METHODS
We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed, and CINAHL until April 2020. We investigated the incidence of linezolid-induced thrombocytopenia and anemia using pooled analysis, and evaluated the impact of linezolid administration period on myelosuppression using meta-analysis.
RESULTS
Thirteen studies with 969 pediatric patients were identified. The pooled incidences of thrombocytopenia and anemia were 9% (95% confidence interval (CI), 3-18%) and 4% (95% CI, 0-12%), respectively. Our meta-analysis showed the extension of linezolid administration period (more than 14 days) resulted in higher incidence of thrombocytopenia (OR 4.86, 95% CI 1.10-21.55) and anemia (OR 4.57, 95% CI 0.13-160.49).
CONCLUSIONS
The incidence of linezolid-induced myelosuppression in pediatric patients was less than 10%. However, our meta-analysis revealed linezolid administration period for more than 14 days was one of risk factors associated with linezolid-induced myelosuppression. Therefore, especially for pediatric patients treated with linezolid for more than 14 days, careful monitoring of myelosuppression is required.
Topics: Adult; Child; Gram-Positive Bacterial Infections; Humans; Leukopenia; Linezolid; Prospective Studies; Thrombocytopenia
PubMed: 33727025
DOI: 10.1016/j.jiac.2021.03.003 -
PloS One 2015Mycophenolate is increasingly being used in the rheumatic diseases. Its main adverse effects are gastrointestinal, myelosuppression, and infection. These may limit use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mycophenolate is increasingly being used in the rheumatic diseases. Its main adverse effects are gastrointestinal, myelosuppression, and infection. These may limit use in systemic sclerosis (SSc) since gastrointestinal involvement is common. The objective of this study is to evaluate gastrointestinal adverse events of mycophenolate in SSc. Secondarily we evaluated other adverse events, and the effectiveness of mycophenolate in skin and lung disease.
METHODS
A literature search of Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL (inception-2013) was performed. Studies reporting use of mycophenolate in SSc patients, adverse events, modified Rodnan skin score (MRSS), forced vital capacity (FVC), or diffusing capacity of carbon monoxide (DLCO) were included. The primary outcome was gastrointestinal events occurring after the initiation of mycophenolate. Secondary safety outcomes included myelosuppression, infection, malignancy, and death after the initiation of mycophenolate.
RESULTS
617 citations were identified and 21 studies were included. 487 patients were exposed to mycophenolate. The mean disease duration ranged between 0.8-14.1 years. There were 18 deaths and 90 non-lethal adverse events. The non-lethal adverse events included 43 (47.7%) gastrointestinal events, 34 (26%) infections, 6 (5%) cytopenias and 2 (2%) malignancies. The most common gastrointestinal events included diarrhea (n=18 (14%)), nausea (n=12 (9%)), and abdominal pain (n=3 (2%)). The rate of discontinuation ranged between 8%-40%. Seven observational studies reported improvement or stabilization in FVC, and 5 studies report stabilization or improvement in MRSS.
CONCLUSION
Mycophenolate-associated gastrointestinal adverse events are common in SSc, but not severe enough to preclude its use. Observational data suggests mycophenolate may be effective in improving or stabilizing interstitial lung disease, and skin involvement.
Topics: Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Mycophenolic Acid; Respiratory Function Tests; Scleroderma, Systemic; Skin; Treatment Outcome
PubMed: 25933090
DOI: 10.1371/journal.pone.0124205