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Frontiers in Pediatrics 2021To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG). Clinical data of children with JXG who...
To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG). Clinical data of children with JXG who were hospitalized in Beijing Children's Hospital, Capital Medical University, from January 2012 to December 2019 were retrospectively analyzed, including clinical manifestations, laboratory determinations, treatment, and prognosis of the children. Patients were treated with vindesine + prednisone as the first-line treatment and cytarabine + vindesine + dexamethasone ± cladribine as the second-line treatment. Ten patients, including 8 males and 2 females, with a median of onset age of 1.95 (0.80-7.30) years, exhibited multi-system dysfunction. The median age of diagnosis was 2.45 (1.30-12.10) years. The most common location of extracutaneous lesions was the central nervous system (6 cases), followed by the lung (5 cases) and bone (4 cases). Nine patients underwent first-line chemotherapy, and 6 patients underwent second-line chemotherapy, including 5 patients with poorly controlled disease after first-line treatment. The median observation time was 29 (3-115) months. Nine patients survived, whereas one patient died of respiratory failure caused by pulmonary infection. At the end of follow-up, 7 patients were in active disease (AD)/regression state (AD-better), and 2 patients were in an AD/stable state (AD-stable). Three patients had permanent sequelae, mainly central diabetes insipidus. The rates of response to the first-line treatment and the second-line treatment were 40.0 and 66.7% respectively. The chemotherapy protocol for Langerhans cell histiocytosis (LCH) may be effective for patients with systemic JXG. Central nervous system involvement may not impact overall survival, but serious permanent sequelae may occur.
PubMed: 34178890
DOI: 10.3389/fped.2021.672547 -
British Journal of Haematology Nov 2021Adult T-cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different... (Comparative Study)
Comparative Study
Adult T-cell leukaemia/lymphoma (ATL) patients have a poor prognosis. Here, we investigated the impact of TP53 gene mutations on prognosis of ATL treated in different ways. Among 177 patients, we identified 47 single nucleotide variants or insertion-deletions (SNVs/indels) of the TP53 gene in 37 individuals. TP53 copy number variations (CNVs) were observed in 38 patients. Altogether, 67 of 177 patients harboured TP53 SNVs/indels or TP53 CNVs, and were categorized as having TP53 mutations. In the entire cohort, median survival of patients with and without TP53 mutations was 1·0 and 6·7 years respectively (P < 0·001). After allogeneic haematopoietic stem cell transplantation (HSCT), median survival of patients with (n = 16) and without (n = 29) TP53 mutations was 0·4 years and not reached respectively (P = 0·001). For patients receiving mogamulizumab without allogeneic HSCT, the median survival from the first dose of antibody in patients with TP53 mutations (n = 27) was only 0·9 years, but 5·1 years in those without (n = 42; P < 0·001). Thus, TP53 mutations are associated with unfavourable prognosis of ATL, regardless of treatment strategy. The establishment of alternative modalities to overcome the adverse impact of TP53 mutations in patients with ATL is required.
Topics: Adult; Aged; Aged, 80 and over; Allografts; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; CD28 Antigens; Carboplatin; Cyclophosphamide; DNA Copy Number Variations; Doxorubicin; Etoposide; Female; Genes, p53; Hematopoietic Stem Cell Transplantation; Humans; INDEL Mutation; Kaplan-Meier Estimate; Lenalidomide; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Mutation; Nitrosourea Compounds; Polymorphism, Single Nucleotide; Prednisolone; Prednisone; Prognosis; Receptors, CCR4; Vincristine; Vindesine
PubMed: 34405395
DOI: 10.1111/bjh.17749 -
Journal of Clinical Pharmacy and... Dec 2022Methotrexate (MTX) is an antimetabolic antitumor drug with high individual differences and may lead to severe toxicities in a considerable number of patients. This study...
WHAT IS KNOWN AND OBJECTIVE
Methotrexate (MTX) is an antimetabolic antitumor drug with high individual differences and may lead to severe toxicities in a considerable number of patients. This study aimed to explore the factors influencing major adverse events in patients with primary central nervous system lymphoma treated with high-dose MTX (HD-MTX), which could be useful in clinical practice.
METHODS
Fifty-four patients who received 175 courses of MTX at 3-8 g/m between January 2015 and December 2016 were enrolled in this study. We assessed the association between clinical characteristics, MTX pharmacokinetics, MTX delayed elimination, and adverse events, including hepatotoxicity, acute kidney injury (AKI), and myelosuppression.
RESULTS AND DISCUSSION
A total of 124 adverse events occurred after MTX infusion. Using independent sample t-tests, we found that patients with myelosuppression had higher MTX area under the concentration-time curve up to 48 h after infusion (AUC ) (p = 0.001) and MTX peak concentration (C ) (p = 0.002). MTX concentrations at 48 and 72 h were higher in patients with AKI than in those without (p = 0.034 and p = 0.041, respectively). Using chi-square tests, we found that AKI was correlated with MTX elimination at either 48 h or 72 h (22.1% vs. 8.2%, p = 0.010). By multivariate logistic regression model, our results showed that baseline level of ALT and WBC had a significant effect on hepatotoxicity (OR = 1.079, 95% CI 1.044-1.116, p = 6.9 × 10 ; OR = 0.808, 95% CI 0.711-0.917, p = 0.001, respectively). Patient's age, eGFR before MTX infusion, and co-administration of vindesine had a significant effect on AKI (OR = 0.960, 95% CI 0.935-0.986, p = 0.003; OR = 1.009, 95% CI 1.001-1.017, p = 0.034; OR = 5.463, 95% CI 1.793-16.646, p = 0.003, respectively). LDH and Co-administration of vindesine had a significant effect on myelosuppression (OR = 0.985, 95% CI 0.972-0.998, p = 0.025; OR = 3.070, 95% CI 1.032-9.133, p = 0.044).
WHAT IS NEW AND CONCLUSION
Our study demonstrated that co-administration of VDS, eGFR before MTX infusion, and the baseline index of laboratory examinations including ALT, WBC, LDH may be useful biomarkers for predicting MTX-induced toxicities.
Topics: Humans; Methotrexate; Antimetabolites, Antineoplastic; Vindesine; Drug-Related Side Effects and Adverse Reactions; Acute Kidney Injury; Risk Factors; Chemical and Drug Induced Liver Injury; Central Nervous System; Lymphoma
PubMed: 36259502
DOI: 10.1111/jcpt.13791 -
European Journal of Medical Research Mar 2023An immune-related gene signature (IGS) was established for discriminating prognosis, predicting benefit of immunotherapy, and exploring therapeutic options in...
BACKGROUND
An immune-related gene signature (IGS) was established for discriminating prognosis, predicting benefit of immunotherapy, and exploring therapeutic options in hepatocellular carcinoma (HCC).
METHODS
Based on Immune-related hub genes and The Cancer Genome Atlas (TCGA) LIHC dataset (n = 363), an immune-related gene signature (IGS) was established by least absolute shrinkage and selection operator (LASSO) analysis. The prognostic significance and clinical implications of IGS were verified in International Cancer Genome Consortium (ICGC) and Chinese HCC (CHCC) cohorts. The molecular and immune characteristics and the benefit of immune checkpoint inhibitor (ICI) therapy in IGS-defined subgroups were analyzed. In addition, by leveraging the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing datasets, we determined the potential therapeutic agents for high IGS-risk patients.
RESULTS
The IGS was constructed based on 8 immune-related hub genes with individual coefficients. The IGS risk model could robustly predict the survival of HCC patients in TCGA, ICGC, and CHCC cohorts. Compared with 4 previous established immune genes-based signatures, IGS exhibited superior performance in survival prediction. Additionally, for immunological characteristics and enriched pathways, a low-IGS score was correlated with IL-6/JAK/STAT3 signaling, inflammatory response and interferon α/γ response pathways, low TP53 mutation rate, high infiltration level, and more benefit from ICI therapy. In contrast, high IGS score manifested an immunosuppressive microenvironment and activated aggressive pathways. Finally, by in silico screening potential compounds, vindesine, ispinesib and dasatinib were identified as potential therapeutic agents for high-IGS risk patients.
CONCLUSIONS
This study developed a robust IGS model for survival prediction of HCC patients, providing new insights into integrating tailored risk stratification with precise immunotherapy and screening potentially targeted agents.
Topics: Humans; Carcinoma, Hepatocellular; Immunotherapy; Interferon-gamma; Liver Neoplasms; Prognosis; Tumor Microenvironment
PubMed: 36918943
DOI: 10.1186/s40001-023-01091-w -
Leukemia Research Sep 2020To explore the effectiveness and safety of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide combination (SVILE regimen) in the treatment of...
SVILE regimen, a combination of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide, for treating relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type.
OBJECTIVE
To explore the effectiveness and safety of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide combination (SVILE regimen) in the treatment of relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (R/R-ENKTL).
METHODS
This descriptive, retrospective medical chart review assessed data from 20 R/R-ENKTL patients treated with the SVILE regimen between November 2014 and August 2019. Complete response (CR) rate, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) since SVILE treatment were analysed.
RESULTS
After receiving 1-5 SVILE regimen chemotherapy cycles (median 2 cycles), patients had ORR and CR rates of 70.0 % and 45.0 %, respectively. Stage Ⅰ/Ⅱ patients had CR rate of 100.0 % and stage Ⅲ/Ⅳ patients had ORR and CR rates of 60.0 % and 26.7 %, respectively. Three-year PFS and OS rates of the 20 patients were 43.8 % and 54.2 %, respectively. Three-year PFS and OS rates of stage Ⅰ/Ⅱ patients and stage Ⅲ/Ⅳ patients were 100.0 % vs. 26.7 % and 100.0 % vs. 40.0 % (P < 0.05), respectively. The PFS and OS of patients who achieved CR after SVILE chemotherapy were significantly better than those of non-CR patients. The main adverse events were reversible haematological toxicity.
CONCLUSIONS
The SVILE regimen is a new treatment option that is effective and safe for R/R-ENKTL patients.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Dexamethasone; Drug Resistance, Neoplasm; Etoposide; Female; Follow-Up Studies; Humans; Ifosfamide; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Nose Neoplasms; Polyethylene Glycols; Prognosis; Retrospective Studies; Salvage Therapy; Survival Rate; Vindesine; Young Adult
PubMed: 32721642
DOI: 10.1016/j.leukres.2020.106422 -
Theranostics 2018Vinca alkaloids, the well-known tubulin-binding agents, are widely used for the clinical treatment of malignant tumors. However, little attention has been paid to their...
Vinca alkaloids, the well-known tubulin-binding agents, are widely used for the clinical treatment of malignant tumors. However, little attention has been paid to their vascular disrupting effects, and the underlying mechanisms remain largely unknown. This study aims to investigate the vascular disrupting effect and the underlying mechanisms of vinca alkaloids. The capillary disruption assay and aortic ring assay were performed to evaluate the vascular disrupting effect of desacetylvinblastine monohydrazide (DAVLBH), a derivate of vinblastine, and the vascular disrupting effect was assessed on HepG2 xenograft model using magnetic resonance imaging, hematoxylin and eosin staining and immunohistochemistry. Tubulin polymerization, endothelial cell monolayer permeability, western blotting and immunofluorescence assays were performed to explore the underlying mechanisms of DAVLBH-mediated tumor vascular disruption. DAVLBH has potent vascular disrupting activity both and . DAVLBH disrupts tumor vessels in a different manner than classical tubulin-targeting VDAs; it inhibits microtubule polymerization, promotes the internalization of vascular endothelial cadherin (VE-cadherin) and inhibits the recycling of internalized VE-cadherin to the cell membrane, thus increasing endothelial cell permeability and ultimately resulting in vascular disruption. DAVLBH-mediated promotion of VE-cadherin internalization and inhibition of internalized VE-cadherin recycling back to the cell membrane are partly dependent on inhibition of microtubule polymerization, and Src activation is involved in DAVLBH-induced VE-cadherin internalization. This study sheds light on the tumor vascular disrupting effect and underlying mechanisms of vinca alkaloids and provides new insight into the molecular mechanism of tubulin-targeting VDAs.
Topics: Animals; Antigens, CD; Cadherins; Capillary Permeability; Cell Line, Tumor; Cells, Cultured; Endothelial Cells; Endothelium, Vascular; Hep G2 Cells; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Rats; Rats, Sprague-Dawley; Vindesine
PubMed: 29290815
DOI: 10.7150/thno.22222 -
Cancer Science Dec 2020Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasm and is classified into four subtypes (acute, lymphoma, chronic, and smoldering) according to the... (Observational Study)
Observational Study
Adult T-cell leukemia/lymphoma (ATL) is a mature T-cell neoplasm and is classified into four subtypes (acute, lymphoma, chronic, and smoldering) according to the Shimoyama classification, established in 1991 through several nationwide surveys based on the clinical diversity of patients diagnosed in 1983-1987 in Japan. Thereafter, no such studies have been conducted. Recently, we conducted a nationwide hospital survey using the method of the 1980s studies, collected baseline data on 996 ATL patients diagnosed in 2010-2011 from 126 hospitals, and reported their unique epidemiological characteristics. Here, we report the follow-up results of registered ATL patients with the goal of evaluating current prognoses and treatment modalities as of 2016-2017. Of 770 evaluable patients, 391 (50.8%) had acute-type, 192 (24.9%) had lymphoma-type, 106 (13.8%) had chronic-type, and 81 (10.5%) had smoldering-type ATL. The initial therapy regimens used for acute/lymphoma-type ATL were vincristine, cyclophosphamide, doxorubicin and prednisone, followed by doxorubicin, ranimustine, and prednisone and then by vindesine, etoposide, carboplatin, and prednisone (VCAP-AMP-VECP)-like in 38.5/41.7% and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like in 14.6/13.7% of patients. Allogeneic hematopoietic stem cell transplantation was used to treat 15.9/10.4% of acute/lymphoma-type ATL patients. The 4-year survival rates (the median survival time, days) for acute-, lymphoma-, unfavorable chronic-, favorable chronic-, and smoldering-type ATL were 16.8% (252), 19.6% (305), 26.6% (572), 62.1% (1937), and 59.8% (1851), respectively. The 4-year survival rates for acute- and lymphoma-type ATL improved compared with those reported in 1991, but those for chronic- and smoldering-type ATL were not. Further efforts are warranted to develop more efficient therapeutic strategies to improve the prognosis of ATL in Japan.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cause of Death; Cyclophosphamide; Doxorubicin; Female; Health Care Surveys; Hematopoietic Stem Cell Transplantation; Hospitals; Humans; Japan; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Nitrosourea Compounds; Prednisone; Prognosis; Retrospective Studies; Survival Rate; Vincristine; Vindesine
PubMed: 32976684
DOI: 10.1111/cas.14658 -
Cancer Management and Research 2018Combined chemotherapy is the cornerstone treatment for patients with advanced Hodgkin lymphoma (HL). The objective of our study was to perform a network meta-analysis of...
BACKGROUND
Combined chemotherapy is the cornerstone treatment for patients with advanced Hodgkin lymphoma (HL). The objective of our study was to perform a network meta-analysis of the efficacy of different chemotherapy regimens in adults with advanced-stage HL.
MATERIALS AND METHODS
We searched for relevant randomized controlled trials (RCTs) in titles/abstracts in PubMed, Embase, and the Cochrane Library. The search was last updated on April 3, 2018. RCTs that assessed the effectiveness of one of the following treatments were included: doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); four cycles of increased dose of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by two or four cycles of standard dose of BEACOPP (4× BEACOPP + 2 or 4× BEACOPP); brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD); doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (Stanford V); mechlorethamine (cyclophosphamide), vincristine, procarbazine, and prednisone (M[C] OPP); sequential or alternating chemotherapy regimens with ABVD as the footstone (eg, COPP/ABVD or mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/ABVD); eight cycles of BEACOPP; hybrid MOPP/ABV; and M[C]EC (M[C]OPP with epidoxorubicin, bleomycin, vinblastine [EBV], and lomustine, doxorubicin, and vindesine [CAD]).
RESULTS
Overall, we screened 3,564 citations and deemed 18 reports of 16 trials eligible and included them in our network meta-analysis. A total of 11,928 participants were randomly assigned to one of the 12 combinations of chemotherapy regimens, of which 11,476 participants were analyzed. For the overall survival (OS), no differences were observed within any interventions when the ABVD regimen was used as the reference treatment. Similarly, relative to A+AVD, 8× BEACOPP and 6× BEACOPP also showed no differences (HR =1.07, 95% credible interval (CrI): 0.58-1.95; HR =0.62, 95% CrI: 0.16-1.83; and HR =0.71, 95% CrI: 0.30-1.72, respectively). In terms of complete remission (CR), enough evidence exists to support a maximum clinical treatment effect for 6× BEACOPP (OR =1.88, 95% CrI: 1.20-2.96; and OR =3.43, 95% CrI: 1.87-6.24).
CONCLUSION
When compared across the 12 combined chemotherapy regimens, six cycles of BEACOPP may be the optimal treatment for patients with advanced-stage HL.
PubMed: 30538551
DOI: 10.2147/CMAR.S179356 -
Anti-cancer Drugs Apr 2023Although Philadelphia chromosome-positive acute leukemia (Ph + -ALL) has been revolutionized with tyrosine kinase inhibitors (TKIs), resistance and mutation are...
Although Philadelphia chromosome-positive acute leukemia (Ph + -ALL) has been revolutionized with tyrosine kinase inhibitors (TKIs), resistance and mutation are universal events during treatment with first-generation and second-generation TKIs. The present third-generation TKI has a dose-dependent, increased risk of serious cardiovascular events and the sensitivity is poor for patients with ≥2 mutations accompanied by the T315I mutation. Thus, novel and well-tolerated TKIs should be explored. This study analyzes the efficacy and advert effects of olverembatinib, a novel third TKI, in the treatment of newly diagnosed adult Ph + -ALL in induction therapy. Four adult patients with newly diagnosed Ph + -ALL were treated with olverembatinib as the first-line treatment. For induction therapy, these patients received 40 mg of oral olverembatinib quaque omni die for 28 days, 1 mg/kg/d of prednisone for 14 days, then tapered and stopped at 28 days and vindesine 4 mg/d at days 1, 8 and 15. After induction therapy, these patients received median or high-dose of cytarabine and methotrexate combined with oral olverembatinib as consolidation therapy. Then the allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed. All patients reached complete remission with a complete cytogenetic response after induction therapy. Two patients reached major molecular remission and one with complete molecular remission. Before allo-HSCT, all the patients achieved complete molecular remission. All the patients have survived disease-free for 3-6 months. No severe advert effects were observed. It is well-tolerated and effective for olverembatinib in the treatment of newly diagnosed adult patients with Ph + -ALL. A prospective study should be performed to further testify the role.
Topics: Adult; Humans; Tyrosine Kinase Inhibitors; Philadelphia Chromosome; Prospective Studies; Protein Kinase Inhibitors; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematopoietic Stem Cell Transplantation
PubMed: 36730312
DOI: 10.1097/CAD.0000000000001455 -
Journal of Cancer Research and Clinical... Jun 2023This single-centre study aimed to determine the clinicopathological characteristics and prognosis for patients with co-existing FL and DLBCL components (FL/DLBCL).
PURPOSE
This single-centre study aimed to determine the clinicopathological characteristics and prognosis for patients with co-existing FL and DLBCL components (FL/DLBCL).
METHODS
We retrospectively analysed the clinical characteristics and prognosis of patients diagnosed with FL/DLBCL (n = 56) and with pure FL (n = 260) or de novo DLBCL (n = 812) (controls) between January 2013 and December 2021.
RESULTS
The median age of patients with FL/DLBCL was 52 years. The amount of the DLBCL component ranged from 5 to 95%. Among the 56 FL/DLBCL cases analysed, 67.9% were of germinal centre B-cell (GCB) origin, 26.8% non-GCB origin, and 5.3% were unclassified. The clinical features of patients with FL/DLBCL were intermediate, falling between those of FL and DLBCL. Propensity-score matching was performed for patients with similar baseline characteristics who were receiving the rituximab plus cyclophosphamide, doxorubicin or epirubicin, vindesine, and prednisone (R-CHOP) regimen. Patients with FL/DLBCL showed inferior outcomes compared to those with FL, with a lower complete remission (CR) rate, progression-free survival (PFS), and overall survival (OS). Bone marrow involvement and B symptoms were identified as independent adverse prognostic factors for PFS among patients with FL/DLBCL. Patients with FL/DLBCL presented a lower CR rate and PFS but similar OS to those with DLBCL when receiving the R-CHOP regimen.
CONCLUSION
Patients with FL/DLBCL showed inferior treatment response and survival than those with pure FL and had a lower CR rate and PFS, but similar OS to those with DLBCL in the rituximab era.
Topics: Humans; Middle Aged; Rituximab; Lymphoma, Follicular; Treatment Outcome; Retrospective Studies; Disease-Free Survival; Prognosis; Lymphoma, Large B-Cell, Diffuse; Vincristine; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin
PubMed: 36219261
DOI: 10.1007/s00432-022-04381-8