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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 -
Frontiers in Oncology 2022mutations are associated with poor prognosis in the vast majority of cancers. In this study, we present a pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient...
mutations are associated with poor prognosis in the vast majority of cancers. In this study, we present a pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient carrying a rare c.C275T mutation. This extremely rare mutation affects an amino acid residue located between the TAD domain and the DNA-binding domain of p53. The patient was resistant to most conventional chemotherapy regimens and remained minimal residual disease (MRD)-positive after five rounds of such regimens. We tested the sensitivity of the patient's leukemic cells to 21 anti-cancer drugs by performing drug sensitivity assays. The results showed that bortezomib had a very strong killing effect on the patient's leukemic cells. Therefore, we subsequently treated the patient with bortezomib combined with vindesine, cytarabine, and fludarabine. After one course of treatment, the patient became MRD-negative, and there was no recurrence during a 9-month follow-up. In conclusion, our report suggests that the c.C275T mutation is associated with poor prognosis in B-ALL. Fortunately, bortezomib combined with chemotherapy could achieve a better therapeutic effect than conventional regimens in this type of ALL.
PubMed: 36798689
DOI: 10.3389/fonc.2022.1018250 -
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 -
Blood Advances Aug 2023Most patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and... (Clinical Trial)
Clinical Trial
Most patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Patients with progression or relapse in the central nervous system (CNS) face dismal outcomes. The impact of more aggressive regimens used in frontline therapy has not been systematically investigated in this context. To this end, we analyzed a large cohort of 2203 younger patients with DLBCL treated on 10 German (German Lymphoma Alliance [GLA]/The German High Grade Non-Hodgkin's Lymphoma Study Group [DSHNHL]) and French (The Lymphoma Study Association [LYSA]) prospective phase 2 and 3 trials after first-line therapy with R-CHOP, R-CHOEP (R-CHOP + etoposide), dose-escalated R-CHOEP followed by repetitive stem cell transplantation (R-MegaCHOEP), or R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, and prednisone) followed by consolidation including multiple drugs crossing the blood-brain barrier (BBB). Patients with DLBCL with an age-adjusted International Prognostic Index (aaIPI) of 0 to 1 showed very low cumulative incidence rates of CNS relapse regardless of first-line therapy and CNS prophylaxis (3-year cumulative incidences 0%-1%). Younger high-risk patients with aaIPI of 2 to 3 had 3-year cumulative incidence rates of 1.6% and 4% after R-ACVBP plus consolidation or R-(Mega)CHO(E)P, respectively (hazard ratio 2.4; 95% confidence interval: 0.8-7.4; P = .118). Thus, for younger high-risk patients, frontline regimens incorporating agents crossing the BBB may reduce often fatal CNS relapse.
Topics: Humans; Rituximab; Prednisone; Prospective Studies; Antibodies, Monoclonal, Murine-Derived; Neoplasm Recurrence, Local; Lymphoma, Large B-Cell, Diffuse; Vincristine; Chronic Disease; Central Nervous System; Cyclophosphamide; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36716220
DOI: 10.1182/bloodadvances.2022008888 -
Frontiers in Immunology 2022Cardiac involvement in hematological malignancies is uncommon, with only a few cases reported to date, and it often leads to a poor prognosis. Here, we report a case of...
Cardiac involvement in a patient with B-cell lymphoblastic lymphoma/acute lymphoblastic leukemia and a history of allogeneic hematopoietic stem cell transplantation and CAR T-cell therapy: A case report.
Cardiac involvement in hematological malignancies is uncommon, with only a few cases reported to date, and it often leads to a poor prognosis. Here, we report a case of a 42-year-old woman with a history of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for B-cell lymphoblastic lymphoma/acute lymphoblastic leukemia in whom cardiac mass and myocardial infiltration were detected. Prior to this presentation, massive pericardial effusion had occurred 6 months after CAR T-cell therapy, which was improved ultrasound-guided pericardiocentesis. We observed elevated cytokine levels and increased copy number of CAR DNA in both pericardial effusion and serum. Upon detecting cardiac mass and myocardial infiltration, the patient was administered tocilizumab (a humanized monoclonal antibody against IL-6 receptor), which controlled the serum cytokine levels, and reduced intensity chemotherapy, including vindesine, cyclophosphamide, and prednisolone. However, the patient finally died of multiple organ failure. To the best of our knowledge, this is the first report on the development of a cardiac mass and occurrence of myocardial infiltration after allo-HSCT and CAR T-cell therapy. This report may provide supporting data for the early diagnosis and immediate treatment of patients with cardiac involvement.
Topics: Female; Humans; Adult; Immunotherapy, Adoptive; Pericardial Effusion; T-Lymphocytes; Hematopoietic Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Antigens, CD19
PubMed: 36685607
DOI: 10.3389/fimmu.2022.1052336 -
Medicine Dec 2022Embryonal rhabdomyosarcoma (ERMS) is a major subtype of rhabdomyosarcoma, mainly affect children. There is seldom report for perineal ERMS in adults, since its rare...
RATIONALE
Embryonal rhabdomyosarcoma (ERMS) is a major subtype of rhabdomyosarcoma, mainly affect children. There is seldom report for perineal ERMS in adults, since its rare location and the age.
PATIENT CONCERNS
A 20-year old male adult was admitted due to the perineal mass.
DIAGNOSES
Diagnosis by histopathological examination of the biopsy sample was ERMS. Magnetic resonance imaging showed the tumor was found in the perineal region, with metastasis to pelvic cavity, right testis, lymph nodes and bone.
INTERVENTIONS
The patient received Isophosphamide and Epirubicin for 4 cycles, followed by Irinotecan and Vindesine Sulfate for 2 cycles, then cisplatin, Dacarbazine and Apatinib for 3 cycles.
OUTCOME
The patient showed no response to chemotherapy.
LESSONS
Perineal ERMS in adults is very rare. There is still no standard therapy for adult ERMS. Personalized therapy might be promising treatment for each individual.
Topics: Male; Child; Humans; Adult; Young Adult; Rhabdomyosarcoma, Embryonal; Rhabdomyosarcoma; Ifosfamide; Irinotecan; Perineum
PubMed: 36596039
DOI: 10.1097/MD.0000000000032529 -
American Journal of Hematology Apr 2023Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm mainly affecting young children. This study aimed to evaluate the outcomes of 449 pediatric patients...
Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm mainly affecting young children. This study aimed to evaluate the outcomes of 449 pediatric patients enrolled in the BCH-LCH 2014 study. 52.6% of patients were classified with single-system (SS) LCH, 28.1% with multisystem (MS) risk organ negative (RO-) LCH, and 19.4% with MS RO+ LCH. Three hundred ninety-six patients (88.2%) were initially treated with first-line therapy based on the vindesine-prednisone combination. One hundred thirty-nine patients who lacked a response to initial treatment were shifted to second-line therapy, 72 to intensive treatment Arm S1 (a combination of cytarabine, cladribine, vindesine, and dexamethasone), and 67 to Arm S2 (without cladribine). The 5-year overall survival (OS), progression-free survival (PFS), and relapse rates were 98.2% (median: 97.6 months), 54.6% (median: 58.3 months), and 29.9%, respectively. MS RO+ patients had the worst prognosis among the three clinical subtypes. For the patients initially treated with first-line therapy, the 5-year OS, PFS, and relapse rates were 99.2%, 54.5%, and 29.3%, respectively. Patients in Arm S1 had a significantly better prognosis than patients in Arm S2 (5-year PFS: 69.2% vs. 46.5%, p = .042; relapse rate: 23.4% vs. 44.2%, p = .031). Multivariate analysis revealed that early treatment response, the involvement of RO, skin, and oral mucosa, as well as laboratory parameters, including CRP and γ-GT, were independent risk factors for the PFS of LCH. Thus, the prognosis of LCH in children has been improved significantly with stratified chemotherapy, and progression and relapse remained the challenges, especially for RO+ patients.
Topics: Child; Humans; Child, Preschool; Prognosis; Treatment Outcome; Cladribine; Vindesine; Risk Factors; Histiocytosis, Langerhans-Cell; Recurrence; Retrospective Studies
PubMed: 36594188
DOI: 10.1002/ajh.26829 -
Translational Cancer Research Sep 2022Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent B cell lymphoma. Its occurrence in the pleura is rare, with atypical clinical manifestations. MALT of...
BACKGROUND
Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent B cell lymphoma. Its occurrence in the pleura is rare, with atypical clinical manifestations. MALT of the pleura is easily misdiagnosed. This is the first case report of pleural MALT lymphoma in China.
CASE DESCRIPTION
We report the case of a 54-year-old Chinese man with no notable medical history who complained of cough, sputum, and shortness of breath for 3 months. He had a positive purified protein derivative (PPD) test. An initial misdiagnosis of pleural tuberculosis was corrected, after 3 thoracoscopic biopsies and tests, to primary pleural MALT lymphoma. He received treatments of R-CHOP (rituximab, cyclophosphamide, epirubicin, vindesine and prednisolone) and traditional Chinese medicine. The patient was followed for 3 years until June 2022, with no obvious respiratory symptoms. Pleural MALT lymphoma is extremely rare, with only a few cases reported. This article describes our case, and includes an overview of 15 previously reported cases to summarize the characteristics, treatments, and prognosis of primary pleural MALT lymphoma.
CONCLUSIONS
Pleural MALT lymphoma is rare, and a correct diagnosis depends on tissue biopsy, immunohistochemical staining, and detection of gene rearrangement. Thoracoscopy is important to diagnose this disease. Multiple thoracoscopic biopsies may be necessary.
PubMed: 36237246
DOI: 10.21037/tcr-22-671 -
World Journal of Clinical Cases Jul 2022Germ cell tumors (GCTs) account for 2% of human malignancies but are the most common malignant tumors among males aged 15-35. Since 1983, an association between...
BACKGROUND
Germ cell tumors (GCTs) account for 2% of human malignancies but are the most common malignant tumors among males aged 15-35. Since 1983, an association between mediastinal GCT (MGCT) and hematologic malignancies has been recognized.
CASE SUMMARY
We report a case in which malignant histiocytosis was associated with mediastinal GCTs. The clinical data of a male patient with MGCT admitted to Beijing Children's Hospital were collected retrospectively. The patient was first diagnosed according to imaging and pathological features as having MGCT, and was treated with surgery and chemotherapy. One year after stopping chemotherapy, imaging showed metastases in the right supraclavicular, mediastinum, hilar region and retroperitoneal lymph node, right pleura, right lung, and right para-cardiac margin. Pathological diagnosis of the liver nodular and hilar lymph nodes included systemic juvenile xanthogranuloma and Rosai-Dorfman lesions with malignant transformation ( morphological characteristics and immunophenotype of histiocytic sarcoma). Following diagnosis, the patient accepted chemotherapy with vindesine, cytarabine and dexamethasone. Positron emission tomography-computed tomography showed partial remission. The patient was followed-up for 10 mo after the diagnosis of malignant histiocytosis, and no sign of progression or relapse was observed.
CONCLUSION
Physicians should recognize the possibility of hematologic malignancies being associated with MGCT. Suitable sites should be selected for pathological examination.
PubMed: 36051154
DOI: 10.12998/wjcc.v10.i20.7116 -
BMC Cancer Jun 2022Concurrent chemoradiotherapy (CCRT) has become the cornerstone of treatment for patients with locally advanced non-small cell lung cancer (LA-NSCLC). The aim of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Concurrent chemoradiotherapy (CCRT) has become the cornerstone of treatment for patients with locally advanced non-small cell lung cancer (LA-NSCLC). The aim of this study was to compare the efficacies and toxicities of different CCRT regimens in the treatment of LA-NSCLC by adopting a network meta-analysis (NMA).
METHODS
An exhaustive search of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted to identify relevant studies from inception to October 1, 2020. Direct and indirect evidence was combined to calculate the odds radios (ORs) and 95% confidence intervals (CIs), as well as to plot the surface under the cumulative ranking (SUCRA) curves. Cluster analyses were adopted to compare the efficacies and toxicities of different CCRT regimens according to the similarity of 2 variables. Publication bias was detected by comparison-adjusted funnel plots.
RESULTS
Twenty-two studies were enrolled in this NMA, including 18 regimens: CCRT (cisplatin + etoposide), CCRT (carboplatin + paclitaxel), CCRT (pemetrexed + carboplatin), CCRT (pemetrexed + cisplatin), CCRT (docetaxel + cisplatin), CCRT (S-1 + cisplatin), CCRT (mitomycin + vindesine + cisplatin), CCRT (cisplatin + vinorelbine), CCRT (cisplatin), CCRT (etoposide + cisplatin + amifostine), RT, CCRT (5-FU), CCRT (paclitaxel + cisplatin), CCRT (irinotecan + carboplatin), CCRT (nedaplatin), CCRT (carboplatin + etoposide), CCRT (paclitaxel), and CCRT (carboplatin). The results indicated that the regimens with CCRT (cisplatin + etoposide), CCRT (carboplatin + paclitaxel), CCRT (pemetrexed + cisplatin), CCRT (S-1 + cisplatin), and CCRT (cisplatin + vinorelbine) had relatively better efficacies compared with other regimens. As for toxicities of different CCRT regimens, the CCRT (carboplatin + paclitaxel), CCRT (pemetrexed + cisplatin), and CCRT (docetaxel + cisplatin) were relatively lower.
CONCLUSIONS
Our study demonstrated that CCRT (pemetrexed + cisplatin) and CCRT (carboplatin + paclitaxel) might be the best options for the treatment of LA-NSCLC, and CCRT (pemetrexed + cisplatin) had the highest 3-year overall survival (OS) rate.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Docetaxel; Etoposide; Humans; Irinotecan; Lung Neoplasms; Network Meta-Analysis; Paclitaxel; Pemetrexed; Vinorelbine
PubMed: 35725420
DOI: 10.1186/s12885-022-09717-8