ABSTRACT
BACKGROUND: The patients with multisystem and risk organ involvement Langerhans cell histiocytosis (MS-RO + LCH) have poor prognosis. The patients with MS-LCH who failed front-line therapy have a high mortality rate and the standard salvage treatment has not been established. The combination of cytarabine (Ara-c), vincristine (VCR) and prednisone might be effective for refractory/relapse MS-RO + LCH, with low toxicity. METHODS: We retrospectively analyzed pediatric refractory/relapse MS-RO + LCH patients treated with the low-dose Ara-c (100mg/m2/d×5days) or high-dose Ara-c (500mg/m2/d×5days) combined with vindesine (VDS) and prednisone in a single center. The efficacy, outcomes and adverse events were analyzed. RESULTS: From January 2013 to December 2016, 13 patients receiving the low-dose Ara-c chemotherapy (LAC) and 7 patients receiving the high-dose Ara-c chemotherapy (HAC) were included in the study. 11 (84.6%) of the 13 patients treated with the LAC regimen and 6 (85.7%) of the 7 patients treated with the HAC regimen had response after four courses of the therapy. All patients in the study were alive during follow-up and the 3-year event-free survival rate (EFS) was 53.7% and 85.7% in the LAC and HAC groups. The most frequent adverse event was Grade 1/2 myelosuppression, which was observed in 38.5% (5/13) and 42.9% (3/7) of the patients receiving the LAC and HAC regimen. CONCLUSIONS: A combination of Ara-c, VDS and prednisone was effective and safe for some patients with refractory/relapse MS-RO + LCH. The high-dose Ara-c regimen was associated with a numerically higher EFS rate.
Subject(s)
Cytarabine , Histiocytosis, Langerhans-Cell , Child , Humans , Cytarabine/adverse effects , Prednisone/adverse effects , Vindesine/therapeutic use , Retrospective Studies , Histiocytosis, Langerhans-Cell/drug therapy , Histiocytosis, Langerhans-Cell/chemically induced , Recurrence , Treatment OutcomeABSTRACT
Vinca alkaloid (VA)-induced ileus, a rare but severe autonomic neuropathy, can be enhanced by concomitant use of antifungal triazole agents. We herein present a case of VA-induced ileus in a 17-year-old girl who was diagnosed with B-cell acute lymphoblastic leukemia. On day 1, the patient received cyclophosphamide, vincristine, and methylprednisolone. On day 2, she began treatment with posaconazole oral suspension at 200 mg three times daily for prophylaxis against invasive fungal infection. On day 5, she began induction therapy consisting of vindesine, methylprednisolone, daunorubicin, and cyclophosphamide. The patient developed severe abdominal pain with marked constipation on day 11 and was diagnosed with incomplete ileus. After switching the antifungal agent to micafungin, performing gastrointestinal decompression, administering parenteral nutrition, and omitting the fourth dose of vindesine, the ileus symptoms were relieved. This case emphasizes the potential interaction between VAs and posaconazole. We also herein present a review of the literature on ileus caused by the combination of VAs and antifungal triazole agents. In clinical practice, physicians and pharmacists should be aware of the possibility of ileus caused by the use of VAs in combination with posaconazole. It is important to reduce complications during chemotherapy to improve patients' prognosis.
Subject(s)
Ileus , Intestinal Obstruction , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Vinca Alkaloids , Female , Humans , Adolescent , Vindesine , Antifungal Agents/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Triazoles/adverse effects , Cyclophosphamide/adverse effectsABSTRACT
Purpose This is a retrospective, single-center PSM study evaluating the efficacy and safety of chidamide combined with the CHOEP (C-CHOEP) regimen versus the single CHOEP regimen in patients with untreated peripheral T cell lymphomas (PTCL). Patients Patients newly diagnosed with PTCL between January 2015 and June 2021 were recruited, and were 1:1 divided into C-CHOEP and CHOEP groups according to their first-line chemotherapy regimens. The PSM method was used to match the baseline variables to balance the confounding factors. Results A cohort of 33 patients each in the C-CHOEP and CHOEP groups was generated after propensity score-matching (PSM). The complete remission (CR) rates of the C-CHOEP regimen were higher than that of the CHOEP regimen (56.3 vs. 25.8%, p = 0.014), whereas the duration of response of the C-CHOEP group was shorter (median DOR 30 vs. 57 months), resulting in roughly similar progression-free survival (PFS) and (overall survival) OS between the two groups. The responding patients who received chidamide maintenance therapy showed a trend of superior PFS and OS compared with patients who did not receive maintenance therapy. Conclusions The C-CHOEP regimen was well tolerated but failed to show advantages over the CHOEP regimen in patients with untreated PTCL; however, the chidamide maintenance may contribute to a more durable response and stable long-term survival (AU)
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, T-Cell, Peripheral/drug therapy , Lymphoma, T-Cell, Peripheral/pathology , Retrospective Studies , Cohort Studies , Prednisone/administration & dosage , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Follow-Up Studies , Propensity Score , Vincristine/administration & dosage , Vindesine/administration & dosageABSTRACT
Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and COVID-19 is still unclear. Here, we explored potential molecular mechanisms and biomarkers for ICM and COVID-19. Common differentially expressed genes (DEGs) of ICM (GSE5406) and COVID-19 (GSE164805) were identified using GEO2R. We performed enrichment and protein-protein interaction analyses and screened key genes. To confirm the diagnostic performance for these hub genes, we used external datasets (GSE116250 and GSE211979) and plotted ROC curves. Transcription factor and microRNA regulatory networks were constructed for the validated hub genes. Finally, drug prediction and molecular docking validation were performed using cMAP. We identified 81 common DEGs, many of which were enriched in terms of their relation to angiogenesis. Three DEGs were identified as key hub genes (HSP90AA1, HSPA9, and SRSF1) in the protein-protein interaction analysis. These hub genes had high diagnostic performance in the four datasets (AUC > 0.7). Mir-16-5p and KLF9 transcription factor co-regulated these hub genes. The drugs vindesine and ON-01910 showed good binding performance to the hub genes. We identified HSP90AA1, HSPA9, and SRSF1 as markers for the co-pathogenesis of ICM and COVID-19, and showed that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis. Vindesine and ON-01910 were predicted as potential therapeutic agents. Our findings will contribute to a deeper understanding of the comorbidity of ICM with COVID-19.
Subject(s)
COVID-19 , Cardiomyopathies , MicroRNAs , Myocardial Ischemia , Humans , Systems Biology , Molecular Docking Simulation , Vindesine , COVID-19/complications , COVID-19/epidemiology , COVID-19/genetics , SARS-CoV-2 , Computational Biology , Myocardial Ischemia/epidemiology , Myocardial Ischemia/genetics , Comorbidity , MicroRNAs/genetics , Biomarkers , Transcription Factors , Gene Expression ProfilingABSTRACT
PURPOSE: This is a retrospective, single-center PSM study evaluating the efficacy and safety of chidamide combined with the CHOEP (C-CHOEP) regimen versus the single CHOEP regimen in patients with untreated peripheral T cell lymphomas (PTCL). PATIENTS: Patients newly diagnosed with PTCL between January 2015 and June 2021 were recruited, and were 1:1 divided into C-CHOEP and CHOEP groups according to their first-line chemotherapy regimens. The PSM method was used to match the baseline variables to balance the confounding factors. RESULTS: A cohort of 33 patients each in the C-CHOEP and CHOEP groups was generated after propensity score-matching (PSM). The complete remission (CR) rates of the C-CHOEP regimen were higher than that of the CHOEP regimen (56.3 vs. 25.8%, p = 0.014), whereas the duration of response of the C-CHOEP group was shorter (median DOR 30 vs. 57 months), resulting in roughly similar progression-free survival (PFS) and (overall survival) OS between the two groups. The responding patients who received chidamide maintenance therapy showed a trend of superior PFS and OS compared with patients who did not receive maintenance therapy. CONCLUSIONS: The C-CHOEP regimen was well tolerated but failed to show advantages over the CHOEP regimen in patients with untreated PTCL; however, the chidamide maintenance may contribute to a more durable response and stable long-term survival.
Subject(s)
Lymphoma, T-Cell, Peripheral , Humans , Lymphoma, T-Cell, Peripheral/drug therapy , Lymphoma, T-Cell, Peripheral/pathology , Prednisone/therapeutic use , Prednisone/adverse effects , Etoposide/therapeutic use , Epirubicin , Vindesine , Follow-Up Studies , Retrospective Studies , Propensity Score , Vincristine/therapeutic use , Vincristine/adverse effects , Doxorubicin , Cyclophosphamide , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
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.
Subject(s)
Cladribine , Histiocytosis, Langerhans-Cell , Child , Humans , Child, Preschool , Prognosis , Treatment Outcome , Cladribine/therapeutic use , Vindesine/therapeutic use , Risk Factors , Histiocytosis, Langerhans-Cell/therapy , Recurrence , Retrospective StudiesABSTRACT
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/m2 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 (AUC0-48h ) (p = 0.001) and MTX peak concentration (Cmax ) (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 × 10-6 ; 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.
Subject(s)
Acute Kidney Injury , Chemical and Drug Induced Liver Injury , Drug-Related Side Effects and Adverse Reactions , Lymphoma , Humans , Methotrexate/adverse effects , Antimetabolites, Antineoplastic/adverse effects , Vindesine , Acute Kidney Injury/chemically induced , Risk Factors , Chemical and Drug Induced Liver Injury/etiology , Central Nervous System , Lymphoma/drug therapyABSTRACT
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.
Subject(s)
Genes, p53 , Leukemia-Lymphoma, Adult T-Cell/genetics , Mutation , Adult , Aged , Aged, 80 and over , Allografts , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CD28 Antigens/genetics , Carboplatin/administration & dosage , Cyclophosphamide/administration & dosage , DNA Copy Number Variations , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Hematopoietic Stem Cell Transplantation , Humans , INDEL Mutation , Kaplan-Meier Estimate , Lenalidomide/administration & dosage , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Leukemia-Lymphoma, Adult T-Cell/mortality , Leukemia-Lymphoma, Adult T-Cell/therapy , Male , Middle Aged , Nitrosourea Compounds/administration & dosage , Polymorphism, Single Nucleotide , Prednisolone/administration & dosage , Prednisone/administration & dosage , Prognosis , Receptors, CCR4/genetics , Vincristine/administration & dosage , Vindesine/administration & dosageABSTRACT
BACKGROUND: Intensified immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP) improves outcomes in younger adults with diffuse large B-cell lymphomas (DLBCL) compared with R-CHOP. Due to vindesine unavailability, we assessed the safety and efficacy of replacing vindesine with vincristine in a modified R-ACVBP protocol (mR-ACVBP). METHODS: This is a retrospective study including all consecutive adult patients with newly diagnosed DLBCL who received first-line mR-ACVBP. Vindesine was replaced with vincristine 1.5 mg on days 1 and 5 of each cycle. Responders continued with published R-ACVBP consolidation. Patients with inadequate response on interim imaging were offered consolidative autologous stem cell transplantation. RESULTS: We identified 56 patients with DLBCL, with a median age of 41 years (range, 21-67). Thirty-seven (66%) patients had an age-adjusted International Prognostic Index of ≥ 2. Complete response was achieved in 41 (80%) patients and partial response in 6 (12%). The most common adverse events during induction were anemia (91%), febrile neutropenia (64%; grade 4 in 46%), thrombocytopenia (39%), and mucositis (21%). Peripheral neuropathy was encountered in 7 (12%) patients (grade 3; n = 1). Two deaths from septic shock were reported in patients with initial poor performance status. After a median follow-up of 17 months, the 2-year progression-free survival and overall survival rates were 86% and 87%, respectively. CONCLUSION: The replacement of vindesine with vincristine in mR-ACVBP seems feasible, with manageable adverse events and excellent 2-year progression-free survival. These data need validation in larger prospective trials.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Vincristine/therapeutic use , Vindesine/therapeutic use , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Bleomycin/pharmacology , Bleomycin/therapeutic use , Cyclophosphamide/pharmacology , Cyclophosphamide/therapeutic use , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Female , Humans , Male , Middle Aged , Prednisone/pharmacology , Prednisone/therapeutic use , Retrospective Studies , Vincristine/pharmacology , Vindesine/pharmacology , Young AdultABSTRACT
ABSTRACT: To investigate the relationship between the changes in circulating CD45RO+T lymphocyte subsets following neoadjuvant therapy for rectal cancer in patients with locally advanced rectal cancer.The clinicopathological data of 185 patients with rectal cancer who received neoadjuvant therapy in the General Surgery Department of Beijing Chaoyang Hospital affiliated to Capital Medical University from June 2015 to June 2017 were analyzed. Venous blood samples were collected 1 week before neoadjuvant therapy and 1 week before surgery, and the expression of CD45RO+T was detected by flow cytometry. The receiver operating characteristic curve analysis was used to determine the optimal cut-off point of CD45RO+ratio. Log-rank test and multivariate Cox regression were used to analyze the overall survival rate (OS) and disease-free survival rate (DFS) associated with CD45RO+ratio.Circulating CD45RO+ratio of 1.07 was determined as the optimal cut-off point and CD45RO+ratio-high was associated with lower tumor regression grade grading (Pâ=â.031), T stage (Pâ=â.001), and tumor node metastasis (TNM) stage (Pâ=â.012). The 3-year DFS and OS rate in the CD45RO+ratio-high group was significantly higher than that in the CD45RO+ratio-low group (89.2% vs 60.1%, P<.001; 94.4% vs 73.2%, P<.001). The multivariate Cox analysis revealed that elevated CD45RO+ratio was an independent factor for better DFS (OR, 0.339; 95% CI, 0.153-0.752; Pâ=â.008) and OS (OR, 0.244; 95% CI,0.082-0.726; Pâ=â.011).Circulating CD45RO+ratio could predict the tumor regression grade of neoadjuvant therapy for rectal cancer, as well as long-term prognosis. These findings could be used to stratify patients and develop alternative strategies for adjuvant therapy.
Subject(s)
Chemoradiotherapy, Adjuvant/methods , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/epidemiology , Rectal Neoplasms/therapy , T-Lymphocyte Subsets/immunology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Separation , Colonoscopy , Cyclophosphamide/therapeutic use , Disease-Free Survival , Doxorubicin/therapeutic use , Flow Cytometry , Follow-Up Studies , Humans , Leukocyte Common Antigens/metabolism , Lymphocyte Count , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/immunology , Neoplasm Staging , Oxaliplatin/therapeutic use , Prednisone/therapeutic use , Preoperative Period , Proctectomy , Prognosis , Radiotherapy, Intensity-Modulated , Rectal Neoplasms/blood , Rectal Neoplasms/immunology , Rectal Neoplasms/mortality , Rectum/diagnostic imaging , Rectum/pathology , Rectum/surgery , Retrospective Studies , Survival Rate , T-Lymphocyte Subsets/metabolism , Vindesine/therapeutic useABSTRACT
High-dose methotrexate (HD-MTX) at 3 g/m2 is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas, especially in diffuse large B cell lymphoma patients with high-risk CNS-International Prognostic Index. The objective of our study was to retrospectively analyze the safety of 2 cycles of systemic HD-MTX administered as an ambulatory regimen. Between January 2013 and December 2016, 103 patients were carefully selected on 6 criteria, including age < 60, albumin > 34, performance status 0 or 1, normal renal and hepatic functions, good understanding of practical medical guidance, and no loss of weight. Strict procedures of HD-MTX infusion were observed including alkalinization, urine pH monitoring, and leucovorin rescue. Renal and hepatic functions were monitored at days 2 and 7. MTX clearance was not monitored. Toxicities and grades of toxicity were collected according to the NCI-CTCAE (version 4.0). Among the 103 selected patients, 92 (89%) patients successfully completed the planned 2 cycles of HD-MTX on an outpatient basis. Eleven patients completed only 1 cycle, 3 because of lymphoma progression and 8 because of toxicity including 3 grade II hepatotoxicity, 2 grade I/II renal toxicity, 1 grade III neutropenia, 1 active herpetic infection, and 1 grade III ileus reflex. Reported adverse events (AE) included 92 (84%) grade I/II and 18 (16%) grade III/IV. Grade III hepatotoxicity, mostly cytolysis, was the most frequent AE observed with 8 (8%) events. Grade III/IV hematologic toxicities concerned 9 patients with 8 grade III/IV neutropenia and 1 thrombocytopenia. Renal toxicity was rare, mild, and transient, observed with 4 (4%) grade I/II events. Ambulatory administration of HD-MTX at 3 g/m2 without MTX clearance monitoring is safe with strict medical guidance. It requires careful selection of patients before administration, and a renal and hepatic monitoring after the administration.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Central Nervous System/pathology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Methotrexate/therapeutic use , Adolescent , Adult , Ambulatory Care , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Chemical and Drug Induced Liver Injury/etiology , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Hematologic Diseases/chemically induced , Humans , Infusions, Intravenous , Kidney Diseases/chemically induced , Kidney Function Tests , Leucovorin/therapeutic use , Liver Function Tests , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Non-Hodgkin/pathology , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Neoplasm Invasiveness , Outpatient Clinics, Hospital , Prednisone/administration & dosage , Retrospective Studies , Rituximab/administration & dosage , Vincristine/administration & dosage , Vindesine/administration & dosage , Young AdultABSTRACT
NonHodgkin lymphoma (NHL) is a form of lymphoid malignancy, with diffuse large B cell lymphoma (DLBCL) being the most common NHL isoform. Approximately half of patients with DLBCL are successfully cured via firstline Rituximab, Cyclophosphamide, Epirubicin, Vindesine, Prednisolone (RCHOP) treatment. However, 3040% of patients with DLBCL ultimately suffer from treatmentrefractory or relapsed disease. These patients often suffer from high mortality rates owing to a lack of suitable therapeutic options, and all patients are at a high risk of serious treatmentassociated dosedependent toxicity. As such, it is essential to develop novel treatments for NHL that are less toxic and more efficacious. Oncolytic Vaccinia virus (OVV) has shown promise as a means of treating numerous types of cancer. Gene therapy strategies further enhance OVVbased therapy by improving tumor cell recognition and immune evasion. Beclin1 is an autophagyassociated gene that, when upregulated, induces excess autophagy and cell death. The present study aimed to develop an OVVBeclin1 therapy capable of inducing autophagic tumor cell death. OVVBeclin1 was able to efficiently kill NHL cells and to increase the sensitivity of these cells to RCHOP, thereby decreasing the dosedependent toxic side effects associated with this chemotherapeutic regimen. The combination of OVVBeclin1 and RCHOP also significantly improved tumor growth inhibition and survival in a BALB/c murine model system owing to the synergistic induction of autophagic cell death. Together, these findings suggest that OVVBeclin1 infection can induce significant autophagic cell death in NHL, highlighting this as a novel means of inducing tumor cell death via a mechanism that is distinct from apoptosis and necrosis.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Beclin-1/immunology , Lymphoma, Large B-Cell, Diffuse/therapy , Oncolytic Virotherapy/methods , Vaccinia virus/genetics , Aged , Aged, 80 and over , Animals , Autophagic Cell Death/drug effects , Autophagic Cell Death/immunology , Beclin-1/genetics , Biopsy , Cell Line, Tumor , Combined Modality Therapy/methods , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Genetic Engineering , Humans , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Mice , Middle Aged , Oncolytic Viruses/immunology , Prednisone/administration & dosage , Rituximab/administration & dosage , Tumor Escape/drug effects , Vaccinia virus/immunology , Vincristine/administration & dosage , Vindesine/administration & dosage , Xenograft Model Antitumor AssaysABSTRACT
The patient was a 56-year-old woman. A modified LSG15(VCAP-AMP-VECP)regimen was initiated as the first-line treatment for acute adult T-cell leukemia/lymphoma. On day 13 from the initiation of the second course of chemotherapy, the onset of hand-foot syndrome(HFS)(hands: Grade 2; feet: Grade 1)occurred. Therefore, the administration of a heparin analog cream and betamethasone butyrate propionate ointment was initiated. On day 20 from the start of the second course of chemotherapy, the foot symptoms improved; however, hand symptoms deteriorated to Grade 3. Frequent use of alcohol-based hand hygiene products is associated with infection prevention during neutropenia, but was likely an exacerbating factor. The symptoms gradually improved after this was taken into consideration, and the usage was discontinued. At the start of the third course, the symptoms had improved to Grade 1, and chemotherapy was continued. On day 11, symptoms worsened(Grade 2). HFS management was performed similar to that in the second course, and symptoms improved again.
Subject(s)
Hand-Foot Syndrome , Leukemia-Lymphoma, Adult T-Cell , Lymphoma , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin , Cyclophosphamide , Doxorubicin , Etoposide , Female , Hand-Foot Syndrome/etiology , Humans , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Middle Aged , Nitrosourea Compounds , Prednisolone , Vincristine , VindesineABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Leukemia-Lymphoma, Adult T-Cell/mortality , Leukemia-Lymphoma, Adult T-Cell/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cause of Death , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Health Care Surveys/statistics & numerical data , Hospitals/statistics & numerical data , Humans , Japan/epidemiology , Leukemia-Lymphoma, Adult T-Cell/blood , Leukemia-Lymphoma, Adult T-Cell/classification , Male , Middle Aged , Nitrosourea Compounds/administration & dosage , Prednisone/administration & dosage , Prognosis , Retrospective Studies , Survival Rate , Vincristine/administration & dosage , Vindesine/administration & dosageABSTRACT
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 â /â ¡ patients had CR rate of 100.0 % and stage â ¢/â £ 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 â /â ¡ patients and stage â ¢/â £ patients were 100.0 % vs. 26.7 % and 100.0 % vs. 40.0 % (P ï¼ 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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm/drug effects , Lymphoma, Extranodal NK-T-Cell/drug therapy , Nose Neoplasms/drug therapy , Adolescent , Adult , Aged , Asparaginase/administration & dosage , Dexamethasone/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Humans , Ifosfamide/administration & dosage , Lymphoma, Extranodal NK-T-Cell/pathology , Male , Middle Aged , Nose Neoplasms/pathology , Polyethylene Glycols/administration & dosage , Prognosis , Retrospective Studies , Salvage Therapy , Survival Rate , Vindesine/administration & dosage , Young AdultABSTRACT
BACKGROUND: Yolk sac tumors (YSTs) of the pancreas are extremely rare, and no drug responsiveness data are available regarding YSTs. METHODS: We report a pancreatic YST in a 70-year-old woman, and its chemotherapeutic responsiveness based on clinical records and evaluation of a patient-derived xenograft (PDX) line of the YST. RESULTS: The YST was an 11-cm, solid mass located in the pancreatic tail. Histologically, the tumor showed medullary proliferation of tumor cells, with a variety of growth patterns including microcystic/reticular, endodermal sinus, and hepatoid patterns. Immunohistochemically, the tumor cells were positive for Sall4, glypican-3, and alpha-fetoprotein. We administered VIP (etoposide, ifosfamide, cisplatin) chemotherapy for a recurrent liver tumor, and obtained complete pathological remission. A drug-response assay using the PDX line from this YST revealed that both VIP and gemcitabine effectively inhibit tumor growth. CONCLUSIONS: These results suggest that differential diagnosis of YST from adenocarcinoma is important for selecting appropriate chemotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Endodermal Sinus Tumor/drug therapy , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/diagnosis , Adenocarcinoma/drug therapy , Aged , Animals , Cell Line, Tumor , Cisplatin/therapeutic use , Diagnosis, Differential , Female , Humans , Ifosfamide/therapeutic use , Liver Neoplasms/complications , Liver Neoplasms/drug therapy , Mice , Vindesine/therapeutic use , Xenograft Model Antitumor AssaysSubject(s)
Antineoplastic Agents, Phytogenic/supply & distribution , Bortezomib/therapeutic use , Leukemia/drug therapy , Lymphoma/drug therapy , Vinblastine/therapeutic use , Vincristine/supply & distribution , Vindesine/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Drug Substitution , Humans , Liposomes , Prednisone/therapeutic use , Vincristine/therapeutic useABSTRACT
We assessed the predictive value of new radiomic features characterizing lesion dissemination in baseline 18F-FDG PET and tested whether combining them with baseline metabolic tumor volume (MTV) could improve prediction of progression-free survival (PFS) and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Methods: From the LNH073B trial (NCT00498043), patients with advanced-stage DLCBL and 18F-FDG PET/CT images available for review were selected. MTV and several radiomic features, including the distance between the 2 lesions that were farthest apart (Dmaxpatient), were calculated. Receiver-operating-characteristic analysis was used to determine the optimal cutoff for quantitative variables, and Kaplan-Meier survival analyses were performed. Results: With a median age of 46 y, 95 patients were enrolled, half of them treated with R-CHOP biweekly (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and the other half with R-ACVBP (rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone), with no significant impact on outcome. Median MTV and Dmaxpatient were 375 cm3 and 45 cm, respectively. The median follow-up was 44 mo. High MTV and Dmaxpatient were adverse factors for PFS (P = 0.027 and P = 0.0003, respectively) and for OS (P = 0.0007 and P = 0.0095, respectively). In multivariate analysis, only Dmaxpatient was significantly associated with PFS (P = 0.0014) whereas both factors remained significant for OS (P = 0.037 and P = 0.0029, respectively). Combining MTV (>384 cm3) and Dmaxpatient (>58 cm) yielded 3 risk groups for PFS (P = 0.0003) and OS (P = 0.0011): high with 2 adverse factors (4-y PFS and OS of 50% and 53%, respectively, n = 18), low with no adverse factor (94% and 97%, n = 36), and an intermediate category with 1 adverse factor (73% and 88%, n = 41). Conclusion: Combining MTV with a parameter reflecting the tumor burden dissemination further improves DLBCL patient risk stratification at staging.