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Leukemia & Lymphoma Oct 2016We report the clinical results of sustainedly integrating imatinib and interferon-α into maintenance therapy in the patients ineligible for allogeneic hematopoietic...
Sustaining integrating imatinib and interferon-α into maintenance therapy improves survival of patients with Philadelphia positive acute lymphoblastic leukemia ineligible for allogeneic stem cell transplantation.
We report the clinical results of sustainedly integrating imatinib and interferon-α into maintenance therapy in the patients ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Maintenance therapy lasted for 5 years with imatinib 400 mg daily, interferon-α 3 million units, 2∼3 doses per week, and chemotherapy including vindesine and dexamethasone scheduled monthly in first year, once every 2 months in second year, and once every 3 months in third year. The chemotherapy was discontinued after 3 years and the imatinib and interferon-α continued for another 2 years. For 41 patients without allo-HSCT with a median follow-up of 32 months, the 3-year DFS and OS were 42.7 ± 8.6% and 57.9 ± 8.4%, respectively. Our study suggests that sustaining maintenance with low-dose chemotherapy, imatinib and interferon-α improved survival of adult Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) patients ineligible for allo-HSCT, and even provided an opportunity for cure. BCR/ABL persistent negativity at 6 and 9 months may have benefit to choose suitable patients for the imatinib/interferon-α maintenance strategy.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Hematopoietic Stem Cell Transplantation; Humans; Imatinib Mesylate; Interferon-alpha; Maintenance Chemotherapy; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Survival Analysis; Transplantation, Homologous; Treatment Outcome
PubMed: 26879808
DOI: 10.3109/10428194.2016.1144882 -
Annals of Work Exposures and Health Oct 2017This paper describes a novel wipe sampling and high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method capable of simultaneously detecting 10...
Wipe Sampling Method and Evaluation of Environmental Variables for Assessing Surface Contamination of 10 Antineoplastic Drugs by Liquid Chromatography/Tandem Mass Spectrometry.
This paper describes a novel wipe sampling and high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method capable of simultaneously detecting 10 antineoplastic drugs (5-fluorouracil, oxaliplatin, methotrexate, vindesine, ifosfamide, cyclophosphamide, vincristine, vinblastine, docetaxel, and paclitaxel). The good overall recoveries and sensitivity values of this method along with the comparatively short run time (8 min) allows for its use in routine monitoring in health care facilities. The long-term behavior of the studied drugs on contaminated surfaces and the effect of surface roughness on drug recoveries were studied to gain insights about how these environmental variables influence the detection, cleaning, and occupational exposure of these drugs. Surfaces with higher roughness parameter (Ra) values (rougher) had the lowest recoveries while those with lower Ra (smoother) presented the highest recoveries. Long-term assessments evidence distinctive drug behaviors with oxaliplatin, vindesine, vincristine, and vinblastine being the less persistent drugs (~20% was recovered after 24 h) and docetaxel and paclitaxel the most persistent drugs with recoveries of 40% and 80% after 1 month. This information indicates the importance of collecting ancillary information about drug usage (throughput, timing, cleaning procedures, etc.) to interpret the results in the context of potential exposure. Finally, the method was successfully applied to evaluate trace surface contamination down to the single picogram per square centimeter in multiple work areas within three local health care centers on Vancouver Island, Canada.
Topics: Analysis of Variance; Antineoplastic Agents; Canada; Chromatography, Liquid; Environmental Monitoring; Equipment Contamination; Health Facilities; Humans; Occupational Exposure; Surface Properties; Tandem Mass Spectrometry
PubMed: 29028255
DOI: 10.1093/annweh/wxx070 -
JAMA Oncology Jun 2021Insufficient data are available regarding the long-term outcomes and cumulative incidences of toxic effects that are associated with chemoradiotherapy (CRT) for patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial.
IMPORTANCE
Insufficient data are available regarding the long-term outcomes and cumulative incidences of toxic effects that are associated with chemoradiotherapy (CRT) for patients with stage III non-small-cell lung cancer.
OBJECTIVE
To evaluate survival and late toxic effects 10 years after patients were treated with curative CRT.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, phase 3 West Japan Thoracic Oncology Group (WJTOG) 0105 randomized clinical trial was conducted between September 2001 and September 2005 in Japan. Patients with histologically or cytologically confirmed non-small-cell lung cancer with unresectable stage III disease were assessed for eligibility. Additional data were analyzed from January 2018 to December 2019.
INTERVENTIONS
A total of 440 eligible patients were randomly assigned to groups as follows: A (control), 4 cycles of mitomycin/vindesine/cisplatin plus thoracic radiotherapy (TRT) of 60 Gy; B, weekly irinotecan/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of irinotecan/carboplatin consolidation; or C, weekly paclitaxel/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of paclitaxel/carboplatin consolidation.
MAIN OUTCOMES AND MEASURES
The primary outcome was 10-year survival probability after CRT. The secondary outcome was late toxic effects that occurred more than 90 days after initiating CRT.
RESULTS
From September 2001 to September 2005, 440 patients (group A, n = 146 [33.2%; median (range) age, 63 (31-74) years; 18 women (12.3%)]; group B, n = 147 [33.4%; median (range) age, 63 (30-75) years; 22 women (15.0%)]; group C, n = 147 [33.4%; median (range) age, 63 (38-74) years; 19 women (12.9%)]) were enrolled. The median (range) follow-up was 11.9 (7.6-13.3) years. In groups A, B, and C, median (range) overall survival times were 20.5 (17.5-26.0), 19.8 (16.7-23.5), and 22.0 (18.7-26.2) months, respectively, and 10-year survival probabilities were 13.6%, 7.5%, and 15.2%, respectively. There were no significant differences in overall survival among treatment groups. The 10-year progression-free survival probabilities were 8.5%, 6.5%, and 11.1% in groups A, B, and C, respectively. Grade 3 or 4 late toxic effect rates were 3.4% (heart, 0.7%; lung, 2.7%) in group A, and those only affecting the lung represented 3.4% and 4.1% in groups B and C, respectively. No other cases of late toxic effects (grades 3/4) were observed since the initial report.
CONCLUSION AND RELEVANCE
In this 10-year follow-up of a phase 3 randomized clinical trial, group C achieved similar efficacy and toxic effect profiles as group A 10 years after initiating treatment. These results serve as a historical control for the long-term comparisons of outcomes of future clinical trials of CRT.
TRIAL REGISTRATION
UMIN Clinical Trial Registry: UMIN000030811.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Female; Follow-Up Studies; Humans; Lung Neoplasms; Neoplasm Staging; Paclitaxel
PubMed: 33734289
DOI: 10.1001/jamaoncol.2021.0113 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Mar 2020To analyze the clinical features and prognostic factors of primary systemic anaplastic large cell lymphoma (ALCL) . 40 ALCL cases treated in the First Affiliated...
To analyze the clinical features and prognostic factors of primary systemic anaplastic large cell lymphoma (ALCL) . 40 ALCL cases treated in the First Affiliated Hospital of Zhejiang University from January 2013 to December 2018 were retrospectively analyzed. ① With a median age of 41 (14-67) years, there were 29 males and 11 females, 36 patients (90.0%) had Ann Arbor stage Ⅲ-Ⅳ tumors, 23 patients (57.5%) were in high-intermediate or high international prognostic index (IPI) risk group. 25 patients (62.5%) had B symptoms, such as fever, emaciation and night sweat.38 patients (95.0%) had extranodal invasion, 25 patients (62.5%) had higher LDH level, and 25 patients (62.5%) had high expression of Ki-67 (80% or more) . With 22 ALK(+) patients (55.0%) and 18 ALK(-) patients (45.0%) , there was a significantly difference in the median age of the two groups [29 (14-67) years old 51.5 (19-67) years old, =0.003]. ② All patients received chemotherapy, 18 cases were treated with CHOP (cyclophosphamide, doxorubicin, vindesine, prednisone) , 12 cases with ECHOP (cyclophosphamide, doxorubicin, vindesine, prednisone, etoposide) , 10 cases with other treatments and 26 patients (65.0%) obtained complete remission (CR) . ALK(-) (=0.029, =13.458) and Ki-67 expression of 80% or more (=0.04, =14.453) were independent factors of CR rate, the CR rate of ECHOP chemotherapy was higher than CHOP chemotherapy (=0.026) . ③ LDH level, IPI score, ALK expression and chemotherapy regimen had significantly effect on progression free survival (PFS) and overall survival (OS) (<0.05) . The study shows that primary systemic ALCL usually occurs in males, the average age of ALK(+) patients were younger than ALK(-) patients. Most patients are in stage Ⅲ-Ⅳ with extranodal invasion, more than half of the patients have B symptoms, elevated LDH, and high expression of Ki-67. The expression level of Ki-67, ALK expression, and chemotherapy regimen have prognostic value for CR rate, the LDH level, IPI score, ALK expression and chemotherapy regimen for PFS and OS. ECHOP is a better choice with improved prognosis.
Topics: Adolescent; Adult; Aged; Anaplastic Lymphoma Kinase; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Anaplastic; Male; Middle Aged; Prednisone; Prognosis; Receptor Protein-Tyrosine Kinases; Retrospective Studies; Vincristine; Young Adult
PubMed: 32311892
DOI: 10.3760/cma.j.issn.0253-2727.2020.03.007 -
Fundamental & Clinical Pharmacology Apr 2015On account of its strong ability to become chemoresistant after a primary response to drugs, malignant melanoma (MM) remains a therapeutic challenge. This study focuses...
On account of its strong ability to become chemoresistant after a primary response to drugs, malignant melanoma (MM) remains a therapeutic challenge. This study focuses on acquired resistance to vinca alkaloids (VAs) using VA-resistant MM cell lines (CAL1R-VCR, CAL1R-VDS, and CAL1R-VRB), established by long-term continuous exposure of parental CAL1-wt cells to vincristine (VCR), vindesine (VDS), or vinorelbine (VRB), respectively. Transcriptomic profiling using rma and rdam methods led to distinguish two cell groups: CAL1R-VCR and CAL1R-VDS, CAL1R-VRB, and CAL1-wt. mgsa of the specifically altered genes in the first group evidenced the GO terms 'lysosomal lumen' and 'vacuolar lumen' linked to underexpressed genes, and 'endoplasmic reticulum (ER) stress response' associated with overexpressed genes. A specific reduction of lysosomal enzymes, independent of acidic vacuole organelle (AVO) turnover, was observed (LTG probe) in CAL1R-VCR and CAL1R-VDS cells. It was associated with the specific lowering of cathepsin B and L, known to be involved in the lysosomal pathway of apoptosis. Confirming gene profiling, the same groups (CAL1R-VCR and CAL1R-VDS, CAL1-wt and CAL1R-VRB) could be distinguished regarding the VA-mediated changes on mean size areas and on acidic compartment volumes. These two parameters were reduced in CAL1R-VCR and CAL1R-VDS cells, suggesting a smaller AVO accumulation and thus a reduced sensitivity to lysosomal membrane permeabilization-mediated apoptosis. In addition, 'ER stress response' inhibition by tauroursodeoxycholic acid induced a higher VA sensitization of the first cell group. In conclusion, lysosomes and unfolded protein response could be key determinants of the differential resistance of MM to VAs.
Topics: Cell Line, Tumor; Drug Resistance, Neoplasm; Humans; Lysosomes; Melanoma; Transcriptome; Unfolded Protein Response; Vinca Alkaloids
PubMed: 25601431
DOI: 10.1111/fcp.12098 -
Anticancer Research Apr 2016In Japan, chemotherapeutic agents that have been approved for the treatment of esophageal cancer include cisplatin, nedaplatin, 5-fluorouracil, vindesine, and docetaxel.... (Clinical Trial)
Clinical Trial
AIM
In Japan, chemotherapeutic agents that have been approved for the treatment of esophageal cancer include cisplatin, nedaplatin, 5-fluorouracil, vindesine, and docetaxel. The aim of this study was to retrospectively investigate the efficacy and safety of docetaxel and nedaplatin combination chemotherapy for unresectable or recurrent esophageal cancer in an outpatient setting.
PATIENTS AND METHODS
In total, 33 patients with recurrent esophageal cancer after initial treatment (esophagectomy, chemotherapy, or chemoradiotherapy) were enrolled. Patients received docetaxel (30 mg/m(2)intravenously) and nedaplatin (30 mg/m(2)intravenously) on day 1 biweekly. The response rate (RR), time to treatment failure (TTF), overall survival time (OS), and toxicity were analyzed.
RESULTS
The median number of cycles of combination therapy was five (range=2-25 cycles). The RR was 21.2%, and the disease control rate was 60.6%. The median TTF was 71 days, and median OS was 211 days. The most frequent toxicities were leukopenia and anemia; non-hematological toxicities were generally mild. There were no treatment-related deaths.
CONCLUSION
This outpatient combination chemotherapy was useful as second-line chemotherapy for unresectable or recurrent esophageal cancer.
Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Taxoids; Treatment Outcome
PubMed: 27069181
DOI: No ID Found -
ENeurologicalSci Sep 2023Langerhans cell histiocytosis (LCH) is a rare disease that usually occurs in children <15 years of age. Adult-onset LCH is extremely rare. Previous published guidelines...
INTRODUCTION
Langerhans cell histiocytosis (LCH) is a rare disease that usually occurs in children <15 years of age. Adult-onset LCH is extremely rare. Previous published guidelines and studies mainly focused on pediatric patients. The rarity and also insufficient knowledge of LCH in adults, especially central neuvous system (CNS) involvement of LCH, often resulted in missed and delayed diagnosis.
CASE PRESENTATION
A 35-year-old woman presented with cognitive impairment, anxietydepression, decreased eyesight, skin rash, hypernatremia, gonadal hormone deficiency and hypothyroidism. She had experienced menstrual disturbance and infertility since 10 years ago. MRI examination showed a mass lesion in the hypothalamic-pituitary region. Sighs of radiologic neurodegeneration were not found on brain MRI scans, however. Biopsy of skin rash confirmed the the diagnosis of multisystem LCH. BRAF V600E mutation was detected in the peripheral blood mononuclear cells. She accepted combination chemotherapy of vindesine and prednisone and accquired partial remission. The patient died of severe pneumonia during the second course of chemotherapy.
CONCLUSION
Given the complicated differential diagnoses of neuroendocrine disorders, it was essential to be aware of CNS involvement of LCH at first, especially in adults. BRAF V600E mutation may participated in disease progression.
PubMed: 37435445
DOI: 10.1016/j.ensci.2023.100471 -
Zhongguo Dang Dai Er Ke Za Zhi =... Oct 2018A boy aged 14 years had abdominal pain as the major manifestation, with elevated serum amylase and lipase. Abdominal ultrasound performed early after onset in another...
A boy aged 14 years had abdominal pain as the major manifestation, with elevated serum amylase and lipase. Abdominal ultrasound performed early after onset in another hospital showed enlargement of the pancreas and a reduction in echo. Magnetic resonance cholangiopancreatography (MRCP) showed pancreatic duct dilation and an unclear image of the head of the pancreas. Acute pancreatitis was considered. However, his symptoms were not relieved after fasting, fluid infusion, anti-acid therapy, and somatostatin therapy. Then, abdominal CT scan and MRCP found multiple low-density lesions of the pancreas and enlargement of the hilar and retroperitoneal lymph nodes. Exploratory laparotomy found pancreatic edema and multiple hilar nodules with unclear boundaries, and pathological biopsy showed anaplastic large-cell lymphoma. Since the liver, the spleen, bone marrow, and the central nervous system were not involved, he was diagnosed with stage III primary pancreatic lymphoma. After vindesine and dexamethasone were used to reduce tumor load, the patient underwent vindesine-pirarubicin-asparaginase-dexamethasone chemotherapy once and vinorelbine-dexamethasone chemotherapy 8 times. Imaging examination still showed multiple low-density lesions of the pancreas and retroperitoneal lymph node enlargement. His parents discontinued treatment. It is concluded that the rare causes of acute pancreatitis with poor response to conventional treatment should be considered, especially for patients with abdominal lymph node enlargement. Extranodal lymphoma should be considered, and lymph node biopsy should be performed as early as possible to confirm diagnosis. The prognosis of pancreatic lymphoma is associated with clinical stage and pathology.
Topics: Adolescent; Cholangiopancreatography, Magnetic Resonance; Humans; Lymph Nodes; Lymphoma; Male; Pancreatic Neoplasms; Pancreatitis
PubMed: 30369361
DOI: 10.7499/j.issn.1008-8830.2018.10.012 -
Cancer Medicine Mar 2024Blinatumomab early-line treatment in B-cell precursor acute lymphoblastic leukemia (B-ALL) might improve clinical outcomes.
BACKGROUND
Blinatumomab early-line treatment in B-cell precursor acute lymphoblastic leukemia (B-ALL) might improve clinical outcomes.
METHODS
We conducted a retrospective real-world cohort analysis in 20 newly diagnosed B-ALL patients who received reduced-dose chemotherapy (idarubicin, vindesine, and dexamethasone) for 1-3 weeks, followed by blinatumomab for 1-4 weeks as an induction therapy.
RESULTS
At the end of the induction therapy, a complete remission rate of 100% was achieved; 17 (85%) patients were minimal residual disease (MRD) negative (<1 × 10 ). Adverse events (AEs) were reported in 12 (60%) patients-43.8% were grade 1-2 and 56.2% were grade 3-4. No incidence of neurotoxicity or grade ≥3 cytokine release syndrome was reported.
CONCLUSIONS
Blinatumomab demonstrated a significant improvement in clinical outcomes in patients with newly diagnosed B-ALL irrespective of their poor-risk factor status and the pretreatment blast burden.
Topics: Humans; Retrospective Studies; Induction Chemotherapy; Antibodies, Bispecific; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma
PubMed: 38491815
DOI: 10.1002/cam4.7062 -
Frontiers in Oncology 2023SSBP2-CSF1R is an important biomarker for clinical diagnosis and prognosis of Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL). This case report...
SSBP2-CSF1R is an important biomarker for clinical diagnosis and prognosis of Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL). This case report presents a pediatric Ph-like ALL patient carrying the SSBP2-CSF1R fusion gene. The patient was resistant to most conventional chemotherapy regimens and to dasatinib, an inhibitor that has been reported to have a therapeutic effect on SSBP2-CSF1R fusion Ph-like ALL, as she remained minimal residual disease (MRD) positive (detection by flow cytometry) and SSBP2-CSF1R fusion gene (detection by RT-PCR) positive after five rounds of such regimens. We thus conducted a large-scale screening to assess the sensitivity of the patient's leukemic cells to anti-cancer drugs. Based on the susceptibility results, we chose to combine cytarabine, homoharringtonine, dexamethasone, fludarabine, vindesine, and epirubicin for treatment. Clinical results showed that after a course of treatment, both MRD and SSBP2-CSF1R fusion gene turned negative, and there was no recurrence during an 18-month follow-up. In conclusion, our study suggests that the SSBP2-CSF1R fusion gene may be an important biomarker of primary drug resistance in Ph-like ALL, and indicate that the combination of cytarabine, homoharringtonine, dexamethasone, fludarabine, vindesine, and epirubicin can achieve optimal therapeutic results in this category of patients.
PubMed: 38107066
DOI: 10.3389/fonc.2023.1291570