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American Journal of Hematology Nov 2014Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based regimen...
A phase 1 dose escalation study of idarubicin combined with methotrexate, vindesine, and prednisolone for untreated elderly patients with primary central nervous system lymphoma. The GOELAMS LCP 99 trial.
Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based regimen including idarubicin, a phase 1 multicenter dose escalation study was conducted to determine the maximum-tolerated dose (MTD) of idarubicin. Thirty-five immunocompetent patients with PCNSL were enrolled. The median age was 65 years (range, 60-70 years). MTX and vindesine (VDS) were given at the fixed dose of 3 g/m(2) (6-hr intravenous [IV]) and 3 mg/m(2) IV on day 1, respectively. Prednisolone (PRED) was given at the fixed dose of 60 mg/m(2) (IV or orally) on days 1-5. Idarubicin was escalated in increments of 2 mg/m(2) with doses ranging from 12-18 mg/m(2) IV on day 1. Treatment was repeated three times every 3 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for more than 7 days, thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2. The MTD of idarubicin was reached at 16 mg/m(2) . At this level, the main haematological toxicities were thrombocytopenia grade 4: 5% and neutropenia grade 3 or 4 (52%); the main nonhaematological toxicities were grade 3 or 4 infectious disease (5%) and grade 2 renal failure (9%). For the study population, median overall and progression-free survival were 19 and 13 months, respectively. Our study suggests that the MTD of idarubicin in combination with HD-MTX, VDS, and PRED, should be 16 mg/m(2) . Further studies will be necessary to challenge a standard treatment in elderly patients with PCNSL.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Chemoradiotherapy; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Humans; Idarubicin; Immunocompetence; Infections; Kaplan-Meier Estimate; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neutropenia; Palliative Care; Prednisolone; Recurrence; Remission Induction; Renal Insufficiency; Thrombocytopenia; Treatment Outcome; Vindesine
PubMed: 25052698
DOI: 10.1002/ajh.23812 -
Bleomycin overdose in a patient with stage II Hodgkin lymphoma: A case report of a medication error.British Journal of Clinical Pharmacology Apr 2023Bleomycin is an antibiotic with cytotoxic properties that is commonly used in combination regimens for the treatment of Hodgkin lymphoma. The inconsistency in the dosage...
Bleomycin is an antibiotic with cytotoxic properties that is commonly used in combination regimens for the treatment of Hodgkin lymphoma. The inconsistency in the dosage nomenclature of bleomycin appears universally, which increases the risk of medication errors. However, to the best of our knowledge, no such cases have been reported. Herein, we present a rare case report of a medication error caused by a bleomycin overdose. At the third cycle of chemotherapy, a 25-year-old patient with stage II Hodgkin lymphoma received a 10 times higher dose of bleomycin (150 USP) than that usually used as part of the doxorubicin, bleomycin, vindesine and dacarbazine protocol (ABVD). After the medication error was discovered, the patient was immediately treated with intravenous rehydration and furosemide to promote drug clearance. Additionally, methylprednisone and acetylcysteine were administered to prevent lung injury. However, the patient developed slight nausea and mild rash, which gradually improved after treatment. After evaluation with positron emission spectrometry-computed tomography (PET-CT), the patient received four cycles of AVD chemotherapy. No other obvious abnormalities were observed during the treatment and 1-year follow-up period. Hence, the toxicities, clinical management and selection of further chemotherapy after bleomycin overdose in such cases deserved serious attention. More importantly, management measures after this error may be used as a reference in other hospitals.
PubMed: 37060160
DOI: 10.1111/bcp.15744 -
The Oncologist May 2024Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the...
BACKGROUND
Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL).
METHODS
Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT).
RESULTS
From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%).
CONCLUSION
This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance.
CLINICALTRIALS.GOV IDENTIFIER
Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.
PubMed: 38821519
DOI: 10.1093/oncolo/oyae108 -
Case Reports in Hematology 2015B cell lymphoma, unclassifiable, with features of diffuse large B cell lymphoma and classical Hodgkin's lymphoma (BCLu-DLBCL/CHL) is more commonly known as gray zone...
B cell lymphoma, unclassifiable, with features of diffuse large B cell lymphoma and classical Hodgkin's lymphoma (BCLu-DLBCL/CHL) is more commonly known as gray zone lymphoma. These cases more often present with mediastinal disease. In this report, we present a very rare case of BCLu-DLBCL/CHL without mediastinal involvement, transformed from follicular lymphoma (FL) to BCLu-DLBCL/CHL. This patient initially presented with a mass in the right neck; biopsy of the lymph node showed predominantly nodular, follicular pattern. Immunohistochemical (IHC) staining of tumor cells expressed positivity for mature B cell markers CD20, CD19, CD10, CD23, CD45, and CD38 but negative for CD5,11c. Hence, diagnosed with FL, he was given rituximab, cyclophosphamide, vincristine, and prednisone (RCVP) regimen, followed by maintenance rituximab. He showed good response. After 2 years, he presented again with a mass in the right side of the neck. Although the needle core biopsy of this mass was suggestive of B cell lymphoma, excisional biopsy showed morphological features of DLBCL as well as foci of histological pattern of CHL. IHC staining expressed positivity for CD20, CD79a, PAX5, and CD15 and CD30 consistent with DLBCL and CHL. He was diagnosed with BCLu-DLBCL/CHL. The patient received "ACVBP" (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) followed by radiation. BCLu-DLBCL/CHL is clinically an aggressive tumor with poorer outcomes, but our case showed complete response to ACVBP regimen with tumor regression.
PubMed: 26380128
DOI: 10.1155/2015/651764 -
Journal of Medical Case Reports Jun 2015The most common cause of central pontine myelinolysis is an overly rapid correction of hyponatremia, although it can also occur in patients with any condition leading to...
INTRODUCTION
The most common cause of central pontine myelinolysis is an overly rapid correction of hyponatremia, although it can also occur in patients with any condition leading to nutritional or electrolyte stress. We report a case of diffuse large B-cell lymphoma with central pontine myelinolysis developing at the onset of disease. To the best of our knowledge, hematological malignancies presenting with central pontine myelinolysis have been rarely reported, especially in previously untreated patients, as in our case report.
CASE PRESENTATION
A 78-year-old Japanese woman presented to a neighborhood clinic with persistent high fever, edema, and general weakness. Despite the absence of specific neurological findings, brain magnetic resonance imaging showed an abnormal lesion in the central pons area of her brain (hyperintense on T2-weighted and hypointense on T1-weighted sequences), compatible with central pontine myelinolysis. She was admitted to our emergency department in a state of shock one month later. The results of her blood tests showed greatly elevated C-reactive protein and lactate dehydrogenase levels. She had severe hypoalbuminemia and mild hyponatremia, and showed signs of disseminated intravascular coagulation. Mild bilateral pleural effusion, prominent subcutaneous edema, and splenomegaly were detected on her systemic computed tomography scan. Her body fluid cultures did not show signs of infection and her spinal aspiration did not show pleocytosis or abnormal cells. A diagnosis of diffuse large B-cell lymphoma was made based on the results of her bone marrow examination. As she was critically ill before the diagnosis was made, she was treated with methylprednisolone pulse therapy, followed by systemic chemotherapy (rituximab with modified THP-COP regimen, including cyclophosphamide, pirarubicin, vindesine, and prednisolone), which resulted in complete remission and recovery without any neurological defects, and resolution of her abnormal findings on magnetic resonance imaging.
CONCLUSIONS
Central pontine myelinolysis is a serious condition that may result in neuropathological sequelae and mortality, and clinicians should be aware of its potential presence in patients with malignancies.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Brain; Female; Glucocorticoids; Humans; Hyponatremia; Lymphoma, Large B-Cell, Diffuse; Magnetic Resonance Imaging; Methylprednisolone; Myelinolysis, Central Pontine
PubMed: 26044457
DOI: 10.1186/s13256-015-0614-8 -
Frontiers in Oncology 2021Epstein-Barr virus (EBV)-associated lymph nodal T/NK cell lymphoma (nodal TNKL) is a rare and aggressive malignancy with an extremely poor prognosis. Although treatments...
Epstein-Barr virus (EBV)-associated lymph nodal T/NK cell lymphoma (nodal TNKL) is a rare and aggressive malignancy with an extremely poor prognosis. Although treatments of extranodal NK/T cell lymphoma are frequently reported, the characteristics and pathogenesis of EBV-associated nodal TNKL are different. However, there is no known effective therapy regimen at present. Here, we reported the clinical efficacy and feasibility of the programmed death 1 (PD-1) blockade therapy regimen in an elderly female patient with EBV-associated nodal TNKL. The patient failed to respond to cyclophosphamide, doxorubicin, vindesine, and prednisone regimen but achieved complete response after three cycles of anti-PD-1 antibody (tislelizumab) combined with gemcitabine and oxaliplatin (GemOx) regimen. The finding indicated that tislelizumab combined with the GemOx regimen may be a potent salvage regimen for EBV-associated nodal TNKL.
PubMed: 34277451
DOI: 10.3389/fonc.2021.706865 -
ERJ Open Research Oct 2015With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to...
With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are frequent and further treatments are disappointing. The goal of the study was to improve second-line therapy of SCLC. The effect of chemotherapeutic agents was evaluated in cell lines (apoptosis, reactive oxygen species, and RNA and protein expression) and in mouse models (tumour development). We demonstrate here that valproic acid, a histone deacetylase inhibitor, improves the efficacy of a second-line regimen (vindesine, doxorubicin and cyclophosphamide) in SCLC cells and in mouse models. Transcriptomic profiling integrating microRNA and mRNA data identifies key signalling pathways in the response of SCLC cells to valproic acid, opening new prospects for improved therapies.
PubMed: 27730151
DOI: 10.1183/23120541.00028-2015 -
Frontiers in Oncology 2021Angioimmunoblastic T-cell lymphoma (AITL) is a kind of peripheral T-cell lymphomas (PTCLs) with a highly invasive feature. At present, patients are often treated with...
Angioimmunoblastic T-cell lymphoma (AITL) is a kind of peripheral T-cell lymphomas (PTCLs) with a highly invasive feature. At present, patients are often treated with CHOP or CHOP-like regimens which is of poor prognosis whilst having high recurrence rate. Once the patient fails to achieve remission or relapse after the first-line treatment, many salvage chemotherapy regimens are always ineffective, and the long-term survival will be difficult to achieve for them. In this circumstance, more effective therapy methods are needed. In this study, two patients with relapsed/refractory AITL were treated with the CAOLD regimen [cyclophosphamide 400 mg/m qd d1, cytarabine 30 mg/m qd d1-d4, vindesine 2 mg/m qd d1, pegaspargase (PEG-ASP) 2,500 IU/m qd d2, dexamethasone 7.5 mg/m qd d1-d5], and long-term remission was achieved after chemotherapy. One is still alive after achieving complete remission (CR) after two cycles of chemotherapy, who has been followed up for 82 months. Besides, another patient achieved partial remission (PR) after the first course of chemotherapy. Then, CR was obtained after four courses of consolidation chemotherapy. The patient has been followed up for 63 months and is still alive. Both of them achieved long-time survival. These two successful cases demonstrated that the CAOLD regimen can be a better choice for relapsed/refractory AITL and offers hope of breakthrough in this medical field.
PubMed: 35047389
DOI: 10.3389/fonc.2021.758445 -
BMC Research Notes Aug 2017Nephroblastoma and neuroblastoma belong to the most common abdominal malignancies in childhood. Similarities in the initial presentation may provide difficulties in...
BACKGROUND
Nephroblastoma and neuroblastoma belong to the most common abdominal malignancies in childhood. Similarities in the initial presentation may provide difficulties in distinguishing between these two entities, especially if unusual variations to prevalent patterns of disease manifestation occur. Because of the risk of tumor rupture, European protocols do not require biopsy for diagnosis, which leads to misdiagnosis in some cases.
CASE PRESENTATION
We report on a 4½-year-old girl with a renal tumor displaying radiological and laboratory characteristics supporting the diagnosis of nephroblastoma. Imaging studies showed tumor extension into the inferior vena cava and bilateral lung metastases while urine catecholamines and MIBG-scintigraphy were negative. Preoperative chemotherapy with vincristine, actinomycine D and adriamycin according to the SIOP2001/GPOH protocol for the treatment of nephroblastoma was initiated and followed by surgical tumor resection. Histopathology revealed an undifferentiated tumor with expression of neuronal markers, suggestive of neuroblastoma. MYCN amplification could not be detected. DNA-microarray analysis was performed using Affymetrix genechip human genome U133 plus 2.0 and artificial neural network analysis. Results were confirmed by multiplex RT-PCR.
RESULTS
Principal component analysis using 84 genes showed that the patient sample was clearly clustering with neuroblastoma tumors. This was confirmed by hierarchical clustering of the multiplex RT-PCR data. The patient underwent treatment for high-risk neuroblastoma comprising chemotherapy including cisplatin, etoposide, vindesine, dacarbacine, ifosfamide, vincristine, adriamycine and autologous stem cell transplantation followed by maintenance therapy with 13-cis retinoic acid (GPOH NB2004 High Risk Trial Protocol) and is in complete long-term remission.
CONCLUSION
The use of gene expression profiling in an individual patient strongly contributed to clarification in a diagnostic dilemma which finally led to a change of diagnosis from nephroblastoma to neuroblastoma. This case underlines the importance of gene-expression profiling in the correct diagnosis of childhood neoplasms with atypical presentation to ensure that adequate treatment regimens can be applied.
Topics: Abdominal Neoplasms; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Diagnosis, Differential; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Magnetic Resonance Imaging; Neoplasm Proteins; Neuroblastoma; Wilms Tumor
PubMed: 28818093
DOI: 10.1186/s13104-017-2724-4 -
Cancer Chemotherapy and Pharmacology Jul 2016Natural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important...
PURPOSE
Natural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important mechanism of action of antibody drugs. We evaluated the effects of chemotherapy on the cell number and activity of NK cells from patients who received the vincristine-cyclophosphamide-doxorubicin-prednisone (VCAP), doxorubicin-ranimustine-prednisone (AMP), and vindesine-etoposide-carboplatin-prednisone (VECP) (mLSG15) or mLSG15-like (-L) regimen, which is one of the standard of cares for newly diagnosed adult T-cell leukemia-lymphoma (ATL), or the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or CHOP-L regimen which is another standard of care for ATL and peripheral T-cell lymphoma (PTCL).
METHODS
The number of lymphocytes and NK cells, and NK cell activity, were assessed using flow cytometry and a (51)Cr release assay, respectively.
RESULTS
A total of 26 patients with untreated ATL or PTCL were enrolled, and blood samples from 25 patients were evaluable. NK cell number in ATL decreased after mLSG15/-L treatment, and the degree of decrease in the NK cell number was more prominent just before VECP therapy (Day 15-17 of each cycle) than just before VCAP therapy (Day 1 of each cycle). The NK cell number in ATL after CHOP/-L treatment also decreased. Interestingly, the NK cell activity showed a tendency to increase after the treatment. NK cell number in PTCL did not decrease by CHOP/-L regimen, but the activity was slightly decreased after the treatment.
CONCLUSIONS
These results indicate that the effects of chemotherapeutic agents on NK cells vary according to the disease type and intensity of chemotherapy.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Case-Control Studies; Cyclophosphamide; Doxorubicin; Etoposide; Female; Flow Cytometry; Humans; Killer Cells, Natural; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, T-Cell, Peripheral; Male; Middle Aged; Nitrosourea Compounds; Prednisone; Vincristine; Vindesine
PubMed: 27289375
DOI: 10.1007/s00280-016-3070-2