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Cancer Medicine Jan 2024High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of...
BACKGROUND
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL.
METHODS
A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results.
RESULTS
Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC).
CONCLUSIONS
The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort.
Topics: Humans; Carmustine; Gemcitabine; Hematopoietic Stem Cell Transplantation; Melphalan; Retrospective Studies; Transplantation, Autologous; Lymphoma, Non-Hodgkin; Cyclophosphamide; Etoposide; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Transplantation Conditioning
PubMed: 38348996
DOI: 10.1002/cam4.6965 -
Frontiers in Immunology 2024Tracheal small cell carcinoma (SCC) is a rare malignancy, for which the optimal treatment strategy has yet to be determined. Currently, treatment largely aligns with the... (Review)
Review
Tracheal small cell carcinoma (SCC) is a rare malignancy, for which the optimal treatment strategy has yet to be determined. Currently, treatment largely aligns with the therapeutic guidelines established for small cell lung cancer, although numerous unresolved issues remain. This paper details a case study of a patient with Stage IIIB primary tracheal SCC, who was treated with an immune-combined etoposide-platinum(EP) regimen. This treatment offers valuable insights into innovative approaches for managing such malignancies. Furthermore, the study includes a comprehensive literature review to better contextualize the findings. The patient, admitted on May 2, 2023, had been experiencing persistent symptoms of airway discomfort for 15 days. A bronchoscopy performed on May 4 revealed tracheal SCC, classified as T4N2M0, IIIB. Following the CAPSTONE-1 study's methodology, the patient underwent six cycles of PD-L1(adebrelimab) combined with EP therapy, leading to significant relief of symptoms and the eventual disappearance of the tracheal mass.
Topics: Humans; Carcinoma, Small Cell; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Small Cell Lung Carcinoma; Lung Neoplasms
PubMed: 38348051
DOI: 10.3389/fimmu.2024.1356268 -
The Oncologist Jun 2024Intensive treatment approaches are required for adult patients with Burkitt lymphoma (BL), although an univocal standard of care still does not exist. The use of...
INTRODUCTION
Intensive treatment approaches are required for adult patients with Burkitt lymphoma (BL), although an univocal standard of care still does not exist. The use of frontline autologous stem cells transplantation (ASCT) is debated.
PATIENTS AND METHODS
Between 2004 and 2020, 50 patients with BL were treated with the Berlin-Frankfurt-Münster (BFM). Treatment plan consisted of 3 blocks, A (ifosfamide, vincristine, methotrexate, etoposide, and cytarabine), B (vincristine, cyclophosphamide, methotrexate, and doxorubicin), and C (vindesine, methotrexate, etoposide, and cytarabine), each repeated twice, every 28 days. Rituximab was given at day 1 each block. Intrathecal prophylaxis was given once per each block. ASCT was scheduled at the end of the 6 blocks after conditioning.
RESULTS
Median age at onset was 38 years (range 16-72); stages III-IV disease was observed in 82% of cases; bulky disease occurred in 44% of the patients, with B-symptoms in 38%. Stem cell harvest was performed in 72% of patients, who all received a subsequent ASCT. The full 6 blocks treatment was completed in 70% of the patients. The overall response rate was 74%, with a complete response rate of 60%. Ten-year overall survival and progression-free survival were 83.7% and 76.0%, respectively, without reaching the median. Ten-year disease-free survival was 80.3%. Grades 3-4 neutropenia, thrombocytopenia, anemia, and mucositis were seen in 96%, 60%, 32%, and 24% of patients. Infections occurred in 60% of patients.
CONCLUSION
Intensive treatment according to BFM protocol, with rituximab and ASCT, appears feasible, safe, and highly effective in adult patients with BL, as confirmed by long-term survival rates reflecting response maintenance.
Topics: Humans; Burkitt Lymphoma; Rituximab; Adult; Male; Female; Transplantation, Autologous; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Adolescent; Young Adult; Aged; Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Etoposide; Doxorubicin; Cytarabine; Vincristine; Methotrexate
PubMed: 38339976
DOI: 10.1093/oncolo/oyae017 -
International Journal of Molecular... Jan 2024In childhood, retinoblastoma (RB) is the most common primary tumor in the eye. Long term therapeutic management with etoposide of this life-threatening condition may...
In childhood, retinoblastoma (RB) is the most common primary tumor in the eye. Long term therapeutic management with etoposide of this life-threatening condition may have diminishing effectiveness since RB cells can develop cytostatic resistance to this drug. To determine whether changes in receptor-mediated control of Ca signaling are associated with resistance development, fluorescence calcium imaging, semi-quantitative RT-qPCR analyses, and trypan blue dye exclusion staining patterns are compared in WERI-ETOR (etoposide-insensitive) and WERI-Rb1 (etoposide-sensitive) cells. The cannabinoid receptor agonist 1 (CNR1) WIN55,212-2 (40 µM), or the transient receptor potential melastatin 8 (TRPM8) agonist icilin (40 µM) elicit similar large Ca transients in both cell line types. On the other hand, NGF (100 ng/mL) induces larger rises in WERI-ETOR cells than in WERI-Rb1 cells, and its lethality is larger in WERI-Rb1 cells than in WERI-ETOR cells. NGF and WIN55,212-2 induced additive Ca transients in both cell types. However, following pretreatment with both NGF and WIN55,212-2, gene expression declines and icilin-induced Ca transients are completely blocked only in WERI-ETOR cells. Furthermore, gene expression levels are larger in WERI-ETOR cells than those in WERI-Rb1 cells. Therefore, the development of etoposide insensitivity may be associated with rises in gene expression, which in turn suppress gene expression through crosstalk.
Topics: Humans; Cell Line; Etoposide; Membrane Proteins; Receptor, Nerve Growth Factor; Retinal Neoplasms; Retinoblastoma; TRPM Cation Channels; Receptor, Cannabinoid, CB1
PubMed: 38339011
DOI: 10.3390/ijms25031733 -
Iranian Journal of Medical Sciences Jan 2024Herbal medicines are the preferred anticancer agents due to their lower cytotoxic effects on healthy cells. Plant lignans play an important role in treating various...
BACKGROUND
Herbal medicines are the preferred anticancer agents due to their lower cytotoxic effects on healthy cells. Plant lignans play an important role in treating various diseases, especially cancer. The present study aimed to evaluate the effect of podophyllotoxin, pinoresinol, and lariciresinol on cellular toxicity and inducing apoptosis in fibroblasts, HEK-293, and SkBr3 cell lines.
METHODS
An study was conducted from 2017 to 2019 at the Faculty of Biological Sciences, Tarbiat Modares University (Tehran, Iran). The cell lines were treated for 24 and 48 hours with different concentrations of lignans. Cell viability and apoptosis were examined using MTT and flow cytometry, respectively. Expression levels of cell cycle and apoptosis regulator genes were determined using quantitative real-time polymerase chain reaction. Data were analyzed using a two-way analysis of variance followed by Tukey's HSD test. P<0.05 was considered statistically significant.
RESULTS
Podophyllotoxin significantly increased apoptosis in fibroblast cells compared to pinoresinol and lariciresinol (P<0.001). The percentage of cell viability of fibroblast cells treated for 48 hours with pinoresinol, lariciresinol, and podophyllotoxin was reduced by 49%, 47%, and 36%, respectively. Treatment with pinoresinol and lariciresinol significantly overexpressed pro-apoptotic genes and underexpressed anti-apoptotic genes in SkBr3 cells (P<0.001). SkBr3 cells treated with lariciresinol significantly reduced gene expression (P<0.001).
CONCLUSION
Pinoresinol and lariciresinol can potentially be used as new therapeutic agents for the treatment of breast cancer.
Topics: Humans; Female; Podophyllotoxin; Oxidoreductases; Breast Neoplasms; HEK293 Cells; Iran; Lignans; Antineoplastic Agents; Furans
PubMed: 38322161
DOI: 10.30476/ijms.2023.94805.2611 -
Investigational New Drugs Feb 2024Part E of the KEYNOTE-011 (NCT01840579) study assessed the safety and antitumor activity of pembrolizumab plus platinum-etoposide chemotherapy in Japanese patients with...
BACKGROUND
Part E of the KEYNOTE-011 (NCT01840579) study assessed the safety and antitumor activity of pembrolizumab plus platinum-etoposide chemotherapy in Japanese patients with previously untreated extensive-stage small-cell lung cancer (ES-SCLC).
METHODS
Patients received 4 cycles of pembrolizumab (200 mg) every 3 weeks in combination with cisplatin (75 mg/m) and etoposide (100 mg/m; days 1, 2, 3) in cohort 1; with carboplatin (AUC 5 mg/mL/min) and etoposide (100 mg/m; days 1, 2, 3) in cohort 2; or with cisplatin/etoposide and pegfilgrastim (3.6 mg; cycle 1, day 4) in cohort 3. Combination therapy was followed by pembrolizumab monotherapy (31 cycles). The primary endpoint was safety and tolerability (including dose-limiting toxicities; DLTs).
RESULTS
Fifteen patients were included in the study (cohort 1, n = 6; cohort 2, n = 6; cohort 3, n = 3). Median time from treatment allocation to data cutoff was 22.1 months (range, 4.1‒32.4 months). DLTs occurred in 3 patients in cohort 1 (one patient with grade 4 laryngeal stenosis and grade 3 febrile neutropenia; two patients with grade 3 febrile neutropenia); no patients in cohorts 2 or 3 experienced DLTs. Grade ≥ 3 treatment-related adverse events included leukopenia (67%) and neutropenia (87%). Among all patients, ORR was 67% (95% CI, 38%‒88%) and median DOR was 4.5 months (range, 2.8‒28.8 months). Median PFS was 4.2 months (95% CI, 3.0‒7.8 months) and median OS was 22.1 months (95% CI, 7.4‒25.9 months).
CONCLUSION
Pembrolizumab in combination with platinum-etoposide therapy had manageable toxicity with no new safety signals and was associated with antitumor activity in Japanese patients with ES-SCLC.
TRIAL REGISTRATION
ClinicalTrials.gov , NCT01840579.
Topics: Humans; Lung Neoplasms; Cisplatin; Etoposide; Platinum; Japan; Small Cell Lung Carcinoma; Antineoplastic Combined Chemotherapy Protocols; Febrile Neutropenia; Antibodies, Monoclonal, Humanized
PubMed: 38300341
DOI: 10.1007/s10637-023-01411-1 -
Pediatric Radiology May 2024Disseminated pulmonary involvement in pediatric Hodgkin lymphoma (pHL) is indicative of Ann Arbor stage IV disease. During staging, it is necessary to assess for...
BACKGROUND
Disseminated pulmonary involvement in pediatric Hodgkin lymphoma (pHL) is indicative of Ann Arbor stage IV disease. During staging, it is necessary to assess for coexistence of non-malignant lung lesions due to infection representing background noise to avoid erroneously upstaging with therapy intensification.
OBJECTIVE
This study attempts to describe new lung lesions detected on interim staging computed tomography (CT) scans after two cycles of vincristine, etoposide, prednisolone, doxorubicin in a prospective clinical trial. Based on the hypothesis that these new lung lesions are not part of the underlying malignancy but are epiphenomena, the aim is to analyze their size, number, and pattern to help distinguish true lung metastases from benign lung lesions on initial staging.
MATERIALS AND METHODS
A retrospective analysis of the EuroNet-PHL-C1 trial re-evaluated the staging and interim lung CT scans of 1,300 pediatric patients with HL. Newly developed lung lesions during chemotherapy were classified according to the current Fleischner glossary of terms for thoracic imaging. Patients with new lung lesions found at early response assessment (ERA) were additionally assessed and compared to response seen in hilar and mediastinal lymph nodes.
RESULTS
Of 1,300 patients at ERA, 119 (9.2%) had new pulmonary lesions not originally detectable at diagnosis. The phenomenon occurred regardless of initial lung involvement or whether a patient relapsed. In the latter group, new lung lesions on ERA regressed by the time of relapse staging. New lung lesions on ERA in patients without relapse were detected in 102 (7.8%) patients. Pulmonary nodules were recorded in 72 (5.5%) patients, the majority (97%) being<10 mm. Consolidations, ground-glass opacities, and parenchymal bands were less common.
CONCLUSION
New nodules on interim staging are common, mostly measure less than 10 mm in diameter and usually require no further action because they are most likely non-malignant. Since it must be assumed that benign and malignant lung lesions coexist on initial staging, this benign background noise needs to be distinguished from lung metastases to avoid upstaging to stage IV disease. Raising the cut-off size for lung nodules to ≥ 10 mm might achieve the reduction of overtreatment but needs to be further evaluated with survival data. In contrast to the staging criteria of EuroNet-PHL-C1 and C2, our data suggest that the number of lesions present at initial staging may be less important.
Topics: Humans; Male; Female; Hodgkin Disease; Child; Neoplasm Staging; Lung Neoplasms; Adolescent; Tomography, X-Ray Computed; Retrospective Studies; Prevalence; Antineoplastic Combined Chemotherapy Protocols; Prospective Studies; Child, Preschool; Doxorubicin; Etoposide; Vincristine
PubMed: 38296856
DOI: 10.1007/s00247-024-05859-y -
Journal of Clinical and Experimental... Mar 2024Peritoneal lymphomatosis (PL) is a rare lymphoma-associated condition defined as the dissemination of lymphoma cells in the peritoneum. An 82-year-old man presented with...
Peritoneal lymphomatosis (PL) is a rare lymphoma-associated condition defined as the dissemination of lymphoma cells in the peritoneum. An 82-year-old man presented with abdominal pain, heartburn, and high fever. Radiological findings, including positron emission tomography-computed tomography (PET-CT), and gastrointestinal fiberscopy, showed diffuse thickening of the peritoneum, omentum, and mesentery; however, no lymphadenopathy, hepatosplenomegaly, or gastrointestinal lesions were observed. Under suspicion of peritonitis carcinomatosa of unknown origin, exploratory laparoscopy was performed that revealed multiple white nodules and masses on the surfaces of the peritoneum, mesentery, and intestinal serosa. The histopathological and cytogenetic findings of the peritoneum revealed high-grade B-cell lymphoma, not otherwise specified, and a gain of MYC by fluorescence in-situ hybridization. The patient was treated with two cycles of R-CHOP therapy, followed by six cycles of dose-adjusted EPOCH-R therapy, and a complete metabolic response was confirmed by PET-CT. Since there are no specific radiological findings to confirm the diagnosis of PL, a histopathological diagnosis is usually required. Most PL exhibit an aggressive lymphoma phenotype and can be cured by appropriate chemotherapy. Therefore, early diagnosis and treatment are desirable.
Topics: Male; Humans; Aged, 80 and over; Peritoneum; Positron Emission Tomography Computed Tomography; Peritoneal Neoplasms; Lymphoma, B-Cell; Lymphoma; Prednisone; Rituximab; Vincristine; Cyclophosphamide; Doxorubicin; Etoposide; Lymphoma, Large B-Cell, Diffuse
PubMed: 38281744
DOI: 10.3960/jslrt.23044 -
Cancer Immunology, Immunotherapy : CII Jan 2024Macrophages constitute a major part of tumor microenvironment, and most of existing data demonstrate their ruling role in the development of anti-drug resistance of...
Macrophages constitute a major part of tumor microenvironment, and most of existing data demonstrate their ruling role in the development of anti-drug resistance of cancer cell. One of the most powerful protection system is based on heat shock proteins whose synthesis is triggered by activated Heat Shock Factor-1 (HSF1); the inhibition of the HSF1 with CL-43 sensitized A549 lung cancer cells to the anti-cancer effect of etoposide. Notably, analyzing A549 tumor xenografts in mice we observed nest-like pattern of co-localization of A549 cells demonstrating enhanced expression of HSF1 with macrophages, and decided to check whether the above arrangement has a functional value for both cell types. It was found that the incubation of A549 or DLD1 colon cancer cells with either human monocytes or THP1 monocyte-like cells activated HSF1 and increased resistance to etoposide. Importantly, the same effect was shown when primary cultures of colon tumors were incubated with THP1 cells or with human monocytes. To prove that HSF1 is implicated in enhanced resistance caused by monocytic cells, we generated an A549 cell subline devoid of HSF1 which did not respond to incubation with THP1 cells. The pharmacological inhibition of HSF1 with CL-43 also abolished the effect of THP1 cells on primary tumor cells, highlighting a new target of tumor-associated macrophages in a cell proteostasis mechanism.
Topics: Animals; Humans; Mice; Cell Line, Tumor; DNA-Binding Proteins; Drug Resistance; Etoposide; Heat Shock Transcription Factors; Heat-Shock Response; Transcription Factors; Tumor-Associated Macrophages
PubMed: 38280079
DOI: 10.1007/s00262-023-03612-2 -
Blood Advances May 2024Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard-of-care for patients with advanced-stage diffuse large B-cell...
Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard-of-care for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL), despite findings that patients with nongerminal center B-cell like (non-GCB) have significantly worse outcome with this regimen. We evaluated the prognostic significance of baseline risk factors, including cell of origin (COO) classified by the Hans algorithm, within an alternative chemoimmunotherapy program. At Memorial Sloan Kettering Cancer Center (MSK), 151 patients with DLBCL received sequential R-CHOP induction and (R)-ICE (rituximab, ifosfamide, carboplatin, and etoposide) consolidation. Outcome analysis based on COO was validated with a propensity score-matched cohort treated with R-CHOP from the Mayo Clinic component of the Molecular Epidemiology Resource (MER). Among the patients with GCB (n = 69) and non-GCB (n = 69) at MSK, event-free survival (EFS) of non-GCB was superior to that of GCB (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.29-0.98). Overall survival (OS) demonstrated an association in the same direction but was not statistically significant (HR, 0.68; 95% CI, 0.33-1.42). Propensity score-matched patients from MSK (n = 108) demonstrated a small attenuation in the HRs for EFS (HR, 0.57; 95% CI, 0.27-1.18) and OS (HR, 0.76; 95% CI, 0.33-1.79) and were no longer statistically significant. In contrast, the matched MER cohort (n = 108) demonstrated an EFS association (HR, 1.17; 95% CI, 0.70-1.95) and OS association (HR, 1.13; 95% CI, 0.64-2.00) in the opposite direction, but were also not statistically significant. R-CHOP induction and (R)-ICE consolidation may overcome the negative prognostic impact of the non-GCB phenotype, per the Hans algorithm, and can be preferentially selected for this population. This trial was registered at www.ClinicalTrials.gov as #NCT00039195 and #NCT00712582.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cyclophosphamide; Doxorubicin; Etoposide; Ifosfamide; Lymphoma, Large B-Cell, Diffuse; Prednisone; Prognosis; Rituximab; Treatment Outcome; Vincristine; Case-Control Studies
PubMed: 38271621
DOI: 10.1182/bloodadvances.2023011408