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Orphanet Journal of Rare Diseases Apr 2022Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a...
BACKGROUND
Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a life-threatening, hyper-inflammatory syndrome. We retrospectively described the clinical-biological characteristics of a series of 28 pediatric LCH patients with MAS-HLH in a single center. We further analyzed the difference in treatment outcomes between second-line chemotherapy (cytarabine and cladribine) and targeted therapy (dabrafenib) for BRAF-V600E-positive patients.
RESULTS
LCH patients with MAS-HLH were aged < 2 years, harbored high frequencies of risk organ, skin, or lymph nodes involvement, and most of them carried BRAF-V600E mutation in lesions (88.0%) or plasma (90.5%). Patients were firstly treated with the initial induction first-line therapy (vindesine-steroid combination), and most of them (26/28) failed to control the active MAS-HLH after one six-week course of induction treatment. Then they were shifted to second-line chemotherapy or targeted therapy dabrafenib. BRAF-V600E-mutant patients treated with dabrafenib had prompt resolution of MAS-HLH signs and symptoms with less toxicity than second-line chemotherapy. Moreover, the progression-free survival (PFS) rate for patients given dabrafenib was much higher than those treated with chemotherapy (4 year-PFS: 75% vs. 14.6%, P = 0.034).
CONCLUSIONS
LCH patients with MAS-HLH harbored specific clinical-biology characteristics compared to the multisystem LCH without MAS-HLH. The BRAF inhibitor dabrafenib provides a promising treatment option for LCH with MAS-HLH.
Topics: Child; Child, Preschool; Histiocytosis, Langerhans-Cell; Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Mutation; Retrospective Studies; Treatment Outcome
PubMed: 35379272
DOI: 10.1186/s13023-022-02276-y -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jun 2020To investigate the clinicopathologic features and prognosis of mediastinal T lymphoblastic lymphoma/leukemia (T-LBL/ALL). Sixty-one patients with mediastinal T-LBL/ALL...
To investigate the clinicopathologic features and prognosis of mediastinal T lymphoblastic lymphoma/leukemia (T-LBL/ALL). Sixty-one patients with mediastinal T-LBL/ALL diagnosed at First Affiliated Hospital of Zhengzhou University from August 1, 2011 to December 31, 2018 were enrolled. Their clinical, pathological, imaging features and prognosis were retrospectively analyzed. Of the 61 patients with mediastinal T-LBL/ALL, 46 were male and 15 were female, with a male to female ratio of approximately 3∶1, aged 5 to 71 years (median 24 years, average of 24.5 years). Radiological findings were mediastinal soft tissue masses (58 cases) or mediastinal multiple enlarged lymph nodes (1 case). The tumor had a diameter of 4.9 to 18.3 cm in size, and data of 2 cases was unavailable. The patient's main symptoms were superior vena cava syndrome (cough, dyspnea, facial or neck edema), shortness of breath and chest pain, while about 1/3 of patients developed B symptoms (high fever, night sweats or significant weight loss). All 61 cases were biopsy specimens, and 2 of the tumors were later resected. Histopathologic examination showed that the thymic tissue epithelial network structure was destroyed or completely disappeared. A large number of lymphocytoid tumor cells were diffusely infiltrative, with infiltration into adipose tissue, starry sky phenomenon, linear-like arrangement, interstitial collagen hyperplasia and tumor cell extrusion. Focal tumor necrosis was present in some cases. Tumor cells were overall small to medium in size. They had little cytoplasm, slightly distorted, round or oval-shaped nuclei, fine chromatin, and innocuous/small nucleoli. Immunohistochemical studies showed that the tumor cells expressed CD7 (100%, 33/33), TDT (93.4%, 57/61), CD99 (83.3%, 25/30), CD1a (4/7), CD10 (8/18), CD34 (13.2%, 5/38), but did not express B cell markers (CD20 and PAX5) or granulocyte monocyte marker (MPO). The Ki-67 proliferation index was usually greater than 50%. One case was tested for TCR clonal rearrangement, which was positive. Several hemotherapy regiments were used. Hyper-CVAD (cyclophosphamide, vindesine, dexamethasone, and epirubicin) were most frequently administrated (60.4%, 32/53), followed by BFM-90 (50.9%, 27/53). Some patients were treated with the above two and other treatment options. Follow-up data were available in 55 of the 61 patients, and 26 patients (47.3%) survived. The average five-year survival rate was 50.6%. The patient's prognosis was not significantly related to the International Prognostic Index, age of onset, gender, or tumor size. The mediastinal T-LBL/ALL is rare, and most of its specimens are needle biopsies. The histological morphology is often difficult to interpret, while the addition of clinical features and immunohistochemistry may help. The combination of CKpan, TDT, CD99, CD7, CD3, PAX5, CD34, CD10, and Ki-67 immunohistochemicl studies may assist in diagnosis of the most cases.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Male; Mediastinal Neoplasms; Middle Aged; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Retrospective Studies; Young Adult
PubMed: 32486538
DOI: 10.3760/cma.j.cn112151-20190929-00538 -
[Rinsho Ketsueki] the Japanese Journal... Oct 2014
Review
Topics: Adenine; Animals; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Discovery; Epigenesis, Genetic; Humans; Lenalidomide; Lymphoma, Large B-Cell, Diffuse; Mice; Molecular Targeted Therapy; Piperidines; Prednisolone; Prednisone; Pyrazoles; Pyrimidines; Radiotherapy, Adjuvant; Rituximab; Thalidomide; Vincristine; Vindesine
PubMed: 25297756
DOI: No ID Found -
Annals of Hematology Apr 2021High-dose methotrexate (HD-MTX) at 3 g/m is one of the strategies for central nervous system (CNS) prophylaxis in the first-line treatment of aggressive lymphomas,...
High-dose methotrexate (HD-MTX) at 3 g/m 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/m 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.
Topics: Adolescent; Adult; Ambulatory Care; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Central Nervous System; Chemical and Drug Induced Liver Injury; Cyclophosphamide; Doxorubicin; Female; Hematologic Diseases; Humans; Infusions, Intravenous; Kidney Diseases; Kidney Function Tests; Leucovorin; Liver Function Tests; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Neoplasm Invasiveness; Outpatient Clinics, Hospital; Prednisone; Retrospective Studies; Rituximab; Vincristine; Vindesine; Young Adult
PubMed: 33608849
DOI: 10.1007/s00277-020-04341-7 -
American Journal of Hematology Apr 2023Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm mainly affecting young children. This study aimed to evaluate the outcomes of 449 pediatric patients...
Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm mainly affecting young children. This study aimed to evaluate the outcomes of 449 pediatric patients enrolled in the BCH-LCH 2014 study. 52.6% of patients were classified with single-system (SS) LCH, 28.1% with multisystem (MS) risk organ negative (RO-) LCH, and 19.4% with MS RO+ LCH. Three hundred ninety-six patients (88.2%) were initially treated with first-line therapy based on the vindesine-prednisone combination. One hundred thirty-nine patients who lacked a response to initial treatment were shifted to second-line therapy, 72 to intensive treatment Arm S1 (a combination of cytarabine, cladribine, vindesine, and dexamethasone), and 67 to Arm S2 (without cladribine). The 5-year overall survival (OS), progression-free survival (PFS), and relapse rates were 98.2% (median: 97.6 months), 54.6% (median: 58.3 months), and 29.9%, respectively. MS RO+ patients had the worst prognosis among the three clinical subtypes. For the patients initially treated with first-line therapy, the 5-year OS, PFS, and relapse rates were 99.2%, 54.5%, and 29.3%, respectively. Patients in Arm S1 had a significantly better prognosis than patients in Arm S2 (5-year PFS: 69.2% vs. 46.5%, p = .042; relapse rate: 23.4% vs. 44.2%, p = .031). Multivariate analysis revealed that early treatment response, the involvement of RO, skin, and oral mucosa, as well as laboratory parameters, including CRP and γ-GT, were independent risk factors for the PFS of LCH. Thus, the prognosis of LCH in children has been improved significantly with stratified chemotherapy, and progression and relapse remained the challenges, especially for RO+ patients.
Topics: Child; Humans; Child, Preschool; Prognosis; Treatment Outcome; Cladribine; Vindesine; Risk Factors; Histiocytosis, Langerhans-Cell; Recurrence; Retrospective Studies
PubMed: 36594188
DOI: 10.1002/ajh.26829 -
Biological & Pharmaceutical Bulletin May 2019In addition to their major targets, clinically effective drugs may have unknown off-targets. By identifying such off-targets it may be possible to repurpose approved...
In addition to their major targets, clinically effective drugs may have unknown off-targets. By identifying such off-targets it may be possible to repurpose approved drugs for new indications. We are interested in the Golgi apparatus as a novel target for cancer therapy, but there is a paucity of candidate Golgi-disrupting drugs. Here, we aimed to identify Golgi-disrupting compounds from a panel of 34 approved anticancer drugs by using HBC-4 human breast cancer cells and immunofluorescence microscopy to visualize the Golgi apparatus. The screen identified five drugs having Golgi-disrupting activity. Four of them were vinca alkaloids (vinorelbine, vindesine, vincristine and vinblastine), and the fifth drug was eribulin. This is the first study to demonstrate that vinorelbine, vindesine and eribulin possess Golgi-disrupting activity. The 5 drugs are known to inhibit tubulin polymerization and to induce microtubule depolymerization. Interestingly, a microtubule-stabilizer paclitaxel did not induce Golgi-disruption, suggesting that the three-dimensionally preserved microtubules are partly responsible for maintaining the Golgi complex. Concerning eribulin, a noteworthy drug because of its high clinical efficacy against advanced breast cancer, we further confirmed its Golgi-disrupting activity in 3 different human breast cancer cell lines, BSY-1, MDA-MB-231 and MCF-7. Golgi-disruption may contribute to anticancer efficacy of eribulin. In conclusion, the present study revealed that 4 vinca alkaloids and eribulin possessed potential Golgi-disrupting activity among a panel of 34 approved anticancer drugs. Other drugs covering various molecular-targeted drugs and classical DNA-damaging drugs showed no Golgi-disrupting effect. These results suggest that tubulin polymerization-inhibitors might be promising candidate drugs with Golgi-disrupting activity.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Furans; Golgi Apparatus; High-Throughput Screening Assays; Humans; Ketones; MCF-7 Cells; Microtubules; Paclitaxel; Tubulin Modulators; Vinblastine; Vincristine; Vindesine; Vinorelbine
PubMed: 30787205
DOI: 10.1248/bpb.b18-01026 -
Diseases of the Esophagus : Official... Aug 2014The effect of adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas is still controversial, and the subgroup of patients who... (Comparative Study)
Comparative Study Meta-Analysis Review
The effect of adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas is still controversial, and the subgroup of patients who will most likely benefit from the adjuvant chemotherapy on long-term survival has not yet been identified clearly. Studies published from 1995 to May 2012 were searched in Medline, Embase, PubMed, Cancerlit, the Cochrane Library, CNKI and major scientific meetings. Randomized controlled trials and nonrandomized studies comparing surgery plus adjuvant chemotherapy with surgery alone in patients with resectable thoracic esophageal squamous cell carcinomas were included. Eleven studies with a total of 2047 patients were identified, consisting of the adjuvant chemotherapy arm (n = 887) and surgery-alone arm (n = 1160). There was not statistically significant benefit on 3-year overall survival for adjuvant chemotherapy (risk ratio [RR] = 0.89, 95% confidence interval [CI], 0.72 to 1.09; P = 0.25). Adjuvant chemotherapy could significantly prolong the 1-year disease-free survival (DFS) (RR = 0.68, 95%CI, 0.51 to 0.89; P = 0.006), but not 3-year DFS (RR = 0.97, 95%CI, 0.73 to 1.29; P = 0.84). Further analysis showed that patients with stage III-IV diseases could benefit from adjuvant chemotherapy on 3-year overall survival (RR = 0.43, 95%CI, 0.31 to 0.61; P = 0.00001), but not in the case of patients with stageI-IIdiseases (RR = 1.12, 95%CI, 0.65 to 1.93; P = 0.68). Additionally, patients with positive lymph node could benefit on 5-year DFS from adjuvant chemotherapy (RR = 0.79, 95%CI, 0.64 to 0.99; P = 0.04). The modality treatment with adjuvant chemotherapy for patients with squamous cell carcinoma of thoracic esophagus might be determined according to pathological stage or the status of lymph node metastasis.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Esophageal Neoplasms; Esophagectomy; Fluorouracil; Humans; Lymphatic Metastasis; Neoplasm Staging; Randomized Controlled Trials as Topic; Survival Rate; Vindesine
PubMed: 23621119
DOI: 10.1111/dote.12073 -
Frontiers in Medicine 2023Primary cardiac tumors are extremely uncommon and primary cardiac lymphoma (PCL) is an even rarer subset. A definite diagnosis can be delayed, which increases the...
Primary cardiac tumors are extremely uncommon and primary cardiac lymphoma (PCL) is an even rarer subset. A definite diagnosis can be delayed, which increases the likelihood of a poor prognosis. We report a case involving a 64-year-old male who presented with dyspnea, palpitation, and third-degree atrioventricular block (AVB) secondary to primary cardiac B-cell lymphoma that was diagnosed endomyocardial biopsy (EMB) and multimodality imaging. Chemotherapy was initiated using rituximab, cyclophosphamide, vindesine, and prednisone (R-COP) followed by implantation of an artificial capsule pacemaker. Third-degree AVB vanished, and the subsequent cycle of treatment was adjusted as R-CDOP (rituximab, cyclophosphamide, doxorubicin liposome, vindesine, and prednisone), with aspirin and rosavastatin to prevent ischemic events. So far, the patient had a good clinical course and normal electrocardiogram. This case underscores the importance of EMB in the diagnosis of heart neoplasms. It is worth noting that anthracycline is not contraindicated in PCL.
PubMed: 37007783
DOI: 10.3389/fmed.2023.1119286 -
Frontiers in Genetics 2022Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart...
Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart disease (CHD) is also rare. We report an MMA case with ALL and CHD in a 5.5-year-old girl. With developmental delay and local brain atrophy in MRI, she was diagnosed with cerebral palsy at 9 months old. Rehabilitation was performed since then. This time she was admitted to hospital because of weakness and widespread bleeding spots. ALL-L2 (pre-B-cell) was confirmed by bone marrow morphology and immunophenotyping. Echocardiography showed patent foramen ovale. The girl was treated with VDLD and CAML chemotherapy, during which she developed seizures, edema and renal insufficiency. Decrease of muscle strength was also found in physical examination. Screening for inherited metabolic disorders showed significantly elevated levels of methylmalonate-2, acetylcarnitine (C2), propionylcarnitine (C3), C3/C2 and homocysteine. Gene analysis revealed a compound heterozygous mutaion in (NM_015,560): c.80A > G (p.Gln27Arg) and c.609G > A (p.Trp203*). CblC type MMA was diagnosed. Intramuscular injection of cyanocobalamin and intravenous L-carnitine treatment were applied. The edema vanished gradually, and chemotherapy of small dosage of vindesine was given intermittently when condition permitted. 2 months later, muscle strength of both lower limbs were significantly improved to nearly grade 5. The levels of methylmalonic acid and homocysteine were improved. Metabolic disease screening and gene analysis are very necessary for diseases with complex clinical symptoms. ALL can be a rare manifestation for MMA. We report a case of methylmalonic acidemia with acute lymphoblastic leukemia and congenital heart disease, which uncovered the importance of genetic testing and metabolic diseases screening in patients with multiple systemic organ involvement.
PubMed: 35495149
DOI: 10.3389/fgene.2022.856552 -
Journal of Pediatric Surgery Mar 2019Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive malignant renal tumor. We describe our experience with neoadjuvant transcatheter arterial...
BACKGROUND
Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive malignant renal tumor. We describe our experience with neoadjuvant transcatheter arterial chemoembolization (TACE) and systematic chemotherapy for the treatment of advanced CCSK in children.
METHODS
Between January 2010 and December 2016, seven patients (3 boys and 4 girls; median 2.2 years) with advanced CCSK received preoperative TACE of renal artery and systemic chemotherapy. The chemoembolic emulsion for TACE consisted of cisplatin, pirarubicin, vindesine, and iodized oil. Preoperative systemic chemotherapy with vindesine, ifosfamide, and etoposide was administered three weeks after TACE. Nephrectomy was performed three weeks after systemic chemotherapy. After surgery, patients received radiotherapy and postoperative chemotherapy.
RESULTS
No cardiotoxicity, renal insufficiency, or hepatic dysfunction was found in any patients. Grade II-III marrow suppression developed in four patients. One patient with tumor progress during neoadjuvant therapy failed to successfully undergo surgery and died. Six patients underwent nephrectomy after neoadjuvant therapy. Median follow-up period was 49.5 months (range, 11-83 months). Five patients have recurrence-free survival. One patient is still in postoperative chemotherapy after nephrectomy, radiotherapy and thoracoscopic resection of lung metastases.
CONCLUSIONS
Neoadjuvant TACE and systemic chemotherapy appeared to be feasible in the treatment of advanced CCSK in this pilot study.
THE TYPE OF STUDY
A case series with no comparison group.
LEVEL OF EVIDENCE
Level IV.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoembolization, Therapeutic; Child; Child, Preschool; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Humans; Infant; Iodized Oil; Kidney; Kidney Neoplasms; Male; Neoadjuvant Therapy; Nephrectomy; Pilot Projects; Retrospective Studies; Sarcoma, Clear Cell; Treatment Outcome; Vindesine
PubMed: 30318310
DOI: 10.1016/j.jpedsurg.2018.09.012