35 research outputs found
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Childhood de novo CD5+ Diffuse Large B-cell Lymphoma: a Separate Entity?
De novo CD5-positive diffuse large B- cell lymphoma (CD5+ DLBCL) is a subtype of DLBCL found predominantly in older individuals. This particular subtype has been associated with a female pre- dominance and a more aggressive clinical course. Conversely, this entity has not been described in the pe- diatric population. We report a case of a 12 year-old boy who presented with an ileocecal intussusception. Radiologic, morphologic, and immunophenotypic analysis revealed an isolated extranodal mass consistent with a CD5+ DLBCL, germinal center cell phenotype. Fluorescent in situ hybridization analysis was nega- tive for cMYC, BCL6, BCL2, MLL, and IGH/CCND1 rearrangement and showed loss of one copy of MLL in 32% cells. The patient was treated with four cycles of cyclophosphamide, vincristine, prednisolone, methotrexate, and doxorubicin and achieved complete remission. To the best of our knowledge, this is the first detailed report of a de novo CD5+ DLBCL occurring in a child
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CUTLL1, a novel human T-cell lymphoma cell line with t(7;9) rearrangement, aberrant NOTCH1 activation and high sensitivity to c-secretase inhibitors
Activating mutations in NOTCH1 are present in over 50% of human T-cell lymphoblastic leukemia (T-ALL) samples and inhibition of NOTCH1 signaling with c-secretase inhibitors (GSI) has emerged as a potential therapeutic strategy for the treatment of this disease. Here, we report a new human T-cell lymphoma line CUTLL1, which expresses high levels of activated NOTCH1 and is extremely sensitive to c-secretase inhibitors treatment. CUTLL1 cells harbor a t(7;9)(q34;q34) translocation which induces the expression of a TCRB-NOTCH1 fusion transcript encoding a membrane-bound truncated form of the NOTCH1 receptor. GSI treatment of CUTLL1 cells blocked NOTCH1 processing and caused rapid clearance of activated intracellular NOTCH1. Loss of NOTCH1 activity induced a gene expression signature characterized by the downregulation of NOTCH1 target genes such as HES1 and NOTCH3. In contrast with most human T-ALL cell lines with activating mutations in NOTCH1, CUTLL1 cells showed a robust cellular phenotype upon GSI treatment characterized by G1 cell cycle arrest and increased apoptosis. These results show that the CUTLL1 cell line has a strong dependence on NOTCH1 signaling for proliferation and survival and supports that T-ALL patients whose tumors harbor t(7;9) should be included in clinical trials testing the therapeutic efficacy NOTCH1 inhibition with GSIs. Leukemia (2006) 20, 1279–1287. doi:10.1038/sj.leu.2404258; published online 11 May 200
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Cutaneous Vesicostomy for Palliative Management of Hemorrhagic Cystitis and Urinary Clot Retention
Interferon administered intralesionally in skin and oral cavity lesions in heterosexual drug addicted patients with AIDS-related Kaposi's sarcoma
Clofarabine with topotecan, vinorelbine, and thiotepa reinduction regimen for children and young adults with relapsed AML.
Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML), as outcomes remain poor. Therapeutic options are limited in this heavily pretreated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline-based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients, <25 years of age, with relapsed/refractory AML treated with up to 2 cycles of the TVTC reinduction regimen from 2007 to 2018. The overall response rate, defined as complete remission or complete remission with partial recovery of platelet count, was 71.4% (95% confidence interval [CI], 41.9-91.6) for those patients in first relapse (n = 14) and 47.4% (95% CI, 24.4-71.1) for patients in second or greater relapse or with refractory disease. Responses were seen across multiple high-risk cytogenetic and molecular subtypes, with 84% of responders successfully bridged to allogeneic stem cell transplantation. The 5-year overall survival for patients in first relapse was 46.2% (95% CI, 19.1-73.3) and 50.0% (95% CI, 26.9-73.1) for patients who responded to TVTC. For pediatric and young adult patients with relapsed/refractory AML, TVTC reinduction compares favorably with currently used salvage regimens and warrants further exploration