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O linfoma de Hodgkin (LH) é uma neoplasia do tecido linfóide de excelente prognóstico, porém, aproximadamente 15% dos pacientes em estádios precoces e 35% dos em estádios avançados progridem após o tratamento inicial. O transplante autólogo de medula óssea ou de células-tronco periféricas (ATMO) é o tratamento de escolha nesses casos. Nosso estudo tem como objetivo avaliar o tipo de tratamento utilizado, a taxa de resposta e a sobrevida de pacientes recidivados ou refratários ao ATMO. De 38 pacientes com LH submetidos a ATMO entre abril de 1996 e novembro de 2005, foram avaliados 17 que apresentaram recidiva/refratariedade ao ATMO. Nesses casos, o tratamento de resgate foi individualizado, a depender das condições clínicas de cada um, sendo constituído usualmente de drogas citotóxicas não utilizadas previamente. Após o ATMO, dez (59%) dos 17 pacientes obtiveram remissão completa, um (6%) remissão parcial e seis (35%) foram refratários. Em 14 dos 17 pacientes foi instituída quimioterapia de resgate com diversos esquemas no momento da recidiva/refratariedade após ATMO; um paciente foi tratado com radioterapia exclusiva e dois foram a óbito antes de qualquer terapia. Observamos uma taxa de resposta global de 57,4% (IC95%: 23,2 - 90,7%). A mediana da sobrevida livre de progressão foi de 19 meses e a mediana de sobrevida global foi de 32 meses. Apesar do LH recidivado/refratário ao ATMO não ser curável com os quimioterápicos atualmente disponíveis, os pacientes apresentaram longa sobrevida, com freqüentes exacerbações da doença.Hodgkin's lymphoma (HL) is a lymphoid malignancy with excellent prognosis, however nearly 15% of the patients in early stages and 35% in advanced stages have progressive disease after initial treatment. Autologous bone marrow or hematopoietic stem cell transplantation (ABMT) are the treatments of choice in these cases. This report presents the therapeutic approach and the outcome of HL patients who experience relapse after or are refractory to ABMT. Of 38 patients with LH who underwent ABMT between April 1996 and November 2005, 17 presented with relapsed/refractory disease and were included in this analysis. In these cases, the choice of rescue therapy varied upon the clinical conditions of each patient and was based on previously unused chemotherapy agents. After ABMT, 10 (59%) of the 17 patients were in complete remission, one (6%) in partial remission and six (35%) were refractory. Fourteen of the 17 patients received different schemes of rescue therapy at the time of ABMT failure, one patient was treated exclusively with radiotherapy and two died before any treatment. We observed an overall response rate of 57.4% (95% CI: 23.2 - 90.7%). The median progression-free survival was 19 months and the median overall survival was 32 months. Despite ABTM, relapsed/refractory LH can not be cured with currently available chemotherapeutic agents, the patients had long survival times with frequent exacerbations of the diseas.

The challenge in classical Hodgkin Lymphoma (cHL) management is the 30-40% of refractory/relapsed cases., Aims: The aim of this work was to determine whether NIK and BCL-2 could be useful as prognosis biomarkers in cHL. In addition, we evaluated BCL-2 as a directed-therapy in cHL cell lines using venetoclax., Main Methods: We evaluated NIK and BCL-2 expression in 112 untreated cHL patients' lymph-node biopsies by immunohistochemistry. cHL cell lines were treated with venetoclax alone or combined with vincristine or doxorubicin. Cell viability, metabolic activity and cell death were analyzed by trypan-blue exclusion method, MTS assay and FDA/IP staining respectively., Key Findings: No correlation between NIK or BCL-2 expression and the majority of the clinical parameters was found. Patients with ≥60% BCL-2+ HRS-cells had a shorter disease-free survival (DFS) and overall survival (OS) (p = 0.002, p = 0.02 respectively). A decision tree analysis, in a 30 patients subgroup, showed that patients with <60% NIK+ HRS-cells but with ≥60% BCL-2+ HRS-cells had a worse outcome in terms of DFS and OS. These parameters performed better as prognosis indicators as compared to the diagnosis bone marrow status. Human cHL cell lines U-H01, KM-H2, L1236, SUPHD1, L540 showed sensitivity to venetoclax. The co-treatment effect of venetoclax and vincristine or doxorubicin on cell viability was diverse depending on the cell line evaluated., Significance: BCL-2 should be considered as a prognosis biomarker as well as a potential new therapeutic target in cHL. We report for the first time the cytotoxic effect of venetoclax in human cHL cell lines., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Treatment options for relapsed/refractory ALL in adult patients remain challenging. Annamycin is a highly lipophilic form of the anthracycline doxorubicin with the ability to bypass multidrug resistance mechanisms of cellular drug resistance., Patients and Methods: We performed a phase I/II multicenter, open-label, study to determine the maximally tolerated dose (MTD) of nanomolecular liposomal annamycin in adult patients with refractory ALL., Results: Thirty-one patients were enrolled; the MTD was determined to be 150 mg/m(2)/d for 3 days. Other than tumor lysis syndrome, there were 3 grade 3 mucositis which comprised the MTD determination. There was also 1 case each of grade 3 diarrhea, typhlitis, and nausea. After determining the MTD, a 10-patient phase IIA trial was conducted. Eight of the patients completed 1 cycle of the 3 days of treatment at the MTD. Of these, 5 (62%) had an efficacy signal with complete clearing of circulating peripheral blasts. Three of these subjects also cleared bone marrow blasts with 1 subsequently proceeding onto successful stem cell transplantation., Conclusion: Single-agent nanomolecular liposomal annamycin appears to be well tolerated, and shows evidence of clinical activity as a single agent in refractory adult ALL., (Copyright © 2013 Elsevier Inc. All rights reserved.)