Adriana M. Damasco Penna

Bleomycin-induced flagellate dermatitis

A 29-year-old woman with stage IVB Hodgkins lymphoma was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine. Two weeks after the first cycle was completed, she developed pruritic, linear erythematous lesions in a flagellate-like pattern on the trunk, neck and arms. After oral prednisone therapy and cessation of bleomycin, the lesions started to recede.

Imbalance of Pro- and Anti-Inflammatory Cytokines in Patients With cHL Persists Despite Treatment Compared With Control Subjects.

BACKGROUND Classical Hodgkin lymphoma (cHL) is a malignant lymphoma that most commonly affects young adults. The lymphomagenesis of cHL depends largely on immune alterations that contribute to proliferation and maintenance of the Hodgkin-Reed-Sternberg (HRS) neoplastic cells. A combination of different immune processes is responsible for the escape of HRS cells, the imbalance between pro- and anti-inflammatory cytokines being one of them. In this study, we aimed to measure serum levels of pro- and anti-inflammatory cytokines in cHL patients before and after treatment compared with a healthy controls group, and to investigate associations with clinical and pathologic characteristics. PATIENTS AND METHODS We prospectively studied all cases of cHL diagnosed between March 2009 to March 2013 at the Universidade Federal de São Paulo and Hospital Santa Marcelina, in Sao Paulo, Brazil. Twenty-nine cases with sufficient clinical data were included in this study. Additionally, 18 healthy control subjects were included and recruited from our University Blood Bank. Serum cytokine levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-17, tumor necrosis factor (TNF)-α, soluble IL-2 receptor (sCD25), vascular endothelial growth factor (VEGF), and interferon (IFN)-γ were determined in serum of patients and controls using a multiplexed immunoassay system. RESULTS Higher International Prognostic Score was positively correlated with increased levels of IL-6 (P = .003); sCD25 levels were higher in patients with low serum albumin (P = .04), and IFN-γ seemed to correlate with B symptoms, although did not reach statistical significance (P = .057). Pretreatment levels of IL-10, IL-6, TNF-α, and sCD25 were increased in cHL patients compared with in healthy control subjects (P < .001), with median values of 7 pg/mL (range, 0.3-230.9), 5.3 pg/mL (range, 0.4-72.7), 14.6 (range, 4.0-60.4), and 575.9 pg/mL (range, 7.5-1813.3), respectively. Treatment significantly reduced levels of IL-10 (7.0 to 0.3; P < .001), IL-6 (5.3 to 0.4; P = .014), and sCD25 (575.9 to 93.5; P < .001), however, levels of IL-4 increased (0.6 to 2.2; P = .002). Compared with normal control subjects, increased levels of IL-6 (0.4 to 0.4; P = .027), sCD25 (93.5 to 7.5; P = .002), and TNF-α (12 to 8.7; P = .003) persisted after treatment. CONCLUSION In this study we showed higher levels of IL-6, IL-10, TNF-α, and sCD25 in cHL patients at diagnosis than in healthy control subjects. After treatment, levels of IL-6, IL-10, and sCD25 decreased gradually but did not normalize. Understanding the cytokine pattern is extremely important in the development of future therapies that target interactions between neoplastic cells and the inflammatory microenvironment.

New treatment approaches for relapsing/refractory Hodgkin’s lymphoma: An overview of the Brazilian scenario

Hodgkin’s lymphoma (HL) is a B-cell malignancy with a classical bimodal distribution with incidence peaking in the third and sixth decades of life. The purpose of this review is to describe the current unmet medical need for relapsing/refractory HL and the main data of emerging treatments, including brentuximab vedotin, the immune checkpoint inhibitors nivolumab and pembrolizumab, as well as other compounds in development. Available guidelines for relapsing/refractory HL are discussed.

Hodgkin’s lymphoma unmet medical needs in Brazil: experts’ perspective

Background: In 2016, Hodgkin’s Lymphoma (HL) was responsible for 2,470 new cases in Brazil and, despite recent scientific advances, there are unmet medical needs that affects patients’ outcome. Therefore, we aimed to explore the unmet medical needs in the management of HL patients in Brazil, based on experts’ perspective. Methods: A questionnaire was developed to address the unmet medical needs including barriers for the diagnosis and treatment of HL in Brazil. The questionnaire results were presented in a panel discussion to validate participants’ responses and to collect additional data. Main results: Eight experts participated in the panel. On both healthcare systems, public and private, a slight majority of patients was women and most of them were under 60 yearsold. In addition, the majority of patients were referred from another specialty on both systems. The time from onco-hematologist appointment to diagnosis was different between public and private sector (median of 30 and 12.5 days, respectively). Most patients in the public sector were on stage III (33%) and IV (33%); in the private sector, most patients were on stages II (36%) and III (24%). The most common barriers were the delayed diagnosis and the unavailability of diagnostic procedures and treatment options. Conclusion: According to participants, issues related to infrastructure and healthcare resource allocation affects the management of HL. Improvements in the infrastructure and educational measures for physicians and patients may contribute to minimize the barriers. RESUMO Introdução: Em 2016, o Linfoma de Hodgkin (LH) foi responsável por 2.470 novos casos no Brasil e, apesar dos recentes avanços científicos, há necessidades médicas não atendidas que afetam os pacientes. Portanto, o estudo teve como objetivo explorar as necessidades médicas não atendidas no manejo de pacientes com LH no Brasil, com base na perspectiva de especialistas. Métodos: Um questionário foi desenvolvido para abordar as necessidades médicas não atendidas, incluindo as barreiras para o diagnóstico e tratamento do LH no Brasil. Os resultados do questionário foram Received on: 08/05/2018. Approved for publication on: 04/08/2018. 1. Faculdade de Medicina da Universidade de São Paulo/Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, São Paulo – SP, Brazil. 2. Hospital Albert Einstein, São Paulo – SP, Brazil. 3. Hospital Santa Marcelina, São Paulo – SP, Brazil. 4. Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo – SP, Brazil. 5. Instituto Nacional de Câncer, Rio de Janeiro – RJ, Brazil. 6. Hospital Napoleão Laureano, João Pessoa – PB, Brazil. 7. Quanta, Curitiba – PR, Brazil. 8. Laboratório Bacchi, Botucatu – SP, Brazil. 9. Evidências-Kantar Health, Campinas – SP, Brazil. 10. Takeda Pharmaceuticals, São Paulo – SP, Brazil. Funding: This study was supported by Takeda Pharmaceutical, São Paulo, Brazil. Acknowledgments: The authors are grateful to Guilherme S. Julian, Eloisa S. Moreira and Renata Eiras Martins, from Evidencias Kantar Health, for collaboration in the development of the questionnaire, data acquisition and analysis, and elaboration of the manuscript, which were supported by a grant from Takeda-Pharmaceuticals. Declaration of interest: Tânia Barreto is currently a Takeda ́s employee. Renato Watanabe de Oliveira is currently a Evidências-Kantarhealth’s employee. Carlos Bacchi is the medical diretor from Laboratório de Patologia Bacchi. Guilherme Perini has first degree relative in Merck and financial relatioship with Takeda and Janssen. Valeria Buccheri present lectures for Takeda. Flavia Pimenta is a speaker for Janssen. The other authors declared no conflicts of interest. Reprint requests and correspondence should be addressed to: Tania Barreto. Rua Estilo Barroco, 721. São Paulo, SP, Brazil. Zip code 04709-011. E-mail: tania.barreto@takeda.com. Telephone: (+55 11) 5188 450. ORIGINAL ARTICLE ARTIGO ORIGINAL