Matheus Vescovi Gonçalves

Diagnosis and treatment of chronic lymphocytic leukemia: recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia is characterized by clonal proliferation and progressive accumulation of B-cell lymphocytes that typically express CD19+, CD5+ and CD23+. The lymphocytes usually infiltrate the bone marrow, peripheral blood, lymph nodes, and spleen. The diagnosis is established by immunophenotyping circulating B-lymphocytes, and prognosis is defined by two staging systems (Rai and Binet) established by physical examination and blood counts, as well as by several biological and genetic markers. In this update, we present the recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia for the diagnosis and treatment of chronic lymphocytic leukemia. The following recommendations are based on an extensive literature review with the aim of contributing to more uniform patient care in Brazil and possibly in other countries with a similar social–economic profile.

Frequency of polycythemia in individuals with normal complete blood cell counts according to the new 2016 WHO classification of myeloid neoplasms.

Polycythemia vera (PV) is a disorder characterized by clonal proliferation of myeloid cells and increased red blood cell mass. Recently, the revised 2016 WHO classification of myeloid neoplasms decreased the threshold levels of hemoglobin and hematocrit for the diagnosis of PV. However, the new proposed cutoffs have remarkable overlap with the normal reference values reported and the clinical impact of these new cutoffs has not been widely assessed in the general population.

Treatment of refractory autoimmune hemolytic anemia with venetoclax in relapsed chronic lymphocytic leukemia with (del17p)

Dear editor, We present the case of a 68-year-old male with chronic lymphocytic leukemia (CLL). He was diagnosed with CLL in September 2007 and del (17p) was detected by FISH. In 2008, due to progressive splenomegaly, he received six cycles of fludarabine and cyclophosphamide and achieved complete response. In July 2015, he relapsed with progressive lymphocytosis, moderate splenomegaly, and severe autoimmune hemolytic anemia (AIHA), with transfusion requirement and no response to steroids. The patient had a direct antiglobulin test positive for IgG and C3d. Elution tests were positive. Titration was not performed. Considering the cytogenetic risk and the limited treatment options at our public institution, he was started compassionate use of alemtuzumab in August 2015, with improvement of lymphocytosis and splenomegaly, but persistent anemia. He had a cytomegalovirus (CMV) reactivation in September 2015, successfully treated with ganciclovir and alemtuzumab withdrawal. The patient relapsed in October 2015, with severe AIHA in spite of normal lymphocyte count and spleen size. He received rituximab plus high-dose dexamethasone, with improvement of transfusion requirement, but stable anemia. He had a second CMV reactivation in November 2015, successfully treated with ganciclovir. He persisted with symptomatic anemia and was started on venetoclax in July 2016, through a compassionate use program, with standard dosage (400 mg) after the ramp-up weeks. After 3 months, he showed improvement of symptoms and sustained hemoglobin levels, with no transfusion requirement. His latest flow cytometry study showed 0.05% CLL cells in peripheral blood. No CMV reactivation occurred. Two episodes of neutropenia were observed, without fever or documented infection, responding to venetoclax interruption and reduction to 300 mg in April 2017. No other adverse effects were noticed. He has received 10months of venetoclax and remains in treatment and in remission. AIHA and other autoimmune cytopenias in CLL have complex pathogenesis andmay occur in up to 10% of patients [1, 2], with AIHA being the commonest. They influence treatment and have a distinct prognosis from cytopenias related to extensive CLL infiltration in the bone marrow [1]. Steroid therapy is standard for autoimmune cytopenias in CLL, but evidence regarding the best approach for refractory patients is lacking [2]. CLLwith del (17p) is associated with inferior survival and a higher incidence of refractory disease. Until recently, outcomes with standard therapy have been very unfavorable for del (17p) CLL. However, novel therapies have yielded encouraging perspectives for these patients, most noticeably with ibrutinib and venetoclax. Promising rates of complete response and even minimal residual disease eradication have been observed, and further changes in practice are expected [3, 4]. While some evidence is available on ibrutinib therapy and AIHA in CLL [5], to the best of our knowledge, this is the first report of refractory AIHA responding to venetoclax in CLL. The careful evaluation of safety and efficacy in specific clinical settings, such as refractory AIHA in CLL, is particularly in need [1, 2]. We believe that a clearer understanding of clinical outcomes in such settings is key for proper decisionmaking, and for the benefit of a greater number of CLL patients. * Marcelo Pitombeira de Lacerda

Simultaneous Quantification of the 8 Human Herpesviruses in Allogeneic Hematopoietic Stem Cell Transplantation.

Background Human herpesviruses may cause severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of some of these infections on transplant outcomes is still unclear. A prospective survey on the incidence and clinical features of herpesviruses infections after HSCT has not yet been conducted in Brazilian patients, and the impact of these infections on HSCT outcome remains unclear. Methods We prospectively analyzed the incidence of infection of the eight human herpesviruses simultaneously in 1 045 peripheral blood samples from 98 allogeneic HSCT recipients. Samples were collected weekly starting at the time of transplant until day +100. All herpesviruses were screened and quantified in plasma by quantitative real-time polymerase chain reaction. Median follow up time was 24 months. Results The incidences of infection for each herpesvirus were as follows: cytomegalovirus (CMV), 44%; human herpesvirus [HHV] 6, 18%; HHV8, 6%; Epstein-Barr virus, 3%; herpes simplex virus 1, 3%; varicella zoster virus, 3%; HHV7, 2%; and herpes simplex virus 2, 1%. The CMV infection was significantly more frequent among adults and was associated with a higher risk of developing acute graft-versus-host disease. The HHV6 infection was significantly more frequent after umbilical cord blood transplant and was associated with an increased risk of platelet engraftment failure. There was no significant impact of these infections on the other transplant outcomes. Conclusions Herpesviruses infections were uncommon after HSCT, except for CMV and HHV6, which, although relatively frequent, had no clinically relevant impact on the outcomes.

Plasma cell leukemia with t(11;14)(q13;q32) simulating lymphoplasmacytic lymphoma – a diagnostic challenge solved by flow cytometry

Plasma cell leukemia (PCL) is a rare and aggressive manifestation of malignant plasma cell proliferation and corresponds to 2–4% of multiple myeloma (MM) cases.1,2 The World Health Organization (WHO) defines PCL by the presence of high levels (at least 2 × 109/L) of clonal plasma cells in the peripheral blood (PB) or at least 20% of the leukocyte differential count.1 Primary PCL (pPCL) corresponds to 60% of the cases and presents as leukemia at diagnosis, usually with tissue infiltration, organomegaly and lymphadenopathy and a lower frequency of bone lesions (15–40% cases) than multiple myeloma.2 Secondary PCL is the terminal phase of MM and corresponds to the remaining 40% of PCL cases; it usually has a poor response to standard MM treatment.2,3 The diagnosis of plasma cell neoplasms is easily suggested by the characteristic plasma cell

Erratum to “Diagnosis and treatment of chronic lymphocytic leukemia: Recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia” [Rev Bras Hematol Hemoter. 2016;38(4):346–357]

Celso Arrais Rodrigues, Matheus Vescovi Gonçalves, Maura Rosane Valério Ikoma, Irene Lorand-Metze , André Domingues Pereira, Danielle Leão Cordeiro de Farias , Maria de Lourdes Lopes Ferrari Chauffaille, Rony Schaffel, Eduardo Flávio Oliveira Ribeiro, Talita Silveira da Rocha , Valeria Buccheri, Yuri Vasconcelos , Vera Lúcia de Piratininga Figueiredo, Carlos Sérgio Chiattone , Mihoko Yamamoto, on behalf of the Brazilian Group of Chronic Lymphocytic Leukemia a Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil b Hospital Sírio Libanês, São Paulo, SP, Brazil c Fleury Medicina e Saúde, São Paulo, SP, Brazil d Hospital Amaral Carvalho, Jaú, SP, Brazil e Universidade Estadual de Campinas (UNICAMP), São Paulo, SP, Brazil f Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil g Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil h Hospital Santa Lúcia, Brasília, DF, Brazil i A.C Camargo Cancer Center, São Paulo, SP, Brazil j Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil k Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, SP, Brazil l Instituto Goiano de Oncologia e Hematologia (INGOH), Goiânia, GO, Brazil m Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE), São Paulo, SP, Brazil n Hospital Samaritano, São Paulo, SP, Brazil

Chronic lymphocytic leukemia in Brazil: A retrospective analysis of 1903 cases

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