Davimar Miranda Maciel Borducchi

Geographic diversity of adult t-cell leukemia/lymphoma in Brazil

We describe 195 cases of adult T‐cell leukemia/lymphoma (ATLL) reported to the national registry of T‐cell malignancies in Brazil between 1994 and 1998. We compared the effect of demographic differences and clinical features of 150 consecutive ATLL cases in different regions of this diverse country. At diagnosis, the predominant clinical sub‐type was the acute type (60%), followed by lymphoma (22%), chronic (10%) and smoldering (8%) types. Although we expected that different sub‐types would be present in different regions, on the basis of immunogenetic factors determined by ethnicity, we did not demonstrate these differences. There were no significant differences among ATLL subtypes by age or gender. No ethnic group predominated in the total population of patients, but significant differences were noted when examining ethnic distribution by region. Reflecting the general population distribution, white patients were seen more often in São Paulo and black patients in Bahia, than in other regions. In most regions, cases were equally distributed between blacks and mulattos, except in Pernambuco, where blacks were less frequent. The main clinical features were lymphadenopathy, skin lesions, hypercalcemia and hepatomegaly. Fourteen patients (9%) suffered from HTLV‐I‐associated myelopathy (HAM/TSP), either at diagnosis or during follow‐up of ATLL. All cases but one had antibodies to HTLV‐I, with concordant results with ELISA, WB and PCR analyses. For the antibody‐negative case, pol and tax gene sequences were present in tumor cells when subjected to PCR analyses. The prognosis was generally poor, suggesting that the disease in Brazil behaves in similar fashion regardless of ethnic or geographical differences. Int. J. Cancer 83:291–298, 1999.

Genetic mutation and early onset of T-cell leukemia in pediatric patients infected at birth with HTLV-I.

T-cell leukemia/lymphoma (T-c LL) associated with prior infection with HTLV-I is rarely described in children. We present herein, the clinical, morphological, and virologic features of T-c LL, which occurred in eight pediatric cases with similar features of ATLL described in adults. There were three girls and five boys with age ranging from 2 to 18 years. Lymphoadenopathy, hepatosplenomegaly and marked skin lesions were presented in all cases. Five patients had hypercalcemia. The diagnostic criteria of T-c LL were based on both morphological and immunophenotypical analyses characterized by T-cell markers positively. Seven cases were cCD3+, CD4/CD25+, whereas CD1a and TdT were negative in all cases tested. HTLV-I antibodies were detected in all cases. HTLV-I provirus integration of at least one provirus was seen in all cases tested by molecular analysis. Mother-to-child transmission of HTLV-I was demonstrated in six cases. Interestingly, a homozygous deletion in p16 gene locus was observed in all four cases studied, while exons 7 and 8 of p53 were deleted in one child. The deletion of the p16(INK4A)/p14(ARF) or mutation of p53, key regulatory protein of cell cycle checkpoint in G1/S progression, found in five of the eight pediatric patients suggests that in these cases genetic lesions associated with HTLV-I infection may predispose for an early onset of leukemia.

Adult T-Cell Leukemia/Lymphoma and Cluster of HTLV-I Associated Diseases in Brazilian Settings

We studied the transmission routes of human T-cell lymphotropic virus type I (HTLV-I) within families of 82 Brazilian patients diagnosed with adult T-cell leukaemia/lymphoma (ATL). Diagnosis of ATL in 43 male and 39 female patients was based on clinical and laboratory criteria of T-cell malignancy and detection of HTLV-I monoclonal integration. Samples were tested for HTLV antibodies and infection was confirmed as HTLV-I by Western Blot and/or polymerase chain reaction (PCR) assays. Overall 26/37 (70%) of mothers, 24/37 (65%) of wives, 8/22 (36%) of husbands, 34/112 (30%) of siblings and 10/82 (12%) offspring were HTLV-I infected. In 11 ATL patients, mothers were repeatedly HTLV-I seronegative, but HTLV-I pol or tax sequences were detected in 2 out of 6 cases tested by PCR. ATL patients with seronegative mothers related the following risk factors for HTLV-I infection: 6 were breast-fed by surrogate mothers with unknown HTLV-I status, 4 had a sexually promiscuous behaviour and 1 had multiple blood transfusions at a young age. Familial aggregation of ATL and other HTLV-I associated diseases such as HTLV-I myelopathy (HAM/TSP) and or uveitis, ATL in sibling pairs or in multiple generations was seen in 9 families. There were 6 families with ATL and TSP sibling pairs. In 3 families at least one parent had died with lymphoma or presenting neurological diseases and 2 offspring with ATL. Further to the extent of vertical and horizontal transmission of HTLV-I infection within ATL families, our results demonstrate that mothers who provide surrogate breast-milk appear to be an important source of HTLV-I transmission and ATL development in Brazil.

Human leucocyte antigen and human T-cell lymphotropic virus type 1 associated diseases in Brazil

Universidade Federal de Sao Paulo, Escola Paulista Med, Hematol & Transfus Med Serv, Sao Paulo, Brazil

Post-Transplant Lymphoproliferative Disorders (PTLD) after Renal Transplantation: Management and Evolution of Seven Cases Among 1002 Renal Transplants in Sao Paulo, Brazil

We reported seven cases (0.7%) of PTLD among 1002 renal transplants performed at Renal Transplant Service from Hospital Sao Paulo - Universidade Federal de Sao Paulo/Escola Paulista de Medicina, Sao Paulo, Brazil, between 1976 and 1997. There were three male and four female patients with median age of 37 year-old. According to Ann Arbor staging system there were four localized extra-nodal intermediate-grade NHL, one disseminated low-grade NHL and two polyclonal lymphoid hyperplasia. Four patients received cadaveric, two received related and one received unrelated renal transplant. PTLD occurred after a median latency period of 36 months (ranging from 5 to 84 months). In situ hybridization for EBER1 was performed in five patients and molecular evidence of EBV was found in 3 cases (two DLCL and one lymphoplasmocytoid lymphoma). All patients were treated with immunosuppression withdrawal, four patients received anthracyclin-based chemotherapy for control of localized or systemic clonal disease and three were treated with resection of primary PTLD. Four of seven patients (57%) are in complete remission 11, 20, 25 and 79 months after PTLD onset. One patient lost follow-up and two patients died due to lymphoma relapse, respectively 4 and 10 months after completion of treatment. In conclusion, our experience with this small group of patients showed that: 1) immunosuppression withdrawal is not necessarily associated with loss of renal transplant and can be used as the only treatment for polyclonal PTLD; 2) chemotherapy can simultaneously lead to clonal PTLD remission and periodic immunosuppression, avoiding graft rejection after immunosuppression withdrawal.

Transcranial Direct Current Stimulation Effects on Athletes’ Cognitive Performance: An Exploratory Proof of Concept Trial

Among the 2016 Olympic and Paralympic Games’ unforgettable moments, one could not overlook performances by Phelps and Bolt, which challenge old premises about the maximum extension of individual supremacism in ultracompetitive modalities and the doping scandals. Different media channels resonated these two trends, with an unseen rise on discussions about traits and practices that may set ultrahigh performance athletes apart from the more ordinary ones. Yet, some key issues remain undebated. This paper aims to add to this debate, with a proof of concept trial, which investigates whether transcranial direct current stimulation (tDCS) may serve as an aid for professional athletes. Ten professional athletes of three different modalities (judo, N = 4 athletes, swimming, N = 3 athletes, and rhythmic gymnastics, N = 3 athletes) received anodal stimulation (2 mA) for 20 min on the left dorsolateral prefrontal cortex for ten consecutive weekdays. We observed a positive effect of tDCS in their cognitive performance, including a significant improvement in alternated, sustained, and divided attention and in memory scores. We also observed a decrease in Beck Depression Inventory scores (4.50 points) in this non-clinical population. These preliminary results suggest that tDCS sessions may translate into competitive advantages for professional athletes and recommend the deepening of the discussion on its ethical use in sports, which is ultimately tied to the wider debate around the risks and opportunities that neuromodulation brings to the table.

HTLV-I Infection Among Relatives of Patients with Adult T-Cell Leukemia/Lymphoma in Brazil: Analysis of Infection Transmission

We examined the presence of HTLV-I infection among 66 family members of 13 patients with well documented ATL to investigate the routes of HLTV-I transmission in a Southeast region of Brazil. HTLV-I infection was screened by an enzyme immunossay (ELISA) test and all repeatedly positive or indeterminate ELISA samples were further tested by a Western-Blot (WB) technique. Indeterminate and inconclusive WB samples were confirmed by a polymerase chain reaction (PCR). ELISA results showed that 40 (60.6%) individuals were not infected; 16 (24.2%) were positive; and 10 (15.2%) were undetermined. Among 16 ELISA positive subjects, 14 (87.5%) were confirmed to be positive by WB while 2 (12.5%) showed inconclusive results. Based on the laboratory data, questionnaire analysis, and family/epidemiological studies, we concluded that HTLV-I vertical transmission occurred in 6 of the 13 families. In 3 of these 6 families, the horizontal transmission also could be demonstrated. An isolated horizontal transmission was detected in one family, and in 6 families we did not find any infected family member. All HTLV-I-infected persons were clinically asymptomatic. The occurrence of an effective HTLV-I vertical transmission detected by the present study suggest that HTLV-I infection is endemic in the Southeast region of Brazil. Consistent with the modes of transmission, the HTLV-I antibody seroprevalence was greater in relatives of ATL patients than in the general blood donor Brazilian population (0.4%). In addition, the present data suggest that HTLV-I carries a high infectivity rate but a low virulence.

Clinical management of six cases of low-risk primary tonsillar non-Hodgkin´s lymphoma

CONTEXT There have been many reports that favor aggressive systemic treatment with chemotherapy and radiotherapy, even for well-localized lymphomas, avoiding the need for tonsillectomy of the normal tonsil. CASE REPORT We report six cases of primary tonsillar lymphoma with a median patient age of 42 years. There were two lymphoma cases with diffuse large cells, two cases with mixed small and large cells, one with small cells and one indeterminate. They were treated with six cycles of chemotherapy and cervical radiotherapy. All patients achieved durable complete remission. Our data agree with previous reports that suggested that primary tonsillar high-grade B-cell NHL has a good prognosis if aggressively treated.

Granuloma letal da linha média: abordagem clínica e terapêutica de três casos

OBJETIVO: Relato de tres casos do GLLM acompanhados pela Disciplina de Hematologia e Hemoterapia da Unifesp-EPM que tiveram boa resposta a terapeutica e evolucao favoravel. METODOS: Apos confirmacao histologica e histoquimica, os pacientes foram submetidos a tratamento quimio e radioterapico com boa resposta terapeutica. RESULTADOS: Atualmente estes pacientes encontram-se em remissao total da doenca, com sobrevida media de 45 meses. CONCLUSAO: Levando-se em consideracao nossa pequena experiencia, acreditamos que o tratamento radioterapico e a abordagem quimioterapica inicial agressiva sao fundamentais para uma boa evolucao deste tipo de linfoma.