Benigna Maria de Oliveira

Primary hepatic non-Hodgkin's lymphoma in children: a case report and review of the literature.

Non-Hodgkins lymphomas presenting exclusively in the liver are rather uncommon in adults and extremely rare in children. We describe a six-year-old white boy with jaundice, abdominal pain, and weight loss of two weeks duration. Physical examination disclosed asthenia, jaundice, abdominal swelling, large hepatomegaly, and ascitis. Aminotransferases bilirubin, and alkaline phosphatase were significantly elevated. Bone marrow aspiration, cerebrospinal fluid, chest x-ray, renal function tests, and uric acid were normal. Abdominal ultrasound showed liver enlargement with irregular regular borders, many parenchymal nodules in both liver lobes, a large hypoechogenic mass in the inferior segment of the liver, normal biliary ducts and two pancreatic nodules resembling those in the liver. Liver needle biopsy disclosed diffuse lymphomatous infiltration. Blast cells were positive for leukocyte common antigen (CD 45). Immunohistochemistry study for T or B cell lineage differentiation was not done. The child showed an excellent response to chemotherapy based on the BFM-83 protocol for B cell non-Hodgkins lymphomas. The patient had his therapy discontinued in June 1995 and remains in first complete remission as of May 20th, 1996.

Thiopurine S-methyltransferase (TPMT) gene polymorphism in Brazilian children with acute lymphoblastic leukemia: association with clinical and laboratory data.

The frequency of allele variants of gene TPMT*2, *3A, *3B, and *3C was estimated in a population of 116 Brazilian children with acute lymphoblastic leukemia. The association between genotype and clinical and laboratory data obtained during chemotherapy maintenance phase and the correlation of intraerythrocyte concentration of 6-mercaptopurine metabolites (6-tioguanine nucleotide nucleotides and methylmercaptopurine) were analyzed. A multiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was used in DNA amplification. Twelve patients presented TPMT gene mutation, all in heterozygous form. The most frequent allele variation was TPMT*3A (3.9%), followed by *3C (0.9%), *2 (0.4%), and *3B (0%). There was no significant association between clinical and laboratory data and the presence of mutation in TPMT gene. Of the 36 patients who were monitored for 6-mercaptopurine metabolite levels, only 1 had the mutation. In this patient, high 6-tioguanine nucleotide and low methylmercaptopurine concentrations were found. Event-free survival (EFS) for the whole group was 73.4%. There was no significant difference in event-free survival in the comparison between the groups with and without mutation (P = 0.06).

Clinical course of autoimmune hemolytic anemia: an observational study

OBJECTIVE Autoimmune hemolytic anemia is characterized by the production of autoantibodies against erythrocyte membrane antigens. This study was carried out to identify the clinical, immunological and outcome characteristics of autoimmune hemolytic anemia patients treated at the (HC-UFMG) Pediatric Hematology Unit and the Hemocentro de Belo Horizonte. METHODS We evaluated 17 patients younger than 15 years old admitted from 1988 to 2003 were evaluated. Autoimmune hemolytic anemia diagnosis was based on the presence of acquired hemolysis and confirmed by positive direct Coombs polyspecific test results. Clinical, laboratory, and outcome data were obtained from patient records. RESULTS The median age at diagnosis was 10.5 months. The direct Coombs polyspecific test was positive in 13 and negative in four patients. Monospecific testing was performed for 14 patients. The most frequent red cell autoantibody was IgG (five patients), followed by IgM in two. Thirteen patients had severe anemia and needed blood transfusions. Underlying diseases were identified in four patients: systemic lupus erythematosus, Hodgkins lymphoma, autoimmune hepatitis and Langerhans cell histiocytosis. The remaining patients were classified as having primary disease. The median follow-up period was 11 months (5 to 23 months). Three children died, two after splenectomy and one with complications of the underlying disease. CONCLUSION Autoimmune hemolytic anemia is rare in children and adolescents. Although patients usually respond to corticosteroids and/or immunoglobulin, fatal cases can occur. Prognosis is worse in patients with chronic underlying diseases.

Curso clínico da anemia hemolítica auto-imune: um estudo descritivo

OBJETIVO: A anemia hemolitica auto-imune e caracterizada pela producao de auto-anticorpos contra antigenos de superficie das hemacias. O objetivo do estudo foi identificar as caracteristicas clinicas, imunologicas e evolutivas dos pacientes com anemia hemolitica auto-imune acompanhados no servico de hematologia pediatrica do HC-UFMG e no Hemocentro de Belo Horizonte. METODOS: Foram avaliadas 17 criancas menores de 15 anos, diagnosticadas entre 1988 e 2003. O diagnostico de anemia hemolitica auto-imune foi baseado no quadro de hemolise adquirida e confirmado por meio do teste de Coombs direto poliespecifico. Os dados clinicos, demograficos, laboratoriais e referentes a evolucao dos pacientes foram obtidos retrospectivamente nos prontuarios medicos. RESULTADOS: A mediana de idade ao diagnostico foi de 10,5 meses. O teste de Coombs direto poliespecifico foi positivo em 13 pacientes e negativo em quatro. Em 14 pacientes, foi realizado o teste de Coombs direto monoespecifico. Nestes, a classe de anticorpo mais frequente foi IgG (cinco pacientes), seguida pela IgM em dois. Em 13 (76%) pacientes, a anemia foi considerada grave, o que tornou necessaria a hemotransfusao. Em quatro pacientes, foi identificada uma doenca de base: lupus eritematoso sistemico, linfoma de Hodgkin, hepatite auto-imune e histiocitose de celulas de Langerhans. Os demais casos foram considerados como primarios. A mediana de seguimento foi de 11 meses (5 a 23 meses). Ocorreram tres obitos, sendo dois apos esplenectomia e um pela doenca de base. CONCLUSAO: A anemia hemolitica auto-imune e rara em criancas e adolescentes. Apesar de apresentar resposta ao corticoide e imunoglobulina, casos fatais tem sido relatados. O prognostico e pior na presenca de uma doenca cronica de base.

Hemophagocytic lymphohistiocytosis: a case series of a Brazilian institution

Objective To describe the clinical and laboratory presentation of hemophagocytic lymphohistiocytosis in children treated at a referral institution. Methods A retrospective descriptive study was carried out of seven children diagnosed with hemophagocytic lymphohistiocytosis between 2010 and 2012. The criteria for diagnosis were those proposed by the Histiocyte Society. When indicated, immunochemotherapy was prescribed according to the HLH94 and HLH2004 protocols of the Histiocyte Society. Results The patients’ ages at diagnosis ranged from one month to nine years. All patients had splenomegaly, fever, anemia, thrombocytopenia, hyperferritinemia and hypertriglyceridemia. Bone marrow hemophagocytosis was detected in six patients. In six cases, infectious diseases triggered the syndrome. In two cases, associated with visceral leishmaniasis, remission was achieved after treatment of the underlying infection. Three patients, who had Epstein–Barr-related hemophagocytic lymphohistiocytosis, required treatment with immunochemotherapy. They are alive and in remission; one patient had symptoms of juvenile rheumatoid arthritis and another, who was suspected of having primary hemophagocytic lymphohistiocytosis, entered into remission after bone marrow transplantation. Two deaths (28.6%) occurred in patients with suspected primary hemophagocytic lymphohistiocytosis; one whose clinical picture was triggered by cytomegalovirus infection did not respond to immunochemotherapy and the other died before any specific treatment was provided. Conclusion As reported before, hemophagocytic lymphohistiocytosis has a multifaceted presentation with nonspecific signs and symptoms. In secondary forms, remission may be achieved by treating the underlying disease. In the primary forms, remission may be achieved with immunochemotherapy, but bone marrow transplantation is required for cure.

A perspectiva dos pais sobre a obtenção do diagnóstico de leucemia linfóide aguda em crianças e adolescentes: uma experiência no Brasil

Objectives: to investigate how parents perceive a diagnosis of lymphoid leukemia in their children. Methods: qualitative research based on the sociological theory of social representations was used. Data was gathered by way of semi-structured interviews. Twenty parents of children diagnosed as having acute lymphoid leukemia (ALL). The content analysis technique was used to analyze data. Data analysis was guided by the principles of bioethics and humane care. Results: the parents clearly recalled the progression of symptoms up to diagnosis. The word leukemia was associated with cancer and death. Difficulties related to listening to the symptoms, the specific clinical features of leukemia and the referral system were the main reasons for delay in arriving at a final diagnosis. The parents highlighted the need to move about a lot from one place to another, the lack of resolution, unnecessary costs, emotional strain and the slowness of the health services. Conclusions: cancer brings with out cultural values concerning death and these bear greater weight when a child is involved. The search for a diagnosis of leukemia by parents is a good example of the tortuous path they have to tread when what is wrong with their children is not something that bears the label of a “common” disease.

Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count < 50 x 109/L (p-value = 0.0008). There was no difference in cumulative central nervous system relapse (isolated or combined) for the other analyzed variables: immunophenotype, traumatic lumbar puncture, interval between diagnosis and first lumbar puncture and place where the procedure was performed. Conclusions These results suggest that a leukocyte count > 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

Health-related Quality of Life Among Teenagers During Cancer Treatment in a Developing Country: Patients’ and Proxies’ Reports

Few studies have been performed during adolescents’ cancer treatment to evaluate its interference on health-related quality of life (HRQL). The purpose of this prospective cohort study was to evaluate adolescents’ HRQL during cancer treatment. The Health Utilities Index (HUI) was used for scoring. Forty-five individuals were questioned 1 month after the onset of treatment (T1) and at 4 or 6 months depending on disease type (T2). Median age was 14 years. Pain was the most frequent troublesome attribute referred to, but scores were significantly better from T1 to T2 for patients and proxies. A high correlation between patients’ and family’ HRQL scores was observed both at T1 and T2. Correlation of the general health scores between patients and their families was high at T1, but not so high at T2. Physicians’ evaluation tended to underestimate HRQL of their patients. In conclusion, most patients and proxies reported a HRQL reduction during the initial phase of treatment, but HRQL was better later on. Generally, patient and proxy scores correlated well. Pain was the most frequently reported troublesome attribute. The patients’ opinion concerning their own health and well-being should be of primary importance to assess QoL and determine therapeutic regimens.

Isolated relapse in the oral cavity of a child with t-lineage acute lymphoblastic leukemia

Despite high cure rates, approximately 20% of patients with acute lymphoblastic leukemia (ALL) have disease relapse. Isolated recurrence in oral cavity is extremely unusual. The aim of this paper is to report a case of an isolated relapse occurred in a child with T-lineage ALL. Clinical picture included swelling and pain in the right upper gingiva of the oral cavity, with no other clinical or hematological alterations. Diagnosis was confirmed by biopsy and immunohistochemical staining. Bone marrow aspiration was normal. Five months later leukemic infiltration of the bone marrow was detected and systemic chemotherapy was reintroduced. This case report highlights the relevance of dental care during and after chemotherapy, not only to treat lesions in the oral cavity resulting from the disease itself or from treatment side effects, but also to detect unusual sites of ALL relapse.

Gene rearrangement study for minimal residual disease monitoring in children with acute lymphocytic leukemia

Objective To detect markers for minimal residual disease monitoring based on conventional polymerase chain reaction for immunoglobulin, T-cell receptor rearrangements and the Sil-Tal1 deletion in patients with acute lymphocytic leukemia. Methods Fifty-nine children with acute lymphocytic leukemia from three institutions in Minas Gerais, Brazil, were prospectively studied. Clonal rearrangements were detected by polymerase chain reaction followed by homo/heteroduplex clonality analysis in DNA samples from diagnostic bone marrow. Follow-up samples were collected on Days 14 and 28-35 of the induction phase. The Kaplan-Meier and multivariate Cox methods were used for survival analysis. Results Immunoglobulin/T-cell receptor rearrangements were not detected in 5/55 children screened (9.0%). For precursor-B acute lymphocytic leukemia, the most frequent rearrangement was IgH (72.7%), then TCRG (61.4%), and TCRD and IgK (47.7%); for T-acute lymphocytic leukemia, TCRG (80.0%), and TCRD and Sil-Tal deletion (20.0%) were the most common. Minimal residual disease was detected in 35% of the cases on Day 14 and in 22.5% on Day 28-35. Minimal residual disease on Day 28-35, T-acute lymphocytic leukemia, and leukocyte count above 50 x 109/L at diagnosis were bad prognostic factors for leukemia-free survival in univariate analysis. Relapse risk for minimal residual disease positive relative to minimal residual disease negative children was 8.5 times higher (95% confidence interval: 1.02-70.7). Conclusion Immunoglobulin/T-cell receptor rearrangement frequencies were similar to those reported before. Minimal residual disease is an independent prognostic factor for leukemia-free survival, even when based on a non-quantitative technique, but longer follow-ups are needed.