Marlene Pereira Garanito

Deficiência de ferro na adolescência

Iron deficiency is the most common nutritional disorder in the world and is a major cause of anemia associated with situations involving chronic blood loss or rapid growth such as during infancy, pregnancy and adolescence. This deficiency leads to impairment in psychomotor development, learning ability, appetite, growth and immune response. In adolescence, inadequate dietary habits are often observed and intensive physiological and psychological changes are seen that when combined can impair growth and increase the risk of developing iron deficiency or other nutritional disorders, especially during puberty. Thus, the diagnosis of iron deficiency among adolescents should always be considered so that measures can be taken to reduce the incidence of anemia, impairment of the immune system and improve school performance.

Repeat course of rabbit antithymocyte globulin as salvage following initial therapy with rabbit antithymocyte globulin in acquired aplastic anemia

The treatment for the majority of patients with acquired aplastic anemia (AA) who are not suitable for hematopoietic stem cell transplant (HSCT) is immunosuppression with standard horse antithymocyte globulin (h-ATG) and cyclosporine (CSA) where hematologic responses are observed in 60–70%.[1][1]

Essential thrombocythemia: a rare disease in childhood

Essential thrombocythemia is an acquired myeloproliferative disorder characterized by the proliferation of megakaryocytes in bone marrow, leading to a persistent increase in the number of circulating platelets and thus increasing the risk for thrombotic and hemorrhagic events. The disease features leukocytosis, splenomegaly, vascular occlusive events, hemorrhages and vasomotor disorders. The intricate mechanisms underlying the molecular pathogenesis of this disorder are not completely understood and are still a matter of discussion. Essential thrombocythemia is an extremely rare disorder during childhood. We report on a case of essential thrombocythemia in a child and discuss the diagnostic approach and treatment strategy.

Outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine A

OBJECTIVE To evaluate the outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine as first-line treatment at this institution. METHODS Retrospective analysis of 26 pediatric patients with aplastic anemia, treated between 1996 and 2011 with rabbit antithymocyte globulin plus cyclosporine. RESULTS The overall response rate at six months was 34.6% (9/26), and the cumulative incidence of relapse was 26.5% (95% confidence interval [CI]: 1.4%-66%) at 5 years. The cumulative incidence of clonal evolution after immunosuppressive therapy was 8.3% (95% CI: 0.001%-53.7%) at five years with both clonal evolutions in non -responders who acquired monosomy 7 karyotype. The overall survival at five years was 73.6% (95% CI: 49.2%-87.5%). CONCLUSIONS The present results confirm the poor response rate with rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to what has been reported for patients of all ages. This confirmation is problematic in Brazil, given the lack of horse antithymocyte globulin in many markets outside the United States.

The brazilian cooperative group on Pediatric Myelodysplastic Syndrome from 1997 to 2009: is it relevant to improve educational approach and correct diagnosis?

Purpose: Langerhans Cell Histiocytosis (LCH) is a rare disease characterized by heterogeneous lesions containing CD207þ Langerhans cells and lymphocytes that can arise in almost any tissue and may cause significant morbidity and mortality. After decades of research, the pathogenesis of LCH remains speculative. This study was performed to test the prevailing model of LCH pathogenesis that lesions arise due to malignant transformation of epidermal Langerhans cells (LCs). Method: LCH CD207þ cells were isolated from LCH lesions, control LCs were isolated from normal skin, and gene expression was compared. Similarly, gene expression in LCH lesion CD3þ cells was compared to gene expression in peripheral blood CD3þ cells from LCH patients with active disease. Results: Compared to control epidermal CD207þ cells, the LCH CD207þ cells yielded 2900 differentially-expressed probes. Expression of many genes previously associated with LCH, including cell-cycle regulators, pro-inflammatory cytokines and chemokines were not significantly different from control LCs in our study. The study also identified several interesting genes not previously associated with increased expression in LCH including genes involved in regulation of cell cycle (CDC2A, AFF3, SMYD3, HOXB7), apoptosis (BAX, BCL2L1, CFLAR) signal transduction (DUSP4, JAK3, PRKCA, TLR2, TLR4, SOCS3, JAG2), tumor invasion and metastasis/tissue invasion (CEACAM6, MMP1, TGFB1), myeloid cell maturation (CD1d, CD13, CD14, CD33, ITGA2B, ITGAX, ITGAM, CD300LF) and lymphocyte trafficking (SPP1, VNN1, NRP1, CCR1). A large number of the cells with decreased or absent expression in the LCH-CD207 cells are involved in cell-cell adhesion, including TACSTD1. Compared to the peripheral CD3þ cells from LCH patients, the LCH lesion CD3þ cells yielded only 162 differentially-regulated probes, and the expression profile of the LCH lesion CD3þ cells was consistent with an activated regulatory T cell phenotype, including increased expression of FOXP3 and CTLA4. SPP1 had the highest relative expression in both LCH lesion CD207þ and CD3þ cells. IL-17 is a proinflammatory cytokine recently associated with LCH pathogenesis. In this study, IL-17 expression was absent from control and LCH CD207þ cells. Very little IL-17 expression was detected in T cells from LCH lesions, but abundant message was detected from tonsil lymphocytes. Conclusion: We propose a revised model of LCH pathogenesis in which lesions do not arise from epidermal Langerhans cells, but from accumulation of bone-marrow derived immature myeloid dendritic cells that recruit activated lymphocytes. Until the cell of origin can be identified, perhaps ‘‘LCH’’ should return to ‘‘Histiocytosis X’’.Purpose: The SIOP WT 2001 trial introduced a new ‘high risk’ entity: ‘blastemal type’ WT. However, the largest absolute number of relapses among localised tumours emanates from the ‘intermediate risk’ histology subgroup. We therefore investigated whether different thresholds for percentage necrosis/blastema might improve risk stratification based on histological response to pre-operative chemotherapy. Method: Data on 2,071 patients with localised unilateral WT treated with preoperative chemotherapy in the SIOP 2001 trial (to Sept 2009) were analysed. Martingale plots of excess risk of relapse versus overall% necrosis or%blastema in the viable residue were interrogated for thresholds at which risk altered. Event free survival was analysed by Kaplan-Meier methods and subgroups compared by log rank. Results: For the entire group, 2yr EFS was 88.2% (95%CI:86.6–89.8) and 5yr OS: 93.7% (95% CI:92.2–95.2). Histological risk group was a better discriminator of outcome than tumour stage (2yr EFS low risk:95.9%, intermediate risk:89.8% and high risk:76.9%, p<0.001; 2yr EFS stage I:91.0%, stage II:87.8% and stage III:83.2% p<0.001). Martingale plots showed no threshold effect for%necrosis but a reduced risk of relapse in those with <20% blastema in the viable tumour, with a small but steadily increasing risk of relapse with >50% blastema. For intermediate risk tumours, there was a significant decrease in EFS with increasing% blastema (comparing 0–10%, 10–90%, 90–100%). This persisted in the regressive subtype but was at the borderline for statistical significance in the mixed subtype (p¼0.05). The worst outcome group had 2 yr EFS of 79%. Conclusion: Survival of blastema after pre-operative chemotherapy in Wilms tumour is a better prognostic factor than% necrosis. Improved definition of chemoresistant blastema requires molecular characterisation of the disrupted biological pathways to improve risk stratification and inform discussions of new therapeutic approaches for these higher risk tumours.

Aplasia medular após transplante hepático em pediatria

A aplasia de medula e uma das mais raras (<1%) e serias complicacoes apos o transplante hepatico por insuficiencia hepatica aguda grave viral nao A, nao B e nao C. Esta condicao clinica, que acomete simultaneamente o tecido hepatico e o hematopoetico, foi descrita pela primeira vez em 1987, por Stock, e a fisiopatologia relacionada e uma condicao imunomediada, provavelmente secundaria a infeccao viral desconhecida, e associada a grave prognostico. A recuperacao espontânea da aplasia medular adquirida habitualmente e muito rara e 50%-70% dos pacientes respondem ao tratamento imunossupressor com ciclosporina A (CsA) e glubulina antitimocitica (ATG), mesmo apos o transplante hepatico. Alem do tratamento imunossupressor, outra opcao e o transplante de medula ossea (TMO). Apresentamos o caso de uma crianca com aplasia medular grave apos transplante hepatico, por insuficiencia hepatica aguda grave, que recebeu tratamento imunossupressor com CsA e ATG e evoluiu com recuperacao completa das tres series do hemograma.