Desordem linfoproliferativa pós-transplante em paciente pediátrico

Abstract

Immunosuppressive therapy for transplanted patients exposes them to a high risk of developing posttransplantation lymphoproliferative disorders (PTLD). We report the case of a child undergoing heart transplantation at seven months of age who developed PTLD at nine years of age, diagnosed by resection of a pulmonary nodule. In the past few years, because of the improved preservation of donated organs and of the larger experience with immunosuppressive therapy, a significant increase in the survival of children after heart transplantation has been observed. Thus, transplantation has become a broadly accepted therapeutic option for children and adolescents with congenital heart defects or cardiomyopathies in advanced stages 1-3 .Immunosuppressive therapy that transplanted patients have to undergo in order to prevent organ rejection exposes them to a high risk of developing neoplasms, mainly posttransplantation lymphoproliferative disorders (PTLD) 2-7 . The exact incidence of PTLD is unknown, ranging from 2% to 20%; however it is known to be higher among children 5,8 .A higher frequency of PTLD is observed among children because the great majority of them had not been exposed to the Epstein-Barr virus (EBV) prior to heart transplantation. Therefore, post-transplantation seroconversion is a significant risk factor for the development of PTLD 5,9,10 . Of the pediatric patients who seroconvert after heart transplantation, approximately 63% develop PTLD 9 .The EBV is believed to play a key role in the pathogenesis of PTLD 4 . This virus is able to enter B cells and induce their proliferation, which is normally controlled by many immune mechanisms such as proliferation and activation of cytotoxic T lymphocytes. Anti-rejection immunosuppressive drugs inhibit the response of these cytotoxic T lymphocytes, which results in the proliferation of B cells induced by EBV 7 .Treatment modalities for PTLD are varied and include reduction of the immunosuppressive therapy, control of EBV replication, conventional antineoplastic therapy (radiotherapy, chemotherapy, and surgery) and immunotherapy 8 . However, mortality rates are quite significant, varying according to prognostic factors and the treatment chosen 8,10 .The purpose of this publication is to report the case of a child undergoing heart transplantation at seven months of age who developed PTLD eight years and nine months later, diagnosed by resection of a pulmonary nodule. Case ReportMale, nine years old, male, who underwent heart transplantation at seven months of age because of dilated cardiomyopathy.In 2000, he had a respiratory disorder characterized by persistent cough with yellowish sputum, and was diagnosed with bronchopneumonia. He was initially treated with amoxicillin for fourteen days, and cefepime for thirteen days. In 2001, a control chest computed tomography (CT) revealed perihilar lymph nodes and solid masses within the lungs with a progressive evolution, suggestive of an infectious and secondarily tumoral disorder, and the patient was hospitalized for invest...

Pediatric and Congenital Heart Transplant: Twenty-year Experience in a Terciary Brazilian Hospital

“…The occurrence of lymphoproliferative disease, especially in children, may be related to soroconversion of the Epstein-Barr virus post-HTx. However, the exact incidence of this disease is unknown, ranging from 2 to 20% [ 8 ] .…”

“…We have several publications in this area, from 1996, when we published our initial experience [ 3 , 5 - 8 ] , to our two most recent studies, one addressing the results of HTx in patients with cardiogenic shock [ 9 ] and another in patients with rejection and cyclosporine intolerance [ 10 ] .…”

O uso da imunossupressão e a presença do vírus EBV como fatores estimulantes de PTLD posterior à rejeição de enxerto renal: relato

“…Em segundo lugar, a falta de reparo de DNA proteico, pode ter influenciado a condição do paciente, uma vez que aumenta probabilidade de mutações no DNA das células. 7 Dessa forma, a PTLD é uma condição potencialmente fatal que se manifesta por expansão anormal de células linfocitárias. Pode ter uma distribuição variável, envolvendo inúmeros órgãos e tecidos.…”

“…No caso do paciente em questão, ocorreu o surgimento de um linfoma. 7 Em relação a essa condição específica do paciente A ação do rituximab sobre a proteinúria presente na síndrome nefrótica surgiu como efeito colateral no tratamento de pacientes com PTLD e recidiva de GESF pós transplantes. Ainda não existe um consenso sobre o adequado tratamento da GESF, entretanto, por mais que se apresente ineficaz, a primeira terapêutica adotada é a plasmaférese, uma vez que foi descrito em alguns estudos a presença de um fator circulante que altera a permeabilidade para albumina nos glomérulos renais.…”

“…Essa situação pode, assim, gerar um quadro de PTLD em indivíduos transplantados. 3,5,7,12 Cabe ressaltar que existem quatro tipos de padrões de PTLD. A do tipo lesão precoce é característica de indivíduos EBV positivos e envolve hiperplasia de células de defesa, como os plasmócitos.…”