Primary Myelofibrosis In Children

Abstract 3079

Primary myelofibrosis is a chronic myeloproliferative disorder characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. It is a serious medical condition in adults, often requiring major interventions such as hematopoietic stem cell transplantation (HSCT) for cure. In comparison to adults, children are rarely affected by this entity; the largest case series reports on four such patients. Most of these reports suggest that the majority of affected children have spontaneous resolution of their myelofibrosis with no long term complications. To better describe the clinical characteristics and outcomes of pediatric primary myelofibrosis, we performed a retrospective chart review of children diagnosed with myelofibrosis by bone marrow pathology at our institution from 1996 to 2009. Eighteen patients with primary myelofibrosis were identified. At presentation, all patients had one or more cytopenias and only one had leukoerythroblastosis. Three of 11 patients tested (27%) had cytogenetic abnormalities, as opposed to up to two-thirds of adults with primary myelofibrosis. Eleven of 18 patients (61%) demonstrated erythroid hypoplasia in the bone marrow, which is uncommon in adults. Based on recent molecular studies of myeloproliferative disorders in adults, the World Health Organization now includes the presence of a clonal marker such as JAK2V617F as a major criterion for diagnosis of myelofibrosis in adults. In contrast to approximately half of adults (43-63%) with primary myelofibrosis, JAK2V617F mutation in the bone marrow has not been reported in children. JAK2V617F mutation analysis was negative on 16 of 18 bone marrow specimens tested. In this series, only 5 of the 18 children (27.8%) had spontaneous recovery. No child developed malignant transformation. Eight children underwent HSCT, four of whom were cured of their myelofibrosis; the remaining four children died from infections acquired during transplantation. Four children died prior to transplantation, or were identified as having myelofibrosis at autopsy. One child transferred care to another facility and thus outcome data was not available. In all children, infection was the most common cause of death. Notably, the degree of bone marrow fibrosis did not correlate with outcome. Our series demonstrates that children with primary myelofibrosis have hematologic, bone marrow and molecular features that differ from adults. In contrast to what is found in the literature, our series of pediatric patients with primary myelofibrosis, the largest reported thus far, indicates a poor outcome for the majority of these patients.