RESUMO
Transient abnormal myelopoiesis occurs exclusively in patients with Down syndrome (constitutional trisomy 21), manifests in the neonatal period, and is characterized by circulating megakaryoblasts with varied degrees of multisystem organ involvement. In most cases, this process resolves spontaneously by 3 to 6 months of age, but for some, the disease can be fatal. Affected patients are particularly prone to develop acute megakaryoblastic leukemia in early childhood. Somatic GATA1 mutations are believed to be pivotal in the development of transient abnormal myelopoiesis and have proven to be a marker of clonal identity in its evolution to megakaryoblastic leukemia. We describe a study case of transient abnormal myelopoiesis and review the clinical manifestations, laboratory features, natural history, molecular genetics, and postulated disease pathogenesis of this disorder.
Assuntos
Biomarcadores Tumorais/genética , Síndrome de Down/diagnóstico , Fator de Transcrição GATA1/genética , Leucemia Megacarioblástica Aguda/diagnóstico , Células Progenitoras de Megacariócitos/patologia , Mutação , Proteínas de Neoplasias/genética , Biomarcadores Tumorais/sangue , Síndrome de Down/sangue , Síndrome de Down/genética , Síndrome de Down/patologia , Fator de Transcrição GATA1/sangue , Humanos , Recém-Nascido , Leucemia Megacarioblástica Aguda/sangue , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/patologia , Masculino , Células Progenitoras de Megacariócitos/metabolismo , Proteínas de Neoplasias/sangueRESUMO
BACKGROUND: Central nervous system (CNS) malignancies represent 20% of all childhood cancers. To improve outcomes in infants and children with high-risk disease, treatment can include adjuvant chemotherapy and early autologous peripheral blood human progenitor cell collection (AHPCC), followed by high-dose chemotherapy and stem cell rescue. In many protocols, postoperative chemotherapy includes the administration of weekly vincristine (VCR) between induction chemotherapy cycles, regardless of scheduled AHPCC. We observed anecdotal AHPCC failures in children receiving midcycle VCR (MC-VCR). STUDY DESIGN AND METHODS: The study was an 8-year retrospective chart review of all children with a CNS malignancy and who underwent AHPCC. Information included patient demographic and clinical data, mobilization regimen, VCR administration, product yields, infusion toxicity, and patient charges. Data were analyzed relative to MC-VCR administration. Graphics and statistical analysis (t-test, chi-square, linear regression) were performed with commercial software. RESULTS: Twenty-four patients and 47 AHPCCs were available for analysis. Nine patients (37%) received MC-VCR within 7 days of scheduled AHPCC. MC-VCR was associated with delayed marrow recovery (17.9 days vs. 14.9 days, p=0.0012), decreased median peripheral CD34 counts (75 × 10(6) CD34/L vs. 352 × 10(6) CD34/L, p=0.03), decreased median CD34 yields (2.4 × 10(6) CD34/L vs. 17.8 × 10(6) CD34/kg, p=0.08), more AHPCCs per mobilization (2.9 vs. 1.1, p=0.01), and an increased rate of remobilization (33% vs. 6%). Mean patient charges were 2.5× higher in patients receiving MC-VCR than controls (p=0.01). CONCLUSION: MC-VCR should be withheld before scheduled AHPCC to optimize CD34 collection.
