Screening for myeloid mutations in patients with myelodysplastic syndromes and AML with myelodysplasia-related changes

ABSTRACT Introduction: One of the most critical complications in myelodysplastic syndromes (MDS) is the progression to acute myeloid leukemia (AML). The dynamics of clonal evolution in MDS and how acquired mutations can be used as biomarkers to track disease progression remains under investigation. Objective and method: Herein, we investigated the frequency of common myeloid clonal mutations (FLT3, NPM1, JAK2, IDH1 and IDH2) in 88 patients with MDS and 35 AML patients with myelodysplasia-related changes, followed at a single reference center in northeastern Brazil. Results: Overall, 9/88 (10%) ofthe MDSpatients and 9/35 (26%) of the secondary AML patients had at least one mutation. While the JAK2 V617F mutation was the most frequent in the MDS patients, the FLT3, NPM1, IDH1 and IDH2 mutations were more frequently found in the secondary AML group. Furthermore, there was a higher frequency of FLT3, NPM1, IDH1 and IDH2 mutations in MDS patients classified as high-risk subtypes than in those of lower risk. Conclusion: Despite the limited sample size, our data suggest that mutations in FLT3, NPM1, IDH1 and IDH2 genes could be potential biomarkers to detect early disease progression in MDS.

Hidroxiuréia em pacientes com síndromes falciformes acompanhados no Hospital Hemope, Recife, Brasil / Hydroxyurea in sickle cell disease patients in Recife, Brazil

O uso de hidroxiuréia promove a elevação dos níveis de hemoglobina fetal (Hb F) em pacientes portadores de síndromes falciformes (SF) e o medicamento vem sendo estudado em vários grupos de pacientes, incluindo adultos e crianças. O presente trabalho analisou a eficácia e tolerabilidade do uso de hidroxiuréia em crianças na faixa etária entre 5 e 17 anos de idade e em adultos jovens acima de 18 anos, portadores de hemoglobinopatia SS ou Sbeta0 que foram acompanhados regularmente no ambulatório do Hospital Hemope. Os pacientes pediátricos foram tratados com dose inicial de hidroxiuréia de 10 mg/kg/dia, a qual era aumentada em 5 mg/kg por dia em intervalos de oito semanas, até a dose máxima de 25 mg/kg/dia. Para os adultos, o tratamento foi iniciado com 500 mg/dia de hidroxiuréia até a dose máxima de 1g/dia. Foi observada redução do número de crises álgicas assim como do número de internações hospitalares, elevação do nível de Hb F e do Volume Corpuscular Médio, no grupo pediátrico. Entre os pacientes maiores de 18 anos, também se observou melhora clínica e significância estatística com aumento dos valores da hemoglobina e redução dos valores de reticulócitos, leucócitos e plaquetas. Não foram observados sinais ou sintomas sugestivos de toxicidade medicamentosa em ambos os grupos. O uso de hidroxiuréia em todos os pacientes parece ser seguro e eficaz e assegura melhora da qualidade de vida e benefícios a seus familiares. Ademais, as doses preconizadas de hidroxiuréia aparentemente não foram mielotóxicas, não tendo sido necessária a suspensão do tratamento em nenhum dos pacientes.

The use of hydroxyurea increases concentrations of fetalhemoglobin (Hb F) in sickle cell disease patients. It has beenused in adults and in trials with children with the aim of preventingevents such as episodes of pain or stokes. The objective of thisstudy was to analyze the efficacy and side effects of Hydroxyureain children with ages ranging from 5 to 17 years and also inyoung adults with SS or Sâ0 hemoglobinopathies. The patientswere treated in the outpatient clinic of the Hemope Hospital.Young patients were treated with hydroxyurea at 10 mg/kg/daywhich was increased by 5 mg/kg/day at 8-week intervals untilreaching a maximum dose of 25 mg/kg/day. For adults, thetreatment started at 500 mg/day and increased until a dose of1000 mg/day was reached. Total Hb F levels and the MeanCorpuscular Volume rose with hydroxyurea therapy and therewas a reduction of events involving pain as well as the necessityof hospitalization among the pediatric patients. With the over 18-year-old patients, a better clinical state was noticed together witha rise in hemoglobin levels and a reduction in the reticulocyte,leukocyte and platelet counts. No signs or symptoms in respect todrug toxicity were evidenced in either group. The use ofhydroxyurea seems to be safe and effective in both children andyoung adults with sickle cell disease. The drug also improves thequality of life of these patients and their families. Additionally, thedosages of hydroxyurea used in this group of patients did notcause any bone marrow toxicity or other side effects.