Juvenile myelomonocytic leukemia in 12 children

Abstract

Objective To analyze the clinical and cytogenetic features of juvenile myelomonocytic leukemia(JMML), and to provide a genotype-phenotype based management. Methods Clinical data of 12 cases of JMML who were diagnosed at Department of Pediatrics, Sun Yat-sen Memorial Hospital , Sun Yat-Sen University from October 2009 to October 2015 were analyzed.Either chemotherapy management or hematopoietic stem cell transplantation (HSCT) was chosen according to the disease risk factors. Results (1) All 12 cases displayed fever and abdominal distention, 3 cases (25%) had rashes, mucocutaneous hemorrhage as well as hepatosplenomegaly and lymphadenopathy.(2)The medium WBC count, hemoglobin and platelet in peripheral blood were 39.93×109/L, 76.87 g/L, 34.63×109/L respectively, and monocytosis could be seen and median of absolute monocyte count was 1.63×109/L.(3)A markedly increased synthesis of fetal hemoglobin(HbF) could be seen in 8 cases (66.7%). (4)Chromosomal studies of bone marrow cells showed absence of Philadelphia chromosome in all cases, and monosomy 7 was found in 2 cases while other abnormal karyotypes were found in another 2 cases.(5)Analysis of genetic mutations showed 8 cases (66.7%) with JMML positive gene mutation, 1 case with PTPN11+ NF1 mutation, 7 with NRAS genes mutation(2 of them combined with CBL mutation simultaneously and progressed to blast crisis; 1 case showed KRAS+ NF1 mutation simultaneously). (6)Nine of them received chemotherapy with the protocol of A-3V [Cytarabine 100 mg/(m2·d)+ Vincristine 1.5 mg/(m2·d)+ Etoposide 100 mg/(m2·d)+ Isotretinoin 75-100 mg/(m2·d)]. Complete remission(CR) could be seen in 6 cases(66.7%). Two cases progressed and received HSCT.Three cases were treated with low-dose Cytarabine and 6-thioguanine and none obtained CR, and 1 case of them progressed to blast crisis and died of severely infection after intensive chemotherapy.(7) Four patients with high risk were treated with HSCT and remained disease free at present. Conclusions JMML is rare in clinical practice without specific features.Chromosomal studies and genetic analysis are key diagnostic procedures for JMML.The protocol A-3V is suitable for JMML and patients without high risk factors, who could obtain continuous CR after chemotherapy.Intensive chemotherapy was not recommended.HSCT were mandatory therapeutic option for the patients with high risk.Genotype-phenotype based management can further improve the therapeutic efficacy of JMML. Key words: Myelomonocytic leukemia; Juvenile; Hematopoietic stem cell transplantation; Child