P1072: NATURAL HISTORY OF JUVENILE MYELOMONOCYTIC LEUKEMIA

Abstract

Background: Juvenile Myelomonocytic leukemia (JMML) is a rare clonal disease that occurs in infants and young children, and most patients respond poorly to chemotherapy. Hematopoietic stem cell transplantation (HSCT) is the only way to cure this disease. The clinical heterogeneity of JMML is large, and the disease progresses rapidly in most patients, whereas a few patients progress slowly and survive for long periods without treatment. Aims: This study retrospectively analyzed clinical data of untreated JMML patients from our department. Explore their natural course of disease and prognosis factors and provide clinical research data for screening the prognostic factors for natural history of JMML. Methods: Patients who were diagnosed JMML from January 2008 to December 2021 in our center were included in this study. The clinical characteristics, bone marrow morphology, cytogenetics, mutated genes, hypersensitivity of GM-CSF, abdominal ultrasound and other laboratory test results were retrospectively analyzed. Results: In this study，88 patients were diagnosed JMML from 2008 till now in our single institute, 44 cases (50%) without treatment (including chemotherapy and HSCT) in the whole course. The median age of onset was 13 months (range 2-48), and the incidence was mostly male, with the male to female ratio =32: 12, median time between onset and diagnosis was 2 (0.3-36.0) months. Among them, 15 cases (34.1%) had simple abnormal blood image as chief complaint, and 17 cases (38.6%) had non-specific rash on physical examination. Lymphadenopathy was found in 23 cases (52.3%) with a median subcostal value of 3.9 (0-11) cm in liver and 5.4 (1-16) cm in spleen. The median WBC count at initial diagnosis was 28.2 (range 9.1-128.6) ×109/L, and the hemoglobin value was 88.8 (range 52.0-153.0) g/L. Platelet count(PLT) was 44.0 (range 1.0-389.0) ×109/L, absolute value of monocyte was 4.5 (1.3-30.5) ×109/L, absolute value of median lymphocyte was 8.2 (2.4-48.7) ×109/L, and median fetal hemoglobin was 10 (0-88) %. Thirty-four patients underwent cytogenetic examination, of which 31 (91.2%) had normal karyotype and 3 patients had chromatid 7. Thirty patients underwent gM-CSF hypersensitive examination, with a median CFU-GM-3 (0-73) BMMNC. JMML mutations were detected in 36 children, including 6 patients with second-generation sequencing, and 30 patients with first-generation sequencing JMML hotspot mutations, including 13 (36.1%) PTPN11 mutations, 4 (11.1%) KRAS mutations, 9 (25.0%) NRAS mutations, and 1 (2.8%) NF1 mutations. One (2.8%) had mutations of NRAS and PTPN11, and 8 (22.2%) had no known JMML mutants. The study was followed up to 2022.1, with a median follow-up time of 20.6 (range 1-132) months. Among the 44 patients, 8 cases (18.2%) were lost to follow-up, 28 cases (63.6%) died, and 8 cases (18.2%) survived. To explore the influence of clinical characteristics and laboratory test results on patients’ OS, the study found that PLT < 40×109/L, spleen subcostal > 5 cm and PTPN11 were important adverse factors affecting OS. The 5-year overall survival rate of 44 children was 40%, and the 5-year overall survival rate of those with PTPN11 mutation was significantly lower than that of other mutation gene types. Summary/Conclusion: The natural history of JMML was significantly different among different mutated gene types, among which PLT, spleen size and PTPN11 mutated gene type were independent prognostic factors affecting the natural course of JMML.