·To analyze the clinical characteristics and prognosis of pediatric acute leukemia (AL) patients with positive mixed linage leukemia (MLL) gene rearrangement (MLL-r).Methods
·Forty-five children with MLL-r AL admitted to Shanghai Children′s Hospital, Shanghai Jiao Tong University from January 1, 2009 to December 31, 2019 were retrospectively analyzed. Fluorescence in situ hybridization and/or fluorescent real-time PCR were used to detect the MLL-r. Kaplan-Meier method was used to evaluate the survival of children. Log-rank test was used to compare the difference of survival rate. Univariate analysis and multivariate analysis were performed on the factors influencing survival, such as gender, age and the number of white blood cells.Results
·The incidence rate of MLL-r in children with AL in our center was 7.1%, and the incidence rate of MLL-r in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were 5.4% and 13.3%, respectively. The difference between the two groups was statistically significant (P=0.002). The age of the two groups of children (>1 year and ≤1 year) and the number of white blood cells at the time of onset (≥50×109/L and <50×109/L) were compared. The differences were statistically significant (P=0.032 and 0.021). The main immunophenotype of children with MLL-r ALL was early precursor B-ALL, accounting for 79.2%. The main immunophenotype of children with MLL-r AML was M5, accounting for 77.8%. MLL partner gene analysis showed that MLL/AF4 accounted for 59.2% (16/27) of MLL-r ALL children, of which 68.7% (11/16) were children younger than 1 year old. Compared with the children younger than 1 year old in the non-MLL/AF4 group, the difference was statistically significant (P=0.034). The majority of children with MLL-r AML were MLL/AF9, accounting for 33.3%. Of the 45 patients, 42 cases were included for the prognosis analysis. The complete remission rate was 97.6% (41/42), and the median follow-up time was 26 (2?138) months. The median event-free survival (EFS) and overall survival (OS) time were 21 months and 24.5 months, respectively. The 3-year EFS and OS rates were (41.8±9.4) % and (60.9±9.3) %, respectively. The median duration of EFS and OS in children with MLL-r ALL were 21.5 months and 28 months, respectively, and the 3-year EFS and OS rates were (44.3±11.7) % and (58.2±12.1) %, respectively. The median EFS and OS time in children with MLL-r AML were 16 months and 23 months, respectively. The 2-year EFS and OS rates were (36.5±15.8) % and (64.7±14.5) %, respectively. Eight cases of ALL children relapsed, with a median recurrence time of 20 (2?36) months; 7 cases of AML children relapsed, with a median recurrence time of 16 (5?38) months, and the cumulative recurrence rates were 48.4% and 63.9%, respectively. There was no statistically significant difference between them (P=0.398). Univariate analysis showed that between the groups of MLL-r ALL children >1 year and ≤1 year, white blood cell count ≥50×109/L and <50×109/L, platelet count ≥30×109/L and <30×109/L, there were statistically significant differences in the EFS rate. The P values were 0.028, 0.024 and 0.027 respectively. Multivariate analysis showed that the number of white blood cells at onset was an independent prognostic factor affecting EFS in children with MLL-r ALL (RR=6.113, 95% CI 0.017?1.050, P=0.013).Conclusion
·The incidence of MLL-r in children with AML is higher than that in children with ALL. The main immunophenotype of MLL-r ALL is early precursor B-ALL. The main immunophenotype of MLL-r AML is M5. Conventional chemotherapy produces a high response rate, which is likely to relapse. The number of white blood cells at the onset ≥50×109/L is a poor prognostic factor for children with MLL-r ALL.