[Clinical Features and Prognosis of Acute T-cell Lymphoblastic Leukemia in Children--Multi-Center Data Analysis in Fujian].

OBJECTIVE: To evaluate the efficacy of acute T-cell lymphoblastic leukemia (T-ALL) in children and explore the prognostic risk factors. METHODS: The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed, and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia (B-ALL) in the same period. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event-free survival (EFS), and COX proportional hazard regression model was used to evaluate the prognostic factors. Among 116 children with T-ALL who received standard treatment, 78 cases received the Chinese Childhood Leukemia Collaborative Group (CCLG)-ALL 2008 protocol (CCLG-ALL 2008 group), and 38 cases received the China Childhood Cancer Collaborative Group (CCCG)-ALL 2015 protocol (CCCG-ALL 2015 group). The efficacy and serious adverse event (SAE) incidence of the two groups were compared. RESULTS: Proportion of male, age≥10 years old, white blood cell count (WBC)≥50×109/L, central nervous system leukemia, minimal residual disease (MRD)≥1% during induction therapy, and MRD≥0.01% at the end of induction in T-ALL children were significantly higher than those in B-ALL children (P <0.05). The expected 10-year EFS and OS of T-ALL were 59.7% and 66.0%, respectively, which were significantly lower than those of B-ALL (P <0.001). COX analysis showed that WBC≥100×109/L at initial diagnosis and failure to achieve complete remission (CR) after induction were independent risk factors for poor prognosis. Compared with CCLG-ALL 2008 group, CCCG-ALL 2015 group had lower incidence of infection-related SAE (15.8% vs 34.6%, P =0.042), but higher EFS and OS (73.9% vs 57.2%, P EFS=0.090; 86.5% vs 62.3%, P OS=0.023). CONCLUSIONS: The prognosis of children with T-ALL is worse than children with B-ALL. WBC≥100×109 /L at initial diagnosis and non-CR after induction (especially mediastinal mass has not disappeared) are the risk factors for poor prognosis. CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

[Clinical Characteristics and Prognosis of MLL Rearranged Childhood Acute Lymphocyte Leukemia].

AbstractObjective: To investigate the clinical characteristics and prognostic factors in childhood acute lymphoblastic leukemia with MLL gene-rearrangement-positive (MLL-r+ ALL). METHODS: The clinical data of 1 414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed. The clinical characteristics and efficacy of MLL-r+ and MLL-r- subgroup were compared. The prognostic factors of MLL-r ALL were analyzed by COX regression model. RESULTS: Among all children with ALL, the proportion of patients aged less than 1 year old was 1.8%, and the detection rate of MLL-r+ was 3.4% (48/1 414). The positive detection rate of MLL-r in the age groups <1 year old, and ≥1 year old and ≤14 years old was 38.5% (10/26) and 2.7 (38/1 388), respectively, the difference was statistically significant (P<0.000). Compared with MLL-r- group, the MLL-r+ group had a higher proportion of patients with age <1 year, white blood cell (WBC) count ≥50×109/L, combined central nervous system leukemia (CNSL) and testicular leukemia(TL), while MRD <0.01% on d 33 or d 46 of induction chemotherapy was lower (all P<0.05). The expected 10-year event free survival(EFS) rate and overall survival(OS) rate of the MLL-r+ group were significantly lower than those of the MLL-r- group （EFS： 49.9% vs 77.0%； OS: 55.3% vs 82.9%， P<0.05). COX regression model analysis showed that age <1 year, minimal residual disease (MRD) ≥0.01% on d 33 or d 46 of induction chemotherapy were independent risk factors for worse OS and EFS in MLL-r+ ALL patients (all P<0.05). CONCLUSION: Age <1 year old, high WBC, concomitant CNSL and TL are more common in children with MLL-r+ ALL at initial diagnosis, with poor early treatment response and long-term prognosis. Age <1 year old at initial diagnosis and MRD positive after induction chemotherapy may be risk factors for poor prognosis.

[Clinical features and prognosis of high hyperdiploid childhood acute lymphoblastic leukemia: a multicenter retrospective analysis in Fujian Province, China]. / é«˜è¶ äºŒå€ä½“æ ¸åž‹å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— çš„ä¸´åºŠç‰¹å¾åŠé¢„åŽ.

OBJECTIVES: To study the clinical features and prognosis of high hyperdiploid (HHD) childhood acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed on the medical data of 1 414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020. According to karyotype, they were divided into two groups: HHD (n=172) and non-HHD (n=1 242). The clinical features and treatment outcome were compared between the two groups, and the factors influencing the prognosis were further explored. RESULTS: Among the 1 414 children with ALL, 172 (12.16%) had HHD. Compared with the non-HHD group, the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis (age of onset ≥10 years or <1 year, white blood cell count ≥50×109/L, and T-cell phenotype) or positive fusion genes (TEL-AML1, BCR-ABL1, E2A-PBX1, and MLL gene rearrangement) (P<0.05). The HHD group had a significantly higher proportion of children with minimal residual disease (MRD) <0.01% at the end of induction chemotherapy (P<0.05). The 10-year event-free survival (EFS) rate and overall survival (OS) rate in the HHD group were significantly higher than those in the non-HHD group (P<0.05). The univariate analysis showed that the number of chromosomes of 58-66, trisomy of chromosome 10, trisomy of chromosome 17, bone marrow MRD <1% on day 15 or 19 of induction chemotherapy, and bone marrow MRD <0.01% on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate (P<0.05), and trisomy of chromosome 10 was associated with a higher OS rate (P<0.05). The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate (P<0.05). CONCLUSIONS: The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis. The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.

[Analysis of Gene Mutation and Clinical Characteristics in 19 Children with Juvenile Myelomonocytic Leukemia].

OBJECTIVE: To analyze the gene mutations of children with juvenile myelomonocytic leukemia (JMML) and their correlation with clinical characteristics. METHODS: The genetic mutation results and clinical data of 19 children with JMML in Fujian from January 2015 to December 2018 were collected and analyzed retrospectively. According to the results of gene mutation, they were divided into PTPN11 gene mutation group and non-PTPN11 gene mutation group, and the clinical characteristics and prognosis of children with JMML between two groups were compared. RESULTS: Among the 19 children with JMML, 14 cases were male and 5 cases were female, and male/female ratio was 2.8∶1. The median age at diagnosis was 13(3-48) months, and 14 cases (73.68%) were less than 2 years old. Abdominal distension and pyrexia were the common initial symptoms, and all the children with JMML had splenomegaly. The median white blood cell count was 39.82(4.53-103.4)×109/L，and monocyte count was 4.37(1.04-23.12)×109/L. HbF was higher than the normal high value of the same age in 8 cases (42.11%). All JMML children's Philadelphia chromosome and BCR-ABL1 fusion gene were negative. Among the 19 patients, there were 1 case without any JMML related gene mutation, 7 cases (36.84%) with PTPN11 mutation, 6 cases (31.58%) with K-Ras mutation, 2 cases with NF1 mutation (10.53%), 2 cases with N-Ras mutation (10.53%), and 1 case (5.26%) with NF1 and N-Ras mutations simultaneously. Fifteen patients who only received supporting therapy all died, with a median survival time 9.2 (0.4-58.1) months. Whereas, among the four JMML children who received hematopoietic stem cell transplantation(HSCT), three cases survived and only one case died. Compared with the non-PTPN11 gene mutation group, the proportion of patients with hemoglobin F higher than the normal value of the same age was higher, and the median survival time was shorter in PTPN11 gene mutation group, and the differences were statistically significant (P=0.048 and 0.046, respectively). CONCLUSION: JMML is more common in male infancy and toddlerhood, and the main gene mutation types are PTPN11 and Ras mutations. Because the JMML children with PTPN11 mutations show particularly rapid disease progression, if there is no timely intervention, most children die in a short period of time. Therefore, early HSCT may improve the prognosis of the children with JMML.