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Background: ASXL1 mutation is an independent prognostic factor in adult acute myeloid leukemia (AML), but its effect on the prognosis of pediatric AML is poorly understood. Aims: This study aimed to investigate the clinical characteristics and prognostic factors of ASXL1‐mutant pediatric AML from a large Chinese multicenter cohort. Methods: A total of 584 pediatric patients with newly diagnosed AML from 10 centers in South China were enrolled. The exon 13 of ASXL1 was amplified by polymerase chain reaction (PCR), and then analyzed the mutation status of the locus. (n = 59 for ASXL1‐mut group, n = 487 for ASXL1‐wt group). Results: ASXL1 mutations were found in 10.81% of all patients with AML. A complex karyotype was significantly less common in the ASXL1‐mut AML group than in the ASXL1‐wt group (1.7% vs. 11.9%, p = 0.013). Furthermore, TET2 or TP53 mutations were predominantly found in the ASXL1+ group (p = 0.003 and 0.023, respectively). The 5‐year overall survival (OS) and event‐free survival (EFS) of the total cohort were 76.9% and 69.9%. In ASXL1‐mut AML patients, a white blood cell (WBC) count ≥50 × 109/L had significantly poorer 5‐year OS and EFS than a WBC count <50 × 109/L (78.0% vs. 44.6%, p = 0.001; 74.8% vs. 44.6%, p = 0.003, respectively), while receiving hematopoietic stem cell transplantation (HSCT) had a higher 5‐year OS and EFS (84.5% vs. 48.5%, p = 0.024; 79.5% vs. 49.3%, p = 0.047, respectively). In the multivariate Cox regression analysis, patients with high‐risk AML undergoing HSCT tended to have a better 5‐year OS and EFS than those receiving chemotherapy as a consolidation (HR = 0.168 and 0.260, both p < 0.001), and WBC count ≥50 × 109/L or failure to achieve complete response after the first course were independent adverse predictors of OS and EFS (HR = 1.784 and 1.870, p = 0.042 and 0.018; HR = 3.242 and 3.235, both p < 0.001). Conclusion: The C‐HUANA‐AML‐15 protocol is a well‐tolerated and effective in the treatment of pediatric AML. ASXL1 mutation is not an independent adverse prognosis predictor for survival in AML, whereas ASXL1‐mut patients tend to have a poor prognosis if WBC count ≥50 × 109/L, but they can benefit from HSCT. [ABSTRACT FROM AUTHOR]

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment for thalassaemia major (TM). Cord blood (CB) from a sibling has different characteristics from marrow and has potential advantages and disadvantages as a stem cell source. We retrospectively analyzed 68 children with beta-thalassaemia major (β-TM) who underwent fresh cord blood transplantation (F-CBT) from an HLA-matched sibling donor (MSD) between June 2010 and July 2018 in the Department of Pediatrics, Nanfang Hospital and Haematology-Oncology, Shenzhen Children's Hospital. The median infused doses of total nucleated cells (TNCs) and CD34 + cells were 8.51×107/kg and 3.16×105/kg, respectively. The median time to neutrophil and platelet engraftment were, respectively, 27 and 31 days. The cumulative probabilities of acute and chronic graft-versus-host disease (GVHD) were very low after F-CBT (7.8% and 0.0%, respectively). Of the 68 paediatric patients, 67 patients survived during a median follow-up period of 61 months. The estimated 5-year probability of overall survival (OS) and disease-free survival (DFS) were 98.5% and 87.9%, respectively. Three patients experienced graft rejection (GR) (4.5%), and we identified CD34 + cell dose as a significant risk factor for graft failure (p = 0.036) in stratify analysis. The above results indicate that patients with β-TM have excellent outcomes after F-CBT from an HLA-MSD. [ABSTRACT FROM AUTHOR]

Background: A high ecotropic viral integration site 1 (EVI1) expression (EVI1 high) is an independent prognostic factor in adult acute myeloid leukemia (AML). However, little is known of the prognostic value of EVI1 high in pediatric AML. This study aimed to examine the biological and prognostic significance of EVI1 high in uniformly treated pediatric patients with AML from a large cohort of seven centers in China. Methods: A diagnostic assay was developed to determine the relative EVI1 expression using a single real-time quantitative polymerase chain reaction in 421 newly diagnosed pediatric AML patients younger than 14 years from seven centers in southern China. All patients were treated with a uniform protocol, but only 383 patients were evaluated for their treatment response. The survival data were included in the subsequent analysis (n = 35 for EVI1 high, n = 348 for EVI1 low). Results: EVI1 high was found in 9.0% of all 421 pediatric patients with de novo AML. EVI1 high was predominantly found in acute megakaryoblastic leukemia (FAB M7), MLL rearrangements, and unfavorable cytogenetic aberrance, whereas it was mutually exclusive with t (8; 21), inv (16)/t (16; 16), CEBPA , NPM1 , or C-KIT mutations. In the univariate Cox regression analysis, EVI1 high had a significantly adverse 5-year event-free survival (EFS) and overall survival (OS) [hazard ratio (HR) = 1.821 and 2.401, p = 0.036 and 0.005, respectively]. In the multivariate Cox regression analysis, EVI1 high was an independent prognostic factor for the OS (HR = 2.447, p = 0.015) but not EFS (HR = 1.556, p = 0.174). Furthermore, EVI1 high was an independent adverse predictor of the OS and EFS of patients with MLL rearrangements (univariate analysis: HR = 9.921 and 7.253, both p < 0.001; multivariate analysis: HR = 7.186 and 7.315, p = 0.005 and 0.001, respectively). Hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) provided EVI1 high patients with a tendential survival benefit when compared with chemotherapy as a consolidation (5-year EFS: 68.4% vs. 50.8%, p = 0.26; 5-year OS: 65.9% vs. 54.8%, p = 0.45). Conclusion: It could be concluded that EVI1 high can be detected in approximately 10% of pediatric AML cases. It is predominantly present in unfavorable cytogenetic subtypes and predicts adverse outcomes. Whether pediatric patients with EVI1 high AML can benefit from HSCT in CR1 needs to be researched further. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for thalassemia majorTM. Graft rejection (GR) and graft-versus-host disease (GVHD) are the primary obstacles to a successful outcome. Methods: We conducted a retrospective study of HSCT in 29 children (median age at transplantation: 6 years) with Beta-thalassemia (β-TM) after the combined infusion of granulocyte colony-stimulating factor-primed bone marrow (G-BM) and cord blood (CB) from the human leukocyte antigen (HLA)-identical sibling donors. We also compared the outcomes of the co-transplanted children with those of children with β-TM who received G-BM alone from an HLA-identical sibling donor (n = 26). Results: Compared to the G-BM transplant (G-BMT) recipients, those who received a co-transplant had a lower incidence of grade ≥II acute (17.24 vs. 30.7%, p = 0.047) and limited chronic (0 vs.15.4%, p = 0.022) GVHD as well as a lower incidence of GR (0 vs. 7.7%, p = 0.132). Neutrophil recovery time was faster in the co-transplant group (18.5 vs. 21 days, p = 0.04). All the patients were monitored until December 31, 2016; the median follow-up time was 74 months, and the 5-year thalassemia-free survival rate was 89.7% in the co-transplant group and 84.6% in the G-BMT-alone group (p = 0.590). Conclusions: A combined CB and G-BM graft from an HLA-identical sibling donor is an effective treatment option for TM in children, with less acute and chronic GVHD. [ABSTRACT FROM AUTHOR]

Background: Long-term health-related quality of life (HRQoL) of pediatric patients after hematopoietic stem cell transplantation (HSCT) is increasingly studied worldwide. However, few studies have been performed in China, where no uniform scale is available; the PedsQL™ Cancer Module 3.0 Chinese Mandarin version has been used to evaluate HRQoL of patients after HSCT in China. This study aimed to assess the reliability and validity of the Chinese Mandarin version of PedsQL™ 3.0 Transplant Module.Methods: Patients between 2 and 18 years old, who underwent HSCT from January 2006 to June 2014, were recruited in Beijing Children's Hospital affiliated to Capital Medical University, the First Affiliated Hospital of Southern Medical University and Beijing Daopei Hospital. 207 parent reports and 182 child self-reports of the PedsQL™ 3.0 Transplant Module Chinese Mandarin version were assigned, of which 362 were returned.Results: No missing item response was observed in the returned reports. Cronbach's alpha coefficient exceeded 0.7 in total scale and every dimension. The intraclass correlation coefficient exceeded 0.8 in all dimensions of child self-reports and parent reports. Spearman's rank correlation coefficients of items and their respective dimensions were 0.6-0.94 in parent reports, and 0.62-0.93 in child self-reports, while a weak association was found between the items and other dimensions. Exploratory factor analysis indicated a good extraction effect, and construct validity of the scale was >60 %.Conclusions: The Chinese Mandarin version of PedsQL™ 3.0 Transplant Module has good feasibility, reliability and validity. Its use may help improve the HRQoL of children after HSCT in China. [ABSTRACT FROM AUTHOR]