Association between IL-10 Gene -592(C→A) (rs1800872) SNP and GVHD after Allogeneic Hematopoietic Stem Cell Transplantation in Children / 中国实验血液学杂志

OBJECTIVE@#To study the association between IL-10 gene-592(C→A) (rs1800872) single nucleotide polymorphism (SNP) and the graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children.@*METHODS@#Ninety-seven childhood patients and seventy-one donors in the Hematology Oncology Center of Beijing Children's Hospital from Jan 2011 to Jul 2017 were enrolled in this study. The genomic DNA was extracted from peripheral blood cells and the SNP genotype was analyzed using TaqMan SNP genotyping assay.@*RESULTS@#In malignant patients with AA genotype, the incidence of Ⅱ-Ⅳ grade acute GVHD (aGVHD) was lower than that in patients with AC and CC genotype (9.1% vs 43.5%) (P＜0.01), and the gastrointestinal aGVHD rate was also lower (9.1% vs 39.1%) (P＜0.05). There's no significant association between patients' genotype and Ⅱ-Ⅳ grade aGVHD in total patients and non-malignant patients. Also, the genotype in patients did not corelate with chronic GVHD (cGVHD) and 1 year transplantation-related mortality (TRM). In cases who received HSCT of donors with AA genotype, the liver aGVHD rate was higher than that in cases who received HSCT of donors with AC and CC genotype (23.1% vs 0.0%) (P＜0.05), but the genotype in donors did not correlate with Ⅱ-Ⅳ grade aGVHD, cGVHD and 1 year TRM.@*CONCLUSION@#AA genotype in the IL-10 gene-592 (C→A) (rs1800872) single nucleotide polymorphism in patients protects pediatric malignant patients against Ⅱ-Ⅳ grade aGVHD and gastrointestinal aGVHD after allo-HSCT. AA genotype in donors is a risk factor for liver aGVHD after allo-HSCT in non-malignant disease.

Acute Myeloid Leukemia: Advancements in Diagnosis and Treatment / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Leukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment.</p><p><b>DATA SOURCES</b>We searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML. Clinical trial information was obtained from ClinicalTrials.gov. For the major purpose of this review that is to outline the latest therapeutic development of AML, we only listed the ongoing clinical trials for reference. However, the published results of complete clinical trials were also mentioned.</p><p><b>STUDY SELECTION</b>This article reviewed the latest developments related to the diagnosis and treatment of AML. In the first portion, we provided some novel insights on the molecular basis of AML, as well as provided an update on the classification of AML. In the second portion, we summarized the results of research on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/Fms-like tyrosine kinase 3 (FLT3) inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents. We will also highlight ongoing research and clinical trials in pediatric AML.</p><p><b>RESULTS</b>We described clonal evolution and how it changes our view on leukemogenesis, treatment responses, and disease relapse. Pediatric-specific genomic mapping was discussed with a novel diagnostic method highlighted. In the later portion of this review, we summarized the researches on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/FLT3 inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents.</p><p><b>CONCLUSION</b>Gene sequencing techniques should set the basis for next-generation diagnostic methods of AML, and target therapy should be the focus of future clinical research in the exploration of therapeutic possibilities.</p>

Infections during induction therapy of protocol CCLG-2008 in childhood acute lymphoblastic leukemia: a single-center experience with 256 cases in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Infections remain a major cause of therapy-associated morbidity and mortality in children with acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>We retrospectively analyzed the medical charts of 256 children treated for ALL under the CCLG-2008 protocol in Beijing Children's Hospital.</p><p><b>RESULTS</b>There were 65 infectious complications in 50 patients during vincristine, daunorubicin, L-asparaginase and dexamethasone induction therapy, including microbiologically documented infections (n = 12; 18.5%), clinically documented infections (n = 23; 35.3%) and fever of unknown origin (n = 30; 46.2%). Neutropenia was present in 83.1% of the infectious episodes. In all, most infections occurred around the 15 th day of induction treatment (n = 28), and no patients died of infection-associated complications.</p><p><b>CONCLUSIONS</b>The infections in this study was independent of treatment response, minimal residual diseases at the end of induction therapy, gender, immunophenotype, infection at first visit, risk stratification at diagnosis, unfavorable karyotypes at diagnosis and morphologic type. The infection rate of CCLG-2008 induction therapy is low, and the outcome of patients is favorable.</p>

Correlation analysis of FPGS rs10760502G>a polymorphism with prognosis and MTX-related toxicity in pediatric B-cell acute lymphoblastic leukemia / 中国实验血液学杂志

This study was aimed to explore the relation between folylpolyglutamate synthetase (FPGS) rs10760502 polymorphism and prognosis and methotrexate (MTX)-related toxicities in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Sequenom MassARRAY was used to genotype rs10760502. The χ(2) test, Kaplan-Meier method and Cox regression models were used to analyze the data. The results indicated that A allele carriers (GA+AA) had poor relapse free survival (RFS, log-rank: P = 0.004) and event free survival (EFS, log-rank: P = 0.022) compared with the GG genotype carriers. Multivariate Cox-regression analysis results showed that A allele is an independent prognosis factor for poor RFS [hazard ratio (HR), 20.173; 95% CI, 2.535-160.545; P = 0.005] and EFS (HR, 8.133; 95% CI, 1.718-38.512; P = 0.008). No relationship was found between any MTX toxicity and rs10760502 polymorphism. It is concluded that FPGS rs10760502G>A polymorphism may affect the treatment outcome of B-ALL patients.

Evaluation of early response to treatment and its prognostic value in childhood acute lymphoblastic leukemia / 中国实验血液学杂志

This study was purposed to investigate the prognostic value of early response to treatment in childhood acute lymphoblastic leukemia (ALL). Four indexes were used to assess early response to treatment including response to prednisone on day 8 (D8-PR), percentage of lymphoblast in bone marrow on day 22 (D22-BM) and day 33 (D33-BM), the level of minimal residual disease (MRD) on day 33 (D33-MRD) by morphological and molecular biological method in 426 children with ALL. Prognostic impact of early response to treatment was analyzed, and multivariate analysis of the predictive value was performed by Cox-regression analysis. All patients were followed up until October 31, 2013, with a median follow-up time of 80 months (0.5 to 106 months). The results showed that there were significant differences between event free survivals (EFS) of the sub-groups divided according to the four indexes. The 8 years-EFS in patients with prednisone good response (PGR) was significantly higher than that in patients with prednisone poor response (PPR);patients with M1 in bone marrow on day 22 or day 33 had the better outcomes than that of patients with M2/M3;patients with high level of MRD ( ≥ 10(-4)) had the worse outcomes as compared with patients with low level of MRD (<10(-4)) (P < 0.001). Cox proportional hazard model analysis showed that BCR/ABL fusion gene positive, D8-PR, D33-BM and D33-MRD were the independent prognostic factors for childhood ALL, and the hazard ratio of D33-MRD ≥ 10(-2) was highest (HR:11.886, P < 0.001). It is concluded that early response to treatment is an independent prognostic factor with important prognostic values, and it has important clinical guiding instructive significance for risk stratification in the treatment of children ALL.

Preliminary analysis of aberrant expression of plasma miR-223 in pediatric acute lymphoblastic leukemia with a direct RT-PCR assay / 中国实验血液学杂志

This study was aimed to investigate the expression of plasma miR-223 in pediatric acute lymphoblastic leukemia (ALL) in different treatment time point. A total of 64 pediatric ALL samples were selected from patients treated in Beijing Children's Hospital from May 2005 to January 2012, including 30 samples at new diagnosis (ND), 30 samples at complete remission (CR) and 4 samples at relapse. Without RNA extraction, the miR-223 levels in plasma were directly detected by a reverse-transcription quantitative real-time PCR assay. The results indicated that the expression of plasma miR-223 in pediatric ALL was lower at ND but elevated after CR. The miR-223 expression in plasma of relapse patients didn't show significant difference probably due to a few cases of relapse. The miR-223 levels in plasma had not displayed significant difference between TEL-AML1 positive patients and no fusion gene B lineage ALL patients either at ND or at CR. It is concluded that the plasma miR-223 decreases at ND and increases in CR of children with ALL. miR-223 may act as an anti-oncogene and may be taken as a potential predictive biomarker for evaluating the therapeutic effect of leukemia.

Progress of studies on genetics of childhood acute leukemia / 中国实验血液学杂志

This study on determination of leukemia-specific chromosomal abnormalities and their relationship with prognosis of childhood acute leukemia (AL) had an important significance for childhood acute leukemia. In recent years, the efficacy of treatment of childhood AL has been greatly improved, but relapse is still a main factor affecting prognosis. Treatment based on the risk stratification by cytogenetic abnormalities can improve the prognosis and survival rate. In the past 3 decades, the genetic techniques have developed rapidly and many new genetic abnormalities have been found. This review highlights the main chromosomal and genomic abnormalities of 3 common childhood AL, including B-cell precursor acute lymphoblastic leukemia (BCP-ALL), T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML).

Clinical features and therapeutic effect of 38 children with anaplastic large cell lymphoma / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and prognostic factors of children's anaplastic large cell lymphoma (ALCL), summarize the therapeutic effect and toxicities.</p><p><b>METHOD</b>A total of 38 ALCL patients admitted to Beijing Children's Hospital from Jan. 2003 to Apr. 2010 were treated with BCH-ALCL-2003 regimen (modified from HK-ALCL-2000).</p><p><b>RESULT</b>Thirty-four cases were ALK(+), male:female ratio = 2.16:1. The median age was 9 years; 86.8% had B symptoms. 94.7% evolved to Stage III and IV on admission. The median follow-up duration was 48 months (12 to 99 months). Median event-free survival (EFS) time was 43 months. Thirty-four patients (89.5%) achieved a remission. The disease relapsed in 3 patients within 20 months after diagnosis. Estimated 4-year EFS was (81.2 ± 6.4)%, estimated 4-year overall survival (OS) rate was (86.4 ± 5.7)%. Univariate analysis indicated that the unfavorable prognostic factors included: more than 3 extra nodal involvement, hepatosplenomegaly (> 3 cm), elevated lactate dehydrogenase (LDH), stage IV, hemophagocytosis in bone marrow, and age < 3 years. The major toxicity was myelosuppression and mucositis. no chemotherapy related death occurred.</p><p><b>CONCLUSION</b>(1) Childhood ALCL patients often have B symptoms and extranodal involvement. (2) In the study, therapeutic effects was good. The disease relapsed mostly within the first 2 years, maintenance therapy with vinblastine is necessary. (3) The regimen is safe to patients.</p>

Epigenetic mechanism of RUNX1 in pathogenesis of leukemia / 中国实验血液学杂志

RUNX1, also called AML1, is a member of RUNX transcriptional factor family, and also is the most frequent target for chromosomal translocations in leukemia. RUNX1 is a very important transcription factor, can enhance or repress the expressions of many hematopoiesis related genes. RUNX1 may receive a series of post-translational modifications, and the activity of RUNX1 can be affected by these post-translational modifications, thus RUNX1 regulates the differentiation, apoptosis and self-renewal of hematopoietic cells. This article reviews the role of RUNX1 in the pathogenesis of leukemia mainly including its target genes, transcriptional mechanism and post-translational modifications.