[Risk factors for recurrence of childhood acute lymphoblastic leukemia after treatment with the Chinese Children's Cancer Group ALL-2015 protocol]. / CCCG-ALL-2015æ–¹æ¡ˆæ²»ç–—å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— å¤å‘çš„å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence. METHODS: A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed. RESULTS: Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group (P>0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage (n=62, 42.5%) and the early stage (n=46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene (HR=4.177, 95%CI: 2.086-8.364, P<0.001) and minimal residual disease≥0.01% on day 46 (HR=2.013, 95%CI: 1.163-3.483, P=0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol. CONCLUSIONS: There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

[Role of Telomere in Clonal Evolution of Acquired Aplastic Anemia--Review].

Studies have found that 1/3 patients with acquired aplastic anemia have shortened telomere length, and the shorter the telomere, the longer the disease course, the more prone to relapse, the lower the overall survival rate, and the higher the probability of clonal evolution. The regulation of telomere length is affected by many factors, including telomerase activity, telomerase-related genes, telomere regulatory proteins and other related factors. Telomere shortening can lead to genetic instability and increases the probability of clonal evolution in patients with acquired aplastic anemia. This article reviews the role of telomere in the clonal evolution of acquired aplastic anemia and factors affecting telomere length.

[The Efficacy and Influencing Factors of Cyclosporine Alone in the Treatment of Children with Acquired Aplastic Anemia].

OBJECTIVE: To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA). METHODS: The clinical data of children diagnosed with AA and treated with CsA alone from January 1, 2016 to December 31, 2020 in the Children's Hospital of Chongqing Medical University were collected, and the efficacy and influencing factors of CsA treatment were evaluated. RESULTS: Among the 119 patients, there were 62 male and 57 female, with a median age of 7 years and 1 month. There were 45 cases of very severe AA (VSAA), 47 cases of severe AA (SAA), and 27 cases of non-severe AA (NSAA). At 6 months after treatment, the efficacy of VSAA was lower than that of SAA and NSAA, and there was a statistical difference (P < 0.01). 6 cases died early, 16 cases relapsed, 2 cases progressed to AML and ALL. The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA, while high PLT count was a protective factor (P =0.008, P =0.002). The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5×109 /L, 68.5%, respectively. Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST (P =0.020, OR =0.062), and high PLT count was a protective factor (P =0.044, OR =1.038). At 3 months of treatment, CsA response and NSAA were the risk factor for recurrence (P =0.001, 0.031). CONCLUSION: The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone. A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA, and a high proportion of bone marrow lymphocyte was an unfavorable factor. CsA response at 3 months and NSAA were risk factors for recurrence.

Predictive model for early death risk in pediatric hemophagocytic lymphohistiocytosis patients based on machine learning.

Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening disease in children, with a high early mortality rate. This study aimed to construct machine learning model to predict the risk of early death using clinical indicators at the time of HLH diagnosis. Methods: This observational cohort study was conducted at the National Clinical Research Center for Child Health and Disease. Data was collected from pediatric HLH patients diagnosed by the HLH-2004 protocol between January 2006 and December 2022. Six machine learning models were constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) to select key clinical indicators for model construction. Results: The study included 587 pediatric HLH patients, and the early mortality rate was 28.45 %. The logistic and XGBoost model with the best performance after feature screening were selected to predict early death of HLH patients. The logistic model had an AUC of 0.915 and an accuracy of 0.863, while the XGBoost model had an AUC of 0.889 and an accuracy of 0.829. The risk factors most associated with early death were the absence of immunochemotherapy, decreased TC levels, increased BUN and total bilirubin, and prolonged TT. We developed an online calculator tool for predicting the probability of early death in children with HLH. Conclusions: We developed the first web-based early mortality prediction tool for pediatric HLH to assist clinicians in risk stratification at diagnosis and in developing personalized treatment protocols. This study is registered on the China Clinical Trials Registry platform (ChiCTR2200061315).

Case report: Gene mutations and clinical characteristics of four patients with osteopetrosis.

Osteopetrosis is characterized by increased bone density caused by decreased osteoclasts or dysfunction of their differentiation and absorption properties, usually caused by biallelic variants of the TCIRG1(OMIM:604592)and CLCN7(OMIM:602727) genes. Herein, the clinical, biochemical, and radiological manifestations of osteopetrosis in four Chinese children are described. Whole-exome sequencing identified compound heterozygous variants of the CLCN7 and TCIRG1 genes in these patients. In Patient 1, two novel variants were identified in CLCN7:c.880T > G(p.F294V) and c.686C > G(p.S229X). Patient 2 harbored previously reported a single gene variant c.643G > A(p.G215R) in CLCN7. Patient 3 had a novel variant c.569A > G(p.N190S) and a novel frameshift variant c.1113dupG(p.N372fs) in CLCN7. Patient 4 had a frameshift variant c.43delA(p.K15fs) and variant c.C1360T in TCIRG1, resulting in the formation of a premature termination codon (p.R454X), both of which were reported previously. Our results expand the spectrum of identified genetic variation in osteopetrosis and provide a deeper understanding of the relations between genotype and clinical characteristics of this disorder.

Clinical and genetic features of Chinese pediatric patients with severe congenital protein C deficiency who first presented with purpura fulminans: A case series study and literature review.

INTRODUCTION: Purpura fulminans (PF) is a hematological emergency that can be caused by severe congenital protein C (PC) deficiency. It has been rarely reported in the Chinese population. We aimed to characterize the clinical and genetic features of Chinese pediatric patients with severe congenital PC deficiency who first presented with PF. MATERIALS AND METHODS: Twelve pediatric patients were diagnosed with severe congenital PC deficiency with PF, which was diagnosed based on our hospital records and previous reports from 1988 to July 2021 in China. We evaluated the clinical and genetic features of these patients. RESULTS: Nine patients (9/12, 75%) had onsets that were observed within the first 48 h after birth. Six patients had a family history of thromboembolism. There was no consanguinity. Other symptoms were intracranial thrombosis or hemorrhage (4, 33.3%), ocular lesions (2, 16.7%), gastrointestinal hemorrhage (2, 16.7%) and kidney infarction before birth (1, 8.3%). All but one of the patients (one case not detected) had a plasma PC activity of <10%. The genetic study indicated that in the eight patients with inherited PC deficiency, two were homozygous, five were compound heterozygous and one was heterozygous for PC deficiency. CONCLUSION: This is the first and largest case series of Chinese pediatric patients with severe congenital PC deficiency who first presented with PF. It has been shown that treatment with both fresh frozen plasma and anticoagulants is recommended when PC concentrate is not easily available, especially in developing countries.

Prognostic significance of measurable residual disease based on multiparameter flow cytometry in childhood acute myeloid leukemia. / åŸºäºŽæµå¼ç»†èƒžæœ¯çš„å¯æµ‹é‡æ®‹ç•™ç— å¯¹å„¿ç«¥æ€¥æ€§é«“ç³»ç™½è¡€ç— é¢„åŽæ„ä¹‰çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the prognostic value of measurable residual disease (MRD) for childhood acute myeloid leukemia (AML) by analyzing MRD-guided risk stratification therapy. METHODS: A total of 93 children with AML were prospectively enrolled in this study. Chemotherapy with the 2015-AML-03 regimen was completed according to the risk stratification determined by genetic abnormality at initial diagnosis and MRD and bone marrow cytology after induction therapy I. Multiparameter flow cytometry was used to dynamically monitor MRD and analyze the prognostic effect of MRD on 3-year cumulative incidence of recurrence (CIR) rate, event-free survival (EFS) rate, and overall survival (OS) rate. RESULTS: The 93 children with AML had a 3-year CIR rate of 48%±6%, a median time to recurrence of 11 months (range 2-32 months), a 3-year OS rate of 65%±6%, and a 3-year EFS rate of 50%±5%. After induction therapy I and intensive therapy I, the MRD-positive children had a significantly higher 3-year CIR rate and significantly lower 3-year EFS and OS rates than the MRD-negative children (P<0.05). There were no significant differences in 3-year CIR, EFS, and OS rates between the MRD-positive children with a low risk at initial diagnosis and the MRD-negative children after adjustment of chemotherapy intensity (P>0.05). The multivariate analysis showed that positive MRD after intensive treatment I was a risk factor for 3-year OS rate in children with AML (P<0.05). CONCLUSIONS: MRD has predictive value for the prognosis of children with AML. Based on the MRD-guided risk stratification therapy, reasonable application of chemotherapy may improve the overall prognosis of children with AML.

Clinical features and prognosis of children with acute leukemias of ambiguous lineage under different diagnostic criteria. / ä¸åŒè¯Šæ–­æ ‡å‡†ä¸‹å„¿ç«¥æ€¥æ€§ä¸æ˜Žè°±ç³»ç™½è¡€ç— çš„ä¸´åºŠç‰¹ç‚¹å’Œé¢„åŽåˆ†æž.

OBJECTIVES: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria. METHODS: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group (n=28) and myeloid expression group (n=11). The clinical features, treatment, and prognosis were compared between the two groups. RESULTS: The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% (P<0.05). The children with negative minimal residual disease (MRD) after induction therapy had a significantly higher 3-year EFS rate than those with positive MRD (96%±4% vs 38%±28%, P<0.05). Positive ETV6-RUNX1 was observed in the myeloid expression group, and positive BCR-ABL1, positive MLL-r, and hyperleukocytosis (white blood cell count ≥50×109/L) were observed in the ALAL group. There was no significant difference in the 3-year EFS rate between the myeloid expression and ALAL groups (100%±0% vs 66%±11%, P>0.05). CONCLUSIONS: ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.

Application of high-throughput sequencing for hereditary thrombocytopenia in southwestern China.

BACKGROUND: The aim of this study was to design and analyze the applicability of a 21-gene high-throughput sequencing (HTS) panel in the molecular diagnosis of patients with hereditary thrombocytopenia (HT). METHODS: A custom target enrichment library was designed to capture 21 genes known to be associated with HTs. Twenty-four patients with an HT phenotype were studied using this technology. RESULTS: One pathogenic variant on the MYH9 gene and one likely pathogenic variant on the ABCG8 gene previously known to cause HTs were identified. Additionally, 3 previously reported variants affecting WAS, ADAMTS13, and GP1BA were detected, and 9 novel variants affecting FLNA, ITGB3, NBEAL2, MYH9, VWF, and ANKRD26 genes were identified. The 12 variants were classified to be of uncertain significance. CONCLUSION: Our results demonstrate that HTS is an accurate and reliable method of pre-screening patients for variants in known HT-causing genes. With the advantage of distinguishing HT from immune thrombocytopenia, HTS could play a key role in improving the clinical management of patients.

[Serious adverse events associated with chemotherapy in children with acute lymphoblastic leukemia].

OBJECTIVE: To study the occurrence of serious adverse events (SAEs) related to chemotherapy with CCCG-ALL-2015 regimen in children with acute lymphoblastic leukemia (ALL) and the risk factors for death after the SAEs. METHODS: A retrospective analysis was performed on the medical data of 734 children with ALL. They were treated with CCCG-ALL-2015 regimen from January 2015 to June 2019. The occurrence of SAEs during the treatment was investigated. The children with SAEs were divided into a death group with 25 children and a survival group with 31 children. A multivariate logistic regression analysis was used to analyze the risk factors for death after the SAEs. RESULTS: Among the 734 children with ALL, 56 (7.6%) experienced SAEs (66 cases) after chemotherapy, among which 41 cases occurred in the stage of remission induction therapy. Of all 66 cases of SAEs, 46 (70%) were infection-related SAEs, including 25 cases of septic shock (38%), 20 cases of severe pneumonia (30%), and 1 case of severe chickenpox (2%), and 87% of the children with infection-related SAEs had neutrophil deficiency. The most common infection sites were blood and the lungs. The most common pathogens were Gram-negative bacteria, viruses, fungi, and Gram-positive bacteria. There were 16 cases (24%) of hemorrhage-related SAEs, with 11 cases of gastrointestinal bleeding (17%), 4 cases of pulmonary bleeding (6%), and 1 case of intracranial bleeding (2%). Of all 734 children with ALL, 66 (9.0%) died, among whom 25 died due to SAEs. The treatment-related mortality rate was 3.4%, and infection (72%) and bleeding (24%) were the main causes of death. Severe pneumonia was an independent risk factor for treatment-related death in ALL children (OR=4.087, 95%CI: 1.161-14.384, P=0.028). CONCLUSIONS: SAEs often occur in the stage of remission induction therapy, and infection-related SAEs are more common in ALL children accepting chemotherapy with CCCG-ALL-2015 regimen. The development of severe pneumonia suggests an increased risk for death in these children.

Clinical efficacy and safety of imatinib treatment in children and adolescents with chronic myeloid leukemia: A single-center experience in China.

Chronic myeloid leukemia (CML) is relatively rare in childhood and few studies have reported the clinical use of imatinib (IM) in pediatric CML. In this study, we evaluated the efficacy and tolerability of IM in children and adolescents with CML.We investigated 21 patients under 18 years of age with newly diagnosed CML and treated with IM in Children's Hospital of Chongqing Medical University between May 2014 and February 2018. The disease was staged according to the European LeukemiaNet criteria and the IM dose was determined based on the disease stage. Cumulative responses and survival probabilities were estimated according to the Kaplan-Meier method.The estimated complete hematologic response rate of chronic phase-chronic myeloid leukemia (CML-CP) was 89.5% at 3 months. The complete cytogenetic response rates increased with time, reaching 47.4%, 73.7%, and 80.3% at 6, 12, and 24 months, respectively. The cumulative major molecular response rates were 42.1% and 76.3% at 12 and 24 months, respectively. With a median follow-up time of 33.8 months (range, 3.2-61.7 months), the estimated 2-year overall survival (OS) rate for CML was 95.2% (95% confidence interval [CI], 70.7%-99.3%). None of the CML-CP patients progressed to the accelerated phase or had a blast crisis. The 2-year OS and progression-free survival rates for the CML-CP cohort were both 100%, while the estimated 2-year event-free survival rate was 68% (95% CI, 42.1%-84.2%). None of the patients in this group had treatment-related deaths or IM discontinuation due to drug toxicities, and only 1 patient had a grade III-IV nonhematologic adverse event. Overall, anemia was the most common adverse effect and 42.9% of patients had a decrease in bone mineral density.IM was effective and the adverse effects were well-tolerated throughout the follow-up period in Chinese CML patients under 18 years of age.

Lnc-SOX6-1 upregulation correlates with poor risk stratification and worse treatment outcomes, and promotes cell proliferation while inhibits apoptosis in pediatric acute myeloid leukemia.

INTRODUCTION: To investigate the correlation of long noncoding RNA-SOX6-1 (lnc-SOX6-1) with clinicopathological features and treatment outcomes in pediatric acute myeloid leukemia (AML) patients, and further explore its function in AML cell proliferation and apoptosis. METHODS: A total of 146 de novo pediatric AML patients and 73 nonhematologic malignancy patients/donors were recruited. Bone marrow samples were obtained, followed by measurement of lnc-SOX6-1 expression by qPCR. Besides, lnc-SOX6-1 expression in various AML cells and control cells was detected. Blank overexpression (NC (+)), lnc-SOX6-1 overexpression (Lnc RNA (+)), blank shRNA (NC (-)), and lnc-SOX6-1 shRNA plasmids (Lnc RNA (-)) were transferred into KG-1 cells and THP-1 cells. Cell proliferation rate and cell apoptosis rate were detected by CCK-8 assay and AV/PI assay, respectively. RESULTS: Lnc-SOX6-1 expression was upregulated in pediatric AML patients compared to controls, and its high expression correlated with the presence of monosomal karyotype, severer risk stratification, lower possibility of complete response achievement, shorter event-free survival, and poor overall survival. Furthermore, lnc-SOX6-1 expression was elevated in various AML cells compared to normal cells. In KG-1 cells and THP-1 cells, cell proliferation rate was elevated in Lnc RNA (+) group but reduced in Lnc RNA (-) group at 48 and 72 hours, and cell apoptosis rate was decreased in Lnc RNA (+) group but increased in Lnc RNA (-) group at 72 hours compared to the corresponding control groups. CONCLUSION: Lnc-SOX6-1 is highly expressed and correlates with worse risk stratification and poor treatment outcomes, and promotes cell proliferation while represses apoptosis in pediatric AML.

High expression of PRPS1 induces an anti-apoptotic effect in B-ALL cell lines and predicts an adverse prognosis in Chinese children with B-ALL.

Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is closely associated with a number of diseases; however, its influence in B-cell acute lymphoblastic leukemia (B-ALL) and the potential molecular mechanisms involved remain unclear. The present study aimed to evaluate the expression of PRPS1 in Chinese children with B-ALL and to investigate the mechanism of action of PRPS1 in this disease. A Cell Counting Kit-8 (CCK-8) assay was performed to examine the proliferation of B-ALL Sup-B15 and Raji cells, and flow cytometric analysis was conducted to determine the cell cycle distribution and rate of apoptosis. The mRNA and protein expression levels of PRPS1, MYC proto-oncogene, bHLH transcription factor, cyclin E1, B-cell lymphoma-2 (Bcl-2), cyclin dependent kinase 2 and caspase-3 were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Elevated PRPS1 expression was associated with a high-risk stratification and poor prognosis in patients with B-ALL. Furthermore, overexpression of PRPS1 accelerated the growth of and inhibited apoptosis in Sup-B15 and Raji cells as well as increasing the expression of Bcl-2 to induce an anti-apoptotic effect in B-ALL cell lines. The results of the present study indicate that PRPS1 regulates multiple processes in B-ALL and may be an attractive therapeutic target.

Clinical Significance of Antinuclear and Antiextractable Nuclear Antigen Antibody in Childhood Immune Thrombocytopenia.

This study aims to determine the clinical significance of positive antinuclear/antiextractable nuclear antigen (ANA/A-ENA) antibody on manifestation and therapeutic response of childhood immune thrombocytopenia (ITP). Overall, 1,330 patients aged between 1 and 15.6 years diagnosed with primary ITP were retrospectively analyzed, excluding those with secondary ITP. Bleeding manifestations were recorded. All patients underwent autoantibody testing and follow-up for 32 months on average (range: 23-54 months). Steroid response was also assessed. Response rates were compared between ANA/A-ENA-positive and ANA/A-ENA-negative patients. Of all the patients enrolled, 84 tested positive only for ANA, 102 tested positive for A-ENA, 54 tested positive for both ANA and A-ENA, and 1,090 tested negative for both. Patients who were ANA/A-ENA positive were more likely to be female and older than 10 years. Patients who were A-ENA positive were more likely to have either persistent or chronic disease and suffer from life-threatening bleeding as well as poor short-term therapeutic response. We conclude that autoantibody testing is important to determine the short-term prognosis of ITP patients. Females, patients older than 10 years of age, and patients with either mixed positivity or A-ENA positivity should be more closely monitored.

[Acute leukemia associated with Down syndrome: clinical analysis of 21 cases].

OBJECTIVE: To summarize the clinical characteristics, laboratory findings and prognosis of patients with Down syndrome-related acute leukemia (DS-AL). METHODS: The clinical data, laboratory findings, chemotherapy and prognosis of 21 children with DS-AL were analyzed. RESULTS: Most of the children had disease onset of leukemia at 1 to 5 years of age (85.7%), and acute myeloid leukemia accounted for 57.1% of these cases; 61.9% of the patients had increased lactate dehydrogenase level by 2 folds or more. Of the 13 cases undergoing echocardiaography, 10 (67.9%) showed abnormal findings, and complex congenital heart disease was common (38.5%). Six of the children received chemotherapy and complete remission was achieved in 4 cases; 2 patients died of infection, and the treatment-related mortality was 33.3%. The 2 patients receiving reduced intensive chemotherapy have so far had event-free survival for 21 and 43 months. CONCLUSION: Acute myeloid leukemia is the most common subtype of DS-AL. Patients with DS-AL are sensitive to chemotherapy and the prognosis was favorable with reduced intensive chemotherapy.

[Clinical analysis of 144 cases of infant leukaemia].

OBJECTIVE: To explore the clinical features, laboratory findings and treatment of infant leukemia. METHODS: A retrospective analysis of the clinical data was performed of the cases with the diagnosis of infant acute leukemia from August 1993 to October 2014 in our hospital. RESULTS: A total of 144 cases of infant leukemia were diagnosed in the defined period, including 83 cases of acute lymphoblastic leukemia, 55 myeloid leukemia, 1 hybrid acute leukaemia and 5 with incompatible cytological and immunophenotyping findings. The patients at the age of 9 to 12 months accounted for the largest proportion (38.2%), and 87.5% of the patients had hepatosplenomegaly; Six patients below 6 months old had skin infiltration. In about 1/3 of the patients, the white blood cells count was no greater than 100 × 109 /L. Ninety-five patients had chromosome examinations, which identified chromosome abnormalities in 67 patients, including 18 positive for t(4;11)or t(9;11)or t(11;19), and younger patients were more likely to have chromosome abnormalities. Thirty-seven patients underwent MLL gene detection and 11 of them had positive results; the positive patients had higher rate of chromosome 11 abnormalities than the negative patients. Most of the patients gave up treatments after diagnosis and only 6 patients older than 6 months completed regular chemotherapeutic treatments and were now in complete remission. CONCLUSION: Infant leukemia is a rare type of leukemia with different clinical features from other types of leukemia. The patients often present with hepatosplenomegaly, high white blood cell counts, MLL gene fusion, and chromosome 11 abnormalities. The prognosis of infant leukemia is not favorable, and the current treatment still relies on chemotherapy.

[Clinical study on cytomegalovirus infection after hematopoietic stem cell transplantation in 26 patients with primary immunodeficiency diseases].

OBJECTIVE: To explore the risk factors, and control measures of cytomegalovirus (CMV) infection after hematopoietic stem cell transplantion (HSCT) in children with primary immunodeficiency diseases(PID). METHODS: We retrospectively analyzed results of 26 patients with PID-Wiskott-Aldrich syndrome (WAS, n=20), severe combined immunodeficiency (SCID, n=1) , X-linked chronic granulomatous disease (XCGD, n=2) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n=3)-who underwent HSCT from June 2007 to December 2012 in our center. Serologic studies (ELISA) and weekly CMV infection surveillance (quantitative PCR, qPCR) were routinely performed before and after HSCT. Ganciclovir or forcarnet was used for pre-emptive and curative therapy. RESULTS: All 26 patients were male with the median age at HSCT of 27 months (range 7-77 months). At a median follow up of 24 months (range 5-66 months), the 5-year overall survival rate was (75.0 ± 9.0) %. CMV infection occurred in 42.3% (11 of 26) of the patients, two of them developed CMV interstitial pneumonia (CMVIP). Univariate analysis revealed that the incidence of pre-transplant CMV infection between with and without CMV activation groups after HSCT was significantly different (62.5% vs 10.0%, P=0.010). Additional variables not associated with CMV infection were stem-cell sources, donor type, HLA disparity and acute GVHD (all P values>0.05). CONCLUSION: CMV infection was a major complication of HSCT. Sensitive monitoring, early diagnosis, timely treatment may improve the survival rate for these PID undergoing HSCT.

[A clinical study of drug-related toxicities of CCLG-ALL 08 protocol for childhood acute lymphoblastic leukemia].

OBJECTIVE: The Chinese Children's Leukemia Group (CCLG)-acute lymphoblastic leukemia (ALL) 08 protocol for childhood ALL was established in 2008. This study aims to evaluate the drug-related toxicities of CCLG-ALL 08 protocol in the treatment of childhood ALL. METHODS: A total of 114 children with newly diagnosed ALL were treated with the CCLG-ALL 08 protocol. The protocol was divided into five phases: remission induction (VDLD), early reinforcement (CAM), consolidation therapy, delayed reinforcement (DIa & DIb) and maintenance treatment. Drug-related toxicities in each phase were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Toxicities were more frequent in phase VDLD than other treatment phases, including hepatotoxicity (87.7%), dental ulcer (20.2%), hyperglycemia (20.2%), prolonged activated partial thromboplastin time (21.1%) and decreased fibrinogen (34.2%), with the incidence rates of severe adverse events at 7%, 0, 1.3%, 0.8% and 2.7% respectively. The incidence of allergic reaction to L-ASP was significantly higher in phase DIa than in phase VDLD (28.0% vs 7.9%; P<0.01), and there were no longer any allergic reactions in 15 patients who received continuing treatment with pegaspargase instead. There was no severe arrhythmia, myocardial ischemia, decreased left ventricular function, osteonecrosis, myopathy, organ failure or treatment-related mortality. CONCLUSIONS: The drug-related toxicities of CCLG-ALL 08 protocol are common in phase VDLD, but they are mild and reversible. There is no treatment-related mortality. The CCLG-ALL 08 protocol for childhood ALL is safe.