[Clinical effect of allogeneic hematopoietic stem cell transplantation in children with hyper-IgM syndrome]. / å¼‚åŸºå› é€ è¡€å¹²ç»†èƒžç§»æ¤æ²»ç–—å„¿ç«¥é«˜IgM综合征的临床分析.

OBJECTIVES: To evaluate the clinical effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with hyper-IgM syndrome (HIGM). METHODS: A retrospective analysis was performed on the medical data of 17 children with HIGM who received allo-HSCT. The Kaplan Meier method was used for the survival analysis of the children with HIGM after allo-HSCT. RESULTS: After allo-HSCT, 16 children were diagnosed with sepsis; 14 tested positive for virus within 100 days after allo-HSCT, among whom 11 were positive for Epstein-Barr virus, 7 were positive for cytomegalovirus, and 2 were positive for JC virus; 9 children were found to have invasive fungal disease. There were 6 children with acute graft-versus-host disease and 3 children with chronic graft-versus-host disease. The median follow-up time was about 2 years, and 3 children died in the early stage after allo-HSCT. The children had an overall survival (OS) rate of 82.35%, an event-free survival (EFS) rate of 70.59%, and a disease-free survival (DFS) rate of 76.47%. The univariate analysis showed that the children receiving HLA-matched allo-HSCT had a significantly higher EFS rate than those receiving HLA-mismatched allo-HSCT (P=0.019) and that the children receiving HLA-matched unrelated allo-HSCT had significantly higher OS, EFS, and DFS rates than those receiving HLA-mismatched unrelated allo-HSCT (P<0.05). Compared with the children with fungal infection after allo-HSCT, the children without fungal infection had significantly higher EFS rate (P=0.02) and DFS rate (P=0.04). CONCLUSIONS: Allo-HSCT is an effective treatment method for children with HIGM. HLA-matched allo-HSCT and active prevention and treatment of fungal infection and opportunistic infection may help to improve the prognosis of such children.

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.

[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.

[Several Common Respiratory Viral Pathogens in Hematopoietic Stem Cell Transplantion Patients with Primary Immunodeficiency Disease].

OBJECTIVE: To investigate the prevalence of respiratory viral infections in patients with primary immunodeficiency disease (PID) during hematopoietic stem cell transplantation. METHODS: 108 specimens of nasopharyngeal aspirate were collected from 22 PID patients before and after hematopoietic stem cell transplantation from July 2016 to July 2018 in the Department of Hematology. The TR-PCR was used to detect for respiratory viruses including respiratory syncytial virus(RSV)，human metapneumoviros(hMPV)，coronavirus(CoV) and parainfluenza 1-3 (PIV1-3). And the clinical characteristics and co-infection were analyzed. RESULTS: Among the total 108 specimens, viral pathogens were identified in 41 (37.96%) specimens. Among which the pathogens of highest detection rate was RSV (25.9%). Different types of PID showed different virus infection rates, among which the highest infection rate was severe combined immunodeficiency disease (SCID) patients, with the virus detection rate was 57.9%. The incidence of co-infection with two or more than two viruses was 19.5%. CONCLUSION: Patients with PID who undergo hematopoietic stem cell transplantation are more susceptible to respiratory viruses. RSV is an important respiratory tract virus pathogen after hematopoietic stem cell transplantation.

[Expression of ß-integrin family members in children with T-cell acute lymphoblastic leukemia].

OBJECTIVE: To study the expression of ß-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance. METHODS: Quantitative real-time PCR analyses were performed to assess the expression levels of ß-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide. The cell viability and apoptosis rate were determined by CCK8 assay and flow cytometry respectively. RESULTS: The mRNA levels of integrins ß2, ß3, and ß5 were significantly lower in children with T-ALL than in controls (P<0.05). In T-ALL patients, high integrin ß3 expression was associated with lower white blood cell counts (<100×109/L), minimal residual disease (MRD) positivity, and day 33 bone marrow negative remission (P<0.05). In T-ALL patients, higher integrin ß5 expression was associated with relapse of T-ALL (P<0.05). Based on survival curve analysis, higher integrin ß3 expression was related to lower event-free survival and overall survival rates. RGD peptide treatment inhibited the proliferation of Jurkat cells and increased their apoptosis rate (P<0.05). CONCLUSIONS: ß-Integrin may play a role in the occurrence and development of T-ALL by affecting cell proliferation and apoptosis. The expression of integrin ß5 is closely related to the risk of relapse of T-ALL. The expression of integrin ß3 is closely related the treatment response and prognosis of T-ALL.

[PRPS1 Expression in Children with Acute Leukemia and Its Clinical Significance].

OBJECTIVE: To investigate the correlation between the expression level of PRPS1 and the clinical characteristics in children with acute leukemia(AL). METHODS: Real-time quantitative RT-PCR and Western blot were used to detect the level of PRPS1 mRNA and protein expression in bone marrow samples from 176 patients diagnosed as AL (126 cases were newly diagnosed and 50 cases in complete remission), and its relevance with clinical indicators was statistically analyzed. The bone marrow samples from 21 children with non-malignant hematological disease were used as controls. RESULTS: (1)In B-ALL group, the level of PRPS1 mRNA in newly diagnosed patients were significantly higher than that in control and than that in complete remission patients (both P<0.0001). In T-ALL and AML group, differences was only observed between newly diagnosed patients and complete remission patients(both P<0.0001); (2)In B-ALL group, the expression level of PRPS1 increase with along risk enhancement (P<0.01), while no significant difference was observed in T-ALL (P>0.05). In AML patients, expression difference was shown between low risk group and high risk group(P<0.05); (3)High PRPS1 mRNA expression level were associated with high WBC counts and MRD positive in B-ALL patients (P=0.020, P=0.026, respectively); (4)Expression of NT5C2, an essential gene for relapse and drug resistance, was found to be positively correlated with PRPS1 expression in AL samples(P<0.05). CONCLUSION: High expression of PRPS1 is relevant factor of unfavourable prognosis in B-ALL children, which suggest PRPS1 may be a new indicator for prognosis of pediatric B-ALL and an index to guide individualized chemotherapy.

[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.

[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.

[Successful treatment of a patient with Wiskott-Aldrich syndrome using hematopoietic stem cell transplantation--case report and literature review].

OBJECTIVE: Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency diseases. The patients with classical WAS have poor prognosis. The hematopoietic stem cell transplantation is the most effective method to cure WAS at present. In this report, a patient with WAS was cured with HLA identical sibling bone marrow transplantation (BMT). METHODS: Wiskott-Aldrich syndrome protein (WASP) was detected using flow cytometry and WASP were analyzed for the diagnosis. The bone marrow was collected from the elder sister who was the HLA identical sibling donor. A total of 4.38x10(8)/kg mononuclear cell (MNC) and 3.78x10(6)/kg CD34+ cells were collected and transfused into the patient after the conditioning regimen with busulfan/cyclophosphamide. Cyclosporine only was used for graft-versus-host disease prophylaxis. WASP and short tandem repeats (STR) were detected as the evidence of engraftment. RESULTS: The diagnosis was WAS: WASP (-IVS9+2T>C, WASP-negative). The patient received busulfan/cyclophosphamide 9 days before the transplantation. WBC decreased to 0.1x10(9)/L in d+4; The absolute number of neutrophils (ANC) was 0.8x10(9)/L in d+13, and exceeded 1.0x10(9)/L later on. From d(-9)-d+14 the patient was dependent on platelet transfusion. From d+15 the patient's PLT>50x10(9)/L and returned to normal after d+30. In d+9-d+10 mild GVHD (I degree) occurred but subsided after the steroid treatment. From d+50, WASP was detected positive and STR showed full donor DNA chimera. Follow-up for 510 d post-transplant, the patient suffered only from mild cold twice, no eczema, no bleeding occurred. The PLT is normal and no chronic GVHD occurred. The levels of IgG, IgM and IgA of the patient were approximately normal. CONCLUSION: The HLA-identical sibling's BMT seems to be the periorit treatment of choice for the WAS patient.