Assessment of safety about therapeutic cardiac catheterization in congenital heart disease children with recent upper respiratory tract infection / 上海交通大学学报（医学版）

Objective·To explore the safety of elective therapeutic cardiac catheterization in congenital heart disease (CHD) children with recent upper respiratory tract infection (URI) (within two weeks),so as to provide guidance for clinical anesthesia management.Methods·A total of 140 CHD children of American Society of Anesthesiologist (ASA) Ⅱ～Ⅲ undergoing tracheal intubation general anesthesia for elective therapeutic cardiac catheterization,aged 3 months to 15 years,were divided into URI group and non-URI group according to history of recent URI.The incidence of perioperative respiratory adverse events (PRAEs) [i.e.laryngospasm,bronchospasm,breath holding ≥ 15 s,pulse blood oxygen saturation (SpO2)＜95％(≥ 10 s),cough,and glossoptosis] and postoperative dysphoria,fever,copious sputum,and vomiting within 24 h after operation were observed and compared.Results·Compared with non-URI group,recent URI increased significantly the overall incidence of PRAEs (any complications of PRAEs) (P=0.001),particularly the incidence of SPO2＜95％ (P=0.014) and cough (P=0.000).Compared with children aged from 4-15 in URIgroup,the overall incidence of PRAEs (P=0.003),SPO2＜95％ (P=0.018),and cough (P=0.027) of children younger than 3 years increased significantly.Besides,compared with non-URI group,recent URI increased significantly the incidence of postoperative copious sputum (P=0.002).Conclusion·Recent URI increases significantly the incidence of perioperative complications in CHD children undergoing elective therapeutic cardiac catheterization.These complications are short and easily managed,and no serious adverse events occurred in CHD children.

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.

Clinical analysis of recombinant humanized thrombopoietin for treating 25 children with severe immune thrombocytopenia / 中国实验血液学杂志

This study was aimed to evaluate the efficacy and safety of recombinant humanized thrombopoietin (rhTPO) for treating children with severe immune thrombocytopenia (ITP). A total of 25 patients with severe ITP who accepted rhTPO treatment for 14 days between December, 2009 and November, 2012 in Beijing Children's Hospital was retrospectively analyzed. The results showed that the median platelet counts of all 25 patients increased from the lowest level 4.0×10(9)/L (0×10(9)/L-10×10(9)/L) to the highest level 71×10(9)/L (14×10(9)/L-439×10(9)/L) on median 11 days (range from 3 days to 15 days). After rhTPO discontinuation, the platelet counts of patients gradually decreased. Complete response rate was 44% (11/25), response rate was 32% (8/25), non-response rate was 24% (6/25) and total response rate was 76% (19/25). The platelet count in the patients who showed complete response to rhTPO therapy reached the highest 112×10(9)/L (43×10(9)/L-439×10(9)/L) on median 12 days(range from 7 days to 15 days). The patients showed response to rhTPO treatment on median 4 days (range from 1 days to 11 days). The platelet count decreased gradually after the discontinuation of rhTPO administration but still significantly higher on 28 days than the level before the treatment (P < 0.05). 12 patients who did not respond to γ-globulin before rhTPO treatment showed response to γ-globulin after the discontinuation of rhTPO therapy. 2 patients showed mild clinical adverse reaction. It is concluded that rhTPO is an effective and safe treatment method for children with severe ITP. It will help the patient smoothly through the dangerous period of severe bleeding, but the platelet count decreases gradually after rhTPO discontinuation. Maintenance treatment is needed to consolidate the curative efficacy.

Evaluation of the efficacy of two successive protocols on pediatric acute lymphoblastic leukemia with E2A-PBX1 fusion gene / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of BCH-03 and CCLG-08 protocols in treating E2A-PBX1 pediatric acute lymphoblastic leukemia (ALL).</p><p><b>METHOD</b>From January 2003 to January 2011, 59 ALL patients identified as E2A-PBX1 were analyzed in a retrospective study. There were 37 and 22 patients treated with Protocol BCH-03 and CCLG-08, respectively. The clinical characteristics at diagnosis, response to early treatment, the time of relapse, relapse-free survival (RFS) and event-free survival (EFS) in the two groups were analyzed.</p><p><b>RESULT</b>There were no significant differences in gender, age, initial white blood cell count, the central nervous system involvement, immunophenotype, prednisone response, the rate of complete remission, and the time of relapse between the two groups (P > 0.05). The only difference in induction therapy of the two protocols existed in the glucocorticoids used, that is, BCH-03 used 60 mg/m(2) prednisolone and CCLG-08 used 6 mg/m(2) dexamethasone. The doses of vincristine, daunorubicin and L-asparaginase were the same in the two groups. At the end of induction therapy, the MRD negativity rate in BCH-03 group was significantly higher than that in CCLG-08 group (84.2% vs. 47.1%, P = 0.018). The incidences of severe infection of the two groups during induction of remission were similar (P = 0.135). The EFS of BCH-03 group was significantly superior to that of CCLG-08 group (94.5% vs. 71.5%, P = 0.010), and the RFS of BCH-03 group tended to be better than that of CCLG-08 group (94.5% vs. 78.6%, P = 0.059).</p><p><b>CONCLUSION</b>Compared to Protocol CCLG-08, Protocol BCH-03 was more effective for pediatric E2A-PBX1 ALL, and 60 mg/m(2) prednisolone was more suitable for the induction therapy of this subtype of pediatric ALL.</p>

Clinical research on clearance of leukemic cell during induction of remission therapy in children with precursor B cell acute lymphoblastic leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical value of clearance of leukemic cell during induction of remission therapy in children with precursor B cell acute lymphoblastic leukemia (BCP-ALL), and to assess the applicative value of different indexes.</p><p><b>METHOD</b>From April 2005 to April 2008, 206 children with de novo BCP-ALL were admitted. We firstly analyzed the effect of clearance of leukemic cells during induction of remission therapy on relapse-free survival (RFS). Four indexes were used to assess the clearance of leukemic cells including prednisone response on day 8 (d8-PR), percentage of lymphoblast in bone marrow on day 22 (d22-BM) and day 33 (d33-BM), and bone marrow (BM) minimal residual disease (MRD) detection on day 33 (d33-MRD). Then the sensitivity, specificity, positive predictive value and negative predictive value of the four indexes to assess their ability to predict relapse were analyzed. Finally, the consistency between two of the four indexes to explore the relationships among them were analyzed.</p><p><b>RESULT</b>There were significant differences between RFS of the sub-groups divided according to d8-PR, d22-BM, d33-BM, d33-MRD (P < 0.01); Cox proportional hazard model analysis showed that d33-MRD ≥ 10(-3) and positive BCR/ABL fusion gene were the independent prognostic factors. Sensitivity of d33-MRD was higher than that of morphology detection (d22-BM, d33-BM and d8-PR) in prediction of relapse, and positive predictive value of morphology detection was higher than that of d33-MRD. Sensitivity could be greatly increased by combination with clinical and biological characteristics. Consistency could not be found between d8-PR and d22-BM, d33-BM, d33-MRD, as well as between d22-BM, d33-BM, and d33-MRD. However, all cases of d22-BM, d33-BM M2/M3 were d33-MRD ≥ 10(-3), while the same phenomenon could not be found for patients with poor d8-PR.</p><p><b>CONCLUSION</b>Clearance of leukemic cell during induction of remission therapy in children with BCP-ALL had important clinical value. Sensitivity of MRD detection after induction of remission therapy was higher than that of morphological analysis to predict relapse. Morphological analysis could only identify a few patients with very high risk of relapse and the sensitivity could be increased by combination with clinical biological characteristics. The simple prednisone response may contain some prognostic information that could not be covered by analysis of BM cells. It may be the best way to assess the clearance of leukemic cells to combine the prednisone response with MRD detection after induction of remission therapy.</p>

Gene rearrangement pattern of immunoglobulin and T-cell receptor (Ig/TR) and its clinical characteristics in children with SET-NUP214 fusion gene-positive leukemia/lymphoma / 中国实验血液学杂志

The purpose of this study was to analyze the gene rearrangement pattern of immunoglobulin and T-cell receptor (Ig/TR) and its clinical characteristics in three children with SET-NUP214 fusion gene positive leukemia/lymphoma. The transcript of SET-NUP214 fusion gene was detected by RT-nested PCR. The pattern of Ig/TR gene rearrangement was analyzed by using the BIOMED-2 multiplex PCR assays. Allelic-specific primers were designed for further monitoring the minimal residual disease (MRD). The results indicated that the fusion site located between exon 7 of SET and exon 18 of NUP214 at mRNA level in the three patients. The diagnoses were made as the mixed phenotype of acute leukemia (MPAL) for patients 1, acute T-lymphoblastic leukemia (T-ALL) for patients 2, and stage IV T-lymphoblastic lymphoma (T-LBL) for patients 3, respectively. Patient 1 responded to chemotherapy very poorly and relapsed at month 6 after hematopoietic stem cell transplantation. Patient 2 had high MRD (> 10(-2)) at the end of inducing remission therapy (day 33) which implied poor outcome, and died of toxic epidermal necrolysis and sequent serious infection. Patient 3 achieved hematological complete remission (CR) and MRD negative at day 15 and day 33 respectively. The duration of CR lasted for 30 months. Clonal TR gene rearrangements were detected in all the three patients. The rearrangements of TRD, TRG and TRB were found in patient 1 and 3. The rearrangements of TRD, TRB, IgH and IgK Kde were detected in patient 2. All the 6 TRB rearrangements detected were incomplete rearrangements, whereas 85.7% and 14.3% of the TRD, and TRG rearrangements were complete and incomplete, respectively. It is concluded that the transformation of SET-NUP214(+) leukemia/lymphoma cells may occur after the rearrangements of TRD and TRG and shortly after TRB rearrangement. The leukemia/lymphoma cells of patient 1 and 2 are more immature which may be related with poor outcome or response to chemotherapy.

Effect of RBC lysing solution on CD34(+) cell counting / 中国实验血液学杂志

To investigate whether the RBC lysing solution can affect the results of relative enumeration of CD34(+) cells, 37 mobile peripheral blood apheresis products were stained using CD34-PE and CD45-FITC monoclone antibodies and RBCs were then lysed by two lysing solution commercially available (one named FACS Lysing Solution, FACS; another IOTest 3 Lysing Solution, IOTest) and one lysing solution self-prepared. After being processed by lyse-and-then-washed method, samples were detected by FACSC anto flow cytometer. The percentages of CD34(+) cells were determined based on ISHAGE gating strategy, forward and side scatter (FSC and SSC) characteristics, percentage of CD45(+) cells were recorded simultaneously. The results showed that by lyse-and-then-wash method, the percentages of CD34(+) cells in FACS-treated samples were significantly lower compared with that in IOTest-treated samples (0.50 +/- 0.42 vs 0.92 +/- 0.59, p = 0.004), but no statistical difference was observed between IOTest-treated and ourselves-prepared-treated samples. The intensities of FSC and SSC in cells of IOTest-treated sample were significantly higher compared with that in cells of FACS-treated sample (p < 0.01). The proportion of CD45(+) cells in IOTest-treated samples was lower than that in FACS-treated samples. The WBC count of samples was not correlated to the amount of CD34(+) cells (r(s) = 0.192, p = 0.357). It is concluded that the red cell lysing solution shows unexpected effect on detecting and counting CD34(+) cells, prudence should be taken to select such reagents at FCM performance.

Severe hypercalcemia complicated in acute lymphoblastic leukemia (ALL) with E2A-HLF fusion gene: report of two cases and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To improve the understanding of severe hypercalcemia complicated in acute lymphoblastic leukemia (ALL) with E2A-HLF fusion gene, and to explore the mechanism of pathogenesis and the relationship between the special gene translocation and severe hypercalcemia.</p><p><b>METHODS</b>Two patients with severe hypercalcemia complicated in ALL were reported.</p><p><b>RESULTS</b>Two patients with E2A-HLF fusion gene, which is generated by t(17;19) (q22, p13) translocation, suffered relapse of leukemia three months after chemotherapy, and developed severe hypercalcemia. After further chemotherapy, the hypercalcemia symptoms were corrected or alleviated.</p><p><b>CONCLUSION</b>Severe hypercalcemia is one of rare complications of ALL. In B cell lymphoblastic leukemia with E2A-HLF fusion gene, the fusion gene showed be closely monitored for evaluating the disease situation.</p>