Acute mveloid leukemia(AML) is a heterogeneous group of leukemias that arise from clonal transformation of hematopoietic precursors.This review summarizes classification of pediatric AML,more precise risk-group stratification,ongoing phase Ⅲ studies and minimal residual diseasse monitoring.In addition,we discuss the opportunities for innovative chemotherapy drugs in refractory AML and relapsed AML,such as gemtuzumab ozogamicin,liposomal daunorubicin,clofarabine,cladribine and lmatinib.Finally,the roles of allogeneic hematopoietic stem cell transplantation in pediatric AML are also discussed.

Objective To analysis the clinical characteristics and the long-term effect of children with acute lymphoblastic leukemia (ALL).Methods From 2005 to 2010,80 newly diagnosed ALL children were enrolled and treated with protocol based on ALL-BFM2002.The five-years overall survival (OS)and event-free survival(EFS) were analyzed by the method of Kaplan-Meier.Results For the 80 patients,male to female ratio is 1.22∶1.The median age was 4.3 years.33 were in standard risk(41.2％),37 were in medium risk(46.3％),and 10 were in high risk(12.5％).22 had white blood cell count ≥20 x 109/L(27.5％).three patients with BCR-ABL translocation(3.8％),one patient with MLL gene rearrangement(1.3％),17 patients with TEL-AML translocation (21.3％).During induction therapy,79 patients (98.8 ％) achieved complete remission(CR).The five-years OS and EFS were (85.9 ± 4.0) ％ and (79.2 ± 4.7) ％ respectively.The five-years EFS:SR group (86.6 ± 6.4) ％,IR group (81.1 ± 6.4) ％,HR group (48.0 ± 16.4) ％.The difference among risk groups was statistically significant(x2 =7.03,P ＜0.05).12 patients relapsed(15.0％),the median time from diagnosis to relapse was 23.5 months.11 patients died (13.8 ％).Conclusion According to stratification by risk factors and risk-adapted therapy,the quality of ALL children's life had improved.

Objective To investigate the effects of tongue cancer resistance-associated protein 1 (TCRP1) in proliferation of chronic myeloid leukemia cells (CML),and explore the new thoughts of pathogenesis of CML.Methods The expression of TCRP1 was detected in the peripheral blood mononuclear cells (PBMC) of CML with real-time quantitative polymerase chain reaction (PCR) and Western blot.After the expression of TCRP1 was interfered in K562 cells,the proliferation of cells was detected by 3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and soft agar colony forming assay,and the expression of protein kinase B (AKT) and its phosphorylation were tested by Western blot.Results In PBMC of CML patients,the mRNA and protein levels of TCRP1 were significantly higher than those of normal controls.The results of MTS assay and soft agar colony forming assay showed that the proliferation of K562 cells was significantly decreased after the expression of TCRP1 was interfered.After knockdown of TCRP1 in K562 cells,the phosphorylation of AKT was significantly decreased while the expression of total AKT did not change.Conclusions The expression of TCRP1 was increased in CML cells.High expression of TCRP1 might contribute to proliferation of K562 cells via the phosphorylation of AKT.

Objective To investigate the changes of CD4 +CD25highFoxp3 +regulatory T (Treg) cells and their significance in immune escape of childhood B-cell acute lymphocytic leukemia ( B-ALL ) . Methods Forty-two children with B-ALL and twenty-eight age-matched healthy children were enrolled in this study.Flow cytometry analysis was performed to evaluate the proportion of CD 4 +CD25high Foxp3 +Treg cells as well as CD4 +CD25high ICOS+Foxp3 +and CD4 +CD25high ICOS-Foxp3 +subsets in peripheral blood samples.The expression of associated molecules including IL-10, TGF-β, IL-35, TGF-βRII, ICOS and CD28 at protein level were also measured by flow cytometry analysis .The transcription level of Smad3/4, TIEG1 and Itch by CD4 +T cells were determined by quantitative real-time PCR.The concentration of TGF-βin plasma was detected by enzyme-linked immunosorbent assay.Results (1)The proportion of CD4 +CD25highFoxp3 +Treg cells in children with B-ALL were significantly higher than those of health subjects (P<0.05).The proportion of both ICOS +Foxp3 +and ICOS -Foxp3 +subsets were increased in comparison with those of control group (P<0.05), while the ratio of ICOS +Foxp3 +to ICOS-Foxp3 +was decreased (0.73 ±0.21 vs 1.87 ±0.59, P<0.05).(2) The expression of Foxp3, TGF-β, IL-10 and IL-35 by ICOS+Foxp3 +Treg cells and the expression of membrane bound TGF-βby ICOS -Foxp3 +Treg cells were significantly increased in children with B-ALL (P<0.05).However, the expression of Foxp3 by ICOS -Foxp3 +Treg cells showed no significant difference between the two groups (P>0.05).(3)The concentra-tion of TGF-βin plasma from children with B-ALL were higher than those from control group [ ( 25 .83 ± 12.65) ng/ml vs (8.59 ±5.73) ng/ml, P<0.05].The expression of TGF-βRII and its associated mole-cules (Smad3/4, TIEG1 and Itch) by CD4 +T cells were significantly up-regulated.Moreover, an increased expression of ICOS and CD28 by CD4 +CD25highFoxp3 +Treg cells were also observed in children with B-ALL (P<0.05).Conclusion The hyper-activity of TGF-β, ICOS and CD28 signaling might be closely associ-ated with the increased proportion of CD4 +CD25high Foxp3 +Treg cells and the imbalance of its subsets in children with B-ALL.

Engraftment syndrome (ES) is a clinical syndrome that occurs after hematopoietic stem cell transplantation and during the recovery process of neutrophils.The main clinical manifestations include non-infectious fever, rash, capillary leakage and non-cardiogenic pulmonary edema, which may be similar with many early complications after transplantation.Therefore, it is sometimes difficult to be diagnosed and differentiated among different kinds of complications.Typical ES is self-limiting and has good response to steroids.However, patients with ES may result in encephalopathy and multi-organ failure if it is untreated without notice.In this review, we discussed the pathophysiological mechanisms, clinical manifestations, diagnosis and differential diagnosis, risk factors, treatment and prognosis of ES, aiming to provide guidance and reference for clinicians.

OBJECTIVE:To establish a method for the concentration determination of voriconazole in human plasma.METHODS:Plasma samples were precipitated with acetonitrile.Using ketoconazole as internal standard,HPLC method was adopted.The determination was performed on Dionex U-3000 Dimonsil C18 column with mobile phase consisted of triethylamine-glacial acetic acid-water mixed solution (1 ∶ 1∶98,V/V/V,pH was about 4.0)-acetonitrile (40∶60,V/V) at the flow rate of 1.0 mL/min.The detection wavelength was set at 255 nm.The column temperature was 40 ℃,and sample size was 20 μL.RESULTS:The linear range of voriconazole was 0.2-20.0 μg/mL.The limits of quantification was 0.2 μg/mL,and the minimum detection limit was 0.03 μg/mL.RSDs of inter-day and intra-day were lower than 10％.The method recoveries were 92.06％-106.26％ (RSD＜5％,n=5),and extraction recoveries were 75.62 ％-90.59 ％ (RSD ＜ 5 ％,n=5).The plasma concentration of voriconazole in 10 children ranged 0.22-4.90 μg/mL (n =10).CONCLUSIONS:The method is simple,rapid,specific and can be used for drug monitoring of voriconazole.

Objective:To explore the expressions of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) and clinicopathological characteristics in post-transplant lymphoproliferative disorder (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, with the aim of clarifying whether checkpoint inhibition of PD-1/PD-L1 inhibitors may serve as a therapy option.Methods:The clinical data of 13 cases of PTLD after allo-HSCT pathologically confirmed in Shenzhen Children′s Hospital from January 1, 2012 to December 30, 2019 were retrospectively analyzed.The detection was performed by immunohistochemical staining by MaxVision? method, Epstein-Barr virus(EBV) in situ hybridization and lymphoma gene rearrangement.The relationship between the expression of PD-1 and PD-L1 and the clinicopathological characteristics of PTLD were analyzed.Results:The expression of PD-1 was not correlated with gender, age, primary diseases, histopathological types, transplantation mode and the expression of EBV in situ hybridization (all P>0.05). The expression of PD-L1 was correlated with histopathological types ( P<0.05). Furthermore, the expression rate of PD-L1 on severe β-thalassemia was significantly higher than that of severe aplastic anemia [90.0%(9/10 cases) vs. 66.7%(2/3 cases)] and monomorphic PTLD was higher than that of polymorphic PTLD [100.0%(2/2 cases) vs. 83.3%(5/6 cases)]. Moreover, the positive PTLD in EBV was higher than the negative PTLD in EBV [90.9%(10/11 cases) vs. 50.0%(1/2 cases)]. The positive rates of PD-1 and PD-L1 in 13 cases with PTLD were 46.2%(6/13 cases) and 61.5%(8/13 cases) in tumor cells, 92.3% (12/13 cases) and 76.9% (10/13 cases) in microenvironmental cells, and 84.6%(11/13 cases) in EBV, respectively. Conclusions:PD-L1 has a higher positive rate in tumor cells with monomorphic PTLD; and routine staining for PD-1 and PD-L1 can be performed in all types of PTLD when standard immunotherapy and chemotherapy are ineffective.

Objective:To study the effectiveness of noninvasive embryo chromosome screening (NICS) based on blastocyst culture medium and cystic fluid in preimplantation genetic detection (PGT) of embryos in different age groups.Methods:A retrospective analysis of 62 couples who underwent PGT assisted pregnancy in Shenzhen Hospital of Peking University from January 2019 to June 2021. A total of 310 blastocysts were biopsied. At the same time, D3-6 blastocyst culture medium and blastocyst cavity fluid were collected for NICS. According to the age of the patients, they were divided into three groups: <35 years old group, 35≤age<40 years old group and ≥40 years old group. The results of NICS were compared with those of embryonic trophoblast (TE) biopsy in each group, and the consistency, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Then the consistency, sensitivity, specificity, positive predictive value and negative predictive value of NICS and TE among the three age groups were statistically analyzed.Results:There was no statistically significant difference in the consistency rate of NICS and TE among the three age groups ( P>0.05), but there was an upward trend in the elderly group (35≤age<40 years and ≥40 years). There was no statistically significant difference in specificity, sensitivity and PPV among the three age groups ( P>0.05). There was significant difference in NPV between the ≥40 years group and the other two groups ( P<0.05). Conclusions:There was no statistical difference in the effectiveness of NICS among different age groups, However, there was an increasing trend in people ≥35 years of age.

OBJECTIVETo observe the status of iron deposition in patient with β thalassemia major, and to formulate appropriate treatment strategies.

METHODThe data of status of transfusion and chelation in 135 patients aged from 6 years and 4 months to 17 years and 11 months with β thalassemia major were collected and analyzed. Serum ferritin levels were determined and cardiac and hepatic iron deposition was determined using MRI T2(*) technology.

RESULTOf the 135 cases studied, 66 were male, and 69 were female, their average age was 12.1 years. Serum ferritin (SF) was determined for 111 cases, it varied from 1 086.8 µg/L to 15 011.5 µg/L. Among them, 16 cases had SF level <2 000 µg/L (14.5%) , in 41 cases SF were between 2 000 and 4 000 µg/L (36.0%) ;in 54 cases SF >4 000 µg/L (48.7%) . Liver MRI T2(*) results showed that in only 8 cases (5.9%) iron content in the liver was in normal range, 19 cases (14.9%) showed mild liver iron deposition;34 (25.2%) moderate and 74 (54.8%, the youngest one was only 6 years and 4 months of age) had severe iron deposition respectively. Cardiac MRI T2(*) showed that in 89 cases (65.9%) iron content in the heart was in normal range;19 cases (14.1%) had mild cardiac iron deposition and 27 (20.0%) presented severe iron deposition (the youngest one was only 9 years and 3 months of age) . SF level was obviously related to liver and cardiac iron deposition (MRI T2(*)) r and P value were -0.284, 0.003 and -0.374, 0.000 respectively. In 108 cases regular transfusion and chelation were delayed due to financial problem. The late and insufficient dosage administered and irregular chelation caused the higher SF level and the severe iron deposition.

CONCLUSIONThe survival status of β thalassemia major in China is worrisome. Majority of them had not received regular transfusion and chelation. Liver and cardiac iron deposition occur early and had a high incidence.

Adolescent ; Child ; Female ; Ferritins ; blood ; Humans ; Iron ; metabolism ; Iron Chelating Agents ; adverse effects ; therapeutic use ; Iron Overload ; epidemiology ; etiology ; Liver ; metabolism ; Magnetic Resonance Imaging ; Male ; Myocardium ; metabolism ; Radiography ; Retrospective Studies ; Transfusion Reaction ; beta-Thalassemia ; diagnostic imaging ; metabolism ; therapy