ObjectiveTo investigate the association between cuplike nuclei morphology and FLT3-ITD mutation, so as to provide evidence for the minor classification of AML. MethodsThe articles on the association of cuplike nuclei morphology and FLT3-ITD mutation were retrieved by searching international and national databases from 1999 to 2011. The relationship was assessed by meta analysis with Statal 1 software.The OR value and confidence interval(CI)were calculated, and the publication bias was assessed by Begg test and Egger test.ResultsThere was significant difference between cuplike nuclei morphology appearance and FLT3-ITD mutation (OR =2.59,95 ％ CI 1.55-4.33,P =0.00).Results from both Begg' s test and Egger’ s test did not show significant difference indicating that there was no publication bias existed.ConclusionThe uncommon morphologic variant of AML with cuplike nuclei is highly associated with FLT3-ITD mutation, and the presence of cuplike nuclei in AML represents a distinctive morphologic finding that can be used to prioritize the molecular workup of patients with AML.

Objective To analyze the pathogenesis,therapy and outcome of pediatric cases with coagulation disorders (CD).Methods All these 137 patients were diagnosed as CD with the methods of hemoglutination five items and/or disseminated intravascular coagulation indexes.Then activity of specific coagulation factors,morphology of bone marrow,hepatorenal function and some other relative tests were performed to find out the cause of CD or the primary disease.Results Forty-three cases were diagnosed as genetic CD with 29 as hemophilia A,4 as hemophilia B and 10 as Von Willebrand disease;while the other 94 patients as acquired CD with 15 as vitamin K-dependence coagulation factor deficiency,22 as hepatic dysfunction,30 as disseminated intravascular coagulation and 1 as thrombotic thrombocytopenic purpura.Genetic CD was treated with replacement therapy to reduce the complication.There was 1 case in this group died of intracranial hemorrhage.Acquired CD was treated with short-term,specific and necessary replacement therapy on the basis of reasonable treatment of primary diseases.Eleven cases died finally in this cohort with 7 cases as liver failure and the other 4 cases as terminal leukemia or lymphoma.Conclusion Pediatric patients with CD were caused by genetic or acquired diseases.In clinic the reason of CD was mainly acquired.The treatment of genetic CD is the replacement of specific coagulation factor for life-long term.The outcome dependes on the lack of degree.While the therapy for acquired CD aims at the primary disease.The principle of blood transfusion is short-term and the outcome dependes on the therapic effects of primary diseases.

Objective To explore the adverse effect of arsenic trioxide (As2O3) on liver,kidney and heart function during treating children patients with acute promyelocytic leukemia (APL) at therapeutic dose.Methods Sixty-five APL cases received As2O3 by intravenous drip and organic toxicity were selected as our subjects.The indices of liver,heart and kidney were measured.Results Of all subjects,19 cases(29.2％) occurred liver damage,including 15 cases(23.1％) mild and 4 cases(6.2％) moderate toxicity.The levels of alanine aminotransferase of patients before treatment was (19.9 ±9.5) U/L,and (24.3 ± 11.8) U/L,(25.0 ± 14.4) U/L at 1 st and 2nd weeks after treatment,higher than those before the treatment (P ＜ 0.05).However,level of alanine aminotransferase was back to normal at 3th weeks after treatment.Meanwhile the levels of aspartate aminotransferase at 1st,2nd and 3th weeks after treatment were (38.3 ± 16.5),(39.1 ± 15.5),(35.3 ± 20.6) U/L respectively,higher than that before treatment((28.5 ± 8.8) U/L,P ＜ 0.05 or 0.01),and it was back to normal at 4th weeks.(2) The levels of urinary cystatin C were (2.51 ± 1.45) mg/L,(3.05 ± 1.13) mg/L,(2.46 ± 1.21) mg/L at 2nd,3th,4th weeks after treatment,significantly higher than that before treatment ((1.98 ±0.68) mg/L,P ＜0.05 or 0.01).And the levels of urinary β2 microglobulin at 2nd,3th,4th weeks after treatment were significantly higher than that before treatment (P ＜0.05 or 0.01) and back to normal at 5 weeks after treatment.(3) Nine cases at remission stage showed the symptoms of palpitation,precordial discomfort and increased heart rate,and all those symptoms were mild.And the symptoms disappear at the 3th week after the treatment.Creatine kinase at the 2nd weeks after treatment was (90.2 ± 32.5) U/L,higher than that before treatment ((78.5 ± 22.3) U/L).The levels of creatine kinase isoenzyme at 2nd,3th weeks after treatment were (8.3 ± 4.8) U/L,(8.5 ± 5.6) U/L,higher than that before treatment ((6.3 ± 3.5) U/L).The serum creatine kinase mass at 4th weeks((3.9 ±2.0) g/L) was significantly higher than that before treatment ((2.8 ± 1.9) g/L),and then gradually be back to normal.Conclusion The routine dose As2O3 in treatment of APL children show less toxicity in liver,kidney,and heart Those adverse effects are transient,reversible and they occurred at 1-3 week after As2O3 treatment.Serum alanine aminotransferase,aspartate aminotransferase and urinary cystine protease inhibitors,β2 micro ring protein and serum creatine kinase MB mass might be served as sensitive indicators of organ damage.

Objective To study the renal toxicity of arsenic trioxide (As2O3) with therapeutic dose in acute promyelocytic leukemia (APL) in childhood. Methods Renal toxicity of 37 APL was monitored. The examinations of urinary routine, urinary microproteins[αt1-microglobulin (α1-MG), microalbumin (mAlb),β2-microglobulin (β2-MG), transferrin(TRF)] and renal function were performed. Results Five cases with leukocyturia, three cases with hematuria, six cases with proteinuria were observed before therapy. Ketonuria occurred in six cases associated with fever and less diet; overall abnormality disappeared in the first week. No significant changes of blood uric nitrigen(BUN), serum creatinine(Cr) and uric acid (UA) were founded in induction remission. Compared with tests before As2O3 infusion, obvious increase of uric α1-MG occurred in second week with arsenic trioxide, obvious increase of uric β2-MG in third week (P ＜0.01), slow recovery of uric α1-MG and β2-MG in fifth week. No significant changes of uric mAlb and TRF were seen in induction remission. Conclusion The renal toxicity of As2O3 was gentle in general therapeutic dose, renal tubercular damage could be seen. The important monitoring period were the second to fifth week in induction remission.Influence of As2O3 cumulant on renal function was not serious in the near future in childhood. The combined detection of urinary microproteins with dynamic variety could detect early renal damage with As2O3.

Acute promyelocytic leukemia(APL)is identified as the M3 subtype of acute myelocytic leukemia(AML). One of its clinical features is severe coagulation dysfunction.Most patients could develop disseminated intravascular coagulation(DIC)resulting vital viscera hemorrhage, which is one of the significant causes of early death in APL patients.Early diagnosis and inductive therapy, dynamic monitoring patients′ coagulation index and correcting the abnormal coagulation could prevent the occurrence or progress of DIC, and then improving the early-term survival rate of APL patients.At present, APL is mainly treated from the treatment of primary disease, anticoagulant antifibrinolytic therapy, and alternative therapy.

Objective:Patients with acute promyelocytic leukemia(APL)treated with arsenic trioxide(ATO)have significant coagulation disorders both in pretherapy and post-treatment, and severe cases can progress quickly to the disseminated intravascular coagulation(DIC). This article aims to investigate the risk factors of DIC and observe dynamically the effect of ATO on coagulation function in APL children.Methods:We collected basic characteristics, laboratory characteristics and coagulation index at various time points on admission of 28 children who were first diagnosed APL and treated with ATO at department of pediatric hematology in Shengjing Hospital from January 2012 to January 2018. We retrospectively analyzed the correlation between these factors and the occurrence of DIC, and the trend of dynamic changes in coagulation index in different treatment time.Results:Of the 28 patients, 24(85.7%)were diagnosed as DIC. No relation has been found between the occurrence of DIC and the age, gender, blood routine at initial diagnosis, fibrinogen level, lactate dehydrogenase level in APL children( P>0.05). Different indicators of plasma prothrombin time, fibrinogen at different time point showed significantly difference. In the high-risk group, PT was higher significantly before treatment[(17.58±2.99)s] than those of the 3-4 days after therapy[(15.3±1.86)s], 7-10 days after therapy[(13.81±1.18)s], 14-16 days after therapy[(14.13±0.62)s], 22-26 days after therapy[(14.2±1.59)s]( P=0.016). In the group which PLT was greater than or equal to 20×10 9/L, PT was higher significantly before treatment[(15.02±2.83)s]and the 3-4 days after therapy[(14.59±2.19)s] than those of the 7-10 days after therapy[(13.25±2.01)s], 14-16 days after therapy[(13.31±1.51)s], 22-26 days after therapy[(13.47±1.64)s]( P<0.01). Conclusion:No relation has been found between the occurrence of DIC and the age, gender, blood routine at initial diagnosis, fibrinogen level, lactate dehydrogenase level in APL children. The time points of significantly abnormal of coagulation function occurred in the newly diagnosed APL children were before the ATO induction treatment and the 3-4 days after therapy.

Acute lymphoblastic leukemia（ALL）is the most common pediatric cancer and has good outcome.However，the prognosis of relapsed/refractory ALL in children is poor.Intensive reinduction chemotherapy and hematopoietic stem cell transplantation have become alternative treatments. Bortezomib，as the primary generation proteasome inhibitor，has been approved for the treatment of multiple myeloma and mantle cell lymphoma. In recent years，several clinical studies have confirmed promising responses and well tolerated of bortezomib combined with various chemotherapeutic drugs in treating children with relapsed/refractory ALL，to improve the complete remission rate and survival rate. This article reviews the mechanisms of bortezomib in ALL and the clinical study progress and safety of bortezomib combined with chemotherapy in children with relapsed/refractory ALL.