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Objective:To analyze the risk factors for asparaginase-associated pancreatitis (AAP) in children with acute lymphoblastic leukemia (ALL) after treatment with pegaspargase and evaluate the predictive value of pediatric sequential organ failure assessment (SOFA) score, pediatric acute pancreatitis severity (PAPS) score, Ranson′s score and pediatric Ministry of Health, Labour and Welfare of Japan (JPN) score for severe AAP.Methods:Cross-sectional study.The clinical data of 328 children with ALL who received pegaspargase treatment in the Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University from January 2014 to August 2021, as well as their clinical manifestations, laboratory examinations, and imaging examinations were collected.The SOFA score at the time of AAP diagnosis, PAPS score and Ranson′s score at 48 hours after AAP diagnosis, and JPN score at 72 hours after AAP diagnosis were calculated, and their predictive value for severe AAP was evaluated by the receiver operating characteristic (ROC) curve.Results:A total of 6.7%(22/328) of children had AAP, with the median age of 6.62 years.AAP most commonly occurred in the induced remission phase (16/22, 72.7%). Three AAP children were re-exposed to asparaginase, and 2 of them developed a second AAP.Among the 22 AAP children, 16 presented with mild symptoms, and 6 with severe symptoms.The 6 children with severe AAP were all transferred to the Pediatric Intensive Care Unit (PICU). There were no significant differences in gender, white blood cell count at first diagnosis, immunophenotype, risk stratification, and single dose of pegaspargase between the AAP and non-AAP groups.The age at diagnosis of ALL in the AAP group was significantly higher than that in the non-AAP group ( t=2.385, P=0.018). The number of overweight or obese children in the AAP group was also higher than that in the non-AAP group ( χ2=4.507, P=0.034). The areas under the ROC curve of children′s JPN score, SOFA score, Ranson′s score, and PAPS score in predicting severe AAP were 0.919, 0.844, 0.731, and 0.606, respectively.The JPN score ( t=4.174, P=0.001) and the SOFA score ( t=3.181, P=0.005) showed statistically significant differences between mild and severe AAP. Conclusions:AAP is a serious complication in the treatment of ALL with combined pegaspargase and chemotherapy.Older age and overweight or obesity may be the risk factors for AAP.Pediatric JPN and SOFA scores have predictive value for severe AAP.
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Objective:To investigate the risk factors and prognoses of cerebral venous sinus thrombosis (CVST) caused by pegasparaginase (PEG-Asp).Methods:A total of 252 children with acute lymphoblastic leukemia (ALL) were treated with PEG-Asp chemotherapy in our hospital from December 2016 to July 2021, including 8 children with CVST. The clinical manifestations, laboratory and imaging features, treatments and prognoses of these children with CVST caused by PEG-Asp were analyzed retrospectively.Results:(1) CVST occurred during induction chemotherapy in 4 children, during re-induction chemotherapy in 3 children, and during consolidation stage in one child. CVST occurred in two children who received PEG-ASP chemotherapy once, in one child who received PEG-Asp chemotherapy twice, and 5 children who received PEG-Asp chemotherapy more than twice. The median time between CVST occurrence and last treatment of PEG-Asp was 20.5 d. (2) The clinical manifestations included paroxysmal headache ( n=4), nausea or vomiting ( n=3), convulsions ( n=2) and persistent blurred vision ( n=1). (3) CVST appeared at the sigmoid sinus ( n=6), transverse sinus ( n=4) and superior sagittal sinus ( n=4), of which one child was complicated with hemorrhage in left frontal parietal and right parietal cortex, and one with reversible posterior encephalopathy syndrome; 8 children were not complicated with thrombus in other parts. (4) Some of the children were complicated with abnormal blood coagulation. When CVST occurred, fibrinogen level decreased in 3 children, anti-thrombin III level decreased in 2 children, and D-dimer level increased in 3 children. (5) Six children were treated with low molecular weight heparin (LMWH), of which, 4 were treated with rivasaban and one with warfarin sequentially. The total course of anticoagulation was 56 d. (6) The symptoms of 6 children disappeared after anticoagulation; Magnetic resonance venography (MRV) showed disappeared thrombus in 4 children and reduced thrombus range in 2 children. One child with intracranial hemorrhage did not use PEG-Asp anymore; 7 accepted PEG-Asp further during follow-up chemotherapy, of which one had CVST recurrence and the range of thrombus was reduced after anticoagulant therapy. Conclusions:When children with ALL develop unexplained neurological symptoms during PEG-Asp chemotherapy, CVST should be highly vigilant. Enhanced MRI and MRV should be performed for early diagnosis. Some children are complicated with abnormal blood coagulation, and LMWH, warfarin and rivasaban are effective. The prognosis is good and there are no sequelae. Most children accepted PEG-Asp again will not have CVST again.
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Objective To investigate the efficacy and safety of Posaconazole (Posa) in prophylaxis and salvage treatment of invasive fungal infections (IFI) during neutropenia in pediatric patients with leukemia.Methods A total of 18 pediatric patients (55 case-time) with leukemia in neutropenia stage receiving Posa treatment from December 2015 to August 2017 in Zhujiang Hospital of Southern Medical University,were analyzed retrospectively.Taking one induction chematherapy or one consolidation chemotherapy stage receiving Posa treatment was defined as 1 case-time.Results Out of 18 participants,13 cases were patients with acute myeloid leukemia (AML) and 5 cases were patients with acute lymphocytic leukemia (ALL),including 36 males and 19 females.Median age of the participants was 7 years,ranged from 10 months to 14 years.Out of 55 case times,45 of them were of primary prevention and the neutropenia periods ranged from 4 to 46 days,with the median of 15 days,and 93.33％ of them were prevented from fungal infection.However,3 of the 45 cases had sudden fungal infections and the Voriconazole was an effective treatment,and no one died.Six cases in this study experienced secondary prevention,and no patient experienced reinfection.The neutropenia terms of the 6 cases ranged from 10 to 17 days,with the median of 14 days.Four patients who suffered from Voriconazole and/or Carbophenol therapy failure received Posa as a rescue therapy and the response rate was 100％.None of patients had Posa intolerance due to severe adverse reaction and no Posa treatment-related grade Ⅱ toxic effects occurred.Conclusions Posa is an effective and safe therapy for pediatric patients with leukemia and IFI,and available for long-time usage.Serious adverse reaction is rare.
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Objective@#To investigate the efficacy and safety of Posaconazole (Posa) in prophylaxis and salvage treatment of invasive fungal infections (IFI) during neutropenia in pediatric patients with leukemia.@*Methods@#A total of 18 pediatric patients (55 case-time) with leukemia in neutropenia stage receiving Posa treatment from December 2015 to August 2017 in Zhujiang Hospital of Southern Medical University, were analyzed retrospectively.Taking one induction chematherapy or one consolidation chemotherapy stage receiving Posa treatment was defined as 1 case-time.@*Results@#Out of 18 participants, 13 cases were patients with acute myeloid leukemia (AML) and 5 cases were patients with acute lymphocytic leukemia (ALL), including 36 males and 19 females.Median age of the participants was 7 years, ranged from 10 months to 14 years.Out of 55 case times, 45 of them were of primary prevention and the neutropenia periods ranged from 4 to 46 days, with the median of 15 days, and 93.33% of them were prevented from fungal infection.However, 3 of the 45 cases had sudden fungal infections and the Voriconazole was an effective treatment, and no one died.Six cases in this study experienced secondary prevention, and no patient experienced reinfection.The neutropenia terms of the 6 cases ranged from 10 to 17 days, with the median of 14 days.Four patients who suffered from Voriconazole and/or Carbophenol therapy failure received Posa as a rescue therapy and the response rate was 100%.None of patients had Posa intolerance due to severe adverse reaction and no Posa treatment-related grade Ⅱ toxic effects occurred.@*Conclusions@#Posa is an effective and safe therapy for pediatric patients with leukemia and IFI, and available for long-time usage.Serious adverse reaction is rare.
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Objective To investigate the precipitating factors,clinical manifestations,magnetic resonance imaging (MRI) features and prognoses of children with posterior reversible encephalopathy syndrome (PRES) during the treatment of hematological diseases,and to improve the understanding of the diseases.Methods A total of 9 children with PRES,admitted to our hospital from January 2012 to December 2016,were chosen.The clinical data,including precipitating factors,clinical manifestations,MRI features and prognoses,were retrospectively analyzed.Results (1) Precipitating factors:6 patients with acute lymphoblastic leukemia occurred PRES during remission induction therapy (6/9,66.7％) and 3 occurred PRES during oral cyclosporine A after hematopoietic stem cell transplantation or autoimmune diseases (3/9,33.3％).(2) Clinical manifestations:all of them were acute onset,and the main symptoms were seizures (8/9,88.9％) and hypertension (7/9,77.8％);some patients suffered from headache,vomiting,visual disturbances,disturbance of consciousness and poor mental symptoms.(3) Features of head MR imaging:the lesions were mainly located in the parietal-occipital lobe,showing patchy long T1 and long T2 signals,and bilateral imperfect symmetry;FLAIR imaging showed high signal distinctly,and other parts of brain could also been involved in.(4) Prognoses:7 children (77.8％) recovered well,one (11.1％) left frequent seizures during 2 years of follow up,one (11.1％) left mental retardation.Conclusion Methotrexate,cyclosporine A and other agents are important incentives in children with PRES during the treatment of hematological diseases;seizures and hypertension are the main clinical manifestations;MR imaging is important in diagnosing the disease;and PRES is not completely reversible.
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Objective To investigate the risk factors for childhood acute leukemia complicated with streptococcus mitis bacteriaemia and to explore a better therapeutic regimen of antibiotics.Methods Seventy-eight cases of childhood acute leukemia complicated with bacteriaemia hospitalized in Zhujiang Hospital of Southern Medical University from January 2012 to December 2016 were collected,among them there were 8 cases (10.26％) caused by streptococcus mitis.The susceptible factors,clinical manifestations,drug susceptibility,treatments and outcomes of 8 cases of streptococcus mitis bacteriaemia were summarized and analyzed.Results All of 8 cases were attacked during the agranulocytosis phase lasting for more than 1 week after chemotherapy for acute leukemia.Four cases of them had been exposed to the third-generation cephalosporins for more than 7 days,and 5 cases exposed to proton pump inhibitor (PPI) for more than 10 days.The incidence of remittent fever,shiver,stomatitis and pneumonia was 100.0％ (8/8 cases),62.5％ (5/8 cases),62.5％ (5/8 cases) and 62.5％ (5/8 cases),respectively.And severe pneumonia occurred at a rate of 37.5％ (3/8 cases).The sensitivity to Linezolid,Vancomycin,Penicillin and Cefotaxime was 100.0％,100.0％,37.5％ and 25.0％,respectively.Five of the 7 cases treated with Meropenem had a fever 3 days later and then they took Linezolid as a replacement according to the drug sensitivity.One case was treated with Cefoperazone-Sulbactam.The duration time of fever,positive blood culture,agranulocytosis and course of antibiotics therapy was 1-19 d(10.4 d on average),4-22 d(13.4 d on average),10-30 d (21.6 d on average),9-26 d (18.3 d on average),respectively.Among 3 patients with severe pneumonia,1 patient received the respirator assisted ventilation for 1 week.Conclusions Streptococcus mitis is one of the major causes of severe infection among children with acute leukemia.Agranulocytosis after chemotherapy,stomatitis,exposure to PPI and antibiotics may be the risk factors for streptococcus mitis infection.Fever,stomatitis,respiratory and digestive symptoms are the common clinical manifestations.Streptococcus mitis is resistant to Penicillin and Cefotaxime,but sensitive to Linezolid,which can shorten the course of infection and improve the outcomes.Thus,Linezolid may serve as an optional therapy for streptococcemia mitis bacteriaemia.
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Objective To investigate the relationship between Methotrexate (MTX) and its cognitive dysfunction,and to explore the possible mechanism of neurotoxicity induced by MTX.Methods Thirty healthy male SD rats weighting 180-220 g were divided into 3 groups using random number table:control group,60 mg/kg MTX (MTX60) group and 100 mg/kg MTX (MTXt00) group,with 10 rats in each group.The rats in MTX60 group,MTX100 group received 60 mg/kg MTX and 100 mg/kg MTX,respectively.The rats in control group accepted the same volume of 9 g/L saline injection as MTX group.Spatial memory of rats was evaluated by using Morris water maze test at different time points after pretreatment with MTX.After the Morris water maze test,the hippocampus were harvested and the expressions of C/EBP homologous protein (CHOP),cysteinyl aspartate specific proteinase 12(caspase-12) and cleave cysteinyl aspartate specific proteinase 3 (cleaved caspase-3) were detected by using Western blot.Meanwhile,cell apoptosis and pathological change of hippocampal neurons were detected by terminal dexynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and HE staining respectively.Results In the Morris water maze test,the time in platform quadrant of rats in MTX60 group and MTX100 group was shorter than that of rats in control group during probe training [(27.30 ±3.98) s and (21.63 ±4.22) s vs (33.30 ±6.31) s,F =13.94,P ＜0.05],and the time in target quadrant of MTX100 group was shorter than that of MTX60 group (P ＜ 0.05).Compared with the control group,there were degenerated neurons in hippocampus cornu ammonis 1 (CA1) area in MTX60 group and MTX100 group.The number of TUNEL-positive cells of the hippocampus CA1 area increased significantly in MTX60 group and MTX100 group rats [(4.72 ±0.12)％ and (9.12±0.12)％ vs (1.11 ±0.49)％,F=95.272,P ＜0.05],and the TUNEL-positive cells of rats in MTX100 group were more than those of MTX60 group (P ＜ 0.05).The expressions of CHOP,caspase-12 and cleaved caspase-3 also increased compared with the control group (CHOP:2.98 ±0.31 and 4.15 ±0.61 vs 0.38 ±0.12,F =232.74,P ＜ 0.05;caspase-12:0.33 ±0.04 and 0.43 ±0.06 vs 0.14 ±0.02,F =120.70,P ＜ 0.05;cleaved caspase-3:0.35 ± 0.04 and 0.44 ± 0.06 vs 0.05 ± 0.03,F =198.64,P ＜ 0.05),and the protein expression levels of rats in MTX100 group were higher than MTX60 group (all P ＜ 0.05).Conclusions MTX can induce cognitive impairment in rats,and endoplasmic reticulum stress mediated hippocampal neurons apoptosis may play an important role in the mechanism of MTX-induced cognitive impairment in rats.