Clinical characteristics analysis of children with reversible posterior leukoen-cephalopathy syndrome during the treatment of hematological tumor / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical characteristics of patients with hematological tumor or disease before and after reversible posterior leukoen-cephalopathy syndrome (RPLS).@*METHODS@#Five patients were both from Peking University First Hospital Pediatric Hematology-oncology Department in the period from March 2012 to March 2017. The gender, age, BMI, underlying diseases, with or without renal damage, hypertension family history, clinical manifestations of convulsions, hemoglobin, and blood pressure, serum sodium levels before and after convulsion, and other data of the children with RPLS were retrospectively analyzed. In the meantime, we followed up the five patients for 6 months to 66 months, kept a watchful eye on their original condition and the recovery of symptoms and signs of the nervous system. The relevant literature was reviewed.@*RESULTS@#All of the subjects were females in school-age or pre-school age. The underlying diseases were malignant tumor associated with renal involvement or on one side of nephrectomy in 4 of these subjects, while the other one was refractory autoimmune hemolytic anemia. All of the subjects suffered from mild or moderate anemia. The day before RPLS occurred they received chemotherapy made up with cyclophosphamide, vincristine, and actinomycin-D, or the therapy with cyclosporin A and glucocorticoid. The clinical manifestations were afebrile convulsion after getting up in the mooring or in the afternoon. We observed elevation of blood pressure and cutting down of serum sodium compared with themselves. All of the cases recovered soon after management with diazepam, furosemide and amlodipine besylate. Four of them had a good outcomes and did not remain any sequela, while only one girl became childish in emotion and behavior, and then returned gradually to normal two years later. However, by long-term follow-up, the elevation of blood pressure was mainly reviewed in literature.@*CONCLUSION@#The patients attacked by RPLS, with hematology or oncology cases, could have the underlying disease of renal damage and anemia. Blood pressure elevation and serum sodium falling down at the same time may play an important role during the occurrence of RPLS. Remaining stable of blood pressure and electrolyte level together will possibly reduce or mitigate RPLS.

Adverse effects of high-dose methotrexate therapy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the adverse effects of high-dose methotrexate (HDMTX) therapy, and to provide a theoretical basis for optimizing clinical treatment.</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of 120 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma who underwent 601 times of HDMTX therapy. The adverse effects of various systems were analyzed according to the WHO criteria for the classification of adverse effects of anticancer drugs.</p><p><b>RESULTS</b>Almost all the children experienced bone marrow suppression, and 93.3% had granulocytopenia. The most common adverse effects in the digestive system and urinary system were elevated glutamic-pyruvic transaminase (60.4%) and proteinuria (9.2%) respectively. For skin symptoms, skin erythema had the highest incidence rate (7.2%). The adverse effects in the nervous system (hyperpathia, numbness of extremities, or headache) were only observed in 7 cases. Serious adverse effects were only seen in the blood system and digestive system. Compared with the 3 g/mmethotrexate (MTX) group, the 5 g/mHDMTX group had a significantly higher 24-hour plasma MTX concentration, significant reductions in hemoglobin and platelet count, and significantly higher incidence rates of oral mucositis, proteinuria, and skin symptoms (P<0.05).</p><p><b>CONCLUSIONS</b>Serious adverse effects of HDMTX therapy mainly involve the blood system and digestive system, and the adverse effects such as bone marrow suppression, oral mucositis, proteinuria, and skin symptoms occur in a dose-dependent manner.</p>

Investigation on individualized adjustment of target range of high-dose methotrexate / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the way of individualized adjustment of target range of each high-dose methotrexate (MTX) 24 hours infusion to treat acute lymphoblastic leukemia in children.</p><p><b>METHODS</b>Twenty-four children and 105 infusions were included in the study. According to 1 h and 6 h plasma MTX concentrations after infusion, based on established high-dose MTX population pharmacokinetics model, the course predicted value of drug concentration at steady state (C(SS)) was calculated. MTX infusion rate and dosage was adjusted 8 h after the start according to the predicted value of C(SS). Then MTX concentration at 23 h (actual value of C(SS)) was measured.</p><p><b>RESULTS</b>To achieve the target range of C(SS), adjustments of MTX dosage were required in 17 (71%) patients. Adjustments of MTX dosage were required in 45 (43%) infusions, the dose was increased in 42 infusions and decreased in 3 infusions. There were 29 infusions of high-dose MTX during consolidation therapy (after remission induction therapy). Among them, 16 infusions had increased dosage, and 1 infusion had decreased dosage. There were 76 infusions during maintenance therapy. Among them, 26 infusions increased dosage, and 2 infusions decreased dosage. Overall 95 (90%) infusions achieved the target range of C(SS), while in 8 infusions the doses were lower than the target range in 2 infusions the doses were higher than the target range. If there had been no adjustments, only 74 (70%) infusions could have achieved the target range. Adjustments of MTX dosage, compared with no adjustments, could remarkably enhance the rate of achieving the target range of C(SS) (chi(2) = 13.366, P = 0.000). Among 60 infusions of no adjustments, the actual values of C(SS) were well correlated with the predicted values of C(SS) (r = 0.487, P = 0.000), and the actual values of C(SS) were also correlated with the 6 h plasma MTX concentrations after infusions (r = 0.389, P = 0.002). The actual values of total clearance (CL) of MTX of 105 infusions were 7.01 +/- 2.06 L/(m(2).h). Inter-courses variability in CL was up to 4.4-fold. Intra-patient variability in CL was up to 2.9-fold. Predisposing factors that correlated with decreased CL of MTX were old age, heavy body weight, low blood phosphate, high blood bilirubin and infusions during maintenance therapy (P < 0.05).</p><p><b>CONCLUSIONS</b>High-dose methotrexate chemotherapy needed individualized adjustment, as inter-courses variability of CL was up to 4.4-fold among 105 infusions. According to 1 h and 6 h plasma MTX concentrations after infusion, adjusting MTX infusion rate and dosage, overall 90% infusions achieved the target range of C(SS). High-dose MTX infusions during consolidation therapy needed individualized adjustment of target range more.</p>

Feasibility of Leucovorin Rescue Guided with Methotrexate Plasma Concentration / 实用儿科临床杂志

Objective To evaluate the feasibility of leucovorin(LCV) rescue protocol defined by us,we compared the plasma concentrations,toxicity,LCV doses of different high doses methotrexate(HD-MTX).Methods Seventeen children with acute lymphoblastic leukemia and 1 children with non-Hodgkin′s lymphoma were randomly treated with total 43 courses of HD-MTX.MTX plasma concentrations were measured by fluorescence polarization immuno-assay.Different LCV rescue protocols were prospectively defined for 3 kinds of HD-MTX protocols.Adjusting LCV dose by plasma MTX concentrations.Results No irreversible MTX-related toxicity was observed in all patients.Significant differences of mean steady-state plasma concentrations(Cpss) and total rescue doses were found between 3 groups(P

Concentrations of Methotrexate Elimination after High Dose Infusion and Its Influencing Factors / 实用儿科临床杂志

1 ?mol?L-1,and it was defined as "delayed" MTX elimination.Intra-patient variability in C48 was significant(P=0.000).Risk factors that correlated with increased C48 of MTX were boys,abnormal urine routine tests within 1 week before infusions,concurrent infections within 2 weeks before infusions,and co-administration of ceftriaxone(P