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OBJE CTIVE To investigate the clinical characteristics of a dverse drug reactions of asparaginase-associated pancreatitis（AAP），so as to provide reference for clinical safe medication. METHODS Analysis and identification were performed on a severe adverse reaction case of acute pancreatitis complicated with diabetic ketoacidosis and liver injury in a patient with acute lymphoblastic leukemia in our hospital after using pegaspargase. Retrieved from Wanfang database ，CNKI，PubMed and Embase database，case reports of AAP were collected and summarized in terms of patient demographics ，drug use ，incubation period and adverse reaction outcome. Combined with this case ，the disease characteristics and potential risk factors of AAP were analyzed and discussed. RESULTS After analysis and identification ，it was determined that AAP occurred in this patient. A total of 47 case reports were retrieved from the database ，and a total of 52 patients（including this patient ）were included in the analysis ，including 29 males and 23 females，mainly minors （65.4％）. L-asparaginase was the main asparaginase preparation that causes AAP （80.8％）. Gastrointestinal symptoms were the main prodromal symptoms （92.3％），which could be accompanied by other asparaginase related adverse reactions. AAP could occur after 1-33 times of administration ，and the median latency was 14 days after administration；compared with children ，median latency of AAP in adult patients was shortened significantly （11 d vs. 16 d，P＝ 0.049）；the median latency of AAP had longer tendency in patients treated with pegaspargase than that of L-asparaginase （17 d vs. 12.5 d，P＝0.490）. Of the cases included in the analysis ，8 patients died due to AAP ，1 of which was related to re-exposure to asparaginase preparations. CONCLUSIONS Acute pancreatitis is a serious and potentially fatal adverse drug reaction of ； asparaginase preparations. Clinical medical staff should pay attention to the characteristics of AAP ，consider the possibility ： of AAP when the patients have gastrointestinal symptoms and do a good job in patient education and pharmaceutical care to minimize the damage caused by AAP to patients.
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OBJECTIVE： To mine and evaluate the post-marketing safety alert signals of pegaspargase （PEG-ASP） and L-asparaginase （L-ASP），and compare the safety differences between them ，so as to provide reference for clinical safe and rational drug use. METHODS ： The adverse drug event （ADE） reports of PEG-ASP and L-ASP issued by FDA adverse event reporting system from Jan. 1st，2004-Jun. 30th，2020 were retrieved. BCPNN method was used to mine the safety signals of these two drugs under the condition that the lower limit of information component （IC－2SD）＞0 and the number of events ≥3. The medium and strong signals of two drugs with IC －2SD≥1.5 were evaluated and compared in 8 system organ class，such as gastrointestinal system ，hepatobiliary system ，blood and lymphatic system ，blood vessels and lymphatic vessels ， nervous system ，immune system ，metabolism and nutrition ，various examinations. IC value of specific ADE signal and its 95％ confidence interval were analyzed by time scanning spectrum. RESULTS & CONCLUSIONS ：The reports of PEG-ASP and L-ASP as suspected drugs were 2 324 and 3 824；67 and 68 medium and strong signals were included ，respectively. In gastrointestinal system，the common strong signal of PEG-ASP and L-ASP was necrotic pancreatitis. In hepatobiliary system ，both of them showed strong signal in venoocclusive liver disease ，and this ADE was not included in the drug instruction. In blood and lymphatic system ， common strong signals of the two drugs were febrile neutropenia ，coagulation disorder ，neutropenia and febrile bone marrow regeneration disorder ；in blood vessels and lymphatic vessels ，in addition to haemodynamic instability ，IC values of other signals of L-ASP were higher than those of PEG-ASP. In nervous system ，IC values of other signals of L-ASP were higher than those of PEG-ASP except for intracranial haemorrhage. In immune system ，anaphylactic reaction was a medium signal for L-ASP but was a strong signal for PEG-ASP. In metabolism and nutritional diseases ，except for tumor lysis syndrome ，IC values of other signals of L-ASP were higher than those of PEG-ASP. The results of time scanning spectrum showed that the signals of necrotic pancreatitis and coagulation disorder of PEG-ASP were stable ，while the signals of veno occlusive liver disease and hypersensitivity were unstable and needed to be observed ；above four signals of L-ASP were stable signals. When using PEG-ASP or L-ASP clinically ， close attention should be paid to the safety problems such as hypersensitivity ，coagulation disorder ，thrombosis，necrotic pancreatitis，venoocclusive liver disease and hypoproteinemia.
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Objective@#To summarize the adverse effects of pegaspargase in the treatment of lymphoid malignancies and management experience.@*Methods@#Clinical data of patients who received chemotherapy including pegaspargase in the Department of Hematology of Beijing Tongren hospital during August 2011 to December 2015 were retrospective analyzed, and the adverse effects of pegaspargase and the management experience was summarized.@*Results@#A total of 129 patients with 443 times of pegaspargase used during this period. The common adverse reactions included allergic reactions in 2 cases (1.6%), acute pancreatitis in 19 (14.7%) including 6 acute symptomatic pancreatitis and 13 chemical pancreatitis with elevated pancreatin, hypertriglyceridemia in 15 cases(11.6%), hyperglycemia in 85 (65.9%), hypoglycemia in 7 (5.4%), elevated aminotransferase in 25 (19.4%), hyperbilirubinemia in 21 (15.5%), hypoalbuminemia in 62 (48.1%), prolonged APTT in 61 (47.3%), prolonged PT in 22 (17.1%), prolonged TT in 15 (11.6%), hypofibrinogen in 75 (58.1%), thrombus in 11 (8.5%) and bleeding in 3 (2.3%). The above adverse reactions were improved by symptomatic treatment of anti allergy, inhibition of secretion of pancreatic juice, lipid lowering, hypoglycemic, liver preservation, supplementation of plasma and hemostasis, respectively. Some serious adverse reactions affected the application of pegaspargase, even lead to discontinuation of the aspartate.@*Conclusion@#Though adverse effects associated with pegaspargase are extensive, most patients can successfully complete the chemotherapy containing the pegaspargase with close monitoring and timely treatment.
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Objective To compare the clinical efficacy and adverse effects of pegaspargase (PEGASP) and L-asparaginase (L-ASP) in the treatment of NK/T-cell lymphoma.Methods A retrospective analysis was conducted on the clinical data of 46 patients with NK/T-cell lymphoma in Department of Oncology of Hospital of Qingdao Commercial Staff from September 2009 to July 2015.There were 24 patients treated by PEG-ASP combined with GDP (gemcitabine + cisplatin + dexamethasone) as PEG-ASP group,and 22 patients treated by L-ASP combined with GDP as L-ASP group.The efficacy and adverse reactions were compared between the two groups.Results In the PEG-ASP group,there were 11 patients with complete remission,7 patients with partial remission,and the complete remission rate and objective response rate were 45.83％ and 75.00％.In the L-ASP group,there were 9 patients with complete remission,6 patients with partial remission,and the complete remission rate and objective response rate were 40.91％ and 68.18％.There was no significant difference between the two groups in objective response rate (x2 =0.263,P =0.608).Adverse effects such as myelosuppression (25.00％ vs.22.73％,x2 =0.033,P =0.857),coagulopathy (8.33％ vs.9.10％,x2=0.008,P =0.927),liver and renal dysfunction (8.33％ vs.18.18％,x2 =0.982,P=0.322),gastrointestinal reaction (41.67％ vs.40.91％,x2 =0.003,P =0.958) were similar in the PEGASP group and L-ASP group.But the risk of allergic reaction incurred by PEG-ASP was much lower than L-ASP (4.17％ vs.36.36％),with a significant difference (x2 =7.561,P =0.006).Moreover,the PEGASP group had a shorter duration of hospitalization [(10.04 ± 1.63) d] than the L-ASP group [(13.09 ± 2.76)d],with a significant difference (t=-4.612,P=0.000).Conclusion The efficacy of PEG-ASP and L-ASP in the treatment of NK/T-cell lymphoma is similar,but the rate of allergic reaction of patients treated with PEG-ASP is significantly lower,and the hospitalization time is significantly shorter,which is worthy of further clinical application.
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Objective To evaluate the efficacy of pegaspargase (PEG-ASP) combined with GEMOX regimen for the treatment of extranodal natural killer (NK) / T-cell lymphoma (ENKL),and to observe the changes of coagulation function.Methods 35 patients with histologically confirmed ENKL were enrolled from January 2010 to December 2014.All patients received 180 cycles of PEG-ASP combined with GEMOX chemotherapy and the efficacies were observed.The coagulation items such as prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (Fbg) and international normalized ratio (INR) were tested respectively on day 1st,day 8th and day 14th of every treatment cycle.Results Among 35 patients,11 patients (31.43 ％) were in stage Ⅰ-Ⅱ,and 24 patients (68.57 ％) were in stage Ⅲ-Ⅳ.All patients were subjected to 180 cycles of PEG-ASP combined with GEMOX chemotherapy,and each case was estimated to receive 6 cycles.The overall response (CR+PR) rate (ORR) was 71.43 ％ (25/35),the ORR was 81.82 ％ (9/11) in stage Ⅰ-Ⅱ group,and 66.67 ％ (16/24) in stage Ⅲ-Ⅳ group.The increased PT and APTT and decreased Fbg were observed on day 8th of the chemotherapy.The increased APTT and decreased Fbg were still observed on day 14th of the chemotherapy.Compared the data of patients one day before chemotherapy with healthy persons,the changes had statistical significance (P ＜ 0.05).Conclusions PEG-ASP combined with GEMOX regimen in the treatment of ENKL is safer and more effective compared with traditional chemotherapy,but the abnormal alternations of coagulation might be common during therapy.Dealing with the bleeding risk and supplement with plasma,PPSB or Fbg in time should be necessary.
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Objective:To evaluate the efficacy and safety of pegaspargase plus GEMOX (pegaspargase, gemcitabine, oxaliplatin) regimen in the initial treatment of nasal NK/T-cell lymphoma. Methods: Twelve preliminarily diagnosed nasal NK/T-cell lymphoma patients in Tianjin Medical University Cancer Institute and Hospital from June 2011 to March 2012 were analyzed. All patients took the pegaspargase plus GEMOX regimen (gemcitabine 800-1 000 mg/m2 on days 1 and 8, oxaliplatin 130 mg/m2 on day 1, and pegaspargase 2 500 IU/m2 on day 2), every three weeks for one cycle. The efficacy and toxicity of the regimen were evaluated in the follow-up treat-ment. Results:After two cycle treatments, 1 patient dropped out of treatment because of acute pancreatitis;the remaining 11 patients had response, in which 1 achieved complete response , 7 had partial response, 2 had stable disease, and 1 had progressive disease. The objective response rate was 72.7%, and the disease control rate was 90.9%. The 2-year overall survival rate was 90.9%. With median 6-cycle P-GEMOX regimen treatment, 81.8% of 11 patients presented side effects, primarily myelosuppression and hepatic dysfunc-tion. Conclusion:Pegaspargase plus GEMOX regimen showed high efficacy on the initial treatment of nasal NK/T-cell lymphoma pa-tients, but the incidence of adverse effect was still high.
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10.3969/j.issn.1007-3969.2013.04.010