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Zhonghua Er Ke Za Zhi = Chinese Journal... Dec 2022To investigate the clinical characteristics and treatment of pancreatic pseudocyst after pegaspargase treatment in children. The clinical data of 6 children with...
To investigate the clinical characteristics and treatment of pancreatic pseudocyst after pegaspargase treatment in children. The clinical data of 6 children with pancreatic pseudocyst after pegaspargase treatment in the Department of Pediatrics in Peking University Third Hospital from July 2018 to February 2021 were analyzed retrospectively. There were 4 males and 2 females, and their age of onset was 9.5 (5.8, 13.0) years. The total number of pegaspargase applications was 2.5 (2.0, 3.5) times. The course from the last dose of pegaspargase to the onset of pancreatitis was 11.0 (9.0, 17.2) days, and 42.5 (35.0, 129.5) days from the onset of pancreatitis to the diagnosis of pancreatic pseudocyst. Abdominal pain was the most prominent manifestation of pancreatitis (6/6). All of the 6 children were asymptomatic when pancreatic pseudocyst was noted, and were treated conservatively at first, but one case later developed intermittent abdominal distension or nausea after eating. All the cases had pancreatic pseudocyst enlargement during the conservative treatment. Three children were treated with endoscopic ultrasound-guided transgastric drainage, and the cyst disappeared from 10 days to 4 months after the operation. The other 3 children received endoscopic retrograde cholangiopancreatography (ERCP)-guided transpapillary drainage, but one of them turned to surgery due to pancreatic duct stricture, and in the rest 2 children the cyst disappeared at 1 and 3 months after operation respectively. Regarding safety issues, 1 child who received ERCP-guided transpapillary drainage had acute postoperative pancreatitis, which were improved after treatment, and the other 5 had no complications. Pancreatic pseudocyst after pegaspargase chemotherapy can be asymptomatic in the early stage, and should be diagnosed with a history of pegaspargase treatment and timely imaging examination. Conservative treatment is the first choice for asymptomatic pseudocyst. When the pseudocyst enlarges, different endoscopic drainage treatments are required according to whether the pseudocyst is connected with the main pancreatic duct.
Topics: Female; Male; Humans; Child; Retrospective Studies; Asparaginase; Polyethylene Glycols; Pancreatitis
PubMed: 36444438
DOI: 10.3760/cma.j.cn112140-20220904-00779 -
Journal of Clinical Pharmacy and... Dec 2022Diabetic ketoacidosis (DKA) may occur during asparaginase use. However, limited by the study population, the association between asparaginase and DKA has not been... (Review)
Review
WHAT IS KNOWN AND OBJECTIVE
Diabetic ketoacidosis (DKA) may occur during asparaginase use. However, limited by the study population, the association between asparaginase and DKA has not been elucidated. The purpose of this study was to determine the potential association between asparaginase and DKA and analyse related clinical characteristics and possible risk factor.
METHODS
Disproportionality analysis with the reporting odd ratio (ROR) was used to detect the adverse reaction signals of asparaginase-associated DKA in Food and Drug Administration Adverse Event Reporting System (FAERS). A literature review was conducted to further analyse clinical characteristics, possible risk factor and something noteworthy in asparaginase-associated DKA.
RESULTS AND DISCUSSION
A total of 12 reports of DKA associated with l-asparaginase (l-asp) and 6 reports associated with pegaspargase (PEG-asp) were extracted in FAERS, more than 50% of the cases were classified as serious adverse events. DKA was a positive signal of l-asp (ROR = 2.397, 95% CI 1.360-4.226), while not closely related to the use of PEG-asp (ROR = 1.602, 95% CI 0.719-3.570). Searched in PubMed, Embase and Web of Science, a total of eight patients were collected. The patients were mainly adolescent patients, aged between 11 and 25 years old with a median age of 16 years. Drug dosage form distribution is unbalanced, 7 patients received l-asp and only 1 received PEG-asp.
WHAT IS NEW AND CONCLUSIONS
The ROR of KDA caused by l-asp was statistically significant, but there was not a statistical association for DKA caused by PEG-asp. Asparaginase dosage form may affect the occurrence of DKA, but further research is needed.
Topics: Adolescent; United States; Humans; Child; Young Adult; Adult; Asparaginase; Diabetic Ketoacidosis; Risk Factors; United States Food and Drug Administration; Odds Ratio; Diabetes Mellitus
PubMed: 36411584
DOI: 10.1111/jcpt.13782 -
Blood Advances Jan 2023Asparaginase is a key component of pediatric-inspired regimens in young adults with acute lymphoblastic leukemia (ALL). Truncation of asparaginase therapy is linked to...
Asparaginase is a key component of pediatric-inspired regimens in young adults with acute lymphoblastic leukemia (ALL). Truncation of asparaginase therapy is linked to inferior outcomes in children with ALL. However, a similar correlation in adults is lacking. Here, we studied the prevalence and risk factors associated with pegylated (PEG)-asparaginase discontinuation in young adults with ALL treated on the US intergroup Cancer and Leukemia Group B (CALGB) 10403 study and examined the prognostic impact of early discontinuation (ED) (defined as <4 of 5 or 6 planned doses) on survival outcomes. The analysis included 176 patients who achieved complete remission and initiated the delayed intensification (DI) cycle. The median number of PEG-asparaginase doses administered before DI was 5 (range, 1-6), with 57 (32%) patients with ED. The ED patients were older (median, 26 vs 23 years; P = .023). Survival was apparently lower for ED patients compared with those receiving ≥4 doses, but this finding was not statistically significant (hazard ratio [HR], 1.82; 95% confidence interval [CI], 0.97-3.43; P = .06), with corresponding 5-year overall survival (OS) rates of 66% and 80%, respectively. In patients with standard-risk ALL, the ED of PEG-asparaginase adversely influenced OS (HR, 2.3; 95% CI, 1.02-5.22; P = .04) with a trend toward inferior event-free survival (EFS) (HR, 1.84; 95% CI, 0.92-3.67; P = .08). In contrast, there was no impact of early PEG-asparaginase discontinuation on OS (P = .64) or EFS (P = .32) in patients with high-risk disease based on the presence of high-risk cytogenetics, Ph-like genotype, and/or high white blood cell count at presentation. In conclusion, early PEG-asparaginase discontinuation is common in young adults with ALL and may adversely impact survival of patients with standard-risk ALL.
Topics: Child; Humans; Young Adult; Asparaginase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polyethylene Glycols; Remission Induction
PubMed: 36269846
DOI: 10.1182/bloodadvances.2022007791 -
Clinical Drug Investigation Nov 2022Acute lymphoblastic leukemia (ALL) is an acute, rapidly progressing and life-threatening form of cancer involving immature lymphocytes called lymphoblasts. ALL is the...
BACKGROUND AND OBJECTIVE
Acute lymphoblastic leukemia (ALL) is an acute, rapidly progressing and life-threatening form of cancer involving immature lymphocytes called lymphoblasts. ALL is the most common subtype of leukemia in children and adolescents. The aim of the present study was to assess the cost-utility of pegaspargase versus L-asparaginase, both followed by Erwinase in the therapy sequence, as a treatment option for pediatric, adolescent, and adult patients with ALL in Greece.
METHODS
A published cost-utility model comprising a decision tree and a state-transition Markov model was adapted from a public payer perspective to compare a pegaspargase treatment sequence with an L-asparaginase sequence. Efficacy and safety data, as well as utility values, were extracted from the published literature. Direct costs pertaining to drug acquisition, administration, and management of hypersensitivity were considered in the analysis (€2020). Model-extrapolated outcomes included quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER). All future outcomes were discounted at 3.5% per annum. Sensitivity analyses were used to explore the impact of changing input data.
RESULTS
The analysis showed that the pegaspargase sequence was estimated to produce 0.05 additional QALYs (18.12 vs. 18.07) and lower cost of - €1698 compared with L-asparaginase, indicating that the pegaspargase sequence was a dominant treatment strategy (improved outcomes with reduced costs) compared with L-asparaginase. Deterministic sensitivity analysis confirmed the cost-effective profile of pegaspargase. At the defined willingness-to-pay threshold of €54,000/QALY gained, probabilistic sensitivity analysis showed that pegaspargase had a 100% probability of being cost effective relative to the L-asparaginase sequence.
CONCLUSION
The pegaspargase sequence was found to be less costly and more effective (in terms of QALYs) in relation to the L-asparaginase sequence, representing a dominant strategic option for Greek public payers in ALL.
Topics: Adult; Adolescent; Humans; Child; Asparaginase; Cost-Benefit Analysis; Greece; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Quality-Adjusted Life Years
PubMed: 36227415
DOI: 10.1007/s40261-022-01207-w -
Medicine Sep 2022Extranodal nature killer/T-cell lymphoma (ENKTL) failing in asparaginase-containing treatments is fatal, it has a higher mortality rate when accompanied by secondary... (Review)
Review
Sintilimab combined with chidamide in the treatment of extranodal nature killer/T-cell lymphoma with secondary hemophagocytic lymphohistiocytosis: Two case reports and literature review.
RATIONALE
Extranodal nature killer/T-cell lymphoma (ENKTL) failing in asparaginase-containing treatments is fatal, it has a higher mortality rate when accompanied by secondary hemophagocytic lymphohistiocytosis (HLH). The study reported 2 ENKTL-related HLH patients.
PATIENT CONCERNS
Patient 1 visited for nasal congestion and runny nose for 6 months then got a fever and serious myelosuppression after P-GEP (pegaspargase, gemcitabine, etoposide, and methylprednisolone) chemotherapy. Patient 2 complained of painless lymphadenectasis in the right neck for 4 months and experienced recurrent fever and poor performance status after 3 cycles of P-Gemox (pegaspargase, gemcitabine, and oxaliplatin) chemotherapy.
DIAGNOSES
Patient 1 and patient 2 were diagnosed as ENKTL failing in asparaginase-based chemotherapy and involving secondary HLH.
INTERVENTIONS
The dose of chidamide was 20 mg twice a week for 2 weeks and sintilimab was 200 mg once every 3 weeks.
OUTCOMES
ENKTL was relieved and the HLH was resolved after the therapy of sintilimab and chidamide. The patients had achieved durable survival without immune-related adverse events.
LESSONS
ENKTL-related HLH needs early diagnosis and treatment. The combined strategy of sintilimab plus chidamide help deal with HLH and solve ENKTL, it may be a useful treatment option for ENKTL-related HLH.
Topics: Aminopyridines; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Benzamides; Etoposide; Humans; Lymphohistiocytosis, Hemophagocytic; Lymphoma, Extranodal NK-T-Cell; Methylprednisolone; Oxaliplatin
PubMed: 36197207
DOI: 10.1097/MD.0000000000030731 -
European Journal of Haematology Jan 2023Pediatric patients have a better survival rate for lymphoid malignancies than adolescents and young adult patients (AYA) and current evidence suggests that asparaginase...
BACKGROUND
Pediatric patients have a better survival rate for lymphoid malignancies than adolescents and young adult patients (AYA) and current evidence suggests that asparaginase plays a role in improved response to treatment. This study aimed to evaluate if increasing age as a continuous variable demonstrated increasing toxicities to PEG-asparaginase (PEG-ASP) for those patients treated at a tertiary care pediatric hospital.
METHODS
A retrospective chart review from 2007 to 2017 was conducted in the pediatric population at the Children's Hospital of Eastern Ontario (CHEO). Patients having received PEG-ASP were included. Event incidence and risk related to age at diagnosis were assessed through parameter estimates and Wald chi-square analysis.
RESULTS
In total, 75 adverse events were observed: 34/186 (18.3%) experienced allergic reactions, 8/186 (4.3%) pancreatitis, 31/186 (16.7%) thrombosis, and 2/186 (1.1%) hemorrhage. One hundred and eighty two patients had complete information for inclusion in our model. A correlation between age at diagnosis and higher risk of allergic reaction (p < .001) and pancreatitis (p < .035) was observed.
CONCLUSION
Allergic reaction and pancreatitis following administration of PEG-ASP have a higher risk of occurrence as age of diagnosis increases up to 18 years of age. This includes the lower limit of traditionally defined AYA population of 15-39 and warrants precaution as PEG-ASP is included in older populations treatment regimens at pediatric centers.
Topics: Adolescent; Child; Humans; Young Adult; Antineoplastic Agents; Asparaginase; Hypersensitivity; Pancreatitis; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Tertiary Care Centers
PubMed: 36151599
DOI: 10.1111/ejh.13867 -
Bulletin Du Cancer Nov 2022Pegaspargase (Oncaspar®), a pegylated form of native Escherichia Coli-derived L-asparaginase is an essential component chemotherapy used in the treatment of acute...
[Prevention and management of pegaspargase associated-toxicities (excluding coagulation abnormalities). Recommendations of the French Society of Children and Adolescent Cancers (Leukemia committee)].
Pegaspargase (Oncaspar®), a pegylated form of native Escherichia Coli-derived L-asparaginase is an essential component chemotherapy used in the treatment of acute lymphoblastic leukemia (ALL) in pediatric and adult patients. Its particular toxicity profile requires a specific management to improve safety and tolerability and optimize treatment outcome and therefore survival. Within the framework of workshops of practice harmonization of the French Society of Children and Adolescent Cancers, diagnostic and management of the most commonly occuring toxicities (excluding coagulation abnormalities) during Pegaspargase treatment were reviewed according to the analysis of published studies.
Topics: Adult; Humans; Adolescent; Child; Asparaginase; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome; Blood Coagulation Disorders; Antineoplastic Agents
PubMed: 35987855
DOI: 10.1016/j.bulcan.2022.06.004 -
Leukemia & Lymphoma Dec 2022A total of 548 patients (age range: 1-22 years, 60.4% Hispanic, 55.8% male) diagnosed with acute lymphoblastic leukemia were reviewed for pegaspargase-associated...
A total of 548 patients (age range: 1-22 years, 60.4% Hispanic, 55.8% male) diagnosed with acute lymphoblastic leukemia were reviewed for pegaspargase-associated hypersensitivity (14.8%), hyperbilirubinemia (9.7%), venous thromboembolism (VTE, 9.7%), and pancreatitis (5.3%). Odds ratios (OR) and 95% confidence intervals (CI) evaluated associations between clinical factors and each toxicity, cumulative number of toxicities, and toxicity clusters identified using k-mode analysis. Most (68.9%) did not experience any toxicity, 24.6% experienced one toxicity, and 6.3% two or more. Age >10 years was associated with hyperbilirubinemia (OR = 3.83; 95% CI: 1.64-8.95), pancreatitis (OR = 3.72; 95% CI: 1.29-10.68), VTE (OR = 4.65; 95% CI: 1.96-11.02), and cumulative toxicity burden (OR = 3.28, 95% CI: 1.97-5.47); high-risk therapy with hypersensitivity (OR 2.25; 95% CI 1.25-4.05); and overweight with cumulative toxicity burden (OR = 1.76, 95% CI: 1.20-2.57). Eight unique toxicity profiles were identified. Older age, overweight, and treatment intensity contribute to pegaspargase-associated toxicities.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Male; Young Adult; Antineoplastic Agents; Asparaginase; Demography; Hyperbilirubinemia; Hypersensitivity; Overweight; Pancreatitis; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Venous Thromboembolism
PubMed: 35895075
DOI: 10.1080/10428194.2022.2102621 -
Zhonghua Yi Xue Za Zhi Jul 2022To investigate the efficacy and safety of ruxolitinib, liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase (RU-DEP+/-L) in the treatment of...
[Ruxolitinib combined with liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase in treatment of relapsed/refractory pediatric hemophagocytic lymphohistiocytosis].
To investigate the efficacy and safety of ruxolitinib, liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase (RU-DEP+/-L) in the treatment of relapsed/refractory (R/R) pediatric hemophagocytic lymphohistiocytosis (HLH). The clinical data of R/R pediatric HLH, who accepted the RU-DEP+/-L regimen at Beijing Children's Hospital from January 2018 to December 2019 was retrospectively analyzed. A total of 16 patients were included in this study, including 13 males and 3 females, aged[(,)] 1 (1, 2) years at diagnosis. Thirteen patients were diagnosed with Epstein-Barr virus (EBV)-HLH, 2 with EBV-induced primary HLH, and 1 with unclear etiology, among which 3 patients were co-infected with CMV. After the first-line treatment, 11 patients had no response, and 5 patients relapsed after complete response. Nine patients received the RU-L-DEP regimen, and 7 patients received the RU-DEP regimen. The overall response rate and complete response of RU-DEP+/-L treatment were 10/16 and 3/16, respectively. The negative conversion rate of plasma EBV-DNA was 7/15. The median follow-up time was 35.1 (2.4, 40.7) months, and 9/16 patients were survival. The 3-year overall survival rate after RU-DEP+/-L treatment in response and accepted hematopoietic stem cell transplantation (HSCT) was higher than that without response and did not receive HSCT (=0.048). Among the 16 patients, 9 had varying degrees of myelosuppression, and 13 had an infection. RU-DEP+/-L can be used as a salvage treatment in R/R pediatric HLH, which can provide a bridge to HSCT and play an important role in the control of HLH. The main adverse reactions are myelosuppression and infection, which can be tolerated.
Topics: Aged; Asparaginase; Child; Doxorubicin; Epstein-Barr Virus Infections; Etoposide; Female; Herpesvirus 4, Human; Humans; Lymphohistiocytosis, Hemophagocytic; Male; Methylprednisolone; Nitriles; Polyethylene Glycols; Pyrazoles; Pyrimidines; Retrospective Studies
PubMed: 35872580
DOI: 10.3760/cma.j.cn112137-20211224-02888 -
Infection and Drug Resistance 2022Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a rare and aggressive disease with high mortality and poor prognosis. To date, allogeneic...
BACKGROUND
Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a rare and aggressive disease with high mortality and poor prognosis. To date, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only way to cure EBV-HLH. However, relapse of EBV-HLH after allo-HSCT is common and remains a major challenge.
CASE PRESENTATION
A 22-year-old woman with persistent fever for a month presented to our center with EBV-HLH. After induction of remission using two cycles of the L-DEP (PEG-aspargase, liposomal doxorubicin, etoposide, and high-dose methylprednisolone) regimen, the patient underwent an human leukocyte antigen (HLA)-identical sibling allo-HSCT. However, she experienced disease relapse soon after the procedure, and none of the possible treatment options achieved a sustained response. Finally, she received a sintilimab injection and achieved complete resolution of EBV-HLH.
CONCLUSION
We summarize a case of relapsed EBV-HLH after allo-HSCT that was successfully treated with a programmed cell death protein-1 (PD-1) antibody. Further studies are needed to determine whether PD-1 blockade has therapeutic potential for relapsed EBV-HLH after allo-HSCT.
PubMed: 35859915
DOI: 10.2147/IDR.S372998