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Leukemia & Lymphoma Jul 2018PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence...
Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children's oncology group (COG) clinical trials.
PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3-41%. We evaluated grade ≥3 HSRs when given IM vs. IV on six Children's Oncology Group (COG) leukemia trials (2003-2015) to determine differences in HSR rates. 54,280 doses were administered to 16,534 patients. Considering all doses of pegaspargase during induction, consolidation, and delayed intensification, grade ≥3 HSR rate with IM injection was 5.4% (n = 482/8981) compared to 3.2% for IV (n = 245/7553) (p < .0001). If only the second and third doses of pegaspargase were analyzed, where the majority of grade ≥3 HSRs occur, the rate following IM injection was 10.1% (n = 459/4534) compared to 5.0% (n = 222/4443) for IV (p < .0001). On standardized treatment protocols conducted by the COG during 2003-2015, grade ≥3 HSR rates to pegaspargase occurred less frequently with IV infusion than IM injection.
Topics: Adolescent; Age Factors; Antineoplastic Agents; Asparaginase; Biomarkers; Child; Child, Preschool; Drug Hypersensitivity; Female; Humans; Incidence; Infusions, Intravenous; Injections, Intramuscular; Leukemia; Male; Polyethylene Glycols; Public Health Surveillance; Severity of Illness Index
PubMed: 29115886
DOI: 10.1080/10428194.2017.1397658 -
Pediatric Blood & Cancer Jul 2022Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an effective strategy to prevent serious coronavirus disease 2019 (COVID-19) and is...
Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an effective strategy to prevent serious coronavirus disease 2019 (COVID-19) and is important for oncology patients. mRNA-based COVID-19 vaccines are contraindicated in those with a history of severe or immediate allergy to any vaccine component, including polyethylene glycol (PEG)2000. Patients with acute lymphoblastic leukemia/lymphoma receive asparaginase conjugated to PEG5000 (PEG-ASNase) and those with PEG-ASNase-associated hypersensitivity may be unnecessarily excluded from receiving mRNA COVID-19 vaccines. We, therefore, surveyed oncologists on COVID-19 vaccine counseling practice and vaccination outcomes in COVID-19 vaccination-eligible patients and show safe receipt of mRNA vaccines despite PEG-ASNase hypersensitivity.
Topics: Asparaginase; COVID-19; COVID-19 Vaccines; Counseling; Drug Hypersensitivity; Humans; Oncologists; Polyethylene Glycols; RNA, Messenger; SARS-CoV-2; Vaccination
PubMed: 35353440
DOI: 10.1002/pbc.29686 -
Leukemia & Lymphoma Oct 2018Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial... (Review)
Review
Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial co-factor that can potentially ameliorate the mitochondrial toxicity of asparaginase. In this retrospective case series, we describe the clinical presentation and management of six pediatric and young adult patients (mean age 12.7, range 9-24 years) with ALL who developed Grade 3-4 hyperbilirubinemia following administration of asparaginase as part of induction/re-induction therapy. Five of these patients were treated with levocarnitine with subsequent improvement of hyperbilirubinemia, while one patient was given levocarnitine prophylactically during induction and developed Grade 3 hyperbilirubinemia, but did not require therapy adjustments or delays. Increased awareness in the pediatric oncology community regarding asparaginase-associated hepatic toxicity and the potential role of levocarnitine in management is warranted.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Carnitine; Chemical and Drug Induced Liver Injury; Child; Female; Humans; Hyperbilirubinemia; Liver; Liver Function Tests; Male; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Treatment Outcome; Ultrasonography; Young Adult
PubMed: 29431566
DOI: 10.1080/10428194.2018.1435873 -
Medicine Aug 2020The optimal treatment strategy of newly diagnosed stage I/II, extranodal nasal-type natural killer/T cell lymphoma (NKTCL) remains unclear. This prospective phase II... (Observational Study)
Observational Study
Long-term outcomes of upfront concurrent chemoradiotherapy followed by P-GDP regimen in newly diagnosed early stage extranodal nasal-type NK/T cell lymphoma: A prospective single-center phase II study.
The optimal treatment strategy of newly diagnosed stage I/II, extranodal nasal-type natural killer/T cell lymphoma (NKTCL) remains unclear. This prospective phase II trial was conducted to explore the short-term and the long-term efficacy and safety of upfront concurrent chemoradiotherapy (CCRT) followed by pegaspargase, gemcitabine, dexamethasone, cisplatin (P-GDP) regimen in patients newly diagnosed with early stage NKTCL.Thirty patients newly diagnosed with stage I/II NKTCL were enrolled from January 2013 to December 2016, and treated as the following strategy: upfront CCRT with cisplatin weekly (25 mg/m) for 5 weeks, followed by 3 cycles of P-GDP regimen chemotherapy (pegaspargase 2500IU/m capped at 3750IU, intramuscular on day 4, gemcitabine 850 mg/m intravenous on days 1 and 8; dexamethasone 40 mg/day intravenous on days 1 to 4; and cisplatin 20 mg/m intravenous on days 1-3) 3 weeks after the completion of CCRT. The objective response rate (ORR) and the complete response (CR) rate were the primary endpoints, and the secondary endpoints were the overall survival (OS), progression-free survival (PFS), and the adverse event (AE).The median follow-up period was 51.5 months (range, 5-78months). The ORR was 93.3% (28/30) and all these 28 patients attained CR at the end of the treatment. Two patients suffered from lymphoma associated hemophagocytic syndrome (LAHS) during the period of consolidation chemotherapy and died within 2 months. The 5-year OS was 93.3%, and the 5-year PFS was 89.4%Mucositis was the most common grades 3/4 nonhematologic AEs (10%, 3/30) of CCRT. During the P-GDP chemotherapy, vomiting (6.7%, 2/30), neutropenia (43.3%, 13/30) and thrombocytopenia (23.3%, 7/30) were the major grades 3/4 toxicities during chemotherapy. No treatment-related deaths occurred.The upfront CCRT followed by P-GDP regimen chemotherapy is an effective and well-tolerated first-line treatment strategy for patients diagnosed with early stage NKTCL. Further investigation of larger sample size is warranted.
Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Combined Modality Therapy; Consolidation Chemotherapy; Female; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Nose Neoplasms; Radiotherapy, Intensity-Modulated
PubMed: 32872045
DOI: 10.1097/MD.0000000000021705 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Aug 2018To summarize the adverse effects of pegaspargase in the treatment of lymphoid malignancies and management experience. Clinical data of patients who received...
To summarize the adverse effects of pegaspargase in the treatment of lymphoid malignancies and management experience. 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. 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. Though adverse effects associated with pegaspargase are extensive, most patients can successfully complete the chemotherapy containing the pegaspargase with close monitoring and timely treatment.
Topics: Asparaginase; Humans; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies
PubMed: 30180467
DOI: 10.3760/cma.j.issn.0253-2727.2018.08.009 -
Medicine Mar 2021There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death...
INTRODUCTION
There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell - ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors.
PATIENT CONCERNS
A 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010.
DIAGNOSIS
positron emission tomography-computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014.
INTERVENTIONS
The patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient's condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg.
OUTCOMES
PET-CT imaging showed his lesions obtained remission after 8 months post-treatment.
CONCLUSION
Thus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched.
Topics: Aminopyridines; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Combined Modality Therapy; Histone Deacetylase Inhibitors; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Neoplasm Recurrence, Local; Nose Neoplasms; Programmed Cell Death 1 Receptor; Remission Induction; Treatment Outcome
PubMed: 33725836
DOI: 10.1097/MD.0000000000024824 -
Journal of Clinical Oncology : Official... May 2021Children's Oncology Group (COG) AALL0331 tested whether pegaspargase intensification on a low-intensity chemotherapy backbone would improve the continuous complete...
PURPOSE
Children's Oncology Group (COG) AALL0331 tested whether pegaspargase intensification on a low-intensity chemotherapy backbone would improve the continuous complete remission (CCR) rate in a low-risk subset of children with standard-risk B-acute lymphoblastic leukemia (ALL).
METHODS
AALL0331 enrolled 5,377 patients with National Cancer Institute standard-risk B-ALL (age 1-9 years, WBC < 50,000/μL) between 2005 and 2010. Following a common three-drug induction, a cohort of 1,857 eligible patients participated in the low-risk ALL random assignment. Low-risk criteria included no extramedullary disease, < 5% marrow blasts by day 15, end-induction marrow minimal residual disease < 0.1%, and favorable cytogenetics ( fusion or simultaneous trisomies of chromosomes 4, 10, and 17). Random assignment was to standard COG low-intensity therapy (including two pegaspargase doses, one each during induction and delayed intensification) with or without four additional pegaspargase doses at 3-week intervals during consolidation and interim maintenance. The study was powered to detect a 4% improvement in 6-year CCR rate from 92% to 96%.
RESULTS
The 6-year CCR and overall survival (OS) rates for the entire low-risk cohort were 94.7% ± 0.6% and 98.7% ± 0.3%, respectively. The CCR rates were similar between arms (intensified pegaspargase 95.3% ± 0.8% standard 94.0% ± 0.8%; = .13) with no difference in OS (98.1% ± 0.5% 99.2% ± 0.3%; = .99). Compared to a subset of standard-risk study patients given identical therapy who had the same early response characteristics but did not have favorable or unfavorable cytogenetics, outcomes were significantly superior for low-risk patients (CCR hazard ratio 1.95; = .0004; OS hazard ratio 5.42; < .0001).
CONCLUSION
Standard COG therapy without intensified pegaspargase, which can easily be given as an outpatient with limited toxicity, cures nearly all children with B-ALL identified as low-risk by clinical, early response, and favorable cytogenetic criteria.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Core Binding Factor Alpha 2 Subunit; Female; Humans; Infant; Male; Neoplasm, Residual; Oncogene Proteins, Fusion; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Trisomy
PubMed: 33739852
DOI: 10.1200/JCO.20.02370 -
Hematological Oncology Dec 2017The nasal type of extranodal natural killer/T-cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the...
A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial in Northwest China.
The nasal type of extranodal natural killer/T-cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol-asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T-cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2-year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression-free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment-related deaths. These results will require confirmation in larger prospective trials.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Biomarkers; China; Dexamethasone; Drug Resistance, Neoplasm; Etoposide; Female; Humans; Immunophenotyping; Kaplan-Meier Estimate; Lymphoma, Extranodal NK-T-Cell; Male; Methotrexate; Middle Aged; Neoplasm Staging; Polyethylene Glycols; Prognosis; Recurrence; Retreatment; Treatment Outcome; Young Adult
PubMed: 27723108
DOI: 10.1002/hon.2325 -
Pediatric Blood & Cancer Mar 2018Erwinia asparaginase is a Food and Drug Administration approved agent for the treatment of acute lymphoblastic leukemia (ALL) for patients who develop hypersensitivity...
Outcome of pediatric patients with acute lymphoblastic leukemia/lymphoblastic lymphoma with hypersensitivity to pegaspargase treated with PEGylated Erwinia asparaginase, pegcrisantaspase: A report from the Children's Oncology Group.
BACKGROUND
Erwinia asparaginase is a Food and Drug Administration approved agent for the treatment of acute lymphoblastic leukemia (ALL) for patients who develop hypersensitivity to Escherichia coli derived asparaginases. Erwinia asparaginase is efficacious, but has a short half-life, requiring six doses to replace one dose of the most commonly used first-line asparaginase, pegaspargase, a polyethylene glycol (PEG) conjugated E. coli asparaginase. Pegcristantaspase, a recombinant PEGylated Erwinia asparaginase with improved pharmacokinetics, was developed for patients with hypersensitivity to pegaspargase. Here, we report a series of patients treated on a pediatric phase 2 trial of pegcrisantaspase.
PROCEDURE
Pediatric patients with ALL or lymphoblastic lymphoma and hypersensitivity to pegaspargase enrolled on Children's Oncology Group trial AALL1421 (Jazz 13-011) and received intravenous pegcrisantaspase. Serum asparaginase activity (SAA) was monitored before and after dosing; immunogenicity assays were performed for antiasparaginase and anti-PEG antibodies and complement activation was evaluated.
RESULTS
Three of the four treated patients experienced hypersensitivity to pegcrisantaspase manifested as clinical hypersensitivity reactions or rapid clearance of SAA. Immunogenicity assays demonstrated the presence of anti-PEG immunoglobulin G antibodies in all three hypersensitive patients, indicating a PEG-mediated immune response.
CONCLUSIONS
This small series of patients, nonetheless, provides data, suggesting preexisting immunogenicity against the PEG moiety of pegaspargase and poses the question as to whether PEGylation may be an effective strategy to optimize Erwinia asparaginase administration. Further study of larger cohorts is needed to determine the incidence of preexisting antibodies against PEG-mediated hypersensitivity to pegaspargase.
Topics: Adolescent; Adult; Asparaginase; Bacterial Proteins; Child; Child, Preschool; Drug Hypersensitivity; Erwinia; Female; Humans; Infant; Male; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 29090524
DOI: 10.1002/pbc.26873 -
Blood Cancer Journal Sep 2017
Clinical Trial
Efficacy of pegaspargase, etoposide, methotrexate and dexamethasone in newly diagnosed advanced-stage extra-nodal natural killer/T-cell lymphoma with the analysis of the prognosis of whole blood EBV-DNA.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; DNA, Viral; Dexamethasone; Disease-Free Survival; Etoposide; Female; Herpesvirus 4, Human; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Methotrexate; Middle Aged; Polyethylene Glycols; Survival Rate
PubMed: 29016569
DOI: 10.1038/bcj.2017.88