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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 -
The Journal of Pediatric Pharmacology... 2022The purpose of this study was to evaluate the efficacy of a standardized premedication and therapeutic drug monitoring (TDM) protocol to prevent hypersensitivity...
OBJECTIVE
The purpose of this study was to evaluate the efficacy of a standardized premedication and therapeutic drug monitoring (TDM) protocol to prevent hypersensitivity reactions from pegaspargase infusions. Pegaspargase is an essential therapeutic agent used for the treatment of acute lymphoblastic leukemia (ALL) in pediatric patients.
METHODS
This study was a retrospective cohort study conducted at Wolfson Children's Hospital, Jacksonville, Florida, and included pediatric ALL patients 0 to 21 years old. Patients were excluded if they had not received the appropriate premedication after protocol implementation or had received premedication before protocol implementation. Patients were separated into 2 groups: those who received premedication before pegaspargase infusion and those who did not. The primary endpoint was the incidence of documented hypersensitivity reactions. Observational data endpoints included incidence of silent inactivation and cost savings from reducing complicated drug substitutions.
RESULTS
A total of 38 patients (50 doses in no premedication group; 80 doses in premedication group) were evaluated. There was not a significant reduction in the incidence of hypersensitivity reactions for patients receiving premedication and TDM (5.3% vs 6.4%, p = 1.0). A trend towards patients reacting earlier with more severe reactions in the post-implementation group was observed. There were no incidences of silent inactivation. Observational cost analysis predicts potential drug cost savings of $106,550.45.
CONCLUSIONS
A standardized premedication protocol did not reduce the incidence of hypersensitivity reactions. Premedication to prevent hypersensitivity reactions may provide a potential drug cost savings. Further investigation is warranted to assess the efficacy of a standardized premedication and TDM protocol to prevent hypersensitivity reactions.
PubMed: 35350153
DOI: 10.5863/1551-6776-27.3.232 -
Journal of Clinical Pharmacology Sep 2022
Review
Topics: Antineoplastic Agents; Asparaginase; Chemical and Drug Induced Liver Injury, Chronic; Female; Humans; Middle Aged; Pharmacovigilance; Polyethylene Glycols
PubMed: 35342960
DOI: 10.1002/jcph.2052 -
Pediatric Blood & Cancer Nov 2022
Topics: Antineoplastic Agents; Asparaginase; Child; Cost-Benefit Analysis; Humans; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Premedication
PubMed: 35338677
DOI: 10.1002/pbc.29694 -
Frontiers in Oncology 2022The optimal first-line treatment for extra-nodal NK/T-cell lymphoma (ENKTL) has not been well-defined. This study aimed to evaluate the efficacy and safety of...
BACKGROUND
The optimal first-line treatment for extra-nodal NK/T-cell lymphoma (ENKTL) has not been well-defined. This study aimed to evaluate the efficacy and safety of pegaspargase, cyclophosphamide, vincristine, etoposide and prednisone (COEPL) regimen combined with radiotherapy for patients with newly diagnosed ENKTL.
METHODS
Our study is a prospective, open-label clinical trial. Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment. For patients with stage I/II nasal ENKTL, treatment included 2 cycles of induction COEPL regimen followed by concurrent chemoradiotherapy, then by 2 cycles of COEPL regimen as consolidation. For patients with stage III/IV or primary extra-nasal ENKTL, treatment included 6-8 cycles of COEPL regimen with or without radiotherapy to local sites, and autologous stem cell transplantation was given in selected patients.
RESULTS
A total of 80 patients were enrolled. The median age was 41 years (range, 15-76 years). Sixteen patients (20%) had stage III/IV disease, and 10 (12.5%) had a PINK score≥2. Complete response and overall response rates were 75.9% and 87.3%, respectively. With a median follow-up of 41.4 months (range 2.7-76.2 months), the 3-year progression-free survival (PFS) and overall survival (OS) rates were 71.3% (95%CI 61.1-81.5%) and 73.3% (95%CI 63.1-83.5%), respectively. For patients with stage I/II nasal ENKTL (n=62), the 3-year PFS and OS were 78.1% and 81.2%, respectively. For patients with stage III/IV or primary extra-nasal ENKTL (n=18), 3-year PFS and OS were 48.1% and 45.7%, respectively. Major grade 3-4 adverse events were anemia (21.3%), leucopenia (22.5%), neutropenia (18.8%), and thrombocytopenia (7.6%). No treatment-related death was observed.
CONCLUSIONS
Pegaspargase-COEP chemotherapy in combination with radiotherapy is highly effective and safe for patients with newly diagnosed ENKTL.
PubMed: 35280751
DOI: 10.3389/fonc.2022.839252 -
Journal of Clinical Oncology : Official... Jul 2022To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL.
PATIENTS AND METHODS
Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients.
RESULTS
AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% 86.4% ± 4.0%; = .041); and 4-year OS (78.3% ± 4.9% 89.5% ± 3.6%; = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS ( = .412) and OS ( = .600).
CONCLUSION
Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Child; Disease-Free Survival; Humans; Infant; Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T-Lymphocytes; Young Adult
PubMed: 35271306
DOI: 10.1200/JCO.21.02678 -
Frontiers in Genetics 2022PEG-Asparaginase (also known as Pegaspargase), along with glucocorticoids (predominantly prednisolone or dexamethasone) and other chemotherapeutic agents (such as...
PEG-Asparaginase (also known as Pegaspargase), along with glucocorticoids (predominantly prednisolone or dexamethasone) and other chemotherapeutic agents (such as cyclophosphamide, idarubicin, vincristine, cytarabine, methotrexate and 6-mercaptopurine) is the current standard treatment for acute lymphoblastic leukaemia in both children and adults. High doses of PEG-asparaginase are associated with side effects such as hepatotoxicity, pancreatitis, venous thrombosis, hypersensitivity reactions against the drug and severe hypertriglyceridemia. We report a case of a 28-year-old male who was normolipidemic at baseline and developed severe hypertriglyceridemia (triglycerides of 1793 mg/dl) following treatment with PEG-asparaginase for acute lymphoblastic leukaemia. Thorough genetic analysis was conducted to assess whether genetic variants could suggest a predisposition to this drug-induced metabolic condition. This genetic analysis showed the presence of a rare heterozygous missense variant c.11G > A-p.(Arg4Gln) in the APOC3 gene, classified as a variant of uncertain significance, as well as its association with four common single nucleotide polymorphisms (SNPs; c.*40C > G in APOC3 and c.*158T > C; c.162-43G > A; c.-3A > G in APOA5) related to increased plasma triglyceride levels. To our knowledge this is the first case that a rare genetic variant associated to SNPs has been related to the onset of severe drug-induced hypertriglyceridemia.
PubMed: 35237305
DOI: 10.3389/fgene.2022.832890 -
Frontiers in Immunology 2022Asparaginase/pegaspargase containing regimens combined with radiotherapy are highly effective and considered the cornerstone of localized Natural killer/T-cell lymphoma...
Asparaginase/pegaspargase containing regimens combined with radiotherapy are highly effective and considered the cornerstone of localized Natural killer/T-cell lymphoma (NKTL) treatment. However, these chemotherapy regimens inevitably cause relatively high incidence of treatment-related adverse events (TRAEs). Herein we retrospectively evaluated the efficacy and safety of the combined regimen of anti-PD-1 antibody, anlotinib and pegaspargase "sandwich" with radiotherapy in localized NKTL. Anti-PD-1 antibody and pegaspargase at 2500 U/m were administered on day 1, while anlotinib (12 mg once a day) was orally administered on days 1-14. The treatment was repeated every 3 weeks. All the eight patients included received 3 cycles of the regimen followed by radiotherapy and an additional 3 cycles. The overall response rate was 100%, and the complete response rate was 87.5%. With a median follow-up time of 35.5 months (range, 34.03-40.90 months), median PFS and OS times were not reached. The 3-year PFS and OS rates were 100% and 100%, respectively. All patients were alive at the last follow-up. No treatment-related death and no grade 4 TRAE was reported. No grade 3/4 hematological toxicity was detected, and half of the patients didn't report any hematological toxicity. This study indicates that anti-PD-1 antibody combined with anlotinib and pegaspargase is a promising chemoradiotherapy regimen for localized NTKL, with mild toxicity and good tolerance.
Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Deoxycytidine; Humans; Indoles; Killer Cells, Natural; Lymphoma, Extranodal NK-T-Cell; Polyethylene Glycols; Quinolines; Retrospective Studies
PubMed: 35237257
DOI: 10.3389/fimmu.2022.766200 -
Journal of Gastrointestinal Cancer Mar 2023MEITL is a very rare and highly aggressive peripheral T cell lymphoma with poor prognosis and for which there is no standard treatment. Treatment options for patients...
PURPOSE
MEITL is a very rare and highly aggressive peripheral T cell lymphoma with poor prognosis and for which there is no standard treatment. Treatment options for patients patients with relapsed/refractory disease are scarce and the choice of an appropriate rescue still represents an unmet need.
METHODS
Here, we report the case of a 65-year-old woman affected by MEITL, progressing after initial treatment with an anthracycline-based chemotherapy and surgery, who received single-agent PEG-asparaginase salvage therapy at our institution.
RESULTS
PEG-asparaginase single-agent rescue proved to be rapidly effective in controlling the disease and its associated paraneoplastic features. Nevertheless, toxicity was high and the patient died due to a treatment-related complication.
CONCLUSION
The case we described brings new evidences on the effectiveness of PEG-asparaginase therapy in MEITL patients. Whether PEG-asparaginase should be included in the treatment course of MEITL patients could be the subject of future studies.
Topics: Female; Humans; Aged; Enteropathy-Associated T-Cell Lymphoma; Asparaginase; Polyethylene Glycols
PubMed: 35230648
DOI: 10.1007/s12029-022-00808-0 -
Clinical Laboratory Feb 2022Asparaginase (ASP), a chemotherapy component in the acute lymphoblastic leukemia (ALL) treatment, could impair normal coagulation state. Usually, a decline in the levels...
BACKGROUND
Asparaginase (ASP), a chemotherapy component in the acute lymphoblastic leukemia (ALL) treatment, could impair normal coagulation state. Usually, a decline in the levels of several coagulation factors occurs which ultimately could lead to thrombotic events and abnormal coagulation tests. In this study, we aimed to compare the effects of two different subtypes of ASP, pegylated asparaginase (PEG-ASP) and L-asparaginase (L-ASP) on coagulation markers and test among 40 pediatric patients with ALL.
METHODS
In this cohort study a total of 40 pediatric patients with newly diagnosed ALL were enrolled and divided into two groups by simple randomization. In group A, 20 patients received PEG-ASP while in group B, 20 patients received L-ASP during the induction treatment. Coagulation markers included prothrombin time (PT), partial thrombin time (PTT), protein-C (Pr-C), protein-S (Pr-S), and antithrombin III (ATIII) and were assessed before start and after of induction chemotherapy.
RESULTS
Coagulation profile including PT, PTT, INR, Pr-C, Pr-S, and ATIII before start of treatment were not statistically significant between the two groups. Anticoagulant factors decreased significantly after consuming both drugs. Tests for PT and INR of those who took L-ASP decreased significantly. Overall, when comparing the changes of the six studied factors, ATIII and Pr-C were the significant factors which were different between groups.
CONCLUSIONS
ASP has a negative effect on anticoagulant factors including (ATIII, Pr-C, Pr-S). Additionally, the negative effect of L-ASP on anticoagulant factors was more prominent than PEG-ASP. Therefore, the risk of thrombosis probably was negligible in PEG-ASP in comparison with L-ASP.
Topics: Asparaginase; Child; Cohort Studies; Humans; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 35142188
DOI: 10.7754/Clin.Lab.2021.210502