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Immunotherapy Apr 2022The emergence of antitumor immunotherapy has been beneficial for patients with tumors, but more attention should be paid to the toxic side effects of... (Review)
Review
The emergence of antitumor immunotherapy has been beneficial for patients with tumors, but more attention should be paid to the toxic side effects of chemoimmunotherapy. Here we describe a patient with NK/T-cell lymphoma who developed toxic epidermal necrolysis (TEN) during treatment with a regimen consisting of sintilimab combined with pegaspargase, gemcitabine and oxaliplatin (P-GemOx). A patient received six cycles of P-GemOx chemotherapy as first-line treatment; 1 year later, he received the same dose of P-GemOx combined with sintilimab as chemoimmunotherapy due to recurrence of NK/T-cell lymphoma. He developed a massive rash that quickly developed into TEN after the fourth chemoimmunotherapy. Although rare, cases of fatal TEN caused by single-agent PD-1 inhibitor or gemcitabine have been reported. Careful attention to drug-related cutaneous toxicities is needed when these two agents are combined. This report highlights the significance of TEN as a rapid and serious adverse event induced by chemoimmunotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Humans; Immunotherapy; Lymphoma, Extranodal NK-T-Cell; Male; Oxaliplatin; Stevens-Johnson Syndrome; Treatment Outcome
PubMed: 35128931
DOI: 10.2217/imt-2021-0074 -
Frontiers in Oncology 2021Angioimmunoblastic T-cell lymphoma (AITL) is a kind of peripheral T-cell lymphomas (PTCLs) with a highly invasive feature. At present, patients are often treated with...
Angioimmunoblastic T-cell lymphoma (AITL) is a kind of peripheral T-cell lymphomas (PTCLs) with a highly invasive feature. At present, patients are often treated with CHOP or CHOP-like regimens which is of poor prognosis whilst having high recurrence rate. Once the patient fails to achieve remission or relapse after the first-line treatment, many salvage chemotherapy regimens are always ineffective, and the long-term survival will be difficult to achieve for them. In this circumstance, more effective therapy methods are needed. In this study, two patients with relapsed/refractory AITL were treated with the CAOLD regimen [cyclophosphamide 400 mg/m qd d1, cytarabine 30 mg/m qd d1-d4, vindesine 2 mg/m qd d1, pegaspargase (PEG-ASP) 2,500 IU/m qd d2, dexamethasone 7.5 mg/m qd d1-d5], and long-term remission was achieved after chemotherapy. One is still alive after achieving complete remission (CR) after two cycles of chemotherapy, who has been followed up for 82 months. Besides, another patient achieved partial remission (PR) after the first course of chemotherapy. Then, CR was obtained after four courses of consolidation chemotherapy. The patient has been followed up for 63 months and is still alive. Both of them achieved long-time survival. These two successful cases demonstrated that the CAOLD regimen can be a better choice for relapsed/refractory AITL and offers hope of breakthrough in this medical field.
PubMed: 35047389
DOI: 10.3389/fonc.2021.758445 -
Pediatric Blood & Cancer Jul 2022Chemotherapy regimens containing glucocorticoids and pegaspargase are associated with hyperglycemia; however, the pattern and underlying risk factors are not well...
BACKGROUND
Chemotherapy regimens containing glucocorticoids and pegaspargase are associated with hyperglycemia; however, the pattern and underlying risk factors are not well characterized. We determined the pattern of hyperglycemia and associated factors in children with acute lymphoblastic leukemia (ALL) receiving glucocorticoids and pegaspargase during induction.
METHODS
Retrospective analysis of patients treated between 2010 and 2020 at a single institution. Pretreatment data, glucose values, and insulin regimens were abstracted from the record. Hyperglycemia was defined as two or more random glucose measurements ≥200 mg/dl. Analyses of demographic and clinical factors were conducted with logistic regression.
RESULTS
Two hundred thirteen patients, median age 6 years (range 1.0-18.9 years), 47% female, were included. The prevalence of hyperglycemia was 23% (n = 48). Mean glucose levels peaked 3 days following administration of pegaspargase. In multivariable analysis, age ≥10 years (odds ratio [OR] 6.2, 95% confidence interval [CI]: 2.9-13.4), female sex (OR 2.7, 95% CI: 1.2-6.2), and family history of diabetes (OR 3.2, 95% CI: 1.4-7.3) were predictive of hyperglycemia. Age ≥10 years (OR 19.4, 95% CI: 5.5-68.4), family history of diabetes (OR 8.2, 95% CI: 2.7-25.3), and higher body mass index (BMI) (OR 1.8, 95% CI: 1.1-2.9) were associated with insulin treatment.
CONCLUSIONS
Onset of hyperglycemia in children receiving induction chemotherapy for ALL is temporally linked to administration of pegaspargase. Older age, female sex, and family history of diabetes are predictive of hyperglycemia during induction; older age, family history of diabetes, and higher BMI are associated with insulin treatment. Frequent glucose monitoring is indicated during induction therapy for ALL.
Topics: Adolescent; Asparaginase; Blood Glucose; Blood Glucose Self-Monitoring; Child; Child, Preschool; Diabetes Mellitus; Female; Glucocorticoids; Humans; Hyperglycemia; Induction Chemotherapy; Infant; Insulin; Male; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies
PubMed: 34931744
DOI: 10.1002/pbc.29505 -
Pediatric Blood & Cancer Apr 2022
Topics: Asparaginase; Child; Cost-Benefit Analysis; Dickeya chrysanthemi; Humans; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Premedication; Technology
PubMed: 34889044
DOI: 10.1002/pbc.29474 -
The Journal of Allergy and Clinical... Feb 2022
Topics: Asparaginase; COVID-19; COVID-19 Vaccines; Humans; Hypersensitivity; Polyethylene Glycols; SARS-CoV-2
PubMed: 34883262
DOI: 10.1016/j.jaip.2021.11.025 -
European Journal of Drug Metabolism and... Mar 2022Besides allergic reactions, antibodies against polyethylene glycol (PEG) have been associated with reduced PEG-asparaginase (PEG-ASNase) activity. Population... (Clinical Trial)
Clinical Trial
Impact of Antibodies Against Polyethylene Glycol on the Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukaemia: A Population Pharmacokinetic Approach.
BACKGROUND AND OBJECTIVES
Besides allergic reactions, antibodies against polyethylene glycol (PEG) have been associated with reduced PEG-asparaginase (PEG-ASNase) activity. Population pharmacokinetics (popPK) allow for an in-depth investigation of the influence of anti-PEG antibodies on PEG-ASNase pharmacokinetics.
METHODS
PEG-ASNase activity (6261 samples) and anti-PEG antibodies (2082/6412 samples prior to/post administration) in 1444 children with acute lymphoblastic leukaemia treated in the AIEOP-BFM ALL 2009 trial were evaluated. Patients received two doses of PEG-ASNase during induction (2500 U/m, intravenous, biweekly) and a third dose during reinduction treatment. Anti-PEG IgG and IgM measured prior to and post administration were explored for their influence on the initial clearance of PEG-ASNase using a previously established popPK model. Categorical and continuous antibody data, including each isotype individually as well as in combination, were assessed.
RESULTS
High pre-existing levels of anti-PEG antibodies increase the initial drug clearance. Analysed separately, both anti-PEG IgG and IgM were significant covariates; the stronger effect was observed for anti-PEG IgM. Hockey stick models best described the data. For anti-PEG IgM, each additional log unit above the estimated cut point was related to a 41.4% increase in initial clearance after the first dose in induction. Antibody levels below the cut point were not associated with an effect on clearance. The combination of both isotypes did not provide additional information compared to anti-PEG IgM alone. Antibody levels post administration were not associated with an effect on clearance.
CONCLUSION
Pre-existing antibodies against PEG-ASNase significantly increased the initial clearance in a subgroup of patients showing high antibody levels. (Trial registration: EU clinical trials register; EudraCT No: 2007-004270-43; first registered 23 October 2009.).
Topics: Antineoplastic Agents; Asparaginase; Child; Humans; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 34878584
DOI: 10.1007/s13318-021-00741-w -
Annals of Palliative Medicine Nov 2021Extranodal natural killer (NK)/T-cell lymphoma-nasal type (ENKTL-NT) is a rare, aggressive subtype of non-Hodgkin's lymphoma associated with Epstein-Barr virus (EBV)... (Review)
Review
Extranodal natural killer (NK)/T-cell lymphoma-nasal type (ENKTL-NT) is a rare, aggressive subtype of non-Hodgkin's lymphoma associated with Epstein-Barr virus (EBV) infection and has a poor prognosis. ENKTL-NT primarily involves the nasal cavity, and the colon as the primary site has rarely been reported. Its lack of a characteristic clinical presentation makes early diagnosis difficult to diagnose early, and misdiagnosis is common without the use of immunohistochemistry of specimens. To further understand this rare solid tumor, we report a case in a 51-year-old male patient admitted to hospital with abdominal pain as the primary symptom. A provisional diagnosis of gastrointestinal perforation was made on the basis of enhanced computed tomography of the abdomen, and emergency surgery was performed. However, 58 days after discharge, he suffered a second colonic perforation, underwent emergency surgery and was diagnosed with primary colonic ENKTL-NT based on the immunohistochemical results of the surgical specimen. He was transferred to the oncology department for chemotherapy after recovery from surgery, with gemcitabine, oxaliplatin, and pegaspargase as the chemotherapy regimen. To date, he has completed 11 courses of chemotherapy, and is now in a significantly improved general condition with no signs of tumor recurrence. We also reviewed and compared the literature related to primary colonic ENKTL-NT.
Topics: Colon; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Killer Cells, Natural; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged
PubMed: 34872326
DOI: 10.21037/apm-21-3178 -
European Journal of Cancer (Oxford,... Mar 2022Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of... (Review)
Review
Cancer in neonates and infants is a rare but challenging entity. Treatment is complicated by marked physiological changes during the first year of life, excess rates of toxicity, mortality, and late effects. Dose optimisation of chemotherapeutics may be an important step to improving outcomes. Body size-based dosing is used for most anticancer drugs used in infants. However, dose regimens are generally not evidence based, and dosing strategies are frequently inconsistent between tumour types and treatment protocols. In this review, we collate available pharmacological evidence supporting dosing regimens in infants for a wide range of cytotoxic drugs. A systematic review was conducted, and available data ranked by a level of evidence (1-5) and a grade of recommendation (A-D) provided on a consensus basis, with recommended dosing approaches indicated as appropriate. For 9 of 29 drugs (busulfan, carboplatin, cyclophosphamide, daunorubicin, etoposide, fludarabine, isotretinoin, melphalan and vincristine), grade A was scored, indicating sufficient pharmacological evidence to recommend a dosing algorithm for infants. For busulfan and carboplatin, sufficient data were available to recommend therapeutic drug monitoring in infants. For eight drugs (actinomycin D, blinatumomab, dinutuximab, doxorubicin, mercaptopurine, pegaspargase, thioguanine and topotecan), some pharmacological evidence was available to guide dosing (graded as B). For the remaining drugs, including commonly used agents such as cisplatin, cytarabine, ifosfamide, and methotrexate, pharmacological evidence for dosing in infants was limited or non-existent: grades C and D were scored for 10 and 2 drugs, respectively. The review provides clinically relevant evidence-based dosing guidance for cytotoxic drugs in neonates and infants.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carboplatin; Etoposide; Humans; Infant; Infant, Newborn
PubMed: 34865945
DOI: 10.1016/j.ejca.2021.11.001 -
Journal of Oncology Pharmacy Practice :... Jan 2023Pegaspargase can cause anti-asparaginase antibody formation, which can decrease its effectiveness without causing any clinically apparent reaction (silent inactivation)....
INTRODUCTION
Pegaspargase can cause anti-asparaginase antibody formation, which can decrease its effectiveness without causing any clinically apparent reaction (silent inactivation). When a patient has silent inactivation, a switch to anti-asparaginase is warranted, but there is currently a global shortage of . The only way to identify silent inactivation is to measure an asparaginase level. However, routine asparaginase level monitoring is not currently standard of care at all Canadian centers. This study aims to identify variations in practice regarding asparaginase level monitoring and use.
METHODS
A 21-item survey was developed using OPINIO software and distributed to all Pediatric Hematology-Oncologists in Canada from February to October 2020.
RESULTS
Respondents represented 15 hospitals across each region of Canada (response rate = 52%). Only 39.2% of respondents reported routinely measuring asparaginase levels, yet 53% of respondents have modified therapy from pegaspargase to in up to half of their patients. The most common reason for not measuring asparaginase levels was not knowing how to use levels clinically (25.5%). There was variation in the timing of levels and their target.
CONCLUSIONS
We identified substantial variation in asparaginase activity monitoring practices across Canada. Therefore, future research should aim to develop a national practice guideline on asparaginase activity monitoring.
Topics: Child; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; Canada; Erwinia; Drug Hypersensitivity
PubMed: 34854779
DOI: 10.1177/10781552211055405 -
British Journal of Haematology Feb 2022Early-stage natural killer/T-cell lymphoma (NK/TCL) patients usually receive a combination of chemotherapy and radiotherapy, but the optimal treatment approach has not...
Early-stage natural killer/T-cell lymphoma (NK/TCL) patients usually receive a combination of chemotherapy and radiotherapy, but the optimal treatment approach has not yet been established. This study aimed to investigate the efficacy and safety profile of a novel chemotherapy regimen and sandwiched radiotherapy in early-stage NK/TCL. Patients with newly diagnosed stage IE/IIE disease were eligible. Patients were initially treated with two courses of the GELAD regimen (gemcitabine 1·0 g/m day 1, etoposide 60 mg/m days 1-3, pegaspargase 2000 units/m day 4, and dexamethasone 40 mg days 1-4), followed by intensity-modulated radiotherapy (IMRT; 50-56 Gy in 25-28 fractions) and two additional courses of GELAD chemotherapy. A total of 52 patients were enrolled. The overall response rate and complete response rate per Lugano 2014 criteria were 94·2% and 92·3% respectively. With a median follow-up of 32 months, the estimated four-year overall survival rate and progression-free survival rate were 94·2% [95% confidence interval (CI), 83·2% to 93·1%] and 90·4% (95% CI, 78·4% to 95·9%) respectively. The most common adverse events were related to pegaspargase. Haematological toxicities were mild, with grade 3/4 neutropenia in 15·4% of patients. Our study provides a new approach with high activity and improved safety for the treatment of early-stage NK/TCL patients. This study was registered at www.clinicaltrials.gov as NCT02733458.
Topics: Adolescent; Adult; Aged; Female; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Neoplasm Staging; Progression-Free Survival; Prospective Studies; Treatment Outcome; Young Adult
PubMed: 34806163
DOI: 10.1111/bjh.17960