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Journal of Feline Medicine and Surgery Sep 2023The present study aimed to investigate pegylated-l-asparaginase monotherapy for feline large cell lymphoma as a potential alternative to palliative corticosteroids...
OBJECTIVES
The present study aimed to investigate pegylated-l-asparaginase monotherapy for feline large cell lymphoma as a potential alternative to palliative corticosteroids treatment in animals whose owners declined cytotoxic chemotherapy.
METHODS
A retrospective, descriptive case series of cats treated initially with pegylated-l-asparaginase as a sole therapy for feline large cell lymphoma is reported. The treatment protocol consisted of 12 intramuscular injections of pegylated-l-asparaginase with increasing intervals. If cats were unresponsive to pegylated-l-asparaginase monotherapy, a second-line treatment was initiated. Signalment, origin of lymphoma, staging, treatment, possible adverse events and follow-up data were extracted from the medical records. Responses and survival data were analysed.
RESULTS
Eighty-two cats with lymphoma of five different anatomic types were included: alimentary, abdominal extra-alimentary, peripheral nodal, nasal/nasopharyngeal and other (mediastinal, renal [solitary] and miscellaneous combined in one group for analytical purposes). The response rate was 74.1% (95% confidence interval = 63.4-83.5) with 38.3% (95% confidence interval = 27.8-48.8) in complete remission. The median disease-free period and calculated overall survival time were 70 days (12-1702+) and 79 days (1-1715+), respectively. The response rate was significantly correlated with the origin of the lymphoma and the combined group had a significantly lower response rate ( = 0.035). Twenty-four cats were also treated with corticosteroids. There was no significant difference in outcomes between the group treated with or without corticosteroids. Adverse events were present in a small number of cats (14/82). The majority of these adverse events were mild to moderate in 5/14 cats; however, the adverse events were severe enough to cause discontinuation of therapy.
CONCLUSIONS AND RELEVANCE
Based on the response rate and median disease-free period, treatment with pegylated-l-asparaginase is inferior when compared with historical chemotherapy protocols. However, some cats demonstrated an exceptional long disease-free period. Therefore, pegylated-l-asparaginase could be offered as an alternative to corticosteroid therapy alone. Further studies are needed to evaluate the additional benefit over palliative corticosteroid monotherapy.
Topics: Cats; Animals; Retrospective Studies; Polyethylene Glycols; Asparaginase; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37713175
DOI: 10.1177/1098612X231193536 -
Leukemia & Lymphoma Dec 2021Treatment of pediatric acute lymphoblastic leukemia (ALL) with pegaspargase exploits ALL cells dependency on asparagine. Pegaspargase depletes asparagine,...
Treatment of pediatric acute lymphoblastic leukemia (ALL) with pegaspargase exploits ALL cells dependency on asparagine. Pegaspargase depletes asparagine, consequentially affecting aspartate, glutamine and glutamate. The gut as a confounding source of these amino acids (AAs) and the role of gut microbiome metabolism of AAs has not been examined. We examined asparagine, aspartate, glutamine and glutamate in stool samples from patients over pegaspargase treatment. Microbial gene-products, which interact with these AAs were identified. Stool asparagine declined significantly, and 31 microbial genes changed over treatment. Changes were complex, and included genes involved in AA metabolism, nutrient sensing, and pathways increased in cancers. While we identified changes in a gene () with limited asparaginase activity, it lacked significance after correction leaving open other mechanisms for asparagine decline, possibly including loss from gut to blood. Understanding pathways that change AA availability, including by microbes in the gut, could be useful in optimizing pegaspargase therapy.
Topics: Antineoplastic Agents; Asparaginase; Asparagine; Aspartic Acid; Child; Genes, Bacterial; Glutamic Acid; Glutamine; Humans; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 34279176
DOI: 10.1080/10428194.2021.1953006 -
Cancer Treatment Reviews Sep 2020To date, much progress has been made in early-stage extranodal NK/T-cell lymphoma (ENKTCL), and risk-adapted therapy with radiotherapy (RT) alone for the low-risk group... (Review)
Review
To date, much progress has been made in early-stage extranodal NK/T-cell lymphoma (ENKTCL), and risk-adapted therapy with radiotherapy (RT) alone for the low-risk group and RT combined with asparaginase-based chemotherapy (CT) for the high-risk group yields favorable outcomes. However, optimal treatment strategies have not been defined yet for advanced-stage ENKTCL. Historically, ENKTCL responded poorly to conventional anthracycline-based chemotherapy probably because of inherent multidrug resistance (MDR). The fact that ENKTCL cells lack asparagine synthetase (ASNS) activity warranted the use of L-asparaginase or pegaspargase as frontline chemotherapies. Even though, due to high mortality of the disease, approximately 50% patients failing the frontline therapy arrived at dismal clinical outcomes with a median progression-free survival (PFS) less than 8 months. As distinctive molecular and biological subgroups are increasingly discovered within the disease entity of ENKTCL, novel targeted therapies and immunotherapy are of the urgent need for those heterogeneous subgroups. In this review, we sought to summarize the preclinical and clinical results of 6 categories of promising targeted therapy and immunotherapy for the treatment of ENKTCL, including monoclonal antibodies, immune checkpoint inhibitors, small-molecular inhibitors, epigenetic therapy, immunomodulatory drugs, and adoptive T-cell therapy, and these might change the landscape of treatment for ENKTCL in the near future.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Immunological; Humans; Immunologic Factors; Immunotherapy; Immunotherapy, Adoptive; Lymphoma, Extranodal NK-T-Cell; Molecular Targeted Therapy; Small Molecule Libraries
PubMed: 32653806
DOI: 10.1016/j.ctrv.2020.102065 -
Current Protein & Peptide Science 2020Therapeutic peptides (TPs) are biological macromolecules which can act as neurotransmitters, hormones, ion channel ligands and growth factors. Undoubtedly, TPs are... (Review)
Review
Therapeutic peptides (TPs) are biological macromolecules which can act as neurotransmitters, hormones, ion channel ligands and growth factors. Undoubtedly, TPs are crucial in modern medicine. But low bio-stability and some special adverse reactions reduce their places to the application. With the development of nanotechnology, nanoparticles (NPs) in pharmaceutical science gained much attention. They can encapsulate the TPs into their membrane or shell. Therefore, they can protect the TPs against degradation and then increase the bioavailability, which was thought to be the biggest advantage of them. Additionally, targeting was also studied to improve the effect of TPs. However, there were some drawbacks of nano TPs like low loading efficiency and difficulty to manufacture. Nowadays, lots of studies focused on improving effect of TPs by preparing nanoparticles. In this review, we presented a brief analysis of peptide-combined nanoparticles. Their advantages and disadvantages were listed in terms of mechanism. And several examples of applications were summarized.
Topics: Acetylmuramyl-Alanyl-Isoglutamine; Asparaginase; Biological Availability; Biological Transport; Delayed-Action Preparations; Diabetes Mellitus; Drug Carriers; Drug Compounding; Half-Life; Humans; Insulin; Nanomedicine; Nanoparticles; Neoplasms; Peptides; Phosphatidylethanolamines; Polyethylene Glycols; Protein Stability
PubMed: 32039679
DOI: 10.2174/1389203721666200210103841 -
European Journal of Haematology Mar 2024There are significant disparities in outcomes among Hispanic patients with acute lymphoblastic leukemia (ALL). Recent studies have demonstrated favorable outcomes of...
OBJECTIVE
There are significant disparities in outcomes among Hispanic patients with acute lymphoblastic leukemia (ALL). Recent studies have demonstrated favorable outcomes of pegaspargase-containing ALL regimens (PEG-CAR) in young adults however, outcomes in Hispanic ethnicity continue to be underreported.
METHODS
We evaluated outcomes of newly diagnosed, adult B-cell ALL Hispanic and non-Hispanic patients consecutively treated with a PEG-CAR or HyperCVAD between January 2011 and November 2022. The primary endpoint was event-free survival (EFS) while secondary endpoints included cumulative incidence of relapse and overall survival (OS).
RESULTS
Among 105 included patients, 48 (45.7%) were treated with a PEG-CAR and 57 (54.3%) with HyperCVAD. Median age was 38 years (range, 18-75 years), 61% were Hispanic, and 35.2% had poor-genetic risk. Hispanic patients demonstrated significantly worse 5-year EFS with a PEG-CAR compared to that seen with HyperCVAD (HR, 2.58; 95% CI, 1.32-5.04; p = .006) whereas non-Hispanic patients had better outcomes with PIR (52.4% vs. 42.0%). Hispanic ethnicity (p = .015) and male sex (p = .019) were independent predictors for poor OS.
CONCLUSIONS
Hispanic patients with B-cell ALL had worse EFS with a PEG-CAR as compared with HyperCVAD. Future studies will aim to confirm these findings and establish a tailored treatment approach for this high-risk population.
Topics: Young Adult; Humans; Male; Adult; Asparaginase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polyethylene Glycols; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies
PubMed: 37933194
DOI: 10.1111/ejh.14125 -
Pediatric Hematology and Oncology Mar 2024Due to an evidence gap, the emetogenicity of intravenous (IV) pegaspargase was unable to be included in the clinical practice guideline classifying chemotherapy...
Due to an evidence gap, the emetogenicity of intravenous (IV) pegaspargase was unable to be included in the clinical practice guideline classifying chemotherapy emetogenicity in pediatric patients. This single-center, retrospective chart review describes the proportion of pediatric patients who did not vomit during the acute phase (complete response; CR) after receiving IV pegaspargase and provides an emetogenicity classification using a preexisting framework. Of 44 patients who received IV pegaspargase between 2011 and 2020, 13 received a serotonin receptor antagonist plus dexamethasone or palonosetron alone and all experienced a CR. We, therefore, recommend classifying IV pegaspargase as moderately emetogenic.
PubMed: 38454568
DOI: 10.1080/08880018.2024.2311886 -
Leukemia Research Sep 2020To explore the effectiveness and safety of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide combination (SVILE regimen) in the treatment of...
SVILE regimen, a combination of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide, for treating relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type.
OBJECTIVE
To explore the effectiveness and safety of dexamethasone, vindesine, ifosfamide, pegaspargase, and etoposide combination (SVILE regimen) in the treatment of relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (R/R-ENKTL).
METHODS
This descriptive, retrospective medical chart review assessed data from 20 R/R-ENKTL patients treated with the SVILE regimen between November 2014 and August 2019. Complete response (CR) rate, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) since SVILE treatment were analysed.
RESULTS
After receiving 1-5 SVILE regimen chemotherapy cycles (median 2 cycles), patients had ORR and CR rates of 70.0 % and 45.0 %, respectively. Stage Ⅰ/Ⅱ patients had CR rate of 100.0 % and stage Ⅲ/Ⅳ patients had ORR and CR rates of 60.0 % and 26.7 %, respectively. Three-year PFS and OS rates of the 20 patients were 43.8 % and 54.2 %, respectively. Three-year PFS and OS rates of stage Ⅰ/Ⅱ patients and stage Ⅲ/Ⅳ patients were 100.0 % vs. 26.7 % and 100.0 % vs. 40.0 % (P < 0.05), respectively. The PFS and OS of patients who achieved CR after SVILE chemotherapy were significantly better than those of non-CR patients. The main adverse events were reversible haematological toxicity.
CONCLUSIONS
The SVILE regimen is a new treatment option that is effective and safe for R/R-ENKTL patients.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Dexamethasone; Drug Resistance, Neoplasm; Etoposide; Female; Follow-Up Studies; Humans; Ifosfamide; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Nose Neoplasms; Polyethylene Glycols; Prognosis; Retrospective Studies; Salvage Therapy; Survival Rate; Vindesine; Young Adult
PubMed: 32721642
DOI: 10.1016/j.leukres.2020.106422 -
Leukemia & Lymphoma Dec 2022
Topics: Adult; Humans; Incidence; Hypertriglyceridemia; Pancreatitis; Hispanic or Latino; Acute Disease
PubMed: 35834729
DOI: 10.1080/10428194.2022.2098288 -
Cancer Management and Research 2019To evaluate the clinical efficacy and safety of the DDGP regimen in treating extranodal NK/T-cell lymphoma and investigate the correlation between Epstein-Barr virus...
Clinical efficacy of cisplatin, dexamethasone, gemcitabine and pegaspargase (DDGP) in the initial treatment of advanced stage (stage III-IV) extranodal NK/T-cell lymphoma, and its correlation with Epstein-Barr virus.
To evaluate the clinical efficacy and safety of the DDGP regimen in treating extranodal NK/T-cell lymphoma and investigate the correlation between Epstein-Barr virus (EBV)-DNA variation after treatment and the clinical efficacy of NK/T-cell lymphoma. Sixty-four patients with extranodal NK/T-cell lymphoma received DDGP regimen-based chemotherapy. Short-term and long-term clinical efficacy and adverse reactions were observed. The relationship between EBV-DNA changes before and after therapy and clinical efficacy was investigated. After the DDGP regimen was used as the initial treatment, the short-term clinical efficacy included 39 complete remission (CR) (60.94%), 12 partial remission (PR) (18.75%), 2 stable disease (SD) (3.13%) and 11 progressive disease (PD) (17.18%). Objective response rate (ORR) was 79.69% and 82.82% for disease control rate (DCR). 3-year progression-free survival (PFS) was 62.00% and 3-year overall survive (OS) was 74.90%. Hemocytopenia was the predominant adverse effect. Between EBV-DNA positive group and its negative counterpart, a significant difference was noted in OS (=0.046), but no difference in ORR, DCR or PFS was observed. In the EBV-DNA positive group, ORR, DCR, PFS and OS were higher for patients whose EBV-DNA copy number decreased within a normal range than patients remained positive (93.33% versus 61.53%, =0.041 for ORR; 93.33% versus 61.53%, =0.041 for DCR, =0.003 for PFS, =0.017 for OS). The main adverse reactions included bone marrow suppression, gastrointestinal reaction and coagulation dysfunction, which were mitigated and treated after expectant or dose-decrement treatment. DDGP regimen can significantly improve the clinical prognosis of NK/T-cell lymphoma patients with tolerable adverse reactions. The variation in EBV-DNA is correlated with clinical efficacy and prognosis, which provides a theoretical basis for NK/T-cell lymphoma therapy. : In November 2011, this clinical trial was registered on the website: www.ClinicalTrials.gov (No. NCT01501149).
PubMed: 31118779
DOI: 10.2147/CMAR.S191929 -
Cancer Medicine Nov 2021Pegaspargase (PEG-ASP) is an integral component of therapy for acute lymphoblastic leukemia (ALL) but is associated with hepatotoxicity that may delay or limit future...
BACKGROUND
Pegaspargase (PEG-ASP) is an integral component of therapy for acute lymphoblastic leukemia (ALL) but is associated with hepatotoxicity that may delay or limit future therapy. Obese and adolescent and young adult (AYA) patients are at high risk. Levocarnitine has been described as potentially beneficial for the treatment or prevention of PEG-ASP-associated hepatotoxicity.
METHODS
We collected data for patients age ≥10 years who received levocarnitine during induction therapy for ALL, compared to a similar patient cohort who did not receive levocarnitine. The primary endpoint was conjugated bilirubin (c.bili) >3 mg/dl. Secondary endpoints were transaminases >10× the upper limit of normal and any Grade ≥3 hepatotoxicity.
RESULTS
Fifty-two patients received levocarnitine for prophylaxis (n = 29) or rescue (n = 32) of hepatotoxicity. Compared to 109 patients without levocarnitine, more patients receiving levocarnitine were obese and/or older and had significantly higher values for some hepatotoxicity markers at diagnosis and after PEG-ASP. Levocarnitine regimens varied widely; no adverse effects of levocarnitine were identified. Obesity and AYA status were associated with an increased risk of conjugated hyperbilirubinemia and severe transaminitis. Multivariable analysis identified a protective effect of levocarnitine on the development of c.bili >3 mg/dl (OR 0.12, p = 0.029). There was no difference between groups in CTCAE Grade ≥3 hepatotoxicity. C.bili >3 mg/dl during induction was associated with lower event-free survival.
CONCLUSIONS
This real-world data on levocarnitine supplementation during ALL induction highlights the risk of PEG-ASP-associated hepatotoxicity in obese and AYA patients, and hepatotoxicity's potential impact on survival. Levocarnitine supplementation may be protective, but prospective studies are needed to confirm these findings.
Topics: Adolescent; Adult; Antineoplastic Agents; Asparaginase; Carnitine; Chemical and Drug Induced Liver Injury; Child; Female; Humans; Induction Chemotherapy; Male; Pediatric Obesity; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survival Analysis; Young Adult
PubMed: 34528411
DOI: 10.1002/cam4.4281