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Cancer Medicine Dec 2023The clinicopathologic characteristics and prognosis of nasal and nonnasal extranodal natural killer T-cell lymphoma (ENKTL) are considered to be different. However, the...
BACKGROUND
The clinicopathologic characteristics and prognosis of nasal and nonnasal extranodal natural killer T-cell lymphoma (ENKTL) are considered to be different. However, the underlying features responsible for these differences are not well clarified especially in the era of asparaginase therapy.
METHODS
In total, 1007 newly diagnosed ENKTL patients from 11 medical centers were included in this study. Clinicopathologic characteristics and survival data were collected. The chi-squared test and Kruskal-Wallis test were utilized for the comparison of different groups. Univariable and multivariable Cox proportional hazards models were used to screen prognostic factors.
RESULTS
Overall, 869 (86.3%) patients were nasal forms. Compared to patients with nasal ENKTL, nonnasal patients were at more advanced stages and had poor performance status, bone marrow involvement, elevated serum lactate dehydrogenase (LDH), and CD56-negative status (p < 0.05). The 5-year overall survival (OS) for nasal and nonnasal patients were 65.6% and 45.0%, respectively. The OS of nasal forms patients were superior to nonnasal patients, especially in Eastern Cooperative Oncology Group performance status (ECOG PS) (≥2), advanced stage, KPI (HIR/HR), IPI (HIR/HR), PINK (HR), and high EBV DNA load groups. In patients treated with pegaspargase/L-asparaginase-based regimens, the OS of nasal patients was better than that of nonnasal patients. After adjusting the covariates of age, stage, ECOG PS score, LDH, B symptoms, and BM involvement, results showed that the nonnasal site was associated with poor survival of ENKTL.
CONCLUSIONS
The clinicopathologic characteristics and prognosis of nasal and nonnasal ENKTL patients are different. Nasal forms patients had superior OS than nonnasal patients, especially in the era of asparaginase.
Topics: Humans; Asparaginase; Lymphoma, Extranodal NK-T-Cell; Neoplasm Staging; Prognosis; Retrospective Studies
PubMed: 37902266
DOI: 10.1002/cam4.6674 -
Cancer Chemotherapy and Pharmacology Oct 2021We evaluated effects of asparaginase dosage, schedule, and formulation on CSF asparagine in children with acute lymphoblastic leukemia (ALL). (Comparative Study)
Comparative Study Randomized Controlled Trial
PURPOSE
We evaluated effects of asparaginase dosage, schedule, and formulation on CSF asparagine in children with acute lymphoblastic leukemia (ALL).
METHODS
We evaluated CSF asparagine (2114 samples) and serum asparaginase (5007 samples) in 482 children with ALL treated on the Total XVI study (NCT00549848). Patients received one or two 3000 IU/m IV pegaspargase doses during induction and were then randomized in continuation to receive 2500 IU/m or 3500 IU/m IV intermittently (four doses) on the low-risk (LR) or continuously (15 doses) on the standard/high risk (SHR) arms. A pharmacokinetic-pharmacodynamic model was used to estimate the duration of CSF asparagine depletion below 1 uM.
RESULTS
During induction, CSF asparagine depletion after two doses of pegaspargase was twice as long as one dose (median 30.7 vs 15.3 days, p < 0.001). During continuation, the higher dose increased the CSF asparagine depletion duration by only 9% on the LR and 1% in the SHR arm, consistent with the nonlinear pharmacokinetics of serum asparaginase. Pegaspargase caused a longer CSF asparagine depletion duration (1.3-5.3-fold) compared to those who were switched to erwinase (p < 0.001). The median (quartile range) serum asparaginase activity needed to maintain CSF asparagine below 1 µM was 0.44 (0.20, 0.99) IU/mL. Although rare, CNS relapse was higher with decreased CSF asparagine depletion (p = 0.0486); there was no association with relapse at any site (p = 0.3).
CONCLUSIONS
The number of pegaspargase doses has a stronger influence on CSF asparagine depletion than did dosage, pegaspargase depleted CSF asparagine longer than erwinase, and CSF asparagine depletion may prevent CNS relapses.
Topics: Antineoplastic Agents; Asparaginase; Asparagine; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Models, Biological; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies
PubMed: 34170389
DOI: 10.1007/s00280-021-04315-0 -
Cancer Management and Research 2018l-asparaginase or pegaspargase-based chemotherapies have shown promising results in the treatment of extranodal NK/T-cell lymphoma. A retrospective study was conducted...
Pegaspargase, gemcitabine, dexamethasone, and cisplatin (P-GDP) combined chemotherapy is effective for newly diagnosed extranodal NK/T-cell lymphoma: a retrospective study.
PURPOSE
l-asparaginase or pegaspargase-based chemotherapies have shown promising results in the treatment of extranodal NK/T-cell lymphoma. A retrospective study was conducted to determine the efficacy and safety of pegaspargase, gemcitabine, dexamethasone, and cisplatin (P-GDP) combined chemotherapy in patients with newly diagnosed extranodal NK/T-cell lymphoma.
PATIENTS AND METHODS
From September 2013 to November 2016, 57 patients with newly diagnosed, stages I to IV, extranodal NK/T-cell lymphoma received P-GDP chemotherapy. Clinical data from these patients were collected and analyzed to evaluate the efficacy and safety of P-GDP.
RESULTS
All patients were subjected to 1-6 cycles of P-GDP chemotherapy, and the median number of cycles of P-GDP regimen administered was 3. The overall response rate was 89.5% (51/57), including a complete response rate of 70.2% (40/59) and a partial response rate of 19.3% (11/57). The median follow-up time was 28 months (range 2-54 months). The 2-year overall survival and progression-free survival (PFS) rates were 82.9% and 75.9%, respectively. For stage I/II patients and stage III/IV patients, 2-year PFS were 80.8% and 66.7%, respectively. The most common grade 3/4 adverse events were neutropenia (42.1%), thrombocytopenia (38.6%), and hypofibrinogenemia (26.3%). No treatment-related deaths were observed.
CONCLUSION
P-GDP combination chemotherapy is highly effective and safe for newly diagnosed patients with extranodal NK/T-cell lymphoma, nasal type. Additional large sample prospective trials are required to confirm these results.
PubMed: 30464606
DOI: 10.2147/CMAR.S179567 -
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 -
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 -
Zhongguo Dang Dai Er Ke Za Zhi =... Feb 2014The chemotherapy agent L-asparaginase (L-asp) has been an important part of acute lymphoblastic leukemia therapy for over 30 years. It is evident that L-asp has a... (Review)
Review
The chemotherapy agent L-asparaginase (L-asp) has been an important part of acute lymphoblastic leukemia therapy for over 30 years. It is evident that L-asp has a long-term curative effect. However, L-asp is associated with high incidence of adverse reactions. This has prompted the development of pegylated asparaginase (PEG-asp), which has undergone extensive testing. Apparently, PEG-asp has a prolonged half-life with a better tolerance profile while retaining the antileukemic effect. In this review, we attempt to outline the history of clinical application of L-asp, the pharmacological and clinical potential of various preparations of L-asp, the development of PEG-asp, and the clinical application and adverse events of PEG-asp. The literatures reviewed in this article is collected through online search of the major databases both in English and Chinese.
Topics: Antineoplastic Agents; Asparaginase; Blood Coagulation Disorders; Humans; Pancreatitis; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 24568909
DOI: No ID Found -
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 -
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 -
Oncotarget Sep 2016Extranodal natural killer/T cell lymphoma (ENKL) is a high invasive disease with poor prognosis. Since there is no consensus on standard chemotherapy, we developed an...
Extranodal natural killer/T cell lymphoma (ENKL) is a high invasive disease with poor prognosis. Since there is no consensus on standard chemotherapy, we developed an original chemotherapeutic DDGP (cisplatin, dexamethasone, gemcitabine, and pegaspargase) regimen. We retrospectively analyzed 80 patients who received DDGP chemotherapy. The primary end point was progression-free survival (PFS) and secondary end points were overall survival (OS), complete response rate (CRR), and overall response rate (ORR). The one-year PFS and OS rates were 86.0% and 88.6%, and the 2-year PFS and OS rates were 81.40% and 87.1%, respectively. The ORR and CRR of DDGP chemotherapy were 91.3% and 60.0%. The major adverse events were myelosuppression, digestive tract toxicities, and coagulation disorder. No treatment-related deaths were observed. Our results suggest that the DDGP regimen is a high effective and safe treatment for ENKL.
Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cisplatin; Deoxycytidine; Dexamethasone; Disease-Free Survival; Female; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Natural Killer T-Cells; Nose Neoplasms; Polyethylene Glycols; Prognosis; Retrospective Studies; Treatment Outcome; Young Adult; Gemcitabine
PubMed: 27517317
DOI: 10.18632/oncotarget.11135 -
Medicine Nov 2017Pegaspargase has been used in the treatment of acute lymphoblastic leukemia with promising results. However, it has also been associated with several potentially serious... (Review)
Review
RATIONALE
Pegaspargase has been used in the treatment of acute lymphoblastic leukemia with promising results. However, it has also been associated with several potentially serious complications, including thrombosis. Pegaspargase-induced cerebral venous thrombosis and bone marrow necrosis are very rare.
PATIENT CONCERNS
A 50-year-old female developed headache, weakness of the right lower extremity, fever, and bone pain after chemotherapy including pegaspargase for the treatment of acute lymphoblastic leukemia.
DIAGNOSES
Her imaging studies and bone marrow examinations were compatible with cerebral venous thrombosis and bone marrow necrosis.
INTERVENTIONS
The patient received anticoagulation therapy with rivaroxaban.
OUTCOMES
After treatment with rivaroxaban, she had a good outcome without major or minor bleeding.
LESSONS
Clinicians should be aware of the very rare but possible induction of bone marrow necrosis during pegaspargase treatment when there is necrosis in other organs. Because of its greater safety and convenience, rivaroxaban gains popularity over traditional anticoagulant drugs.
Topics: Antineoplastic Agents; Asparaginase; Bone Marrow; Female; Humans; Middle Aged; Necrosis; Polyethylene Glycols; Remission Induction; Rivaroxaban; Sinus Thrombosis, Intracranial
PubMed: 29145310
DOI: 10.1097/MD.0000000000008715