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American Journal of Hematology Nov 2021Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease....
Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p < 0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.
Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Deoxycytidine; Female; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Organoplatinum Compounds; Polyethylene Glycols; Prognosis; Survival Analysis; Treatment Outcome; Young Adult
PubMed: 34449095
DOI: 10.1002/ajh.26335 -
Journal of Healthcare Engineering 2022To explore the relationship between vitamins levels and disease-related indicators in children with acute leukemia (AL).
OBJECTIVE
To explore the relationship between vitamins levels and disease-related indicators in children with acute leukemia (AL).
METHODS
A total of 107 hospitalized children with AL were enrolled in this study and assigned to one group in each of the following categories: infected group ( = 52) and noninfected group ( = 55); treatment remission group ( = 56) and nonremission group ( = 51); high-risk (HR) group ( = 44), intermediate risk (IR) group ( = 53), and slight risk (SR) group ( = 8); cyclophosphamide + cytosine arabinoside+6-mercaptopurine + pegaspargase group (CAML, = 15); methotrexate group (MTX, = 9); and vindesine + daunomycin + L-asparaginasum + prednisone (VALP, = 38). Hematological and serological parameters, hepatic and renal function, and changes in vitamins A, B1, B2, B6, B9, B12, C, D, and E serum content in children with AL were analyzed to investigate their relationship with AL disease-related factors.
RESULTS
The vitamin D level was significantly higher in the noninfected group than in the infected group ( < 0.05). Compared with the nonremission group, the level of vitamin B1 in the treatment remission group was significantly higher, while the levels of vitamin B6 and B12 were notably lower ( < 0.05). The levels of vitamins B6 and B12 were notably different among the treatment groups. Multivariate analysis showed that hemoglobin (Hb) and C-reactive protein (CRP) were predisposing factors of AL in children. The disease type (acute lymphoblastic leukemia/acute myelogenous leukemia) was the factor affecting remission in AL children. Abnormal kidney function and the occurrence of icterus were the influencing factors for the risk degree in AL children. Platelet (PLT) count, activated partial thromboplastin time (APTT), neutrophils (N), and immunophenotype were shown to affect the choice of therapeutic regimens.
CONCLUSION
There are notable vitamins imbalances in children with AL. The imbalances influence disease-related factors and therefore provide some references for the prognosis and treatment of AL.
Topics: Causality; Child; Humans; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Vitamins
PubMed: 35463661
DOI: 10.1155/2022/5330563 -
Oncotarget Aug 2016To explore a more effective treatment for newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), we conducted a phase 4 study of... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of cisplatin, dexamethasone, gemcitabine and pegaspargase (DDGP) regimen in newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma: interim analysis of a phase 4 study NCT01501149.
To explore a more effective treatment for newly diagnosed, advanced-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), we conducted a phase 4 study of the cisplatin, dexamethasone, gemcitabine, pegaspargase (DDGP) regimen. The primary end point was the 2-year progression-free survival (PFS) after the protocol treatment. Secondary endpoints included response rate (RR), overall survival (OS) and median survival time (MST). The interim analysis included data only from March 2011 to September 2013, who received six cycles of DDGP chemotherapy. A total of 25 eligible patients were enrolled. Seventeen patients (17/24, 70.83%) achieved complete response (CR) and four (4/24, 16.67%) achieved partial response (PR), three (3/24, 12.50%) had progressive disease (PD). The RR after treatment was 87.50%. After a median follow-up duration of 24.67 months (range 4-48 months). The 2-year PFS and OS rate were 61.80% (95% CI, 42.00% to 81.60%) and 68.50 % (95% CI, 48.70% to 88.30%), respectively. The MST was 36.55 months (95% CI, 29.41 months to 43.70 months). Grade 3/4 leukopenia occurred in fourteen patients (58.33%) and grade 3/4 thrombocytopenia occurred in eleven patients (45.83%). Twelve patients (50.00%) experienced Activated Partial Phromboplastin Ptime (APTT) elongation and fourteen patients (58.33%) experienced hypofibrinogenemia. In conclusion, DDGP regimen is an effective and tolerated treatment for newly diagnosed, advanced-stage ENKTL. This trial was registered at www.ClinicalTrials.gov as #NCT01501149.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cisplatin; Deoxycytidine; Dexamethasone; Female; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Polyethylene Glycols; Young Adult; Gemcitabine
PubMed: 27384676
DOI: 10.18632/oncotarget.10124 -
Journal of Feline Medicine and Surgery Aug 2022The aim of this retrospective study was to determine the response to a single injection of pegylated asparaginase ('pegaspargase') and to assess the tolerability and...
OBJECTIVES
The aim of this retrospective study was to determine the response to a single injection of pegylated asparaginase ('pegaspargase') and to assess the tolerability and outcome of prolonged incorporation of pegaspargase into a modified COP (cyclophosphamide, vincristine, prednisolone) regimen in pegaspargase sensitive cats.
METHODS
Fifty-six client-owned cats with confirmed macroscopic high-grade lymphoma at any anatomical site were included. Treatment was commenced with a single pegaspargase injection. Cats showing an objective response were eligible to continue therapy with pegaspargase incorporated into a modified COP protocol and had their survival analysed using the Kaplan-Meier method and log-rank test.
RESULTS
Objective response to pegaspargase was reported in 46 cats (82%), including 21 (38%) complete and 25 (44%) partial responses. Thirty-four responders continued therapy with pegaspargase-COP as the first-line treatment. Of these, 31 cats (92%) achieved complete remission with a median duration of the first remission (disease-free survival [DFS]) of 816 days. The median overall survival time (OST) for all 34 cats treated with pegaspargase-COP was 181 days. Response to the initial pegaspargase injection before COP initiation was significantly associated with DFS ( = 0.04) and OST ( = 0.001). Median DFS/OST for cats with complete response to initial pegaspargase injection was significantly longer compared with those with partial remission (>1273 days/>2066 days vs 77 days/108 days, respectively). Cats with gastric lymphoma showed a significantly longer survival (OST 854 days, 1- and 2-year survival rate 57.1%) compared with cats with intestinal lymphoma (OST 102 days, 1-year survival rate 0%). The pegaspargase-COP protocol was generally well tolerated, but two deaths were likely attributable to treatment-related toxicity during the maintenance phase. Importantly, none of the cats experienced hypersensitivity, despite multiple repeated treatments with pegaspargase.
CONCLUSION AND RELEVANCE
Pegaspargase is an effective agent for feline lymphoma. Its incorporation into a COP chemotherapy protocol may confer a survival benefit, especially in cats with complete response to pegaspargase. Treatment is generally well tolerated, but careful monitoring is recommended. Further studies are required to assess the benefits of pegaspargase as monotherapy or as part of different multi-agent chemotherapy regimens.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cat Diseases; Cats; Cyclophosphamide; Lymphoma; Lymphoma, Non-Hodgkin; Polyethylene Glycols; Retrospective Studies
PubMed: 35748790
DOI: 10.1177/1098612X221101533 -
Clinical Pharmacology and Therapeutics Sep 2021We conducted the first human leukocyte antigen (HLA) allele and genome-wide association study to identify loci associated with hypersensitivity reactions exclusively to...
We conducted the first human leukocyte antigen (HLA) allele and genome-wide association study to identify loci associated with hypersensitivity reactions exclusively to the PEGylated preparation of asparaginase (pegaspargase) in racially diverse cohorts of pediatric leukemia patients: St Jude Children's Research Hospital's Total XVI (TXVI, n = 598) and Children's Oncology Group AALL0232 (n = 2,472) and AALL0434 (n = 1,189). Germline DNA was genotyped using arrays. Genetic variants not genotyped directly were imputed. HLA alleles were imputed using SNP2HLA or inferred using BWAkit. Analyses between genetic variants and hypersensitivity were performed in each cohort first using cohort-specific covariates and then combined using meta-analyses. Nongenetic risk factors included fewer intrathecal injections (P = 2.7 × 10 in TXVI) and male sex (P = 0.025 in AALL0232). HLA alleles DQB1*02:02, DRB1*07:01, and DQA1*02:01 had the strongest associations with pegaspargase hypersensitivity (P < 5.0 × 10 ) in patients with primarily European ancestry (EA), with the three alleles associating in a single haplotype. The top allele HLA-DQB1*02:02 was tagged by HLA-DQB1 rs1694129 in EAs (r = 0.96) and less so in non-EAs. All single nucleotide polymorphisms associated with pegaspargase hypersensitivity reaching genome-wide significance in EAs were in class II HLA loci, and were partially replicated in non-EAs, as is true for other HLA associations. The rs9958628 variant, in ARHGAP28 (previously linked to immune response in children) had the strongest genetic association (P = 8.9 × 10 ) in non-EAs. The HLA-DQB1*02:02-DRB1*07:01-DQA1*02:01 associated with hypersensitivity reactions to pegaspargase is the same haplotype associated with reactions to non-PEGylated asparaginase, even though the antigens differ between the two preparations.
Topics: Alleles; Asparaginase; Cohort Studies; Gene Frequency; Genome-Wide Association Study; Genotype; Haplotypes; Histocompatibility Antigens Class II; Humans; Polyethylene Glycols; Polymorphism, Single Nucleotide
PubMed: 33768542
DOI: 10.1002/cpt.2241 -
Current Hematologic Malignancy Reports Jul 2009The outcome of salvage therapy for relapsed acute lymphoblastic leukemia (ALL) remains poor. Salvage therapy mimics regimens with activity in newly diagnosed ALL. Novel... (Review)
Review
The outcome of salvage therapy for relapsed acute lymphoblastic leukemia (ALL) remains poor. Salvage therapy mimics regimens with activity in newly diagnosed ALL. Novel strategies under investigation as monotherapy or in combination with chemotherapy improve the treatment of relapsed disease. For some ALL subsets, specific therapies are indicated. The addition of targeted therapy in Philadelphia chromo some-positive ALL has improved responses in relapsed patients without resistance to available tyrosine kinase inhibitors. Nelarabine demonstrates activity as monotherapy in T-cell ALL and is approved by the US Food and Drug Administration. Clofarabine, a second-generation purine analogue approved in pediatric leukemia, has shown activity in adult acute leukemias including ALL and acute myeloid leukemia. The role of pegaspargase in adult ALL requires further investigation. The benefit of matched related-donor allogeneic stem cell transplantation is significant for standard-risk ALL but not for high-risk ALL. Development of new drugs and agents tailored to subset-specific cytogenetic-molecular characteristics remains vital to success in treating adult ALL.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Humans; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Treatment Outcome
PubMed: 20425428
DOI: 10.1007/s11899-009-0021-6 -
Haematologica Feb 2022Chemotherapy dosages are often compromised, but most reports lack data on dosages that are actually delivered. In two consecutive acute lymphoblastic leukemia trials...
Chemotherapy dosages are often compromised, but most reports lack data on dosages that are actually delivered. In two consecutive acute lymphoblastic leukemia trials that differed in their asparaginase formulation, native E. coli L-asparaginase in St. Jude Total 15 (T15, n=365) and pegaspargase in Total 16 (T16, n=524), we tallied the dose intensities for all drugs on the low-risk or standard-risk arms, analyzing 504,039 dosing records. The median dose intensity for each drug ranged from 61-100%. Dose intensities for several drugs were more than 10% higher on T15 than on T16: cyclophosphamide (P<0.0001 for the standard- risk arm), cytarabine (P<0.0001 for the standard-risk arm), and mercaptopurine (P<0.0001 for the low-risk arm and P<0.0001 for the standardrisk arm). We attributed the lower dosages on T16 to the higher asparaginase dosages on T16 than on T15 (P<0.0001 for both the low-risk and standard-risk arms), with higher dose-intensity for mercaptopurine in those with anti-asparaginase antibodies than in those without (P=5.62x10-3 for T15 standard risk and P=1.43x10-4 for T16 standard risk). Neutrophil count did not differ between protocols for low-risk patients (P=0.18) and was actually lower for standard-risk patients on T16 than on T15 (P<0.0001) despite lower dosages of most drugs on T16. Patients with low asparaginase dose intensity had higher methotrexate dose intensity with no impact on prognosis. The only dose intensity measure predicting a higher risk of relapse on both studies was higher mercaptopurine dose intensity, but this did not reach statistical significance (P=0.03 T15; P=0.07 T16). In these intensive multiagent trials, higher dosages of asparaginase compromised the dosing of other drugs for acute lymphoblastic leukemia, particularly mercaptopurine, but lower chemotherapy dose intensity was not associated with relapse.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Escherichia coli; Humans; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 34196166
DOI: 10.3324/haematol.2021.278411 -
Blood Dec 2020
Randomized Controlled Trial
Topics: Asparaginase; Drug Elimination Routes; Female; Humans; Male; Metabolic Clearance Rate; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 32750103
DOI: 10.1182/blood.2020006214 -
Blood Jan 2020
Topics: Adolescent; Adult; Antineoplastic Agents; Asparaginase; Child; Child, Preschool; Desensitization, Immunologic; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Hypersensitivity; Male; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Retrospective Studies; Young Adult
PubMed: 31750901
DOI: 10.1182/blood.2019003407 -
Blood Advances Jan 2023Asparaginase is a key component of pediatric-inspired regimens in young adults with acute lymphoblastic leukemia (ALL). Truncation of asparaginase therapy is linked to...
Asparaginase is a key component of pediatric-inspired regimens in young adults with acute lymphoblastic leukemia (ALL). Truncation of asparaginase therapy is linked to inferior outcomes in children with ALL. However, a similar correlation in adults is lacking. Here, we studied the prevalence and risk factors associated with pegylated (PEG)-asparaginase discontinuation in young adults with ALL treated on the US intergroup Cancer and Leukemia Group B (CALGB) 10403 study and examined the prognostic impact of early discontinuation (ED) (defined as <4 of 5 or 6 planned doses) on survival outcomes. The analysis included 176 patients who achieved complete remission and initiated the delayed intensification (DI) cycle. The median number of PEG-asparaginase doses administered before DI was 5 (range, 1-6), with 57 (32%) patients with ED. The ED patients were older (median, 26 vs 23 years; P = .023). Survival was apparently lower for ED patients compared with those receiving ≥4 doses, but this finding was not statistically significant (hazard ratio [HR], 1.82; 95% confidence interval [CI], 0.97-3.43; P = .06), with corresponding 5-year overall survival (OS) rates of 66% and 80%, respectively. In patients with standard-risk ALL, the ED of PEG-asparaginase adversely influenced OS (HR, 2.3; 95% CI, 1.02-5.22; P = .04) with a trend toward inferior event-free survival (EFS) (HR, 1.84; 95% CI, 0.92-3.67; P = .08). In contrast, there was no impact of early PEG-asparaginase discontinuation on OS (P = .64) or EFS (P = .32) in patients with high-risk disease based on the presence of high-risk cytogenetics, Ph-like genotype, and/or high white blood cell count at presentation. In conclusion, early PEG-asparaginase discontinuation is common in young adults with ALL and may adversely impact survival of patients with standard-risk ALL.
Topics: Child; Humans; Young Adult; Asparaginase; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polyethylene Glycols; Remission Induction
PubMed: 36269846
DOI: 10.1182/bloodadvances.2022007791