FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4375852249> ?p ?o ?g. }

• W4375852249 endingPage "e432" @default.
• W4375852249 startingPage "e419" @default.
• W4375852249 abstract "Background T-cell acute lymphoblastic leukaemia has distinct biological characteristics and a poorer prognosis than B-cell precursor acute lymphoblastic leukaemia. This trial aimed to reduce the rate of radiation and haematopoietic stem-cell transplantation (HSCT) while improving outcomes by adding nelarabine, intensified L-asparaginase, and protracted intrathecal therapy in the Berlin-Frankfurt-Münster (BFM)-type treatment. Methods In this nationwide, multicenter, phase 2 trial, we enrolled patients with newly diagnosed T-cell acute lymphoblastic leukaemia (age <25 years at diagnosis) conducted by Japan Children's Cancer Group and Japan Adult Leukemia Study Group. Patients were stratified into standard-risk, high-risk, and very-high-risk groups according to prednisolone response, CNS status, and end-of-consolidation minimal residual disease. We used the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP)-BFM-ALL 2000-backbone chemotherapy. Nelarabine (650 mg/m2 per day for 5 days) was given to high-risk and very high-risk patients. All patients received, until the measurement of end-of-consolidation minimal residual disease, an identical therapy schedule, which included the prednisolone pre-phase remission induction therapy with dexamethasone (10 mg/m2 per day, for 3 weeks [for patients <10 years] or for 2 weeks including a 7-day off interval [for patients ≥10 years]) instead of prednisolone, and consolidation therapy added with Escherichia coli-derived L-asparaginase. On the basis of the stratification, patients received different intensities of treatment; L-asparaginase-intensified standard BFM-type therapy for standard risk and nelarabine-added high risk BFM-type therapy for high risk. In the very high-risk group, patients were randomly assigned (1:1) to group A (BFM-based block therapy) and group B (another block therapy, including high-dose dexamethasone) stratified by hospital, age (≥18 years or <18 years), and end-of-induction bone marrow blast percentage of M1 (<5%) or M2 (≥5%, <25%)+M3 (≥25%). Cranial radiotherapy was limited to patients with overt CNS disease at diagnosis (CNS3; >5 white blood cells per μL with blasts) and patients with no evidence of CNS disease received protracted triple intrathecal therapy. Only very high-risk patients were scheduled to receive HSCT. The primary endpoint was 3-year event-free survival for the entire cohort and the proportion of patients with disappearance of minimal residual disease between randomly assigned groups A and B in the very high-risk group. Secondary endpoints were overall survival, remission induction rate, and occurrence of adverse events. 3 years after the completion of patient accrual, a primary efficacy analysis was performed in the full analysis set and the per-protocol set. This study is registered with the Japan Registry of Clinical Trials, jRCTs041180145. Findings Between Dec 1, 2011, and Nov 30, 2017, of 349 eligible patients (median age 9 years [IQR 6–13]), 238 (68%) were male, and 28 (8%) patients had CNS3 status. 168 (48%) patients were stratified as standard risk, 103 (30%) as high risk, 39 (11%) as very high risk, and 39 (11%) as no risk (patients who had off protocol treatment before risk assessment. The composite complete remission (complete remission plus complete remission in suppression) rate after remission induction therapy was 89% (298 of 335 patients). HSCT was performed in 35 (10%) of 333 patients. With a median follow-up of 5·2 years (IQR 3·6–6·7), 3-year event-free survival was 86·4% (95% CI 82·3–89·7%) and 3-year overall survival was 91·3% (87·7–93·8%). The proportion of minimal residual disease disappearance was 0·86 (12 of 14 patients; 95% CI 0·57–0·98) in group A and 0·50 (6 of 12 patients, 0·21–0·79) in group B. Grade 3 peripheral motor neuropathy was seen in 11 (3%) of 349 patients and sensory neuropathy was seen in 6 (2%) patients. The most common grade 3 or worse adverse event was febrile neutropenia (294 [84%] of 349 patients). Treatment-related death occurred in three patients due to sepsis, gastric perforation, or intracranial haemorrhage during remission induction. Interpretation The ALL-T11 protocol produced encouraging outcomes with acceptable toxicities despite limited cranial radiotherapy and HSCT use. Funding Ministry of Health, Labor and Welfare of Japan, and Japan Agency for Medical Research and Development. Translation For the Japanese translation of the abstract see Supplementary Materials section. T-cell acute lymphoblastic leukaemia has distinct biological characteristics and a poorer prognosis than B-cell precursor acute lymphoblastic leukaemia. This trial aimed to reduce the rate of radiation and haematopoietic stem-cell transplantation (HSCT) while improving outcomes by adding nelarabine, intensified L-asparaginase, and protracted intrathecal therapy in the Berlin-Frankfurt-Münster (BFM)-type treatment. In this nationwide, multicenter, phase 2 trial, we enrolled patients with newly diagnosed T-cell acute lymphoblastic leukaemia (age <25 years at diagnosis) conducted by Japan Children's Cancer Group and Japan Adult Leukemia Study Group. Patients were stratified into standard-risk, high-risk, and very-high-risk groups according to prednisolone response, CNS status, and end-of-consolidation minimal residual disease. We used the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP)-BFM-ALL 2000-backbone chemotherapy. Nelarabine (650 mg/m2 per day for 5 days) was given to high-risk and very high-risk patients. All patients received, until the measurement of end-of-consolidation minimal residual disease, an identical therapy schedule, which included the prednisolone pre-phase remission induction therapy with dexamethasone (10 mg/m2 per day, for 3 weeks [for patients <10 years] or for 2 weeks including a 7-day off interval [for patients ≥10 years]) instead of prednisolone, and consolidation therapy added with Escherichia coli-derived L-asparaginase. On the basis of the stratification, patients received different intensities of treatment; L-asparaginase-intensified standard BFM-type therapy for standard risk and nelarabine-added high risk BFM-type therapy for high risk. In the very high-risk group, patients were randomly assigned (1:1) to group A (BFM-based block therapy) and group B (another block therapy, including high-dose dexamethasone) stratified by hospital, age (≥18 years or <18 years), and end-of-induction bone marrow blast percentage of M1 (<5%) or M2 (≥5%, <25%)+M3 (≥25%). Cranial radiotherapy was limited to patients with overt CNS disease at diagnosis (CNS3; >5 white blood cells per μL with blasts) and patients with no evidence of CNS disease received protracted triple intrathecal therapy. Only very high-risk patients were scheduled to receive HSCT. The primary endpoint was 3-year event-free survival for the entire cohort and the proportion of patients with disappearance of minimal residual disease between randomly assigned groups A and B in the very high-risk group. Secondary endpoints were overall survival, remission induction rate, and occurrence of adverse events. 3 years after the completion of patient accrual, a primary efficacy analysis was performed in the full analysis set and the per-protocol set. This study is registered with the Japan Registry of Clinical Trials, jRCTs041180145. Between Dec 1, 2011, and Nov 30, 2017, of 349 eligible patients (median age 9 years [IQR 6–13]), 238 (68%) were male, and 28 (8%) patients had CNS3 status. 168 (48%) patients were stratified as standard risk, 103 (30%) as high risk, 39 (11%) as very high risk, and 39 (11%) as no risk (patients who had off protocol treatment before risk assessment. The composite complete remission (complete remission plus complete remission in suppression) rate after remission induction therapy was 89% (298 of 335 patients). HSCT was performed in 35 (10%) of 333 patients. With a median follow-up of 5·2 years (IQR 3·6–6·7), 3-year event-free survival was 86·4% (95% CI 82·3–89·7%) and 3-year overall survival was 91·3% (87·7–93·8%). The proportion of minimal residual disease disappearance was 0·86 (12 of 14 patients; 95% CI 0·57–0·98) in group A and 0·50 (6 of 12 patients, 0·21–0·79) in group B. Grade 3 peripheral motor neuropathy was seen in 11 (3%) of 349 patients and sensory neuropathy was seen in 6 (2%) patients. The most common grade 3 or worse adverse event was febrile neutropenia (294 [84%] of 349 patients). Treatment-related death occurred in three patients due to sepsis, gastric perforation, or intracranial haemorrhage during remission induction. The ALL-T11 protocol produced encouraging outcomes with acceptable toxicities despite limited cranial radiotherapy and HSCT use." @default.
• W4375852249 created "2023-05-10" @default.
• W4375852249 creator A5002554232 @default.
• W4375852249 creator A5002642944 @default.
• W4375852249 creator A5016286590 @default.
• W4375852249 creator A5017179381 @default.
• W4375852249 creator A5019098042 @default.
• W4375852249 creator A5025014885 @default.
• W4375852249 creator A5035340824 @default.
• W4375852249 creator A5038183052 @default.
• W4375852249 creator A5040079244 @default.
• W4375852249 creator A5045468227 @default.
• W4375852249 creator A5046980140 @default.
• W4375852249 creator A5049633500 @default.
• W4375852249 creator A5049715323 @default.
• W4375852249 creator A5055616222 @default.
• W4375852249 creator A5056441277 @default.
• W4375852249 creator A5059219075 @default.
• W4375852249 creator A5060274149 @default.
• W4375852249 creator A5068939913 @default.
• W4375852249 creator A5070702322 @default.
• W4375852249 creator A5073119979 @default.
• W4375852249 creator A5078387402 @default.
• W4375852249 creator A5078761978 @default.
• W4375852249 creator A5079998695 @default.
• W4375852249 creator A5080093171 @default.
• W4375852249 creator A5080646427 @default.
• W4375852249 creator A5085013416 @default.
• W4375852249 date "2023-06-01" @default.
• W4375852249 modified "2023-10-03" @default.
• W4375852249 title "Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group" @default.
• W4375852249 cites W1641010126 @default.
• W4375852249 cites W1801876107 @default.
• W4375852249 cites W1846828978 @default.
• W4375852249 cites W1975979722 @default.
• W4375852249 cites W1976767488 @default.
• W4375852249 cites W2030286752 @default.
• W4375852249 cites W2038978021 @default.
• W4375852249 cites W2042987290 @default.
• W4375852249 cites W2059999488 @default.
• W4375852249 cites W2068619849 @default.
• W4375852249 cites W2068835290 @default.
• W4375852249 cites W2091810728 @default.
• W4375852249 cites W2100025372 @default.
• W4375852249 cites W2115482777 @default.
• W4375852249 cites W2121926621 @default.
• W4375852249 cites W2127153931 @default.
• W4375852249 cites W2140556790 @default.
• W4375852249 cites W2141539055 @default.
• W4375852249 cites W2148631711 @default.
• W4375852249 cites W2163926478 @default.
• W4375852249 cites W2180132450 @default.
• W4375852249 cites W2238009057 @default.
• W4375852249 cites W2749830411 @default.
• W4375852249 cites W2794979171 @default.
• W4375852249 cites W2980266363 @default.
• W4375852249 cites W2982248350 @default.
• W4375852249 cites W3063038225 @default.
• W4375852249 cites W3092226633 @default.
• W4375852249 cites W4221105120 @default.
• W4375852249 doi "https://doi.org/10.1016/s2352-3026(23)00072-8" @default.
• W4375852249 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37167992" @default.
• W4375852249 hasPublicationYear "2023" @default.
• W4375852249 type Work @default.
• W4375852249 citedByCount "1" @default.
• W4375852249 countsByYear W43758522492023 @default.
• W4375852249 crossrefType "journal-article" @default.
• W4375852249 hasAuthorship W4375852249A5002554232 @default.
• W4375852249 hasAuthorship W4375852249A5002642944 @default.
• W4375852249 hasAuthorship W4375852249A5016286590 @default.
• W4375852249 hasAuthorship W4375852249A5017179381 @default.
• W4375852249 hasAuthorship W4375852249A5019098042 @default.
• W4375852249 hasAuthorship W4375852249A5025014885 @default.
• W4375852249 hasAuthorship W4375852249A5035340824 @default.
• W4375852249 hasAuthorship W4375852249A5038183052 @default.
• W4375852249 hasAuthorship W4375852249A5040079244 @default.
• W4375852249 hasAuthorship W4375852249A5045468227 @default.
• W4375852249 hasAuthorship W4375852249A5046980140 @default.
• W4375852249 hasAuthorship W4375852249A5049633500 @default.
• W4375852249 hasAuthorship W4375852249A5049715323 @default.
• W4375852249 hasAuthorship W4375852249A5055616222 @default.
• W4375852249 hasAuthorship W4375852249A5056441277 @default.
• W4375852249 hasAuthorship W4375852249A5059219075 @default.
• W4375852249 hasAuthorship W4375852249A5060274149 @default.
• W4375852249 hasAuthorship W4375852249A5068939913 @default.
• W4375852249 hasAuthorship W4375852249A5070702322 @default.
• W4375852249 hasAuthorship W4375852249A5073119979 @default.
• W4375852249 hasAuthorship W4375852249A5078387402 @default.
• W4375852249 hasAuthorship W4375852249A5078761978 @default.
• W4375852249 hasAuthorship W4375852249A5079998695 @default.
• W4375852249 hasAuthorship W4375852249A5080093171 @default.
• W4375852249 hasAuthorship W4375852249A5080646427 @default.
• W4375852249 hasAuthorship W4375852249A5085013416 @default.
• W4375852249 hasConcept C126322002 @default.
• W4375852249 hasConcept C143998085 @default.
• W4375852249 hasConcept C187212893 @default.
• W4375852249 hasConcept C2778461978 @default.
• W4375852249 hasConcept C2778904437 @default.

• next