FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2553823280> ?p ?o ?g. }

• W2553823280 endingPage "3842" @default.
• W2553823280 startingPage "3842" @default.
• W2553823280 abstract "Abstract Background: Acute promyelocytic leukemia (APL) is classified into favorable-risk group and long-term overall survival (OS) is estimated at around 80%. Relapse rate of APL is relatively lower than another acute myeloid leukemia (AML) subtypes, but we still confront relapse in 10-20% and some relapsed cases are hardly cured even after hematopoietic cell transplantation (HCT). Therefore, it is important to find out patients with high-risk of relapse and early intervention should be considered. In APL, PML-RARa RQ PCR is used as a marker for residual disease, but the marker is not useful for pre-emptive management for relapse prevention because its positivity directly indicates relapse of disease. WT1 expression is a well-known marker in AML, and the expression is higher in APL than the other AML subtypes (Cilloni et al., leukemia, 2002). We monitored WT1 decrement along the treatment courses to identify its significant role as a marker for relapse prediction. Methods: In this study, 117 APL patients with a median follow-up duration of 38.5 months (range, 9.7-81.3) from 2008 to 2014 were analyzed. APL was diagnosed by RT-PCR method for detection of PML-RARa and all patients were available with cytogenetic results. All except 5 with normal karyotype was identified with t(15;17)(q22;q21) and 33 (28.2%) showed combination of additional chromosomal abnormalities. Our treatment protocol was based on LPA99 trial using ATRA and idarubicin monotherapy (Sanz et al., Blood, 2004). In relapsed patients, we applied ATO and some high-risk patients were treated with HCT (n=3). PML-RARa and WT1 expression in the BM samples were quantified by RQ-PCR method, and we used WT1 ProfileQuant¢â kit (Ipsogen) for WT1 monitoring. We measured RQ-PCR levels at diagnosis, post-induction and each of the 3 post-consolidation chemotherapies, and 3 months interval after starting maintenance therapy. FLT3- ITD/TKD mutation was evaluated by multiplex allele-specific PCR and concomitantly analyzed. Significant cut-off level of PML-RARa and WT1 expression was calculated by ROC curve analysis. According to the level, we calculated OS, disease free survival (DFS), and cumulative incidence of relapse (CIR). Results: Hematological complete remission (CR) was identified in 117 (100.0%) patients but complete molecular remission (CMR) was identified in 68 (42.7%) after induction. Among 49 patients who failed to achieve CMR, 44 patients achieved CMR after 1st consolidation and 5 patients after 2nd consolidation. Three-year OS and EFS was 92.5% and 82.0%, and CIR rate was 14.7% (n=13). Three patients showed clonal evolution to therapy-related AML and 1 patient died in CR due to lung cancer. FLT3 -TKD and FLT3 -ITD mutation was identified in 6 (5.1%) and 25 (21.4%) patients, and PML-RARa BCR3 and BCR1 subtype was identified in 32 (27.4%) and 85 (72.6%) patients, respectively. For relapse prediction, we analyzed WT1 expression at several time points in association with CMR after induction, FLT3 -ITD/TKD mutation, BCR subtype, and hyperleukocytosis at diagnosis and during first chemotherapy. High WT1 expression (>120 copies/104ABL1) in early period (3 months) after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR was not detected except one sample with early relapse after 3rd consolidation. Patients with high post-maintenance WT1 expression (n=40) showed significantly higher CIR rate (30.7% vs. 4.2%, p=0.0003) and inferior 3-year OS (86.1% vs. 97.9%, p =.0103) and DFS (62.8% vs. 94.1%, p<.0001). Multivariate analysis revealed high leukocyte counts [HR=9.2, 95%CI=2.2-38.5, p =.002], WT1 at 3 months post-maintenance [HR=8.7, 95%CI=1.9-38.9, p =.0051], and FLT3 mutation [HR=5.4, 95%CI=1.5-19.4, p =.0092] were significant factors for relapse prediction. However, even in the BCR3 or FLT3 -positive subgroup (n=48), low WT1 at post-maintenance 3 months was associated with lower CIR rate (13.4% vs. 50.8%, p<.0001) and better DFS (95.2% vs. 49.2%, p<.0001). Conclusion: High post-remission WT1 expression was a reliable marker for the prediction of subsequent relapse in APL, even when PML-RARa was not detected at 3 months post-maintenance. In this high-risk group, early intervention with ATRA±ATO, WT1 vaccination or WT1 -specific cytotoxic cell therapy may be used for relapse prevention. The role of WT1 expression needs to be validated by prospective studies in a large cohort. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare." @default.
• W2553823280 created "2016-11-30" @default.
• W2553823280 creator A5009032518 @default.
• W2553823280 creator A5014324967 @default.
• W2553823280 creator A5026190297 @default.
• W2553823280 creator A5036020306 @default.
• W2553823280 creator A5044372572 @default.
• W2553823280 creator A5050292329 @default.
• W2553823280 creator A5050627824 @default.
• W2553823280 creator A5055206475 @default.
• W2553823280 creator A5059291757 @default.
• W2553823280 creator A5074128691 @default.
• W2553823280 creator A5084426605 @default.
• W2553823280 creator A5086415059 @default.
• W2553823280 creator A5086500437 @default.
• W2553823280 creator A5090633270 @default.
• W2553823280 date "2015-12-03" @default.
• W2553823280 modified "2023-10-18" @default.
• W2553823280 title "High Post-Remission WT1 Expression Is a Predictive Marker for Subsequent Molecular Relapse and Poor Survival Outcome in Adult Patients with Acute Promyelocytic Leukemia (APL)" @default.
• W2553823280 doi "https://doi.org/10.1182/blood.v126.23.3842.3842" @default.
• W2553823280 hasPublicationYear "2015" @default.
• W2553823280 type Work @default.
• W2553823280 sameAs 2553823280 @default.
• W2553823280 citedByCount "0" @default.
• W2553823280 crossrefType "journal-article" @default.
• W2553823280 hasAuthorship W2553823280A5009032518 @default.
• W2553823280 hasAuthorship W2553823280A5014324967 @default.
• W2553823280 hasAuthorship W2553823280A5026190297 @default.
• W2553823280 hasAuthorship W2553823280A5036020306 @default.
• W2553823280 hasAuthorship W2553823280A5044372572 @default.
• W2553823280 hasAuthorship W2553823280A5050292329 @default.
• W2553823280 hasAuthorship W2553823280A5050627824 @default.
• W2553823280 hasAuthorship W2553823280A5055206475 @default.
• W2553823280 hasAuthorship W2553823280A5059291757 @default.
• W2553823280 hasAuthorship W2553823280A5074128691 @default.
• W2553823280 hasAuthorship W2553823280A5084426605 @default.
• W2553823280 hasAuthorship W2553823280A5086415059 @default.
• W2553823280 hasAuthorship W2553823280A5086500437 @default.
• W2553823280 hasAuthorship W2553823280A5090633270 @default.
• W2553823280 hasConcept C104317684 @default.
• W2553823280 hasConcept C121608353 @default.
• W2553823280 hasConcept C126322002 @default.
• W2553823280 hasConcept C143998085 @default.
• W2553823280 hasConcept C203014093 @default.
• W2553823280 hasConcept C2776601000 @default.
• W2553823280 hasConcept C2777408962 @default.
• W2553823280 hasConcept C2778041864 @default.
• W2553823280 hasConcept C2778461978 @default.
• W2553823280 hasConcept C2778729363 @default.
• W2553823280 hasConcept C2779117419 @default.
• W2553823280 hasConcept C2779823535 @default.
• W2553823280 hasConcept C2780521871 @default.
• W2553823280 hasConcept C2781121885 @default.
• W2553823280 hasConcept C2911091166 @default.
• W2553823280 hasConcept C55493867 @default.
• W2553823280 hasConcept C71924100 @default.
• W2553823280 hasConcept C86803240 @default.
• W2553823280 hasConcept C90924648 @default.
• W2553823280 hasConceptScore W2553823280C104317684 @default.
• W2553823280 hasConceptScore W2553823280C121608353 @default.
• W2553823280 hasConceptScore W2553823280C126322002 @default.
• W2553823280 hasConceptScore W2553823280C143998085 @default.
• W2553823280 hasConceptScore W2553823280C203014093 @default.
• W2553823280 hasConceptScore W2553823280C2776601000 @default.
• W2553823280 hasConceptScore W2553823280C2777408962 @default.
• W2553823280 hasConceptScore W2553823280C2778041864 @default.
• W2553823280 hasConceptScore W2553823280C2778461978 @default.
• W2553823280 hasConceptScore W2553823280C2778729363 @default.
• W2553823280 hasConceptScore W2553823280C2779117419 @default.
• W2553823280 hasConceptScore W2553823280C2779823535 @default.
• W2553823280 hasConceptScore W2553823280C2780521871 @default.
• W2553823280 hasConceptScore W2553823280C2781121885 @default.
• W2553823280 hasConceptScore W2553823280C2911091166 @default.
• W2553823280 hasConceptScore W2553823280C55493867 @default.
• W2553823280 hasConceptScore W2553823280C71924100 @default.
• W2553823280 hasConceptScore W2553823280C86803240 @default.
• W2553823280 hasConceptScore W2553823280C90924648 @default.
• W2553823280 hasIssue "23" @default.
• W2553823280 hasLocation W25538232801 @default.
• W2553823280 hasOpenAccess W2553823280 @default.
• W2553823280 hasPrimaryLocation W25538232801 @default.
• W2553823280 hasRelatedWork W1968865933 @default.
• W2553823280 hasRelatedWork W2079966689 @default.
• W2553823280 hasRelatedWork W2193293559 @default.
• W2553823280 hasRelatedWork W2413326439 @default.
• W2553823280 hasRelatedWork W2553823280 @default.
• W2553823280 hasRelatedWork W2914664710 @default.
• W2553823280 hasRelatedWork W2998600066 @default.
• W2553823280 hasRelatedWork W4206141345 @default.
• W2553823280 hasRelatedWork W4308772545 @default.
• W2553823280 hasRelatedWork W93525153 @default.
• W2553823280 hasVolume "126" @default.
• W2553823280 isParatext "false" @default.
• W2553823280 isRetracted "false" @default.
• W2553823280 magId "2553823280" @default.
• W2553823280 workType "article" @default.