Outcomes of Patients with Low Variant Allele Fraction JAK2V617F: A 5-Year Retrospective Analysis
Notice bibliographique
Résumé
Abstract Introduction: JAK2V617F mutation is one of the major criteria in the diagnosis of myeloproliferative neoplasms (MPN). The disease phenotype and outcomes are dependent on variant allele fraction (VAF) of JAK2V617F. Recently, a new entity termed clonal hematopoiesis of indeterminate potential (CHIP) defines patients with normal cell counts and VAF of at least 2%. Outcomes of patients with <2% VAF are scarce and we aimed to retrospectively study characteristics and outcomes of patients with JAK2V617F VAF < 2% compared to patients with VAF 2-10%. Methods: The study population included all patients in the province of British Columbia with JAK2V617F testing performed during 2010-2015. We compared the patient characteristics, disease phenotypes, overall survival (OS), thrombosis-free survival (TFS) and cumulative incidence of thrombotic events between patients with VAF <2% and 2-10%. Parallel real-time quantitative polymerase chain reaction (RQ-PCR) for wild type JAK2 and JAK2V617F was used as detection method. MPN diagnoses were based on the treating physicians' assessment. Results: We identified 216 patients with JAK2V617F VAF < 10%. Twenty-seven patients were excluded due to missing follow-up data. A total of 189 patients were included for final analysis (89 patients with VAF <2% and 100 patients with VAF 2-10%). Patient characteristics, diagnoses and outcomes are shown in the Table. Patients with JAK2V617F >2% have significantly higher rate of splenomegaly, higher platelet counts and higher MPN diagnoses. Ten patients (10.0%) with VAF 2-10% had no hematologic diagnoses, consistent with CHIP, while 24 patients (27.0%) with VAF <2% had no hematologic diagnoses. There were no differences in all outcomes measured including thrombotic complications, progression to hematologic or solid cancers and death. The median follow-up time for the whole cohort was 5.2 years with interquartile range (IQR) 3.5-6.6 years. The 5-year OS were 81.0% for VAF < 2% and 81.7% for VAF 2-10%, log-rank P = 0.922. TFS at 5 years were 71.2% and 69.5%, respectively (P = 0.982). The 5-year cumulative incidences of thrombotic complications (considering death as a competing event) were 8.8% and 11.3%, respectively (Pepe-Mori P = 0.574). Further analysis by clinical diagnoses classified patients into polycythemia vera (PV) 40 (21.2%), essential thrombocythemia (ET) 99 (52.3%), primary myelofibrosis or MPN, NOS (PMF/MPN) 16 (8.5%) and clonal hematopoiesis of indeterminate potential (CHIP) or no hematologic diagnosis 34 (18.0%). Patients with PMF/MPN were significantly older than patients with other diagnoses (median age PV 64.2, ET 64.3, PMF/MPN 80.7 and CHIP 54.1 years, P=0.019). The 5-year OS were: PV 91.4%, ET 90.0%, PMF/MPN 31.3% and CHIP/no hematologic diagnoses 58.7%, P<0.001. TFS at 5 years were 83.1%, 74.7%, 25.0%and 57.4%, respectively, P<0.001. Conclusion: Patients with JAK2V617F VAF < 2% have less splenomegaly and are less likely to have a diagnosis of MPN compared to patients with VAF 2-10%. However, the incidence of thrombotic events was similar between patients with VAF < 2% and 2-10%. In the combined VAF < 10% cohort, PMF/MPN patients were older and had the worst survival outcomes. The mortality in this PMF/MPN group was mostly unrelated to MPN diagnoses. Interestingly, patients with CHIP/no hematologic diagnoses in this study have the next worse OS and TFS. This could be explained by selection bias for performing JAK2 testing in acute or chronically ill patients with reactive changes in the peripheral blood. Table. Table. Disclosures Foltz: Gilead: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Promedior: Research Funding; Incyte: Research Funding.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».