305 research outputs found
Sote-tietoarkkitehtuurin ohjausryhmä : kokousmateriaalit 18.5.2021
No full text Muistio ja esitykset
Muistio
OMOP-tietomallin käyttöönotto HUS-tietoaltaalla – Kimmo Porkka, HUS
OHDSI OMOP CDM – THL:n vastauspuheenvuoro – Arto Vuori, THL
International Patient Summary. Potilastiedon yhteenvedot – standardit ja hankkeet – Juha Mykkänen, THL
Ajankohtaista koodistopalvelusta – Mikko Härkönen, THL
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Chronic myeloid leukemia patients’ adherence to peroral tyrosine kinase inhibitors compared with adherence as estimated by their physicians
No full textMeri Kekäle,1 Kimmo Talvensaari,2 Perttu Koskenvesa,3 Kimmo Porkka,3 Marja Airaksinen1 1Clinical Pharmacy Group, Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland; 2Medical Center Mehiläinen, Nummela, Finland; 3Hematology Research Unit Helsinki, Department of Medicine, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland Purpose: To evaluate chronic myeloid leukemia (CML) patients’ adherence to peroral tyrosine kinase inhibitors in Finland and to compare this with adherence as estimated by their physicians. Other aspects studied included how patients’ knowledge of the disease and its treatment influence adherence.Materials and methods: A total of 120 CML patients were contacted between June 2012 and September 2013 in eight secondary or tertiary care hospitals in Finland. Of these, 86 participated in the study. This covers approximately 20% of all Finnish CML patients. The mean age was 57.8 years and 52% were male. Of the patients, 79.1% were using imatinib, 10.5% dasatinib, and 10.5% nilotinib. The patient-reported adherence (experienced adherence) was evaluated using the eight-item Morisky Medication Adherence Scale (MMAS). In addition, the treating physicians were asked to give their subjective opinion on their patients’ adherence (observed adherence). The experienced adherence was compared with the observed adherence using a three-level rating system (high, medium, low). All patients were personally interviewed and their demographic data collected. The statistical analysis of the data was based on descriptive statistics presented as frequencies, percentages, means, and medians. The kappa coefficient was calculated between the patient’s and the doctor’s assessment of adherence.Results: A total of 23% (20/86) of the patients were fully adherent according to the MMAS, while physicians evaluated 94% (80/86) of the patients as fully adherent. The physicians’ estimate was too optimistic in 73% of cases. The discrepancy was confirmed by a kappa value of -0.004. The patients’ knowledge of the disease and its treatment was poor in all adherence levels.Conclusion: The patient-reported adherence to tyrosine kinase inhibitor treatments in Finland was found to be the same as that found in the majority of previous studies. However, there seems to be a very weak agreement between the patient’s and the physician’s assessment of adherence. This study suggests that physicians overestimate the adherence of CML patients and base their assessment primarily on the clinical treatment response. Keywords: chronic myeloid leukemia, medication adherence, tyrosine kinase inhibitors, Morisky 8-item Medication Adherence Scale, physician’s assessment, knowledge of the diseas
Abstract 424: Landscape of somatic mutations in drug-resistant acute myeloid leukemia
No full textAbstract
Introduction: Most patients with acute myeloid leukemia (AML) initially respond to cytarabine-anthracycline induction chemotherapy. However, in many patients, the disease recurs in a lethal drug-resistant form. Somatic mutations underlying the pathogenesis of AML have been extensively characterized by sequencing of newly diagnosed AMLs. However, the mutations driving therapy resistance and disease progression at relapse have not been well characterized. In this study, we have exome sequenced a cohort of relapsed and refractory AMLs and compared the landscape of somatic mutations at relapse to diagnosis phase AMLs to identify mutations that contribute to therapy resistance and disease progression.
Materials and Methods: We performed exome sequencing of diagnosis phase AMLs (n=70) and relapsed or primary refractory AMLs (n=54). Patients with AML M3 subtype were excluded from the study. Paired diagnosis and relapse samples were available from 27 patients. A skin biopsy was used as the germline control. Nine patients had received an allogeneic hematopoietic stem cell transplant before relapse. Somatic mutations were called using varscan2 and copy number aberrations using copyCat. Since the identification of large insertions from next-generation sequencing data remains challenging using existing algorithms, FLT3 internal tandem duplications (FLT3-ITDs) were identified using a novel custom algorithm optimized for FLT3-ITD detection. Population variants were filtered out to remove donor-derived germline variants in chimeric post-transplant relapse samples.
Results: Comparison of somatic mutation frequencies in diagnosis and relapse and refractory samples showed that on average relapsed tumors have a higher number of driver mutations than tumors at diagnosis. WT1, TP53, CBL, IDH1 and PTPN11 were mutated at a higher frequency in relapsed samples than at diagnosis, with 13 %, 11 %, 11 %, 9 % and 9 % of relapsed or refractory samples and 4 %, 6 %, 3 %, 4 % and 7 % of diagnosis mutated respectively. Analysis of paired diagnosis-relapse samples showed that in patients with WT1, CBL or PTPN11 mutation at diagnosis the second allele is frequently mutated or lost due to uniparental disomy occurring at relapse.
Conclusions: On average relapsed AMLs have a higher number of driver mutations than diagnosis phase AMLs indicating that acquisition of additional driver mutations contributes to relapse. AMLs frequently acquire additional mutations in the same genes and pathways that already harbored mutations at diagnosis.
Citation Format: Samuli Eldfors, Mika Kontro, Yevhen Akimov, Olli Kallioniemi, Kimmo Porkka, Caroline Heckman. Landscape of somatic mutations in drug-resistant acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 424. doi:10.1158/1538-7445.AM2017-424</jats:p
Preliminary Results from a Phase Ib Study Exploring MDM2 Inhibitor Siremadlin (HDM201) in Combination with B-Cell Lymphoma-2 (BCL-2) Inhibitor Venetoclax in Patients with Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (HR-MDS)
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Philadelphia-kromosomipositiivisen akuutin lymfaattisen leukemian yksilöllistetty lääkehoito
No full textPhiladelphia-kromosomipositiivinen (Ph+) akuutti lymfaattinen leukemia (ALL) on aikuisten ALL:n yleisin geneettinen alaryhmä ja yksi syövän kohdennetun hoidon mallitaudeista. Tyrosiinikinaasin estäjien (TKE) kehitys on olennaisesti parantanut aiemmin pelätyn taudin ennustetta, ja pitkäaikaisia hoitovasteita voidaan saavuttaa kevennetyillä TKE-pohjaisilla hoidoilla. ALL:n immunologisen hoidon kehittyminen yhdessä tehokkaampien toisen ja kolmannen polven TKE-lääkkeiden kanssa parantaa todennäköisesti entisestään Ph+ ALL:n ennustetta ja muuttaa hoidon mahdollisesti jopa täysin solunsalpaajattomaksi. Lisääntyneiden vaihtoehtojen myötä hoidon yksilöllisten ennustetekijöiden tunnistamisen merkitys on lisääntynyt, kun pyritään valitsemaan kullekin potilaalle samalla sekä tehokas että haittavaikutuksiltaan hyväksyttävissä oleva hoito.Peer reviewe
Datamassojen hallinta syöpäpotilaiden hoidossa
No full textSyöpäkasvainten molekyylitason profiloinnin tuottaman kliinisen tiedon määrä lisääntyy nopeasti. Täsmällisen käsityksen muodostaminen potilaan taudintilasta ja sen sovittaminen monimutkaisiin hoito- ja seurantaohjelmiin edellyttää suurten tietomassojen sujuvaa integraatiota ja koneellista päätöksenteon tukea. Eräänä ratkaisuna voidaan hyödyntää hajautettuun laskentaan perustuvia edistyneitä algoritmeja, mikä edellyttää yhteisiä kliinisiä tietomalleja ja ratkaisukeskeistä päätöksentekoa lupaprosessien osalta. Uudet teknologiat, kuten konenäköön perustuva kuva-analyysi ja tautiprosessin laaja-alainen ja jatkuva simulaatio tuovat sekä lisähaasteita että mahdollisuuksia yksilöllistetyn syövänhoidon toteutukseen.Peer reviewe
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