Incidence of myelodysplastic syndromes in Finland 1997-2016

Myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic stem cell diseases that may progress to acute myeloid leukemia. Here, we present incidence of myelodysplastic syndromes based on a nationwide, registry-based study. A total of 1906 MDS cases were reported to the Finnish Cancer Registry during 1997-2016. We analysed the age-standardized incidence rates using the new European standard population, incidence trend and changes in trend by sex, age group and calendar year using Poisson regression and joinpoint regression. The average age-standardized incidence rate was 3.92 per 100,000 person-years. The incidence of MDS increased in a linear-quadratic fashion across 10-year age groups and was higher among men (5.43 versus 3.14 per 100,000). The incidence trend increased during the first 15 years followed by a decline towards the end of the study period. A similar trend was found in subgroups by sex and age. Our results show a similar or slightly higher MDS incidence in Finland as in other Western countries, with an increasing trend, but some decrease in the end. The increasing incidence may reflect improved reporting and coding, or there could be a genuine increase in MDS over time.Peer reviewe

Kliininen hematologia - tietolaatikko

Teema : Hematologiset syövä

FinOMOP : terveystietojen kansainvälinen harmonisointi

Kansainvälisen harmonisointistandardin käyttöönotto on keskeistä suomalaisten terveystietojen tehokkaalle yhteiskäytölle.publishedVersio

Rekisteritutkimus uhattuna - toisiolakiin liittyvistä ongelmista kohti ratkaisuja

Vertaisarvioitu.• Toisiolain mukaan henkilötietojen toisiokäyttö perustuu Findatan tietolupa- hakemuksesta tai tietopyynnöstä tekemään päätökseen, kun halutaan yhdistää vähintään kahden eri rekisterinpitäjän tietoja. • Laki on käytännössä osoittautunut vaikeasti sovellettavaksi. • Suostumus ei usein riitä tietojen toisiokäyttöön. • Toisiolaki vaarantaa potilaiden hoitoa sekä tietojohtamista terveyden- huoltomme laadun arviointia, kehittämistä ja tutkimusta varten.Peer reviewe

Lääkärin syntymäpäiviä vietetään useammin alkuvuodesta

Teema : syntymäPeer reviewe

An immunity and pyroptosis gene-pair signature predicts overall survival in acute myeloid leukemia

Treatment responses of patients with acute myeloid leukemia (AML) are known to be heterogeneous, posing challenges for risk scoring and treatment stratification. In this retrospective multi-cohort study, we investigated whether combining pyroptosis- and immune-related genes improves prognostic classification of AML patients. Using a robust gene pairing approach, which effectively eliminates batch effects across heterogeneous patient cohorts and transcriptomic data, we developed an immunity and pyroptosis-related prognostic (IPRP) signature that consists of 15 genes. Using 5 AML cohorts (n = 1327 patients total), we demonstrate that the IPRP score leads to more consistent and accurate survival prediction performance, compared with 10 existing signatures, and that IPRP scoring is widely applicable to various patient cohorts, treatment procedures and transcriptomic technologies. Compared to current standards for AML patient stratification, such as age or ELN2017 risk classification, we demonstrate an added prognostic value of the IPRP risk score for providing improved prediction of AML patients. Our web-tool implementation of the IPRP score and a simple 4-factor nomogram enables practical and robust risk scoring for AML patients. Even though developed for AML patients, our pan-cancer analyses demonstrate a wider application of the IPRP signature for prognostic prediction and analysis of tumor-immune interplay also in multiple solid tumors.Peer reviewe

Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia

In chronic myeloid leukemia (CML), early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor (TKI) treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included (imatinib n = 26, dasatinib n = 21, nilotinib n = 5), and BCR-ABL1 transcript levels were measured at diagnosis (dg) and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response. In our cohort, 21% of patients had no decrease in BCR-ABL1 transcript levels after 1 month and were classified as poor responders. Surprisingly, these patients had lower BCR-ABL1 transcript levels at dg compared to responders (31% vs. 48%, p = 0.0083). Poor responders also significantly more often had enlarged spleen (55% vs. 15%; p<0.01) and a higher percentage of Ph+ CD34+CD38- cells in the bone marrow (91% vs. 75%, p<0.05). The major molecular response rates were inferior in the poor responders (at 12m 18% vs. 64%, p<0.01; 18m 27% vs. 75%, p<0.01; 24m 55% vs. 87%, p<0.01). In conclusion, early treatment response analysis defines a biologically distinct patient subgroup with inferior long-term outcomes.Peer reviewe

Syövän immunologinen täsmähoito geneettisesti muokatuilla T-soluilla

English summaryPeer reviewe

Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion

Errata: 10.1016/j.jcyt.2017.06.003Background. Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype. Methods. Lymphocytes were transduced with third-generation lentiviral vectors and expanded using CD3/CD28 microbeads. The effects of altering the IL-2 supplementation (0-300 IU/mL) and length of expansion (10-20 days) on the phenotype of the T-cell products were analyzed. Results. High IL-2 levels led to a decrease in overall generation of early memory T cells by both decreasing central memory T cells and augmenting effectors. T memory stem cells (T-SCM, CD95(+)CD45RO(-)CD45RA(+)CD27(+)) were present variably during T-cell expansion. However, their presence was not IL-2 dependent but was linked to expansion kinetics. CD19-CART cells generated in these conditions displayed in vitro antileukemic activity. In summary, production of CART cells without any cytokine supplementation yielded the highest proportion of early memory T cells, provided a 10 fold cell expansion and the cells were functionally potent. Discussion. The number of early memory T cells in a T-cell preparation can be increased by simply reducing the amount of IL-2 and limiting the length of T-cell expansion, providing cells with potentially higher in vivo performance. These findings are significant for robust and cost:effective T-cell manufacturing.Peer reviewe