This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed ...Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.
The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid ...leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.
Essential thrombocythemia (ET) is currently diagnosed either by the British Committee of Standards in Haematology (BCSH) criteria that are predominantly based on exclusion and not necessarily on bone ...marrow (BM) morphology, or the World Health Organization (WHO) criteria that require BM examination as essential criterion. We studied the morphological and clinical features in patients diagnosed according either to the BCSH (n=238) or the WHO guidelines (n=232). The BCSH-defined ET cohort was re-evaluated by applying the WHO classification. At presentation, patients of the BCSH group showed significantly higher values of serum lactate dehydrogenase and had palpable splenomegaly more frequently. Following the WHO criteria, the re-evaluation of the BCSH-diagnosed ET cohort displayed a heterogeneous population with 141 (59.2%) ET, 77 (32.4%) prefibrotic primary myelofibrosis (prePMF), 16 (6.7%) polycythemia vera and 4 (1.7%) primary myelofibrosis. Contrasting WHO-confirmed ET, the BCSH cohort revealed a significant worsening of fibrosis-free survival and prognosis. As demonstrated by the clinical data and different outcomes between WHO-diagnosed ET and prePMF, these adverse features were generated by the inadvertent inclusion of prePMF to the BCSH group. Taken together, the diagnosis of ET without a scrutinized examination of BM biopsy specimens will generate a heterogeneous cohort of patients impairing an appropriate clinical management.
Summary
Background
Risk of melanoma is determined by genetic and exogenous factors. Only a few studies have included both characteristics in a comprehensive multivariable analysis.
Objectives
To find ...determinants of patients at high risk of melanoma in Austria, including phenotype, genotype and lifestyle characteristics in comprehensive analyses.
Methods
In total, 1668 patients with melanoma from the M3 case–control study were studied. Overall, 567 participants were sequenced for CDKN2A, 232 for CDK4, 123 for MITF encoding the variant E318K and 964 for MC1R.
Results
Patients with melanoma with a positive family history (n = 190, 11·6%), multiple primary melanomas (n = 261, 15·7%) and younger age (< 50 years, n = 675, 40·5%) were defined as being at high risk. All other patients with melanoma were defined as the reference group. We found significant differences between those two groups and between the high‐risk subgroups (positive family history, multiple primary melanomas and younger age). Pigmentation phenotype was associated with the high‐risk group in general (childhood freckling, odds ratio 1·46, P = 0·007; blond/reddish hair colour, odds ratio 1·43, P = 0·011). Patients with a positive family history and patients with early‐onset disease were similar regarding both their phenotypic characteristics and external factors. Established high‐risk mutations in CDKN2A were found in cases with a positive family history (n = 12) or multiple melanomas (n = 2). Moreover, we found three patients carrying the MITF p.E318K variant, two with a CDK4 variant and seven with nonsynonymous MC1R variants with undescribed biological significance, of which four were predicted as damaging.
Conclusions
Austrian patients could represent a reservoir for novel genetic variants. Further investigation of populations in Central and Eastern Europe might reveal more novel and disease‐relevant variants.
What's already known about this topic?
Melanoma risk is determined by environmental and genetic risk factors.
The frequency and type of disease‐causing gene mutations vary between different countries.
What does this study add?
This is the first comprehensive description of Austrian patients at high risk of melanoma.
The heterogeneity of the different subgroups suggests diverse pathways.
We present functional prediction of MC1R and CDK4 variants with unknown biological significance in high‐risk patients, and three novel cases with MITF variants in high‐risk patients.
What is the translational message?
Identification of high‐risk individuals helps to reduce mortality.
The risk of melanoma is comprised of a complex interplay between genetic and environmental factors; however, genetic mutations associated with melanoma might differ from country to country.
Knowledge of these mutations and adjustment of criteria for testing could be required for adequate risk assessments.
Linked Comment: Stefanaki and Stratigos. Br J Dermatol 2016; 174: 1188–1190.
Plain language summary available online
Highlights • European ALMA score (E-ALMA) takes into consideration ECOG, WBC and cytogenetics. • It may be used in unfit WHO-defined AML patients treated frontline with azacitidine. • Its design ...involved 371 unfit AML patients treated in 4 European countries. • AZA may be a good choice for patients with a favorable or intermediate E-ALMA score.
Summary
Background
Only recently, site‐dependent associations of actinic damage with melanoma were identified in our study population.
Objectives
To elucidate the diverse aetiologies for actinic ...damage at different body sites.
Methods
We performed multivariate logistic regression analyses to identify independent risk factors for actinic damage on the face, hands and the back in 2112 participants of central European origin.
Results
For actinic damage on the face, age was the only risk factor that remained consistently significant in a multivariate analysis, whereas actinic damage on the back was predominantly associated with number of sunburns, freckles in childhood, holiday weeks and male sex. Moreover, we identified a particular significance of MC1R variants and dorsal actinic skin damage.
Conclusions
The particular effect of MC1R variants and sun exposure during recreational time on dorsal actinic damage indicates that actinic damage on the back is more informative regarding susceptibility to sunlight and past sun exposure associated with melanoma risk.
What's already known about this topic?
Signs of actinic skin damage such as solar lentigines and wrinkling are associated with sun exposure in the past.
MC1R variants are associated with increased sun sensitivity and impaired tanning ability.
The association of MC1R variants with signs of actinic skin damage has been rarely investigated, providing diverging results.
What does this study add?
Actinic damage on the back is a better marker of previous harmful sun exposure compared with other body sites.
Actinic damage on the back is more closely related to MC1R variants in contrast to other sites.
Actinic damage on commonly uncovered areas such as the face is not helpful for assessing previous sun exposure.
Transplant recipients are at risk of developing progressive multifocal leukoencephalopathy (PML), an opportunistic infection due to reactivation of JC virus. Post-transplant lymphoproliferative ...disorders (PTLDs) represent a common malignancy in this population, and antiCD20-therapy has become an established component of its treatment.
We describe the first case of a renal allograft transplant recipient with PTLD who received rituximab-based immune-chemotherapy and developed PML shortly thereafter. Despite early suspicion and diagnosis, the disease ran a relentlessly progressive course, and the patient succumbed to his illness shortly thereafter.
PML should be strongly suspected whenever unusual neurologic symptoms appear in the context of immunosuppression. Clinicians and patients should be aware of the potential for PML after rituximab therapy.
•PTLD is a common neoplasia in transplant recipients.•Rituximab has been associated with PML.•PML associated with rituximab for PTLD has not been reported in the literature.•Surveillance of PML-related symptoms in such patients is recommended.
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