ABSTRACT
The evaluation of an animal is based on production records, adjusted for environmental effects, which gives a reliable estimation of its breeding value. Highly reliable daughter yield deviations are used as inputs for genetic marker evaluation. Genetic variability is explained by particular loci and background polygenes, both of which are described by the genomic breeding value selection index. Automated genotyping enables the determination of many single-nucleotide polymorphisms (SNPs) and can increase the reliability of evaluation of young animals (from 0.30 if only the pedigree value is used to 0.60 when the genomic breeding value is applied). However, the introduction of SNPs requires a mixed model with a large number of regressors, in turn requiring new algorithms for the best linear unbiased prediction and BayesB. Here, we discuss a method that uses a genomic relationship matrix to estimate the genomic breeding value of animals directly, without regressors. A one-step procedure evaluates both genotyped and ungenotyped animals at the same time, and produces one common ranking of all animals in a whole population. An augmented pedigree-genomic relationship matrix and the removal of prerequisites produce more accurate evaluations of all connected animals.
Subject(s)
Breeding , Cattle/genetics , Genetic Variation , Genome , Quantitative Trait Loci , Animals , Genetic Markers , Genotype , Models, Genetic , Pedigree , Polymorphism, Single Nucleotide , Quantitative Trait, HeritableABSTRACT
BACKGROUND: Peripheral T-cell lymphoma, unspecified (PTCL-US) is one of the entities from the infrequent family of nodal mature T-cell lymphomas. The clinical course is aggressive, and despite multiagent chemotherapy, the median survival is about 2 years. Published data are limited to retrospective, mostly single-center studies or reviews and usually include more lymphoma subtypes. AIM: To evaluate the current treatment modalities, clinical outcome and prognostic factors in unselected, new diagnosed patients with PTCL-US in the population of the central european region (Czech Republic). METHOD: Czech Lymphoma Study Group is a national scientific organization which provides an on-line database registry which collects a data about almost all new diagnosed lymphoma patients since year 2000. All diagnostic biopsies were reviewed by a reference pathologist. RESULTS: We analyzed 63 patients with new diagnosis of PTCL-US. The median age was 59 years (25-81), chemotherapy (CHT) was administered in 56 of the 63 patients: anthracyclin-based CHT in 51%, intensive CHT in 21% and non-anthracyclin regimen was applied in 13% of the patients. The overall response rate was 74.4%, (CR in 57.4%). After a median follow-up of 19.6 months, 41% of the patients were in CR, 3.4% in PR or stable disease and 55% of the patients died. The estimated survival probability in 3 years was 36%. Clinical stage (IV) and CR achievement were found to be independent survival predictors in a multivariate analysis. CONCLUSIONS: Although the current treatment modalities are mostly ineffective in PTCL-US, appropriate intensive treatment may lead to prolonged remission but not survival.
Subject(s)
Lymphoma, T-Cell, Peripheral , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphoma, T-Cell, Peripheral/diagnosis , Lymphoma, T-Cell, Peripheral/mortality , Lymphoma, T-Cell, Peripheral/therapy , Male , Middle Aged , Survival RateABSTRACT
We have studied the feasibility and efficacy of intensified R-MegaCHOP-ESHAP-BEAM therapy in high-risk aggressive B-cell lymphomas. Altogether 105 patients (19-64 years) with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBL) or follicular lymphoma grade 3 (FL3) with an age-adjusted International Prognostic Index of 2-3 were recruited. Treatment consisted of three cycles of high-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), followed by three cycles of R-ESHAP (rituximab, etoposide, methylprednisolone, cytarabine, cisplatin) and high-dose consolidation with BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem cell transplant. The 5-year progression-free survival (PFS) was 72% (DLBCL 60%, PMBL 89%) and overall survival (OS) was 74% (DLBCL 61%, PMBL 89%) after a median follow-up of 85 months. However, an independent prognostic factor was age only, with patients ≤ 45 years having 5-year PFS 90% and patients > 45 years having PFS 54%. PMBL had better prognosis than DLBCL/FL3 in patients > 45 years (PFS, 88% vs. 48%), but not in younger patients (PFS, 91% vs. 94%).