Harmonisation of the HLA tests for the diagnosis of coeliac disease: experiences from the Czech external proficiency testing program.

Coeliac disease (CD) is an autoimmune disorder caused by the ingestion of gluten-containing grains. One of the prerequisites for the development of the disease is the presence of specific combinations of HLA alleles at the DQA1 and DQB1 loci. The HLA test is a supportive diagnostic test. In the Czech Republic, approximately 3,500 HLA tests for CD diagnosis are performed annually in almost three dozen laboratories. The HLA Department of the Institute of Haematology and Blood Transfusion in Prague has been offering the EPT "Detection of HLA Alleles Associated with Diseases" for more than 10 years. The results are evaluated in terms of the correct determination of predisposing alleles/allelic groups and clinical interpretation. Every year, we notice some problems with the detection of CD-associated alleles and the interpretation of results. Annual workshops are part of this EPT, and they also include recommendations for the interpretation of results. This interpretation is evolving based on the current knowledge in the field. The current recommendation for interpretation was adopted in 2023, dividing HLA-DQA1/DQB1 genotypes into three categories: 1) detected HLA genotype is associated with predisposition to coeliac disease; 2) coeliac disease could not be excluded based on the detected HLA genotype; 3) coeliac disease could be excluded with high probability based on the detected HLA genotype. The quality of examination is increasing but still needs improvement. Correct results and accurate interpretation can inform clinicians' decisions about the diagnosis of coeliac disease in appropriate patients.

Complex karyotype and translocation t(4;14) define patients with high-risk newly diagnosed multiple myeloma: results of CMG2002 trial.

The prognostic impact of chromosomal abnormalities was evaluated by fluorescence in situ hybridization with cytoplasmic immunoglobulin light chain staining (cIg-FISH) and by classical metaphase cytogenetics in a cohort of 207 patients with newly diagnosed multiple myeloma who were treated with high-dose therapy followed by autologous stem cell transplantation in the CMG2002 clinical trial. The incidence of chromosomal abnormalities detected by FISH was as follows: 52.7% for del(13)(q14), 6.5% for del(17)(p13), 18.6% for t(11;14)(q13;q32), 22.8% for t(4;14)(p16;q32) and 45.7% for gain(1)(q21). Metaphase cytogenetic analysis revealed a complex karyotype in 19.1% and hyperdiploidy in 21.7% of patients. The overall response rate was not influenced by the presence of any studied chromosomal abnormality. Patients with a complex karyotype, those with translocation t(4;14) and those with gain of the 1q21 locus had a shorter time to progression (TTP) and overall survival (OS). Other genomic changes such as translocation t(11;14) and del(13q) had less impact on TTP and OS. In multivariate analysis, complex karyotype, translocation t(4;14) and ß(2)-microglobulin level > 2.5 mg/L were independent prognostic factors associated with poor overall survival. Their unfavorable prognostic impact was even more pronounced if they were present in combination. Patients with t(4;14) present together with a complex karyotype had the worst prognosis, with a median OS of only 13.2 months, whereas patients with a normal karyotype or karyotype with ≤ 2 chromosomal changes had the best outcome, with 3-year OS of 85.9%. In conclusion, complex karyotype, gain of 1q21 region and translocation t(4;14) are major prognostic factors associated with reduced survival of patients with newly diagnosed multiple myeloma treated with autologous stem cell transplantation.

Gain of 1q21 is an unfavorable genetic prognostic factor for multiple myeloma patients treated with high-dose chemotherapy.

The prognostic significance of 1q21 gain, del(13)(q14), del(17)(p13), t(4;14)(p16.3;q32), and t(11;14)(q13;q32) detected by interphase fluorescein in situ hybridization (FISH) was studied in a cohort of 91 patients with newly diagnosed multiple myeloma (MM). 1q21 gain was detected in 37 of 91 patients (40.7%). In comparison with patients lacking 1q21 gain, patients with 1q21 gain had significantly shorter progression-free survival (PFS) (14.9 versus 27.4 months; P = .044) and worse 4-year overall survival (OS) (40.1% versus 76.2% of patients; P = <.001). PFS or OS were not influenced by the presence or absence of the other studied chromosomal abnormalities. Although the occurrence of 1q21 gain correlated with deletion of 13q14, the presence of 1q21 gain can be considered an independent prognostic factor, as no impact of del(13)(q14) as an isolated chromosomal abnormality on either PFS or OS has been observed. In comparison with patients lacking 1q21 gain, patients with 1q21 gain were significantly more likely to discontinue the preplanned treatment protocol because of disease progression or death. We conclude that 1q21 gain defines a prognostically unfavorable group of MM patients.