Paroxysmal nocturnal haemoglobinuria phenotype cells and leucocyte subset telomere length in childhood acquired aplastic anaemia

Abstract

SummaryThe significance of paroxysmal nocturnal haemoglobinuria (PNH pos ) cells and leucocyte subset telomere lengths in paediatric aplastic anaemia (AA) is unknown. patients (odds ratio 0Á033; 95% confidence interval 0Á002-0Á468; P = 0Á012). Children with AA had short granulocyte (P = 7Á8 9 10 À9 ), natural killer cell (P = 6Á0 9 10 À4 ), na€ ıve T lymphocyte (P = 0Á002) and B lymphocyte (P = 0Á005) telomeres compared to age-matched normative data.

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

“…In contrast, Tutelman et al [29] demonstrated shorter granulocyte telomeres in a childhood AA cohort than in age-matched healthy controls. Among patients treated with IST, very short granulocyte TL was correlated with inferior IST outcomes [29]. Sakaguchi et al [37] also posited that lymphocyte TL at the time of diagnosis was significantly associated with the response to IST in children.…”

“…An NIH study reported that baseline TL was associated with risk of relapse, clonal transformation, and overall survival, but not related to hematologic response in adult AA patients [36]. In contrast, Tutelman et al [29] demonstrated shorter granulocyte telomeres in a childhood AA cohort than in age-matched healthy controls. Among patients treated with IST, very short granulocyte TL was correlated with inferior IST outcomes [29].…”

“…High sensitive flow cytometry analysis has indicated that 20-70 % of pediatric AA patients possess minor PNH populations at the time of diagnosis [17,[28][29][30]. In several studies, investigators have attempted to reveal the clinical significance of such PNH-type cells in patients with bone marrow failure.…”

“…However, the reliability of results obtained from minor PNH populations remains controversial. For example, several studies conducted on adults and/or children with AA reported that the presence of minor PNH populations was associated with a favorable response to IST [14,17,18,29,[31][32][33]. In contrast, a retrospective National Institutes of Health (NIH) study that included adults and children did not find differences between AA patients who did or did not respond to IST [10].…”

Are mild/moderate acquired idiopathic aplastic anaemia and low-risk myelodysplastic syndrome one or two diseases or both and how should it/they be treated?

“…21 Several other variables such as PNH-type cells are also associated with response to ATG and/or cyclosporine. [22][23][24] Another potential marker of an immunemediated aetiology for bone marrow failure is the presence of leukocytes lacking HLA-A alleles (HLA-LLs). 25,26 These cells develop from HSPCs with copy number-neutral loss of heterozygosity of the HLA-class I allele(s) owing to 6pUPD (uni-parental disomy of the short arm of chromosome 6).…”