Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two‐centre prospective study

Abstract

SummaryParoxysmal nocturnal haemoglobinuria (PNH) clones are frequently detected in patients with aplastic anaemia (AA). To evaluate the prognostic role of PNH clone presence we conducted a prospective study in 125 AA patients treated with combined immunosuppressive therapy (IST). Seventyfour patients (59%) had a PNH clone (PNH+ patients) at diagnosis, with a median clone size of 0Á60% in granulocytes and 0Á15% in red blood cells. The response rate at 6 months was higher in PNH+ patients than that in PNH-patients, both after first-and second-line IST: 68% vs. 45%, P = 0Á0164 and 53% vs. 13%, P = 0Á0502 respectively. Moreover, 42% of PNH+ patients achieved complete remission compared with only 16% of PNH-patients (P = 0Á0029). In multivariate logistic regression analysis, PNH clone presence (odds ratio 2Á56, P = 0Á0180) and baseline absolute reticulocyte count (ARC) ≥30 9 10 9 /l (odds ratio 5Á19, P = 0Á0011) were independent predictors of response to treatment. Stratification according to PNH positivity and ARC ≥30 9 10 9 /l showed significant distinctions for cumulative incidence of response, overall and failure-free survival. The results of this prospective study confirmed the favourable prognostic value of PNH clone presence in the setting of IST for AA.

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

“…When the two predictive parameters of ARC and ALC were combined, patients with higher baseline ANC and ARC had a response rate 40 % higher than those with lower baseline ANC and ARC (83 vs 41 %, p < 0.0001). The utility of ARC in predicting IST outcomes has been confirmed in a proportion of reports, but not in others [12,[14][15][16][17]. Higher absolute neutrophil count (ANC) appears to be correlated with a better response rate of IST [15,18]; however, this result was not confirmed in Japanese and German children [12,19,20].…”

“…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.…”

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).…”

Diagnostic problems in acquired bone marrow failure syndromes

“…Although each disease has a unique manifestation, the immune mechanisms shown in blue are shared by all four diseases. When a patient with BM failure possesses a marker of immune pathophysiology such as PNH-type cells [8] or HLA allele-lacking cells [9], the patient should be treated with immunosuppressive therapy, irrespective of the formal diagnosis.…”