Paroxysmal Nocturnal Hemoglobinuria Clones in Children with Acquired Aplastic Anemia: A Multicentre Study

Abstract

A multicentre study evaluating the presence of glycosil phosphatidyl-inositol (GPI)-negative populations was performed in 85 children with acquired aplastic anemia (AA). A GPI-negative population was observed in 41% of patients at diagnosis, 48% during immune-suppressive therapy (IST), and 45% in patients off-therapy. No association was found between the presence of a GPI-negative population at diagnosis and the response to IST. In addition, the response rate to IST did not differ between the patients who were GPI-positive at diagnosis and later developed GPI-negative populations and the 11 patients who remained GPI-positive. Two patients with a GPI-negative population >10%, and laboratory signs of hemolysis without hemoglobinuria were considered affected by paroxysmal nocturnal hemoglobinuria (PNH) secondary to AA; no thrombotic event was reported. Excluding the 2 patients with a GPI-negative population greater than 10%, we did not observe a significant correlation between LDH levels and GPI-negative population size. In this study monitoring for laboratory signs of hemolysis was sufficient to diagnose PNH in AA patients. The presence of minor GPI-negative populations at diagnosis in our series did not influence the therapeutic response. As occasionally the appearance of a GPI-negative population was observed at cyclosporine (CSA) tapering or AA relapse, a possible role of GPI-negative population monitoring during IST modulation may need further investigation.

Diagnostic screening of paroxysmal nocturnal hemoglobinuria: Prospective multicentric evaluation of the current medical indications

“…In contrast, PNH testing for cases presenting with unexplained thrombosis in the absence of anemia or another cytopenia, as well as for patients diagnosed with other hematological/immunological disorders in the absence of a BM failure syndrome, emerged as worthless, with extremely low rates of PNH positivity. Overall, these results are in line with previous observations reported in the literature mostly in smaller patient series and specific diagnostic groups .…”

Clinicopathological profile of paroxysmal nocturnal haemoglobinuria clone‐positive aplastic anaemia paediatric patients—A single centre study from North India

“…The response rate for IST in these patients was quite similar to those who were negative for PNH clones (55.1% vs 60%) [ P value = .573]. This finding was in concordance with other previous studies …”

“…It has been shown that presence of PNH clone in a case of AA virtually rules out the presence of other IBMF . In contrast to the studies on adult AA which have shown a better response to IST, the studies from paediatric AA patients have failed to show any improved response of IST in PNH‐positive cases . The fate of PNH clones in patients with IST is also variably described in the literature.…”

“…There are limited studies which have described the prevalence of PNH in paediatric AA cases. The frequency described in the literature is variable depending on the sensitivity of the assay and the age group included, and it has varied from 12.9% to 48.8% . In a study by Sreedharanunni et al, PNH clone of more than 1% was found in 12.9% (9/70) of paediatric AA cases.…”

Standardized high‐sensitivity flow cytometry testing for paroxysmal nocturnal hemoglobinuria in children with acquired bone marrow failure disorders: A single center US study

“…Moreover, most of those studies addressed pediatric populations from Asian and European countries (4,5,8,11,12). In previously published pediatric literature the prevalence of PNH population detection in pediatric AAA/MDS, using different methods and cutoff values, varied from approximately 12.9-41% (4,5,7,8,(11)(12)(13). In previously published pediatric literature the prevalence of PNH population detection in pediatric AAA/MDS, using different methods and cutoff values, varied from approximately 12.9-41% (4,5,7,8,(11)(12)(13).…”