Influence of Paroxysmal Nocturnal Hemoglobinuria Clone Positivity on Outcome of Childhood Acquried Aplastic Anemia: A Multicenter Center Study

Abstract Introduction: Paroxysmal nocturnal hemoglobinuria(PNH) in the classical hemolytic form is rare among childhood and children may present with aplastic anemia (AA) phenotype or with an overlapping phenotype of both aplastic and hemolytic components. In the recent years the introduction of FLAER methods prompted a more accurate determination of PNH clones in the suspected patients. Among the patients with aplastic anemia, PNH clone positivity has been detected in 18-59% of these patients with more sensitive FLAER methods. There is limited data related to the effect of PNH clone positivity on treatment outcomes in pediatric AA. Methods: A total of 142 patients, who were diagnosed with acquired AA, from 12 centers were included. All of the patients were tested for PNH clone positivity with either CD55/CD59, FLAER. None of the patients were DEB positive. Results: PNH clone was tested initially at diagnosis with CD55/CD59 flow cytometric analyses in 64 (45%) of the ppatients 66 received IST.atients and with FLAER method in 78 (55%) of the patients. Thirthy three (23.2%) were found to be PNH clone positive, two of them were negative with CD55/CD59 at diagnosis, but were found positive with FLAER during follow-up.Of the PNH clone positive patients 71% were male, compared to 43% in PNH clone nnegative group (p=0.001). The mean ages of patients in PNH clone positive and negative groups were 146±50 vs 121±53 months, respectively(p=0.016). There was no statistically significant difference between clone postive and negative patients in terms of mean Hb, WBC, platelet, AST, ALT, indirect bilirubin and haptoglobin levels measured at diagnosis of AA. However serum creatinin level was significantly higher at diagnosis in PNH clone postive patients compared to negative patients (0.57±0.18 vs 0.49±0.15 mg/dl); whereas MCV levels were significantly higher in clone postive group (93.2±9.7 vs 87±11.5 fl). Of 33 patients with PNH clone positivity, 19 (57.6%) were treated with immunosuppressive treatment (IST), as first line treatment, whereas of the clone negative 109 patients, 66 received IST (60.6%) (p=0.76). Of the 19 clone postive patients 11 (57.9%) had treatment response; whereas 36/65 (55.4%) of clone negative patients responded to IST. There was no statistically significant difference between PNH clone positive and negative groups in terms of IST response. IST response was not affected according to gender, age, ALT, AST, WBC, Hb, thrombocyte count, size of the erythrocyte and granulocyte clone at diagnosis. Thrombosis developed in 2 of clone positive (6.1%) and 2 of clone gative patients (1.8%) (p=0.23). Three year survival was 97.6±2.4% and 37.2±8.7% among IST responders and IST non-responders, respectively (p=0.0). Of the 142 patients, 59 underwent HSCT, five received eculizimab and 1 received eltrombopag treatments. Three patients developed clonality during follow-up. Thirty-seven (26%) of the patients deceased among the all study group and the causes of mortality were fungal infection, sepsis, pneumonia, leukemia progression, HSCT related complications, thrombosis and bleeding. Conclusions: PNH clone positivity was found in 23.2% of our patients with pediatric acquired AA. We found no impact of clone positivity on outcome in terms of IST response. This is one of the largest cohort of pediatric patients which investigated the impact of PNH clone positivity on AA outcome. Disclosures No relevant conflicts of interest to declare.