Severity scoring system to guide transfusion management in pediatric non-deletional HbH.

Abstract

Hemoglobin (Hb) H is generally recognized as mild thalassemia, despite its actual phenotypic diversity. A disease severity scoring system to guide initiation of regular transfusion among severely affected pediatric patients has not previously been reported. Patients with HbH were classified into transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) as a surrogate for disease severity. Alpha-globin genotypes and relevant clinical parameters associated with TDT were identified. Univariate and multiple logistic regression analyses were performed to yield the most suitable severity scoring system. From 246 patients with a median age of 14.3 (interquartile range 9.9-18.4) years initially enrolled into the study, the chance of having severe disease and developing TDT was remarkable only among patients with non-deletional HbH, for whom the scoring system was developed. Univariate and multiple logistic regression analyses resulted in three retained parameters associated with TDT, β-coefficients of which were used to develop the score. The final scoring system comprised age at diagnosis <2 years (score = 1), spleen size ≥3 cm (score = 1) and Hb at steady-state <7 (score = 4) or 7-8 g/dL (score = 3). A cutoff score ≥4 was associated with severe disease likely requiring regular transfusion (sensitivity 89.3%, specificity 81.4%), given regular transfusion resulted in maintained growth. The scoring system was validated in the second cohort of 77 non-deletional HbH, from which comparable sensitivity and specificity were obtained. The newly developed scoring system was practical and helpful to highlight severely affected pediatric non-deletional HbH patients with potential needs of regular transfusion. This can be used as a guide for optimal treatment and disease monitoring in the future.