Red blood cell transfusions for adolescent patients with sickle cell disease & short stature: A long term follow up study

Abstract BACKGROUND: Children with sickle cell disease (SCD) commonly have delayed or impaired growth. Current evidence suggests that children who are treated long term with red blood cell (RBC) transfusions for different SCD related complications achieve better height and growth, although it is not clear when to start such treatment for the maximum benefit. Timing of such treatment(s) may be critical as to achieve optimum height. Children with SCD who are started on transfusion therapy before the age of 14 years, may achieve better height velocity. However, some children may present late during adolescence and whether to adopt measures like regular blood transfusions to improve their growth, remains unclear. The main aim of this study was to observe the effect of regular RBC transfusions on height, along with weight and body mass index (BSA) of adolescent SCD patients with short stature over long term. Methods: Adolescent patients with SCD being followed at our department, who were observed to have short stature or were referred for this problem and received RBC transfusion therapy to improve their height, were included in this study. Patient were started on regular RBC transfusions after thorough counseling and informed about the likely benefits and possible side effects including usual transfusion related adverse events and particularly the likelihood of iron overload and need for iron chelation therapy. A chart review was performed recording patients' demographics, height, weight, and body mass index (BMI) measurements, duration of transfusion therapy along with laboratory parameters. When iron overload (defined as a serum ferritin ≥ 1000 µgm/l) developed, it was treated with deferasirox. RBC transfusions were continued for 3-6 months after achieving the maximum height (plateau phase). Patients were either already receiving hydroxyurea (HU) or were started at the beginning of transfusion therapy. The average dose of HU was 500 mg daily (15-20mg/kg body weight) at the start of transfusion therapy in all patients and was increased according to the weight gain. RESULTS: Six patients received RBC transfusion therapy for short stature (5 males). All 6 patients completed the therapy but one male patient was lost to follow up afterwards. We present here the long-term results of 5 patients after a median follow up of 90 months. Median age at start of therapy was 15.5 years (range 13.9 -17.4). Patients were treated for a median duration of 29 months (range 23-53). Median height at start of therapy was 137.25 cm, 152.2 cm at the end of transfusions and 169.0 cm at the last (long term) follow up (p 0.0067). Pre-therapy median weight was 28 kg, end of therapy 38.2 kg, and 45.0 kg at the last follow up (p 0.0434). Median increase in height was 32.0 cm (p < 0.025) and median increase in weight 16.78 kg (p=0.007). BMI measurements showed improvement in 3 patients but the increase was modest. Four patients received regular RBC transfusions while one patient received exchange transfusions after one year of simple transfusions because of high base line Hb. Three patients were already receiving HU for one year or more, while 2 patients started HU shortly after commencing transfusion therapy. There were no significant SCD related or transfusion related complications but all patients developed or increased iron overload and received chelation therapy. However, 4 (80%) patients had high s/ferritin before starting transfusion therapy and 3 (60%) patients had s/ferritin around or above 1000 µgm/l at the base line. Median pre-transfusion s/ferritin was 967 µgm/l, 2189 µgm/l at the end of transfusion therapy, and 1083 (range; 277-2500) µgm/l at the last follow up (p 0.399). Although, serum ferritin came down at the last follow up, 4 (80%) patients continue to have high s/ferritin due to poor compliance to chelation therapy. CONCLUSIONS: RBC transfusion therapy significantly improved height of patients with SCD and short stature, even if started during late adolescence. There were no significant adverse events other than iron overload, which developed (or increased) in all patients and required chelation therapy. Four (80%) patients continue to have iron overload due to poor compliance to chelation therapy. RBC Transfusion therapy should be considered in adolescents with SCD and short stature, even if they present during late adolescence. RBC exchange therapy may reduce the complication of iron overload and should be explored in future studies.