P1436: ageing impacts hydroxycarbamide dosing in patients with sickle cell disease

Topic: 26. Sickle cell disease Background: Hydroxycarbamide (HU) also known as Hydroxyurea is the only licenced disease modifying treatment available for individuals with sickle cell disease (SCD) in the UK. In our clinical practice it appears older adults with SCD are less able to tolerate higher effective doses of HU. The UK “natural history study” is a real-world multi-site study of adults with SCD in the UK collecting all standard of care clinical data. We chose to investigate the effect of age on HU dosing in patients recruited to this study. Aims: To compare effect of age on Hydroxycarbamide dosing in SCD Methods: Patients on the study were identified to be on Hydroxycarbamide (on-HU) or not (not-on-HU). The on-HU group were divided into subgroups by age, and then the mean HU dose in mg/Kg for each age cohort was compared. We also compared mean reticulocyte (retic) and platelet counts as well as haemoglobin (Hb) levels, fetal haemoglobin (HbF%) and serum creatinine. Results: 241 SCD individuals have been recruited to the natural history study with mean age 40.5 (range 18-79); 149 (61.8%) were female. Sickle genotypes: 156 HbSS (64.7%), 73 (30.3%) HbSC, 11 (4.6%) HbSB+ thal and 1 (0.4%) HbSHPFH. 238 of 241 had data on HU use available, 80 patients (34%) were on HU (on-HU), of whom 55 (69%) were female. On-HU sickle genotypes: 67 HbSS (84%), 11 HbSC (14%) and 2 HbSB+ thal (0.3%). The mean age of on-HU patients was 39 (range 20-79), similar to the not-on-HU mean age of 41 (range 18-70). 40 (25%) of the not-on-HU cohort were on regular transfusions as were 9 (11%) patients in the on-HU group (8HbSS, 1HbSC). Mean hb for the on-HU group was 93 g/L, and 102g/L for the not-on-HU group (the not-on-HU group had a higher non-HbSS genotypes including one HbSHPFH; 39% vs 30% in the on-HU group). Mean HbF% was higher in the on-HU group at 9% (0.3-25.8%) vs 4% (range 0.2- 31.7%) in the not-on-HU group. Mean retic count was similar in the two groups: on-HU 186 x109/L; not-on-HU 182 x109/L, LDH level on-HU 402 U/L; not-on-HU 355 U/L. The 80 patients on HU, when divided into sub groups by age, in incremental groups by 5 years (18≤25years, >25-30, >30-35), untill the oldest group of >75-80 was reached (please see table 1), we found the mean HU dose in mg/Kg decreased steadily after age 35, as shown in figure 1. Focusing on the 67 of 80 patients with HbSS/SB0Thal genotype: the on-HU group aged 18-35 (34 patients, 50%) was compared to the >35 year group: we found a significantly higher mean platelet count 393 (79-1077) vs 280 (84-475) (T test P= 0.01), as well as higher retic count; 207.2 (34-460) vs 182 (29-434), and Hb 88.6g/l(59-120) vs 87g/l(60-137) in the 18-35 group. Mean serum creatinine was higher in the > 35 year old group at 79 (32-194) vs 56.3 (35-102) p=0.0008 and mean MCV was also higher in the over 35 group at 101fl (86-124) vs 96 (143-69) in the 18-36 group. Table 1. - Age Number Mean HC dose Mean HU per kg ≤25 22 1263 19 >25-30 7 1214 16 >30-35 11 1389 21 >35-40 6 1155 17 >40-45 10 957 12 >45-50 5 943 14 >50-55 5 700 10 >55-60 7 1071 14 >60-65 4 625 12 >65-70 2 500 7 >70-75 0 >75-80 1 857 14 Total 80 Figure 1 Summary/Conclusion: This data shows higher mean HU doses in SCD patients aged 18-35 years when compared to patients over 35 years. Despite the higher dose, younger patients had higher blood counts and lower MCV compared to the older patients. This difference in HU dosing is likely contributed to by multiple factors including higher rates of renal impairment in the older group and probably reduced bone marrow reserve. A limitation of the study is that it is unclear how many patients had been dosed to the maximum tolerated HU dose. This is the first and largest cohort of SCD patients demonstrating this effect of age on HU dosing, however it is a small study and, larger prospective cohort studies would be needed to confirm our findings. Keywords: Sickle cell, Hydroxyurea, Sickle cell disease