Abstract
Introduction: Since HU has been FDA-approved for patients with SCD, it is not clear what proportion are taking a therapeutic dose (≥15mg/kg/day). There is also inadequate reporting of the frequency of HU dose modification during follow-up, or whether those who were treated with subtherapeutic doses (<15mg/kg/day) benefit from HU. We conducted this analysis to answer these important questions in a single center in Palermo, Italy.
Methods: Patients were enrolled at the Haematology Department of Ospedale V. Cervello between January 2000 and April 2014. Laboratory parameters and frequency of vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) were recorded. Blood counts, fetal hemoglobin (HbF) response, and changes in SCD complications were compared between the first and last visits to the clinic and across these 3 groups: patients who never took HU were combined with those who suspended HU before the last visit (no HU group, n=50, 36%); HU <15mg/kg (n=30, 21%); or HU ≥15mg/kg (n=60, 43%).
Results: There were a total of 140 patients: 25 HbSS, 54 HbSβ0thal, and 61 HbSβ+thal. Median follow-up was 6.6 years. The median age was 35 years (range 0.4-61 years). 28% of patients never took HU, and 8% suspended HU treatment during the follow-up. Among patients taking <15mg/kg HU at first visit, about half stayed in the same dose range (<15mg/Kg/day) and half increased to the ≥15mg/kg dose range. Among patient taking ≥15 mg/kg, 17% decreased to <15mg/Kg/day due to cytopenia; 83% stayed on the ≥15 mg/kg. White blood cell (WBC) counts were lower in both HU groups, but comparing first and last visits, the change in WBC within each group was insignificant (P all >0.05, Table 1). Similarly, the change in total hemoglobin levels within each group was also insignificant (P all >0.05). HbF decreased in the no HU group, likely due to maturing age of 2 young children included in this group. Both HU treatment groups had modest increases in HbF (P=0.004, 0.001).
With respect to SCD complications, the no HU group had less severe disease at the first visit, with lower percent of subjects with and fewer episodes of VOC and ACS (Table 2). While there was an increase in both VOC and ACS with time, this increase was not statistically significant. Both HU treatment groups had a significant reduction in both complications (p<0.0001 in both), and the magnitude of reduction was similar. The pattern of reduction appeared to be similar in all SCD phenotypes, but the small sample size precluded subtype analysis. Comparing changes in laboratory markers of liver and kidney function as well as TRV and ejection fraction between the first and last visit showed no significant differences.
Conclusions: About one third of patients with SCD never took or discontinued HU. While these patients may have less severe disease initially, their rates of complications increased during follow-up. Among those taking HU, dose adjustment was common. HU increased HbF and is associated with reducing VOC and ACS. Since the increase in HbF and changes in HU dosing parameters were only modest in patients even on the highest HU doses, titrating HU to the maximum HbF response should be explored in order to improve markers of organ function.
Table 1: Hematologic parameters based on HU status First Visit Last Visit NO HU HU <15mg/kg HU >15mg/kg NO HU HU <15mg/kg HU >15mg/kg WBC (k/uL) 11.2 8.74* 10.9 10.7 7.8* 8.3* Hgb (g/dL) 10.0 10.2 10.0 10.2 9.7 9.9 HbF (%) 11.9** 9.4* 10.7* 7.7 11.7* 12.8*
*P<0.05 compared to no HU group
**includes 4 subjects with hereditary persistent of HbF and 2 children aged 3 months.
Table 2: SCD complications based on HU status VOC ACS % of subjects Crisis per patient per year % of subjects Mean episodes per patient F V L V F V L V F V L V F V L V No HU 60 70 2 2.5 22 28 0.2 0.28 HU<15mg/kg 90 56.6 4.3* 1.2* 50 20 0.7* 0.23 HU>15mg/kg 96.6 60 4.1* 1.1* 51 25 1.1* 0.32
FV, first visit; LV, last visit
*P<0.05 compared to no HU group
Disclosures
No relevant conflicts of interest to declare.
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