The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS)

Abstract

The aim of this prospective study was to evaluate the long-term efficacy and safety of hydroxyurea (HU) in patients with sickle cell disease (SCD). Thirty-four patients with sickle cell anemia (hemoglobin S [HbS]/HbS), 131 with HbS/␤ 0 -thal, and 165 with HbS/␤ ؉ -thal participated in this trial. HU was administered to 131 patients, whereas 199 patients were conventionally treated. The median follow-up period was 8 years for HU patients and 5 years for non-HU patients. HU produced a dramatic reduction in the frequency of severe painful crises, transfusion requirements, hospital admissions, and incidence of acute chest syndrome. The probability of 10-year survival was 86% and 65% for HU and non-HU patients, respectively (P ‫؍‬ .001), although HU patients had more severe forms of SCD. The 10-year probability of survival for HbS/ HbS, HbS/␤ 0 -thal, and HbS/IVSI-110 patients was 100%, 87%, and 82%, respectively, for HU patients and 10%, 54%, and 66%, for non-HU patients. The multivariate analysis showed that fetal hemoglobin values at baseline and percentage change of lactate dehydrogenase between baseline and 6 months were independently predicted for survival in the HU group. These results highlight the beneficial effect of HU, which seems to modify the natural history of SCD and raise the issue of expanding its use in all SCD patients. (Blood.

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

“…There are, to date, no controlled studies that implicate either hydroxyurea or busulfan as being leukemogenic in either ET or PV. Similarly, the two largest non-controlled studies in ET [54] and PV [108] do not support the concern that leukemia might arise from the use of hydroxyurea and there is additional evidence to that effect from long-term studies of patients receiving hydroxyurea for sickle cell disease [123]. The evidence for busulfan leukemogenicity in the context of treatment for PV or ET is equally weak and inappropriately extrapolated from older patients with advanced phase disease and exposed to multiple cytoreductive drugs.…”

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…This survival benefit was maintained at 17.5 years [58]. Another study replicated the benefit of hydroxyurea therapy on survival in a 17-year, open-label trial of 330 adult patients with SCD [59]. Adults with SCD treated with hydroxyurea therapy had a significant reduction in the frequency of pain episodes, transfusion requirements, hospital admissions, and the incidence of ACS.…”

“…Adults with SCD treated with hydroxyurea therapy had a significant reduction in the frequency of pain episodes, transfusion requirements, hospital admissions, and the incidence of ACS. Most importantly, the incidence of stroke (3.8% vs. 5.0%), death from liver dysfunction (0.7% vs. 5%), and overall mortality (86% vs. 65%, P 5 0.001) were also significantly lower in the hydroxyurea group comprised of adults with severe disease, defined as 3 or more painful sickle cell crises during the preceding year that needed hospitalization or emergency room visits; the presence of jaundice at presentation or complications of SCD, such as stroke and acute chest syndrome during the last 5 years, compared with the observation group that had less severe disease [59].…”

“…Those that received hydroxyurea therapy had higher survival when compared with those that were untreated with less severe disease, with survival rates of 99Á5% and 94Á5%, respectively, P 5 0Á01 [17]. Thus we have direct evidence from three cohorts (two pediatric and one adult) that hydroxyurea therapy improved survival in individuals with more severe SCD (high rates of vaso-occlusive pain and ACS) compared with individuals with less severe SCD who were not on hydroxyurea therapy [17,21,59].…”

Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

“…Mechanisms underlying these and other beneficial effects of the drug affecting leukocytes and the endothelium (16)(17)(18) have not been fully elucidated. Nevertheless, the consensus for management of SCD care is administration of HU due to its success in both adult and children populations (19)(20)(21)(22)(23). It must be noted, however, that there are patient populations who are unresponsive to HU treatment (24).…”