HU has been shown to be clinically and hematologically efficacious in adults and children with SS and is PDA approved for use in adults. A large number of reports on HU in SS deal mostly with relatively short-term usage (6-12 mo) in a small number of patients (pts). We report on the long-term use of HU in 149 SS pts (69M, 80F), median age 29 (1554), who were treated for a median of 42.1 mo (7-127). Indications for HU: frequent pain crises (59.1%), severe anemia/hemolysis (26.2%), h/o CVA (6%), priapism (4%), leg ulcers (2.7%), and acute chest syndrome (2%). Mean HU dose: 18.6 mg/kg/d (5.6-33.3). Compliance rate: 71.1%. Average weight gain: 3.4 kg . Pain crises decreased from a mean of 8.9 to 2.2/year (p=.0001). HU had no effect on the healing or recurrence rate of leg ulcers; all but one of the pts who developed ulcers had a previous history. Hb, Hct, MCV, and MCH increased significantly with HU (p<.01); while relics, WBC, ANC (p<.01), platelets, and bilirubin (p<. 05) decreased. Hb increased from 8.2 to 9.5 g/dl; and MCV by 21% (92.2 to 111.6 fi). Hb F increased from 5.7 to 18.5% (p<.01). Hb F increase was most pronounced in pts with SEN/SEN haplotype. 36 pts who remained on HU 48 mos had a sustained Hb F response. Hématologie toxicily (ANC<2000, plateletes <80,000, relics <80,000, or Hb <4.5 g/dl) was seen in 26/149 pts (17.4%). There were 62 episodes in 26 pts, (1 -7/pt); 41.8% ANC, 46.3% Hb and/or relics, and 11.9% platelets. Pts who developed toxicity were older (mean age 35.9, range 24-55) and on higher doses of HU (mean 20.6 mg/kg/d, range 11.3-33.3). Minor rare side effects included nausea, melanonychia, and alopecia. No malignancies were observed. 12 deaths occurred during follow-up; acute chesl syndrome (4), multi-organ failure (4), slroke (1), ruplured ectopic pregnancy (1), and unknown (2). 8/12 were on HU al lime of dealh wilh a median age of 38.5 (20-55) and median HU exposure of 39.5 mos (6-108). Our data show that HU significantly improves Ihe clinical course and hematology of SS. It is well accepted and tolerated by the pts although improvement in compliance is desirable. The occurrence of hematological loxicity mandates close monitoring during HU Iherapy. Hb F increase is sustained over 4 years in complianl pis. Despite this, life threatening complications and death occur during therapy. Questions on the efficacy of HU in preventing organ damage and on long term safely (i.e. leukemogenicity/carcinogenicity) will be resolved with long term observation of pts and with resulls of sludies in infants and children.
|Original language||English (US)|
|Issue number||11 PART I|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology