Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia

Charache, Samuel; Dover, GJ; Ma, Min; Jw, Moore

doi:10.1182/blood.v69.1.109.109

Cited by 175 publications

(53 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HU causes an increase in HbF, which interferes with the polymerization of HbS and at a dosage of 20 mg/kg per day reduces the frequency and severity of painful crises. 1,2 There is extensive published work describing the adverse effects of HU on fertility in murine models. HU given to male rats at a dose !60 mg/kg per day (at the higher end of the range generally used in myeloproliferative disease and three times the recommended sickle cell dose) produces testicular atrophy, decreases spermatogenesis, reduces sperm motility and induces abnormalities in sperm morphology andchromatin structure, [3][4][5] although experiments suggest that the germ cell toxicity may be reversible.…”

mentioning

confidence: 99%

Effect of hydroxyurea on sperm count, motility and morphology in adult men with sickle cell or myeloproliferative disease

Grigg

2007

Internal Medicine Journal

View full text Add to dashboard Cite

Hydroxyurea (HU) is not infrequently used in patients with sickle cell disease and myeloproliferative disorders. Despite murine data showing adverse effects on sperm counts, motility and morphology, there is little information on the effect of HU on human spermatogenesis. A retrospective review of four adult men who had semen analysis during HU therapy and in three cases after its cessation suggests that HU generally reduces sperm counts and motility and results in abnormal morphology. Cessation of HU in one case with azoospermia resulted in recovery of spermatogenesis; in two of the three cases, however, sperm morphology and mobility remained impaired. Recommendations for fertility management in adult men receiving long-term HU therapy are proposed.

show abstract

mentioning

confidence: 99%

Effect of hydroxyurea on sperm count, motility and morphology in adult men with sickle cell or myeloproliferative disease

Grigg

2007

Internal Medicine Journal

View full text Add to dashboard Cite

show abstract

“…Hydroxyurea (HU) is beneficial in sickle cell anaemia (Dover et al, 1986;Charache et al, 1987Charache et al, , 1992Charache et al, , 1995Rodgers et al, 1990). Its therapeutic benefit may extend beyond its effect on fetal haemoglobin (Hb F) (Bridges et al, 1994;Horiuchi et al, 1996;Charache et al, 1996).…”

mentioning

confidence: 99%

Cellular effects of hydroxyurea in Hb SC disease

1997

View full text Add to dashboard Cite

Summary. Hb S polymerizes in high-density Hb SC disease erythrocytes. We hypothesized that hydroxyurea -perhaps independent of increasing Hb F -might reduce the density of these cells. Six Hb SC disease patients were given 1000 mg of hydroxyurea daily and blood counts, cell volumes, and cell density were followed for 12 months. There was an increase in MCV and reticulocyte MCV. A fall in absolute reticulocyte counts, high-staining ('stress') reticulocytes, serum bilirubin, and an increase in the ratio of mature red cell haemoglobin to reticulocyte haemoglobin, coupled with a rise in the haematocrit inferred a decrease in haemolysis and 'stress erythropoiesis'. An improvement in cell hydration was suggested by a reduction in reticulocyte mean cell haemoglobin concentration (CHCMr), red cells and reticulocytes with CHCM > 38, and decreased dense cell counts estimated by phthalate ester and Percoll-Larex gradients. After 4-5 months treatment, Hb F rose in a few patients but the overall difference in pre-and post-treatment Hb F was not significant. A decline in cell density should diminish the polymerization tendency of Hb S in Hb SC disease.

show abstract

“…However, and despite this fortunate circumstance, extreme cases of toxicity such as those recently reported by Vichinsky & Lubin (1994) may occur and indicate great caution over the long-term use of high doses of HU. Moreover, and despite the so far virtually negative laboratory and clinical data (Charache et al, 1987(Charache et al, : 1992 : Kaplan et al, 1986), the danger of carcinogenesis is not totally excluded and should always be taken into account when carrying out such trials.…”

Section: Discussionmentioning

confidence: 99%

Clinical and laboratory effects of long‐term administration of hydroxyurea to patients with sickle‐cell/β‐thalassaemia

1995

View full text Add to dashboard Cite

Hydroxyurea (HU), a widely used cytostatic, has been given over a long period of time to 14 adult Caucasian compound heterozygotes for beta s and various beta-thalassaemia genes. All patients had severe pain crises and other complications prior to receiving the drug. After 4-8 weeks on high 'sub-toxic' doses of HU all patients responded with a multifold increase of fetal haemoglobin (HbF) and a marked increase of MCV and MCH; they also felt significantly better and ceased having pains or other complaints. Haematological toxicity was minimal and rapidly reversible. Follow-up of the patients has now exceeded 100 weeks and goes up to 180 weeks in two of them. Pain crises have never recurred. Maintenance of high levels of HBF requires continuous administration of high doses of HU; whenever the latter were decrease in various attempts to avoid potential long-term toxicity, the observed changes gradually faded. The effect of HU in HbS/beta-thalassaemia may be better than that reported for homozygous HbS disease because the synthesized gamma-chains not only inhibit the sickling process but they also neutralize the noxious effects of the excess alpha-chains and cut down the ineffective erythropoiesis of the patients.

show abstract

Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia

Cited by 175 publications

References 53 publications

Effect of hydroxyurea on sperm count, motility and morphology in adult men with sickle cell or myeloproliferative disease

Effect of hydroxyurea on sperm count, motility and morphology in adult men with sickle cell or myeloproliferative disease

Cellular effects of hydroxyurea in Hb SC disease

Clinical and laboratory effects of long‐term administration of hydroxyurea to patients with sickle‐cell/β‐thalassaemia

Contact Info

Product

Resources

About