Hydroxyurea induction of hemoglobin F production in sickle cell disease: Relationship between cytotoxicity and F cell production

G. J. Dover, R. K. Humphries, J. G. Moore, T. J. Ley, N. S. Young, S. Charache, A. W. Nienhuis

Research output: Contribution to journalArticlepeer-review

Abstract

Initial alterations in fetal hemoglobin (HbF) production among eight sickle cell anemia subjects treated with hydroxyurea (Hu) are summarized. Four of these subjects had been previously treated with 5-azacytidine (5-aza). All subjects treated with Hu (50 mg/kg/d for three to five days) had suppression of their total reticulocyte counts by seven days, whereas the four subjects previously treated with 5-aza (2 mg/kg/d for three to five days) had increased reticulocyte counts at day 7. The effect of Hu on increasing the number of HbF-containing reticulocytes (F reticulocytes) is extremely variable, ranging from ten- to less than onefold differences in maximal posttherapy v pretherapy levels. Recovery from marrow suppression did not result in greater than twofold increases in F reticulocyte counts. Mean day 7 F reticulocyte levels in the four subjects treated with both Hu and 5-aza were 4.1 x 10/μL and 15.4 x 104/μL, respectively. Among Hu-treated subjects, increased F reticulocyte production was correlated with low serum creatinine levels and rapid removal of Hu from the plasma. Furthermore, suppression of CFU-E colony formation on day 2 of therapy with Hu was inversely correlated with maximal F reticulocyte response. We conclude that where Hu treatment results in marrow toxicity (decreased reticulocyte counts, decreased CFU-E colony formation) HbF production is less likely to increase. Those sickle cell anemia subjects with minimal renal dysfunction (serum creatinine level, >1.0 mg/dL) exhibit the most cytotoxicity and least F reticulocyte response to Hu.

Original languageEnglish (US)
Pages (from-to)735-738
Number of pages4
JournalBlood
Volume67
Issue number3
DOIs
StatePublished - 1986

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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