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Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production.
Blood 1986; 67(3):735-8Blood

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/microL and 15.4 X 10(4)/microL, 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, greater than 1.0 mg/dL) exhibit the most cytotoxicity and least F reticulocyte response to Hu.

Authors

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Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2418898

Citation

Dover, G J., et al. "Hydroxyurea Induction of Hemoglobin F Production in Sickle Cell Disease: Relationship Between Cytotoxicity and F Cell Production." Blood, vol. 67, no. 3, 1986, pp. 735-8.
Dover GJ, Humphries RK, Moore JG, et al. Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production. Blood. 1986;67(3):735-8.
Dover, G. J., Humphries, R. K., Moore, J. G., Ley, T. J., Young, N. S., Charache, S., & Nienhuis, A. W. (1986). Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production. Blood, 67(3), pp. 735-8.
Dover GJ, et al. Hydroxyurea Induction of Hemoglobin F Production in Sickle Cell Disease: Relationship Between Cytotoxicity and F Cell Production. Blood. 1986;67(3):735-8. PubMed PMID: 2418898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytotoxicity and F cell production. AU - Dover,G J, AU - Humphries,R K, AU - Moore,J G, AU - Ley,T J, AU - Young,N S, AU - Charache,S, AU - Nienhuis,A W, PY - 1986/3/1/pubmed PY - 1986/3/1/medline PY - 1986/3/1/entrez SP - 735 EP - 8 JF - Blood JO - Blood VL - 67 IS - 3 N2 - 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/microL and 15.4 X 10(4)/microL, 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, greater than 1.0 mg/dL) exhibit the most cytotoxicity and least F reticulocyte response to Hu. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/2418898/Hydroxyurea_induction_of_hemoglobin_F_production_in_sickle_cell_disease:_relationship_between_cytotoxicity_and_F_cell_production_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=2418898 DB - PRIME DP - Unbound Medicine ER -