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

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

Research output: Contribution to journalArticle

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
StatePublished - 1986

Fingerprint

Fetal Hemoglobin
Hydroxyurea
Sickle Cell Anemia
Cytotoxicity
Reticulocytes
Reticulocyte Count
Azacitidine
Erythroid Precursor Cells
Creatinine
Bone Marrow
Serum
Toxicity
Kidney
Plasmas
Recovery

ASJC Scopus subject areas

  • Hematology

Cite this

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), 735-738.

Hydroxyurea induction of hemoglobin F production in sickle cell disease : Relationship between cytotoxicity and F cell production. / Dover, George J; Humphries, R. K.; Moore, J. G.; Ley, T. J.; Young, N. S.; Charache, S.; Nienhuis, A. W.

In: Blood, Vol. 67, No. 3, 1986, p. 735-738.

Research output: Contribution to journalArticle

Dover, GJ, Humphries, RK, Moore, JG, Ley, TJ, Young, NS, Charache, S & Nienhuis, AW 1986, 'Hydroxyurea induction of hemoglobin F production in sickle cell disease: Relationship between cytotoxicity and F cell production', Blood, vol. 67, no. 3, pp. 735-738.
Dover, George J ; Humphries, R. K. ; Moore, J. G. ; Ley, T. J. ; Young, N. S. ; Charache, S. ; Nienhuis, A. W. / Hydroxyurea induction of hemoglobin F production in sickle cell disease : Relationship between cytotoxicity and F cell production. In: Blood. 1986 ; Vol. 67, No. 3. pp. 735-738.
@article{f7c4e58d0d89498e8d003818c023e58b,
title = "Hydroxyurea induction of hemoglobin F production in sickle cell disease: Relationship between cytotoxicity and F cell production",
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.",
author = "Dover, {George J} and Humphries, {R. K.} and Moore, {J. G.} and Ley, {T. J.} and Young, {N. S.} and S. Charache and Nienhuis, {A. W.}",
year = "1986",
language = "English (US)",
volume = "67",
pages = "735--738",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

TY - JOUR

T1 - Hydroxyurea induction of hemoglobin F production in sickle cell disease

T2 - Relationship between cytotoxicity and F cell production

AU - Dover, George 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

Y1 - 1986

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/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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0022568850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022568850&partnerID=8YFLogxK

M3 - Article

C2 - 2418898

AN - SCOPUS:0022568850

VL - 67

SP - 735

EP - 738

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -