Growth retardation and depigmentation of hair after high-dose busulfan and congenic hematopoietic cell transplantation in mice

Andrew M Yeager, C. Shinn, E. R. Farmer, J. R. Wingard, M. J. Yeager

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Busulfan, a myeloablative but non-immunosuppressive alkylating agent, is used extensively in clinical bone marrow transplantation (BMT), but the effects of highdose administration have not been previously evaluated in preclinical BMT settings with young murine recipients. We compared the survival and growth of C57BL/6 mice given graded single doses of busulfan (10-100 mg/ kg) or total body irradiation (TBI; 900 cGy) at age 9 days and hematopoietic cell transplantation (HCT; transplantation of congenic bone marrow and spleen cells) 24 h later. The 30-day survival was 87-100% in mice transplanted after 10-40 mg/kg busulfan and 79% after TBI, but fell to 54% and 33%, respectively, after 80 mg/kg and 100 mg/kg busulfan, suggesting that this latter dosage range represents the LD50 for single-dose busulfan in young C57BL/6 mice given stem cell rescue. The weights of 10-week-old mice given HCT after lower doses of busulfan ranged from 87% of control at 10 mg/kg to 64-69% of control in mice conditioned with 35-65 mg/kg busulfan or TBI. Impairment of weight gain was most striking (approximately 50% of control) in mice transplanted after 80-100 mg/kg busulfan. Despite retardation of somatic growth, the brain weights of busulfan-conditioned mice remained at least 90% of control, and there were no obvious neuropathological alterations in the brains of these animals. All mice treated with at least 20 mg/kg busulfan or TBI lost hair by 3-4 weeks after transplant. In the regrown hair of these normally black-coated mice, pigment loss was observed, ranging from minimal scattered graying of some hair after TBI or 20-40 mg/kg busulfan to virtually complete whiteness in animals given 100 mg/kg; depigmentation was associated with loss of melanin in the hair follicles and the appearance of peribulbar melanophages (melanin-containing macrophages). The growth retardation and effects on hair color seen after high-dose busulfan in this preclinical model should be taken into account in clinical BMT regimens that use this agent, especially for younger pediatric patients.

Original languageEnglish (US)
Pages (from-to)199-204
Number of pages6
JournalBone Marrow Transplantation
Volume9
Issue number3
StatePublished - 1992
Externally publishedYes

Fingerprint

Busulfan
Cell Transplantation
Hair
Growth
Bone Marrow Transplantation
Melanins
Inbred C57BL Mouse
Hair Color
Weights and Measures
Hair Follicle
Whole-Body Irradiation
Alkylating Agents
Lethal Dose 50
Brain
Bone Marrow Cells
Weight Gain
Stem Cells
Spleen
Transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Growth retardation and depigmentation of hair after high-dose busulfan and congenic hematopoietic cell transplantation in mice. / Yeager, Andrew M; Shinn, C.; Farmer, E. R.; Wingard, J. R.; Yeager, M. J.

In: Bone Marrow Transplantation, Vol. 9, No. 3, 1992, p. 199-204.

Research output: Contribution to journalArticle

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title = "Growth retardation and depigmentation of hair after high-dose busulfan and congenic hematopoietic cell transplantation in mice",
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AU - Yeager, M. J.

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N2 - Busulfan, a myeloablative but non-immunosuppressive alkylating agent, is used extensively in clinical bone marrow transplantation (BMT), but the effects of highdose administration have not been previously evaluated in preclinical BMT settings with young murine recipients. We compared the survival and growth of C57BL/6 mice given graded single doses of busulfan (10-100 mg/ kg) or total body irradiation (TBI; 900 cGy) at age 9 days and hematopoietic cell transplantation (HCT; transplantation of congenic bone marrow and spleen cells) 24 h later. The 30-day survival was 87-100% in mice transplanted after 10-40 mg/kg busulfan and 79% after TBI, but fell to 54% and 33%, respectively, after 80 mg/kg and 100 mg/kg busulfan, suggesting that this latter dosage range represents the LD50 for single-dose busulfan in young C57BL/6 mice given stem cell rescue. The weights of 10-week-old mice given HCT after lower doses of busulfan ranged from 87% of control at 10 mg/kg to 64-69% of control in mice conditioned with 35-65 mg/kg busulfan or TBI. Impairment of weight gain was most striking (approximately 50% of control) in mice transplanted after 80-100 mg/kg busulfan. Despite retardation of somatic growth, the brain weights of busulfan-conditioned mice remained at least 90% of control, and there were no obvious neuropathological alterations in the brains of these animals. All mice treated with at least 20 mg/kg busulfan or TBI lost hair by 3-4 weeks after transplant. In the regrown hair of these normally black-coated mice, pigment loss was observed, ranging from minimal scattered graying of some hair after TBI or 20-40 mg/kg busulfan to virtually complete whiteness in animals given 100 mg/kg; depigmentation was associated with loss of melanin in the hair follicles and the appearance of peribulbar melanophages (melanin-containing macrophages). The growth retardation and effects on hair color seen after high-dose busulfan in this preclinical model should be taken into account in clinical BMT regimens that use this agent, especially for younger pediatric patients.

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