Cancer in Pregnancy: Chlorambucil

Chlorambucil (Leukeran) is an alkylating antineoplastic agent.

	Setting	Treatment	Outcomes
In vitro studies	Embryonic cells		Blocking of the initiation step of DNA replication ¹
	Species studied
Animal studies *	rats and mice	Teratogenesis	Growth retardation, defects of the nervous system, cleft palate, limb defects, and impairment of renal growth ^1-3
	Male mice	Mutagenesis	Chlorambucil induces specific locus and dominant lethal mutations in germ cells of male mice ⁴
	Study design
Human studies			No epidemiological studies of congenital anomalies among the infants ofwomen treated with chlorambucil during pregnancy were found.
	Case reports	1st trim exposure	There are three case reports of human fetuses aborted after first trimester exposure to chlorambucil:
		5 - 11 weeks	1. A male fetus with agenesis of left kidney and ureter ⁵
		0 - 20 weeks (+ prednisone)	2. One fetus of a set of twins aborted, with unilateral kidney and ureter agenesis. The other fetus was apparently normal ⁶
		3 - 4 weeks	3. A fetus aborted showing retinal defect ⁷ There are also case reports of first trimester exposure to chlorambucil without adverse effects ^8-11
		2nd and 3rd trim	There are few case reports of late pregnancy exposure without adverse effects in the newborn ⁸

* - None of the animal studies reported in this table were conducted at The Hospital for Sick Children, Toronto, or by Motherisk.

References

Ashby et al: Aspects of the teratology of cyclophosphamide (NSC-26271).Cancer Treat Report 60:477-82, 1976.
Sadler & Kochlar: Teratogenic effects of chlorambucil on in vivo and in vitro organogenesis in mice. Teratology12: 71-8, 1975.
Kavlock et al: Chlorambucil induced congenital renal hypoplasia:effects on basal renal function in the developing rat. Toxicology40:247-58, 1986.
Generoso et al: Dominat lethal and heritable translocation tests with chlorambucil and melphalan in male mice. Mutat Res 345: 167-80,1995.
Shotton & Monie: Possible teratogenic effect of chlorambucil on a human fetus. JAMA 186: 180-1, 1963.
Steege & Caldwell: Renal agenesis after first trimester exposure to chlorambucil. South Med J 73: 1414 ? 5, 1980.
Rugh & Skaredoff: Radiation and radiomimetic chlorambucil and the fetal retina. Arch Oftalmol 74:382-393, 1965.
Nicholson: Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynecol Commonw 75:307-12, 1968.
Baynes et al: Pregnancy in a case of chronic lymphatic leukemia. Br J Obstet Gynecol 75:1165-1168, 1968.
Jacobs et al: Management of the pregnant patient with Hodgkin?s disease. Ann Int Med 95:669-75, 1981.
Ba-Thike: Non-Hodgkin's lymphoma in pregnancy. Asia-Oceania Journal of Obstetrics & Gynaecology 16:229-32, 1990

Our Helplines