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Pregnancies following high-dose cyclophosphamide with or without high- dose
busulfan or total-body irradiation and bone marrow transplantation
JE Sanders, J Hawley, W Levy, T Gooley, CD Buckner, HJ Deeg, K Doney, R Storb, K Sullivan, R Witherspoon and FR Appelbaum
Fred Hutchinson Cancer Research Center, University of Washington, Seattle
98104, USA.
Patients successfully treated with a marrow transplant often have concerns
about fertility and pregnancy. This study was performed to determine
pregnancy outcome among patients who had received high-dose chemotherapy
alone or with total-body irradiation (TBI) and marrow transplantation for
aplastic anemia or hematologic malignancy. Records of 1,326 postpubertal
and 196 prepubertal patients currently more than 12 years of age after
marrow transplant in Seattle from August 1971 to January 1992 were reviewed
to determine the patients with normal gonadal function and pregnancies.
Among 708 postpubertal women, 110 recovered normal ovarian function and 32
became pregnant. In addition, nine formerly prepubertal girls with normal
gonadal function became pregnant. Among 618 postpubertal men, 157 recovered
testicular function and partners of 33 became pregnant. An additional two
formerly prepubertal men had partners who became pregnant. Forty-one female
patients and partners of 35 male patients had 146 pregnancies after
transplant. All 76 patients responded to a questionnaire requesting
pregnancy history, outcome, infant birth weight, and congenital anomalies
information for all clinically recognized pregnancies. There were 115 live
births among 146 (79%) pregnancies. Spontaneous abortion terminated four of
56 (7%) pregnancies for 28 female cyclophosphamide (CY) recipients and six
of 16 (37%) pregnancies for 13 TBI recipients (P = .02). Partners of 28
male CY recipients had four of 62 (6.4%) pregnancies terminate with
spontaneous abortion, but there were no spontaneous abortions among eight
pregnancies of five TBI recipients' partners. Preterm delivery occurred for
eight of 44 (18%) and five of eight (63%) live births for 24 CY and eight
TBI female recipients (P = .01). This 25% incidence among all female
patient pregnancies is higher than the expected incidence of 8% to 10% (P =
.0001). The 13 preterm deliveries resulted in 10 low birth weight ([LBW]
1.8 to 2.24 kg) and three very low birth weight ([VLBW] < or = 1.36 kg)
infants, for an overall incidence of 25%, which is higher than the expected
incidence of 6.5% for the general population (P = .0001). Twelve of the 13
premature infants survive. Congenital anomalies were seen among two of 52
(3.8%) live-born infants of female and six of 63 (9.5%) live-born infants
of male patients, which is not different from the 13% of single congenital
anomalies reported for the general population. These data demonstrate that
clinically recognized pregnancies among women who have received a marrow
transplant incorporating TBI are likely to be accompanied by an increased
risk of spontaneous abortion. Pregnancies among all women who received a
marrow transplant are likely to be accompanied by preterm labor and
delivery of LBW or VLBW babies who do not seem to be at an increased risk
of congenital anomalies. However, determination of possible adverse effects
of parental exposure to high- dose alkylating agents with or without TBI on
children born posttransplant requires longer, additional follow-up.
Volume 87,
Issue 7,
pp. 3045-3052,
04/01/1996
Copyright © 1996 by The American Society of Hematology
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