Pregnancies following high-dose cyclophosphamide with or without high- dose busulfan or total-body irradiation and bone marrow transplantation

Abstract

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.

Cyclophosphamide and antithymocyte globulin as a conditioning regimen for allogeneic marrow transplantation in patients with aplastic anaemia: a long‐term follow‐up

“…All but one of the latter patients eventually had successful childbirths. These observations were consistent with previous reports in patients with aplastic anaemia conditioned with 200 mg CY/kg (Sanders et al, 1996).…”

Preservation of fertility in females with haematological malignancy

“…Intensive chemotherapy and/or total body irradiation (TBI) required before bone marrow transplantation (BMT) constitute the treatment combination presenting the greatest risk of POF. Indeed, the high doses of chemotherapy (commonly using the highly cytotoxic cyclophosphamide/busulfan regimen) and/or radiotherapy lead to subsequent ovarian failure in almost all cases, children and adults alike (Sanders et al, 1996;Meirow & Nugent, 2001;Lobo, 2005). The risk of POF was estimated to be 92% in one study (Meirow & Nugent, 2001), and 100% in an earlier study (Teinturier et al, 1998).…”

Preserving Fertility After Cancer

“…Spontaneous abortions occur at a rate of 38% compared with 12% in the general population, preterm labor 62% compared with 9%, and low birth weight infants 62% compared with 6%. [12][13][14][15][16] However, there is no increased risk of subsequent teratogenicity as long as radiation is not administered during a pregnancy. 8,13,14,[27][28][29][30]…”