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.

One hundred eighty-seven women between 13 and 49 years of age had ovarian function evaluated from 1 to 15 years (median, 4) after marrow transplant for aplastic anemia or leukemia. Among 43 women transplanted for aplastic anemia following 200 mg/kg cyclophosphamide (CY), all 27 less than 26 years of age, but only five of 16 greater than 26 years of age recovered normal ovarian function. Nine of the 43 have had 12 pregnancies, resulting in eight live births, and two elective and two spontaneous abortions. All eight children are normal. Nine of 144 women transplanted for leukemia following 120 mg/kg CY and 9.20 to 15.75 Gy total body irradiation (TBI) recovered ovarian function. Two of these nine have had three pregnancies, resulting in two spontaneous and one elective abortion. The probability of having ovarian failure was 0.35 by 7 years for patients receiving CY alone and was 1.00 at 1 year for patients receiving CY plus TBI (P less than .0001). By 7 years after transplant the probabilities of having normal ovarian function were 0.92 after CY alone and 0.24 after CY plus TBI (P less than .0001). Multivariate analysis showed that TBI was the only factor significantly influencing ovarian failure and that both TBI and greater patient age at transplant were significantly associated with a decreased probability of recovering normal ovarian function. These data demonstrate that after high-dose CY, recovery of ovarian function occurs in younger women and in a minority of older women, but after CY and TBI, recovery occurs in only a few younger women and none of the older women.

Allogeneic stem cell transplantation is curative for certain cancers, but the high doses of chemotherapy/radiotherapy lead to toxicity. Here, we treat patients with refractory cancer with 100 cGy total body irradiation (TBI) followed by infusion of nonmobilized pheresed allogeneic peripheral blood cells. Twenty-five patients, with a median age of 47 years, with refractory cancers were enrolled. Eighteen patients received sibling and 7 received unrelated cord blood cells. Donor chimerism was assessed at weeks 1, 2, 3, 4, and 8 after transplantation. Seven patients with solid tumors received a sibling transplant and 6 received a cord blood transplant; none achieved donor chimerism, but 1 treated at the higher dose level of 1 ؋ 10 8 CD3 ؉ cells/kg had a transient nodal response. Twelve patients with hematologic malignancies were treated; 1 received a cord blood transplant and 11 received sibling donor cells. Nine of these 11 patients achieved donor chimerism, ranging from 5% to 100%. Four patients had sustained complete remission of their cancers, including one patient with transient 5% donor chimerism. The development of chimerism correlated with hematologic malignancy (P < .001), total previous myelotoxic chemotherapy (P < .001), T-cell dose (P ‫؍‬ .03), and graft-versus-host disease (P ‫؍‬ .01). Tumor response correlated with donor chimerism (P ‫؍‬ .01). Engraftment was achieved in patients with hematologic malignancies who had been heavily pretreated, suggesting the degree of immunosuppression may be a determinant of engraftment. Low-dose TBI and allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. (Blood. 2002; 100:442-450)