Early High Dose Chemotherapy Intensification with Autologous Bone Marrow Transplantation in Lymphoma Associated with Retention of Fertility and Normal Pregnancies in Females

Abstract

As more centres consider autologous bone marrow and peripheral blood stem cell transplantation for patients with high risk Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) in first complete remission (CR1) the long term sequelae of such treatments have to be considered. One of the most important side effects of such intensive treatment is loss of fertility. Sperm banking before treatment commences is available for males but unfortunately cryopreservation of ova/ovarian tissue is not yet possible for females. We have transplanted 30 women, 23 were under 40 years and report ten females who have had successful pregnancies (including two twin pregnancies and one triplet pregnancy), leading to live births following autologous bone marrow transplantation (ABMT) for poor prognosis HD and NHL in first or second complete remission. None of these children have shown evidence of birth defects (median follow up of two years). Of the twenty one pregnancies reported to the European Bone Marrow Transplantation Registry (EBMTR) following ABMT for lymphoma, eight of the seventeen unassisted cases came from our centres. The Newcastle/SNLG autotransplant differs from the approach in many EBMTR centres in that it uses melphalan or melphalan/etoposide alone instead of the more common four drug containing regimens and yet sustained complete remission rates indicate that the non-ablative approach is equally effective as more aggressive regimens on the disease with the huge advantage of preserved fertility in females. This approach to conditioning for ABMT should be considered when treating women in the reproductive age group.

Ovarian recovery after stem cell transplantation

“…6 Successful pregnancies in women after SCT are well documented. 3,23,24 Similarly, a recent study showed that 85% of pregnancies after SCT resulted in live births. 21 A large cohort study by Sanders et al 4 showed that out of 708 post-pubertal women, 110 resumed normal ovarian function, of which only 32 subsequently became pregnant.…”

Nonmalignant late effects after allogeneic stem cell transplantation

“…138 Melphalan alone or associated with VP16 or cyclophosphamide in SCT conditioning is compatible with return of fertility in up to 50% of cases. 141,146 Fewer studies have evaluated gonadal function following autologous SCT, and most of these studies have involved small numbers of patients. The use of BEAM (bischolorethylnitrosourea, etoposide, ara-C, melphalan) conditioning for autografts may be associated with a high incidence of gonadal recovery in women, 147 but in men azoospermia is almost always the rule.…”

Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: report from the bone marrow transplant survivor study

“…3,4 The risk of gonadal damage is higher with increasing doses of alkylating agents, total body irradiation (TBI), and older age in women at the time of transplant. 5 Although successful pregnancies after HCT have been reported previously, [6][7][8][9][10][11] the evidence suggests that female survivors may be at an increased risk of spontaneous abortions and miscarriages, pre-term delivery and low birth weight babies. 12,13 To further investigate pregnancy outcomes and describe the magnitude of compromise in reproductive function, as indicated by prevalence of selfreported pregnancy occurrence and pregnancy outcomes, we utilized the cohort of survivors participating in the Bone Marrow Transplant Survivor Study (BMTSS) and compared their experience with a sibling comparison group.…”