Seventeen Live Births after Myeloablative Doses (12Gy+) of Total Body Irradiation (TBI)

Female patients who receive myeloablative doses of TBI to treat haematological diseases, are counselled that future pregnancy is unlikely. This is primarily due to the effects of high doses of radiation to the ovaries, causing premature ovarian insufficiency. While this can be addressed to some extent using fertility preservation techniques including oocyte or embryo cryopreservation prior to TBI, or IVF using donor oocytes, a second important factor reducing the chance of successful pregnancy is radiation damage to the uterus and surrounding vessels. Reduced elasticity of uterine musculature may restrict expansion during pregnancy, increasing the risk of spontaneous late miscarriage or pre-term birth. Although patients are advised that occasional cases of spontaneous pregnancy do occur, it is generally considered to be an extremely rare event.

UCLH is the largest dedicated haematology centre in the UK, typically allografting 100 adult patients and 20 adolescent patients each year. Our specialist late effects clinic at the Reproductive Medicine unit at UCLH (for patients following transplant or chemotherapy), receives referrals from UCLH, the Royal Marsden and from our local paediatric centre at Great Ormond Street. Patients were identified who attended the late effects clinic between 2000-2023 and conceived following HSCT. Information on patient demographics, medical history and pregnancy outcome was collected from electronic patient records. Here we present data describing seventeen live births in nine patients treated at our centre who received at least 12Gy total body irradiation as part of their myeloablative conditioning for stem cell transplantation to treat haematological disease. The majority of patients received specialist pregnancy care at UCLH.

Seven patients had acute leukaemia (ALL, AML or APML) as their primary diagnosis, one patient MDS, one patient had B cell lymphoma and one patient congenital neutropenia with high risk of transformation to AML. Age at myeloablative stem cell transplantation ranged from 3 years to 30 years with a median age of 11 years. The majority of patients (6/9) received 14.4Gy TBI given in 8 fractions. One patient received 13.2Gy and two patients received 12Gy. No patient relapsed from their disease following stem cell transplantation. All transplants were from matched unrelated donors except one patient who received a sibling graft and one where the patient received a myeloablative autograft in 1990. No patient had significant chronic graft versus host disease (GVHD) post transplantation. One patient had mild skin GVHD.

Of the seventeen successful pregnancies, ten were conceived spontaneously without assisted fertilisation techniques, one was conceived using the patient’s eggs frozen prior to stem cell transplantation and six were conceived using assisted donor techniques with donor eggs. Age of pregnancy ranged from 18 to 43 years with a median age of 32 years.

Eleven of the seventeen successful pregnancies had cervical cerclage as part of their antenatal care, (where a stitch is inserted to reduce risk of spontaneous preterm birth when a short cervical length is identified) between 12 and 22 weeks. The majority of babies were delivered by caesarean section. Length of gestation ranged from 23 weeks to term with a median gestation of 31 weeks. Eight out of seventeen babies were born at 35 weeks or later gestation. There was only one neonatal death in a baby born at 23 weeks who died 2 weeks after delivery.

In summary, this is the largest reported series of live births in women who previously received myeloablative doses of total body irradiation (12Gy+) for haematological disease, that we are aware of. Although pregnancy leading to live birth is rare in this group of patients and these pregnancies are high risk, successful pregnancy with specialist antenatal care after myeloablative TBI is possible, including pregnancies where patients spontaneously conceive with their own eggs.