‘Realistic Chance for Pregnancy’ After Stem Cell Transplant, German Study Suggests

While women who undergo allogeneic hematopoietic cell transplantation (alloHCT) face significant treatment-related challenges regarding fertility, successful pregnancies are possible, according to results from a retrospective German study.

Out of 2,654 women who underwent alloHCT from 2003 to 2018 in the German Transplant Registry, 50 experienced 74 pregnancies, with 57 pregnancies resulting in live births (77%), reported Katja Sockel, MD, of the University Hospital Carl Gustav Carus in Dresden, and colleagues.

Of note, according to German population data, the live birth rate for women in 2019 was 6.43%, with a first live birth rate of 3.02% — a rate six times higher than the annual first birth rate of 0.45% among women after alloHCT.

“Although the annual first birth rate after alloHCT is more than six times lower than in the general German population, our findings suggest a realistic chance for pregnancy,” Sockel and colleagues wrote in Blood.

In an email to MedPage Today, Sockel noted that “the results of this study show that female alloHCT recipients can achieve successful and safe pregnancies. These findings help provide a basis for counseling young women of childbearing age and raising awareness of and funding for different ART [assisted reproductive technologies] techniques so that patients can have a normal life after alloHCT.”

She also stressed that all cancer patients of childbearing age, irrespective of cancer type, as well as patients with non-malignant diseases facing intensive therapies such as alloHCT, should receive fertility counseling.

“Ideally, fertility counseling should be implemented as early as possible before the initiation of treatment,” she said.

She also suggested that counseling and recommendations on different fertility-preserving interventions “should be individualized, considering factors such as disease stage, hormone status, and, in case of alloHCT, the underlying disease.”

In the case of women who either underwent alloHCT or have breast cancer, Sockel pointed out that the intensity of the conditioning regimen used in alloHCT will likely result in a higher risk of permanent infertility compared with standard breast cancer treatments.

“Moreover, patients who undergo alloHCT due to an underlying malignant disease have often been exposed to various toxic chemotherapies before the transplant,” she said. “Additionally, young patients typically receive intensive conditioning protocols, including total body irradiation, further elevating the risk of infertility in these patients.”

The likelihood of pregnancy in transplanted women was positively correlated with younger age (18 to 35 years at the time of transplantation, with a median age of 29.6 years), with most pregnancies occurring in women ages 18 to 25. No pregnancies were reported in women who underwent transplantation at over 35 years of age.

Other factors associated with a higher likelihood of pregnancy included the use of non-myeloablative/reduced-intensity conditioning (rate ratio [RR] 2.78, 95% CI 1.26-6.59, P=0.01) and non-malignant transplant indications such as hemoglobinopathy/bone marrow failure syndrome (RR 2.65, 95% CI 1.27-5.51, P=0.01).

Factors associated with a lower likelihood of a pregnancy after alloHCT included higher age at alloHCT (RR 0.36, 95% CI 0.25-0.50, P<0.001) and the use of total body irradiation ≥8 Gy (RR 0.29, 95% CI 0.08-0.83, P=0.03).

While some of the study’s recorded pregnancies were the result of ART, 72% of women reported spontaneous pregnancies.

The underlying diseases of the women who became pregnant included acute leukemia/myelodysplastic neoplasia in 23 patients, acquired bone marrow failure syndrome and hemoglobinopathies in 17, chronic myeloid leukemia in six, and Hodgkin lymphoma in four.

Of the women, 80% underwent non-myeloablative or reduced-intensity conditioning, and 20% underwent myeloablative conditioning.

With a median follow-up of 8.9 years since alloHCT, and 3.7 years since first pregnancy, all 50 patients who became pregnant after alloHCT remained alive, with just one relapse reported.

Sockel and colleagues observed that fetal outcomes collected from 44 pregnancies were “generally positive,” without increased rates of childhood illnesses or developmental delays compared with the general population.

There were higher incidences of preterm delivery and low birth weight in this group. Ten pregnancies resulted in preterm delivery, with the majority occurring from 28 through 32 gestational weeks. Six newborns had low birth weight, while one had a very low birth weight.

Sockel and colleagues acknowledged that the study had limitations due to its retrospective nature, and added that despite the use of retrospective telephone interviews, “it was challenging to collect comprehensive information from all pregnant women.”

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