Pregnancy outcomes in women conceiving after hematopoietic stem cell transplantation versus conventional chemotherapy for childhood or adolescent acute leukemia.
In a multicenter observational cohort of female childhood or adolescent acute-leukemia survivors, pregnancies after TBI-based HSCT conditioning had worse obstetric outcomes than pregnancies after alkylator-based conditioning, while the latter were reported to resemble outcomes after conventional chemotherapy.
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In a multicenter observational cohort of female childhood or adolescent acute-leukemia survivors, pregnancies after TBI-based HSCT conditioning had worse obstetric outcomes than pregnancies after alkylator-based conditioning, while the latter were reported to resemble outcomes after conventional chemotherapy.
Research significance
The evidence supports an association between prior TBI-based myeloablation and adverse later pregnancy outcomes; it can be inferred—but is not established—that reducing ovarian and uterine radiation exposure, selecting non-TBI conditioning when oncologically appropriate, or intensifying reproductive and obstetric surveillance could improve survivorship outcomes.
Source abstract
Myeloablative conditioning before hematopoietic stem cell transplantation (HSCT) during childhood or adolescence reduces adult uterine volume, but its impact on future pregnancies remains uncertain. This multicenter study, nested within the LEA cohort, compared 86 pregnancies after HSCT (55 following total-body irradiation [TBI], 31 after high-dose alkylating agents) with 180 pregnancies after conventional chemotherapy in matched leukemia survivors (total: 266 pregnancies, 117 women). Twenty-nine percent of post-HSCT pregnancies required oocyte donation; 70% occurred spontaneously. Notably, 8% (n = 7) of HSCT pregnancies were unintended and ended in induced abortion. TBI markedly worsens obstetric outcomes. Live-birth rate was 35% after TBI vs. 61% after alkylating conditioning (p = 0.02). Compared with alkylating agents, TBI conferred higher risks of late pregnancy loss (24% vs. 3%), preterm birth (50% vs. 5%), low birth weight infants (33% vs. 0%), and postpartum hemorrhage (37% vs. 5%). By contrast, pregnancies after alkylating conditioning resembled those after conventional chemotherapy (live-birth 70% vs. 82%, p = 0.2) with no excess maternal or perinatal morbidity. Thus, TBI-based myeloablation during childhood or adolescence substantially compromises subsequent pregnancy outcomes, whereas high-dose alkylating conditioning appears obstetrically safe. These data may inform reproductive counseling and obstetric surveillance in female leukemia survivors treated with HSCT during childhood and adolescence.