CML Case: Reduced Intensity Conditioning After HSCT Preserves Fertility

A case study of a 15-year-old chronic myeloid leukemia patient suggests that a reduced intensity conditioning (RIC) regimen following hematopoietic stem cell transplantation (HSCT) could be a good treatment option for young CML patients. The patient in this case study had two pregnancies following the treatments, both brought to term with no neonatal complications.

HSCT remains an important treatment option in CML patients who fail to achieve a long-term response to tyrosine kinase inhibitor (TKI) therapy, wrote study authors led by Maura Faraci, MD, of the G. Gaslini Research Institute in Genova, Italy. Premature ovarian insufficiency, however, is a relevant late complication following the conditioning treatments after HSCT. “The relatively high transplant-related mortality after [myeloablative conditioning] regimen and the lack of evidence of any advantage of this approach have led to several studies on RIC in the treatment of TKI-resistant CML.”

The current case study concerned a 15-year-old Romanian girl diagnosed with CML. It was published online ahead of print in Pediatric Transplantation.

She received hydroxyurea and interferon for 6 months, followed by imatinib for 1 year. After a failure to achieve a cytogenetic response, she was switched to dasatinib, which yielded a complete cytogenetic response within 3 months. Though she remained in cytogenetic remission, a search for an unrelated donor was started because her BCR-ABL1 levels persisted at 0.7%.

The patient married early, and refused contraception due to cultural reasons. An unrelated donor was identified when she was 19 years old. The patient underwent HSCT and received a RIC regimen. The regimen included thiotepa, fludarabine, and melphalan. She also received graft-vs-host disease prophylaxis in the form of cyclosporine and mycophenolate mofetil; these were discontinued 3 and 6 months following HSCT, respectively, with no evidence of GVHD.

The patient achieved complete molecular and cytogenetic remission, which were checked and confirmed every month and every 3 months, respectively, for the first year following transplant.

After 3 months, amenorrhea persisted, which the authors wrote was consistent with a biochemical pattern of hypergonadotropic hypogonadism. At 6 months menstrual cycles resumed normally, and after 8 months, the patient became pregnant. The pregnancy was marked by moderate thrombocytopenia at 4 months, but this resolved without therapy.

The patient gave birth by cesarean section with no complications. After 1 year, she became pregnant again, and the baby was again delivered complication-free by cesarean section. The patient was still disease-free in her fifth year following transplantation.

This regimen, the authors concluded, “could be a promising treatment option for adolescents or young adults with CML who are eligible for HSCT.”