Updated Clinical Outcomes of Hematopoietic Stem Cell Transplantation Using Myeloablative Total Body Irradiation with Ovarian Shielding to Preserve Fertility

Masahiro Ashizawa, Yu Akahoshi, Hirofumi Nakano, Shunto Kawamura, Junko Takeshita, Nozomu Yoshino, Yukiko Misaki, Kazuki Yoshimura, Ayumi Gomyo, Masaharu Tamaki, Machiko Kusuda, Kazuaki Kameda, Hidenori Wada, Koji Kawamura, Miki Sato, Kiriko Terasako-Saito, Aki Tanihara, Shun ichi Kimura, Hideki Nakasone, Shinichi KakoKeiko Akahane, Masaru Wakatsuki, Katsuyuki Shirai, Yoshinobu Kanda

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Myeloablative conditioning regimens are associated with severe gonadal toxicity. To preserve ovarian function, we have been investigating ovarian shielding during total body irradiation (TBI) with a myeloablative dose. In this report, we update the clinical outcomes. Female patients with standard-risk hematologic diseases, aged 40 years or younger, who desired to have children, were included (n = 19). The conditioning regimen consisted of TBI at 12 Gy with ovarian shielding and cyclophosphamide (120 mg/kg) or cytarabine (24 g/m2). Ovarian shielding reduced the actual irradiation dose applied to the ovaries from 12 Gy to 2 to 3 Gy. The median age at hematopoietic stem cell transplantation (HSCT) was 24 years (range, 19 to 33 years). With a median follow-up period of 1449 days (range, 64 to 3694) after HSCT, 5-year overall survival and 1- and 5-year relapse rates were 67%, 17%, and 31%, respectively. Only 2 of 14 patients with acute myeloid or lymphoid leukemia in remission have relapsed thus far. The 6-month and 1-year cumulative rates of menstrual recovery were 42% and 78%, respectively. In all patients with menstrual recovery, menstruation recovered within 1 year. The serum anti-Müllerian hormone (AMH) level tended to gradually increase after menstrual recovery. Three patients with extensive chronic graft-versus-host disease experienced delayed recovery of menstruation and serum AMH. Five pregnancies in 3 patients resulted in normal delivery in 1, selective cesarean operation in 1, current pregnancy in 1, and natural abortion in 2. These results suggest that a myeloablative TBI regimen with ovarian shielding could preserve fertility after HSCT without an apparent increase in relapse in standard-risk patients. Because serum AMH recovered gradually over time, the AMH level during the early phase after HSCT may have little value as a marker of ovarian reserve.

Original languageEnglish
Pages (from-to)2461-2467
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number12
DOIs
StatePublished - Dec 2019
Externally publishedYes

Keywords

  • Fertility
  • Hematopoietic stem cell transplantation
  • Ovarian shielding
  • Total body irradiation

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