Takayuki Nakamura, Fumihiko Mouri, Yoshimi Maehiro, Yuichiro Semba, Masahiro Umeda, Toshinobu Fukuyama, Yoshitaka Yamasaki, Shuki Oya, Maki Yamaguchi, Takahiro Maeda, Koji Nagafuji
Acute lymphoblastic leukemia (ALL) following lenalidomide (LEN) therapy is rare. A 64-year-old man developed myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) six years after LEN maintenance therapy following autologous stem cell transplantation for multiple myeloma, followed by Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (ALL) 14 months later. A genomic analysis at diagnosis revealed PRPF8, XBP1, and BCORL1 mutations with IKZF1 and PAX5 deletions. No abnormalities were detected in the archived samples from the myeloma or MDS phases. He achieved complete molecular remission after chemotherapy. Although clonal continuity could not be demonstrated, a comprehensive genomic analysis provided insights into the complex clonal architecture of the clinical course.