De novo adult T-cell leukemia/lymphoma of donor cell origin after allogeneic hematopoietic stem cell transplantation from an HTLV-1 negative sibling: a case report

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays an important role in achieving long survival in adult T-cell leukemia/lymphoma (ATLL). Donor-derived hematopoietic cells can become infected with human T-cell leukemia virus type I (HTLV-1) following allo-HSCT from HTLV-1-negative donors; however, subsequent development of de novo ATLL of donor cell origin in this setting remains exceedingly rare. We encountered a 50-year-old woman who developed de novo unfavorable chronic-type ATLL of donor cell origin merely 2 years after receiving allo-HSCT from an HLA-matched, HTLV-1-negative sibling donor. Although she initially achieved complete remission following allo-HSCT, her clinical course was complicated by refractory acute graft-versus-host disease (GVHD). Consequently, she received additional prolonged immunosuppressive therapies, including ruxolitinib and mesenchymal stem cells, but adequate disease control could not be achieved. Approximately 2 years after allo-HSCT, a small proportion of atypical lymphocytes was recorded in her peripheral blood. HTLV-1-infected cell analysis using flow cytometry and Southern blotting analysis of the atypical lymphocytes revealed the development of ATLL. The patient’s disease status was considered to be at high risk of acute transformation; however, peripheral blood chimerism revealed complete donor type. A proviral load of 80.6 copies/100 cells was recorded alongside an expansion of multiple small clones and a dominant clone that accounted for 26.1% of the total proviral burden. Curative treatment was considered unfeasible and she passed away due to worsening GVHD. We hypothesize that profound post-transplant immunosuppression allowed the HTLV-1 oncogenes Tax and HTLV-1 bZIP factor to remain functionally active, thereby contributing to the unusually rapid development of de novo ATLL of donor cell origin.