To increase the availability of alternative stem-cell donors for patients with adult T-cell leukemia (ATL), we examined the feasibility of HLA-incompatible family transplantation, especially from a grown-up child (donor) to a parent (recipient). Since January 2004, seven patients with advanced-phase ATL (three males and four females, median age 59 years), for whom a timely HLA-compatible donor was unavailable, were enrolled. All patients received allografts from their HLA-incompatible sons with reduced-intensity conditioning stem cell transplantation (RIST). Combined graft-versus-host disease (GVHD) prophylaxis involved cyclosporine A or tacrolimus, mycophenolate mofetil or corticosteroid, and short-term methotrexate. All patients achieved prompt engraftment, and there was no 100-day relapse-related mortality. Only one patient had grade-IV acute-GVHD, but this was resolved. The median follow-up period was 251 days (range 112-1,018 days), and the estimated 1-year overall and 1-year progression-free survival rates were 57.1 and 28.6%, respectively. Four patients died, with causes of death being relapse (n = 2), transplantation-associated microangiopathy (n = 1), and septicemia (n = 1). Three are currently alive: two are in complete remission and one has stable disease. Despite a high rate of relapse, RIST using an allograft from an HLA-incompatible grown-up child donor may be feasible for patients with advanced-phase ATL, and may prolong survival.