Allogeneic stem cell transplantation in aggressive Adult T cell leukemia/lymphoma: a prospective multicenter study.

Adult T-cell leukemia/lymphoma (ATL) is associated with a dismal prognosis in aggressive subtypes, with a median overall survival (OS) of less than one year. In Japan, first line chemotherapy followed by allogeneic stem cell transplantation (allo-SCT) is recommended for eligible patients, yet this strategy is scarcely reported elsewhere, especially among ethnic minorities. We prospectively evaluated the feasibility and outcome of allo-SCT in this setting. Between 2016 and 2024, 80 ATL patients were enrolled; 74 (median age 50 years) received frontline chemotherapy (CHO(E)P regimen +/-Brentuximab Vedotin in CD30 positive cases). Of these, 39 subsequently proceeded to allo-SCT using a Thiotepa-Busulfan-Fludarabine conditioning regimen after at least one line of chemotherapy. Two-year OS from first line therapy was 45 %. Time-dependent analysis demonstrated a significant survival benefit for allo-SCT (hazard ratio, 0.32). Uncontrolled disease was the primary reason for transplant ineligibility. At transplantation, 27 patients were in complete remission (CR,) 5 in partial response (PR) and 7 had stable/progressive disease. Donor sources included haploidentical (56%), matched sibling (26%), and unrelated donors (18%). Three-year OS and progression-free survival were both 52%, while one-year non-relapse mortality and cumulative relapse incidence were 15% and 35%, respectively. Absence of CR/PR at allo-SCT was the main risk factor for poor outcomes. Tailored HTLV-1/ATL molecular and flow-cytometric monitoring of assessable patients in remission, revealed that tumor clones became undetectable after allo-SCT, suggesting a potent graft-versus-ATL effect. Overall, our findings support the benefit of allo-SCT in eligible ATL patients. Clinical Trial Identifier: NCT05237245.