The objective of this study was to determine the efficacy and safety of low-dose recombinant interleukin-2(IL-2) administered to patients with acute lymphoblastic malignancy at high-risk of relapse after unmanipulated HLA-identical or HLA-haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). We studied 19 patients with acute lymphoblastic malignancy who underwent IL-2 treatment for a high probability of disease recurrence after allo-HSCT between July 2004 and June 2006 at Peking University Institute of Hematology. With a median follow-up of 6 months (range, 3-19 months) after the first IL-2 therapy, 14 of 15 evaluable patients in our cohort were disease-free (93.33%), whereas one patient in 'high risk' pretransplantation category relapsed. Toxicities from IL-2 were mainly fever, pain, redness and swelling at the injection site. Four patients left the study because of hyperpyrexia. Local and reversible chronic GVHD was observed in 6 of 15 patients (40%). Similar cGVHD occurrences were observed between the two groups of patients undergoing HLA-identical HSCT (three of seven patients) and HLA-haploidentical HSCT (two of six patients), respectively. In conclusion, low-dose IL-2 subcutaneous administration from 100 days for a prolonged period could be a safe and effective strategy to prevent relapse in acute lymphoblastic malignancy patients with high risk of recurrence after unmanipulated allo-HSCT.