Prognosis of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation (SCT) is dismal. Immunotherapy with donor lymphocyte infusion (DLI) and imatinib are rarely and/or transiently effective. Here we describe the case of a patient with imatinib-resistant post-transplant relapse of ALL, who received a combination of standard dose nilotinib and monthly DLI infusion. Therapy was well tolerated and the patient achieved and maintained a complete molecular remission. Our case provides a rationale for the combined use of a second line tyrosine kinase inhibitor and DLI in the treatment of relapsed Ph+ ALL.