Long-term follow-up of relapsed acute leukemia treated with immunotherapy after allogeneic transplantation: the inseparability of graft-versus-host disease and graft-versus-leukemia, and the problem of extramedullary relapse

Long-term outcome of 23 acute myeloid (AML, n = 16) or lymphoblastic (ALL, n = 7) leukemia patients who had received immunotherapy for treatment of pe rsistent or recurrent disease 1.5-26 (median 4) months after allogeneic tra nsplantation was studied to determine eventual survival. Immune manipulatio n comprised donor leukocyte infusion (n = 18), interferon-alpha 2b and/or i nterleukin-2 (n = 15), and cyclosporine withdrawal (n = 11) in various comb inations. Graft-versus-host disease (GVHD) developed in 12 patients. Thirte en of 20 evaluable patients responded; 6 relapsing again. Eight patients di ed of toxicity, and 10 of progressive disease at 3-206 weeks (median 11). F ive patients (3 AML, 2 ALL) are alive in remission with GVHD 2-46 months (m edian 23) after immunotherapy with Karnofsky scores of 70-100% (median 80). The overall survival of the whole group is 1-206 weeks (median 12), with a n actuarial survival of 22% at 2 years. The development of GVHD was associa ted with superior survival in multivariate analysis (P = .007). Seven patie nts received immunosuppression because of the severity of GVHD (grade III/I V acute or extensive chronic): 3 died of GVHD, 3 improved but relapsed conc omitantly, and 1 is alive in remission with extensive chronic GVHD. Four ep isodes of extramedullary relapse (granulocytic sarcomas) were seen in 3 pat ients with AML whose marrow remained in remission. We conclude that GVHD ap pears to be inseparable from graft-versus-leukemia in relapsed acute leukem ia patients undergoing immunotherapy with a high proportion of patients dyi ng due to toxicity or progressive disease, and isolated extramedullary rela pse seems to be unusually common.