CLOSE SIMULATION OF ACUTE GRAFT-VERSUS-HOST DISEASE BY INTERLEUKIN-2 ADMINISTERED AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR HEMATOLOGIC MALIGNANCY

The high relapse rate of hematologic malignancy treated with autologou s bone marrow transplantation (ABMT) may reflect the absence of a graf t-versus-leukemia (GVL) effect usually associated with graft-versus-ho st disease (GVHD). The purpose of this study was to determine whether administration of interleukin-2 (IL-2) early after ABMT might induce o r exacerbate acute skin GVHD, Fourteen patients at high risk for post- transplant relapse, eight with NHL and six with AML greater than or eq ual to first relapse, were conditioned with chemotherapy and total bod y irradiation (13) or chemotherapy alone (1), and received purged (10) or unpurged (4) marrow, A median of 35 days (range 25-58) after ABMT, they received a 5-day induction course of Roche IL-2 (9 x 10(6) U/m(2 )/day) followed by apheresis, reinfusion of LAK cells, and a 10-day ma intenance course of IL-2 (0.9 x 10(6) U/m(2)/day), all by continuous i .v. infusion, Serial skin biopsies were obtained before and after IL-2 therapy and were read blindly, Patients were studied prospectively fo r the development of acute cutaneous GVHD as reflected by rash (greate r than or equal to 25% body surface area), skin biopsy (greater than o r equal to grade II histologic changes) and T cell infiltration as ass essed by staining of the biopsy with antibodies UCHL-1 and TIA-1, No p atient had a rash before IL-2 therapy, but 12 of 14 (85%) developed a rash during the IL-2 induction course, Before IL-2 therapy, biopsies f rom three of 10 patients (30%) revealed histologic GVHD; after inducti on IL-2, biopsies from 11 of 14 patients (79%) revealed grade II acute GVHD, Biopsies from all patients with histologic GVHD after IL-2 ther apy contained TIA-1 positive T cells, HLA-DR was negative in the kerat inocytes of these paraffin-embedded sections, One patient died early o f sepsis, one patient required and responded to topical corticosteroid s and 12 had spontaneous resolution of the rash, Six patients relapsed at 3-13 months, while seven remain in complete remission 32+ to 41+ m onths after ABMT, The results demonstrate that IL-2 therapy after ABMT can induce effects which histologically and clinically mimic cutaneou s acute GVHD in most patients, Prospective, randomized trials of IL-2 vs observation after transplantation of autologous marrow or stem cell s for high-risk NHL and AML have been initiated which may allow us to determine whether this phenomenon is associated with a clinical GVL ef fect as reflected by a decreased relapse rate.