Deletion of immunosuppressive prophylaxis after marrow transplantation increases hyperacute graft-versus-host disease but does not influence chronic graft-versus-host disease or relapse in patients with advanced leukemia
Sixteen patients < 30 years of age with advanced leukemia who were given unmodified marrow grafts from HLA-identical siblings without posttransplant immunosuppression were compared to 44 age- and disease-matched controls who received methotrexate (MTX) to prevent graft-versus-host disease (GVHD). All 60 patients were prepared with cyclophosphamide (60 mg/kg x 2) and total body irradiation (2.25 Gy daily x 7). Grade 2-4 acute GVHD developed in all 15 engrafted patients not given immunosuppression compared to 10 of 44 engrafted MTX recipients (p < 0.0001). The onset of Grade 2-4 GVHD was hyperacute (median d 8) compared to a median onset at d 18 in the MTX group (p = 0.005). Treatment of hyperacute GVHD with prednisone ± cyclosporine or ATG + cyclosporine produced sustained improvement in 6, response with subsequent flare in 4, and no response in 4 patients. Despite the prevalence of hyperacute GVHD in patients not given immunosuppression, there was no statistically significant difference in the probability of chronic GVHD (31% versus 33%), interstitial pneumonia (47% versus 22%), or recurrent leukemia (41% versus 38%) compared to the MTX recipients. Six patients not given immunosuppression and 19 given MTX survive with a median follow-up of 4.4 (range 3.2-6.4) yr after transplant. The probability of death from causes other than recurrent malignancy was 58% in the no-immunosuppresion and 34% in the MTX group (p = 0.1). Actuarial 3-yr relapse-free survival is 25% and 41%, respectively (p = 0.3). We conclude that deletion of immunosuppression after unmodified HLA-identical marrow transplantation leads to an increase in hyperacute GVHD without apparent influence on chronic GVHD or relapse. Although nonrelapse mortality was higher and relapse-free survival was lower in patients not given immunosuppression, differences did not reach statistical significance in this study.
Sullivan, KM; Storb, R; Witherspoon, RP; Weiden, PL; Anasetti, C; Appelbaum, FR; Beatty, P; Buckner, CD; Deeg, HJ; Doney, K; Fisher, L; Loughran, TP; Martin, P; Meyers, J; McDonald, GB; Sanders, J; Shulman, H; Stewart, P; Thomas, ED
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