Prednisone and Azathioprine Compared With Prednisone and Placebo for Treatment of Chronic Graft-v-Host Disease: Prognostic Influence of Prolonged Thrombocytopenia After Allogeneic Marrow Transplantation

• Published in: Blood Vol. 72; no. 2; pp. 546 - 554
• Main Authors: Sullivan, K.M., Witherspoon, R.P., Storb, R., Weiden, P., Flournoy, N., Dahlberg, S., Deeg, H.J., Sanders, J.E., Doney, K.C., Appelbaum, F.R., McGuffin, R., McDonald, G.B., Meyers, J., Schubert, M.M., Gauvreau, J., Shulman, H.M., Sale, G.E., Anasetti, C., Loughran, T.P., Strom, S., Nims, J., Thomas, E.D.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.08.1988; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Azathioprine - administration & dosage; Azathioprine - adverse effects; Biological and medical sciences; Bone Marrow Transplantation; Child; Child, Preschool; Chronic Disease; Clinical Trials as Topic; Drug Therapy, Combination; Female; Graft vs Host Disease - complications; Graft vs Host Disease - drug therapy; Graft vs Host Disease - mortality; Humans; Immunomodulators; Infant; Infections - etiology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Prednisone - administration & dosage; Prednisone - adverse effects; Prognosis; Thrombocytopenia - complications; Transplantation, Homologous; Human; Thrombocytopenia; Corticosteroid; Homograft; Graft versus host reaction; Prednisone; Prevention; Chemotherapy; Chronic; Treatment; Placebo; Double blind study; Bone marrow; Immunosuppressive agent; Comparative study
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V72.2.546.546

We conducted a randomized, double-blind comparison of prednisone and placebo (group I) v prednisone and azathioprine (1.5 mg/kg/day) (group II) as early treatment of extensive chronic graft-v-host disease (GVHD). Patients with platelet counts <100,000/μL - were placed into therapy with prednisone alone (group III). All three groups received identical doses of prednisone (1 mg/kg every other day) and one double-strength trimethoprim-sulfamethoxazole (TMP-SMX) tablet twice daily. Between January 1980 and December 1983, 179 previously untreated patients were enrolled and 164 were evaluable. Patients randomized to group I (n = 63) and group II (n = 63) were well matched for prognostic factors; those placed into group III (n = 38) had more frequent acute GVHD and progressive onset of chronic GVHD. Median duration of therapy was 2 years. Complications included diabetes (5%), aseptic necrosis (5%) and infection. For groups I, II, and III, the respective incidence of infection was disseminated varicella, 11%, 24%, 34%; bacteremia, 6%, 11%, 34%; and interstitial pneumonia, 5%, 14%, 18%. Recurrent malignancy was the most frequent cause of death and did not differ significantly across the groups. Nonrelapse mortality, however, did differ: 21% in group I, 40% in group II, and 58% in group III (I v II, P = .003; I v III, P = .001 ). Forty patients in group I, 30 in group II, and 10 in group III survive with a minimum follow-up of 3.8 years. Karnofsky performance scores for 68 survivors are 90% to 100%, scores for seven survivors are 70% to 89% and scores for five survivors are <70%. Actuarial survival at 5 years after transplant is 61% in group I, 47% in group II, and 26% in group III (I v II, P = .03; I v III, P = .0001). Treatment with prednisone alone results in fewer infections and better survival than prednisone and azathioprine in standard-risk chronic GVHD. Treatment with prednisone alone is less effective in high-risk patients with thrombocytopenia, and other strategies are required. © 1988 by Grune & Stratton, Inc.