Early antithymocyte globulin therapy improves survival in patients with steroid-resistant acute graft-versus-host disease.
Second-line therapies for steroid-resistant acute GVHD have been used with limited success. We have reviewed the responses of 79 hematopoetic stem cell transplant (HSCT) patients uniformly treated from 1990-1998 with equine antithymocyte globulin (ATG) for steroid-resistant acute GVHD, defined as progression of acute GVHD after 4 days of treatment with prednisone or no improvement of acute GVHD after 7 days of treatment with prednisone. Patients received HSCT from 34 related (32 matched sibling/2 partially matched) and 45 unrelated (14 HLA-A, -B, -DRB1 matched/31 partially matched) donors. Prior to ATG therapy, severe (grade III-IV) GVHD was observed in 34 patients (43%). Organs involved included skin in 81% of patients, lower GI tract in 52%, upper GI tract in 28%, and liver in 11%. Treatment consisted of 1-5 courses (median, 2 courses) of ATG (15 mg/kg per dose bid x 5 days) given for a median of 16 days (range, 5 to 44 days) after the onset of GVHD. All patients continued to receive prednisone, 60 mg/m2 per day (or methylprednisolone IV equivalent), plus CSA (75%) or tacrolimus (4%). At day 28 of treatment, overall improvement was observed in 54% of patients; durable (> or = 28 days) complete response was observed in 20% of patients, and partial response was observed in 34% of patients. In multivariate analysis, patients with CML or a malignant disease other than acute leukemia had a greater likelihood of overall response than did those with nonmalignant diseases. Patients with acute skin GVHD (with or without other organ involvement) responded most frequently. Chronic GVHD developed in 51% of patients by 1 year after HSCT. One patient developed EBV lymphoproliferative disease. For the entire cohort, the probability of survival at 1 year was 32% (95% CI, 22%-42%). In multivariate analysis, factors associated with better survival included earlier onset of acute GVHD, shorter time from initial treatment for GVHD to treatment with ATG, and the use of non-T-cell-depleted stem cell grafts. These data suggest that treatment with ATG can be an active therapy, especially in patients with skin GVHD and early signs of steroid resistance.
MacMillan
Margaret L
ML
Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis 55455, USA. macmi002@umn.edu
Weisdorf
Daniel J
DJ
Davies
Stella M
SM
DeFor
Todd E
TE
Burns
Linda J
LJ
Ramsay
Norma K C
NK
Wagner
John E
JE
Blazar
Bruce R
BR
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000401:mortality; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D003625:Data Collection; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007223:Infant; D007239:Infections / Q000382:microbiology / Q000401:mortality; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D013256:Steroids / Q000627:therapeutic use; D016019:Survival Analysis; D013997:Time Factors
D000961:Antilymphocyte Serum; D013256:Steroids