title: Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems.
abstract: Acute GVHD remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). In a retrospective analysis, the response of 443 HSCT patients who received prednisone, 60 mg/m2, for 14 days followed by an 8-week taper, as initial therapy for acute GVHD from 1990 through 1999 at a single institution was examined. Median patient age was 29.0 years (range, 0.3-60.3 years), with 40% of patients <20 years old. Patients received HSCT from 201 related (189 matched sibling/12 partially matched) and 242 unrelated (130 HLA-A, B, DRB1 matched/112 partially matched) donors. GVHD score was measured and outcomes compared using the Minnesota, Consensus, and International Bone Marrow Transplant Registry (IBMTR) grading systems. Prior to initiation of steroid therapy, severe (grades III-IV) acute GVHD was observed in 57 (13%) patients (Minnesota or Consensus grading) and in 192 (43%) patients (IBMTR grading). At day 28 of treatment, overall improvement was observed in 55% of patients, with durable (> or = 28 days) complete response observed in 35% and partial response observed in 20% of patients. Patients with acute lower gastrointestinal GVHD (+/- other organ involvement) had lower response rates. In multivariate logistic regression analysis, recipients of related donor grafts and recipients of GVHD prophylaxis other than methotrexate alone had the highest likelihood of overall response. Initial Minnesota GVHD grade or Consensus GVHD grade was not associated with significant differences in overall response, whereas patients with an initial IBMTR grade of B or C had a higher likelihood of response. Chronic GVHD developed in 42% of patients by 1 year after HSCT. The probability of survival at 1 year after initiation of steroid therapy was 53% (95% confidence interval, 48%-58%). In Cox regression analysis, factors associated with better survival included patients' youth, receipt of related or HLA-matched unrelated grafts, and administration of GVHD prophylaxis other than T-cell depletion in all 3 grading systems. Lower initial GVHD grade (I-II or A-B) led to better survival. These data suggest that steroids provide an active but inadequate therapy for acute GVHD, especially with higher grade GVHD. More effective prophylaxis and therapy for acute GVHD is needed for mismatched unrelated donor recipients and for those with severe GVHD.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA. macmi002@tc.umn.edu
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Todd E
authors.initials: TE
authors.lastname: DeFor
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Burns
authors.forename: Norma K C
authors.initials: NK
authors.lastname: Ramsay
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000209:etiology; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013256:Steroids / Q000008:administration & dosage*; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000401:mortality
chemical_list: D000893:Anti-Inflammatory Agents; D013256:Steroids; D011241:Prednisone