Chronic graft-versus-host disease: a prospective cohort study.
Chronic graft-versus-host disease (CGVHD) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT). We studied 159 patients with CGVHD longitudinally to characterize the natural history of CGVHD and identify reliable predictors of response and long-term mortality. Rates of response to treatment were 61%, 53%, and 50% at 6 months, 1 year, and 2 years, respectively. A high incidence of infections (7 of 1,000 patient-days at 0 to 6 months, 2.5 of 1,000 patient-days at 6 months to 1 year, and 0.6 of 1,000 patient-days at 1 to 2 years) was observed. After a median follow-up of 8.4 years, an overall survival rate of 40% was observed. The overall survival rate was 63% (95% confidence interval [CI], 56%-71%) at 1 year, 51% (95% CI, 43%-59%) at 2 years, and 39% (95% CI, 31%-47%) at 10 years. In multivariate analysis, age older than 20 years (RR = 1.5; 95% CI, 0.9%-2.5%; P =.09), progressive onset of CGVHD (RR = 1.6; 95% CI, 1.0%-2.4%; P =.04), platelet count of <100,000/ microL (RR = 2.1; 95% CI, 1.3%-3.4%; P =.001), and GI involvement (RR = 1.5; 95% CI, 1.0%-2.4%; P =.05) were associated with increased mortality. Among patients surviving more than 6 months, no response (RR = 4.5; 95% CI, 1.9%-10.5%; P =.0006) and partial response (RR = 2.5; 95% CI, 1.1%-6.1%; P =.04) to treatment at 6 months also were significant predictors of mortality. The prevalence of active CGVHD was 33% at 2 years. However, the cumulative incidence of successful discontinuation of therapy was only 13% at 2 years. Among patients with clinical resolution of CGVHD, only 18% were off immunosuppressive therapy by 2 years, and 89% by 4 years. Despite high initial response rates, a large majority of patients had active disease requiring prolonged immunosuppression. This requires improved infection prevention for a longer time. Recognition of a high-risk group should facilitate assignment of more intensified regimens. Better treatment regimens need to be identified to improve survival and limit toxicity of prolonged immunosuppression.
Arora
Mukta
M
Department of Medicine, Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota, USA.
Burns
Linda J
LJ
Davies
Stella M
SM
Macmillan
Margaret L
ML
Defor
Todd E
TE
Miller
Wesley J
WJ
Weisdorf
Daniel J
DJ
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000401:mortality / Q000628:therapy; D006801:Humans; D015994:Incidence; D007223:Infant; D007239:Infections; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome