Non-relapse mortality increases without apparent plateau in patients with chronic GVHD.
The most common reported causes of death were chronic GVHD and infection.
Chronic graft-versus-host disease (GVHD) is the leading cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation. To better understand patients at highest risk for non-relapse mortality (NRM), we analyzed patient, transplant, and chronic GVHD-related variables, risk factors, and causes of non-relapse deaths in an updated cohort of 937 subjects enrolled on two prospective, longitudinal observational studies through the Chronic GVHD Consortium. The median follow-up of survivors was 4 years (0.1 months - 12.5 years). Relapse accounted for 25% of the 333 deaths. The cumulative incidence of NRM was 22% at 5 years and increased over time with a projected 40% (95%CI, 30-50) at 12 years. Centers reported that chronic GVHD (37.8%) was the commonest cause of NRM and was associated with organ failure, infection, or additional cause not otherwise specified. The next most frequent causes without mention of chronic GVHD were infection (17%) and respiratory failure (10%). In multivariate analysis, an increased risk for NRM was significantly associated with the use of reduced intensity conditioning, higher total bilirubin, NIH skin score 2-3, NIH lung score 1-3, worse modified HAP adjusted activity score, and decreased distance on walk test. In conclusion, chronic GVHD NRM does not plateau but increases over time and is most commonly attributed to GVHD or infection, presumably associated with immunocompromised status. Severe skin and lung chronic GVHD remain challenging manifestations associated with increased NRM, for which novel therapeutic options are needed that do not predispose patients to infections.