Systemic steroid treatment of grade I acute GVHD increases steroid-refractory GVHD and NRM

The use of systemic corticosteroids is recommended only for grades II to IV acute graft-versus-host disease (GVHD), but many patients are often treated at the onset of grade I in real-world practice. We retrospectively analyzed outcomes of 1143 patients with grade I GVHD from 24 Mount Sinai Acute GVHD International Consortium (MAGIC) transplant centers. Approximately half received "up-front" systemic steroids, whereas the remainder received topical steroids alone; GVHD progressed to grade II to IV in only one-third of these patients. Up-front steroids decreased the risk for grade II to IV GVHD but not grade III to IV acute GVHD or the need for a second line of treatment. Systemic steroids were equally effective at treating grade I or II GVHD; however, up-front therapy exposed 3 times more patients to systemic steroids, with a corresponding threefold increase in GVHD that required additional therapy and a threefold rise in infection-related deaths. In multivariable analyses, up-front steroids were significantly associated with higher nonrelapse mortality (NRM; P = .026). MAGIC biomarkers identified most patients with grade I GVHD as low risk and unlikely to progress to severe GVHD regardless of treatment. Nevertheless, low-risk patients who received up-front steroids experienced a threefold increase in infectious deaths compared with those treated topically. This study supports the consensus recommendation of topical therapy for patients with low-risk grade I GVHD, a strategy that can be supported by biomarkers to avoid unnecessary steroid exposure and increased NRM.