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Long-term outcomes and risk factor analysis of steroid-refractory graft versus host disease after hematopoietic stem cell transplantation

Abstract

Steroid-refractory graft versus host disease (GVHD) represents a fearsome complication after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a retrospective study on outcomes and risk factors associated with acute and chronic steroid-refractory GVHD in a large cohort of 1207 patients receiving HSCT in Saint Louis Hospital between 2007 and 2017. Among patients who developed an acute and/or a chronic GVHD, the cumulative incidences of acute and chronic steroid-refractory disease were 31% and 48%, respectively, at day +100 and 1-year post-HSCT. Through a multivariable analysis we selected several risk factors associated with the development of a steroid-refractory disease. For acute GVHD steroid refractoriness, we identified (1) a very high disease risk index, (2) an unrelated donor, (3) the absence of in vivo T-depletion as GVHD prophylaxis, and (4) a reduced intensity conditioning regimen. For chronic GVHD, (1) the use of peripheral blood stem cells, (2) unrelated donors, and (3) absence of in vivo T-depletion were more likely associated with a steroid-refractory disease. After the construction of a multistate dynamic model, we found that the probability of being alive without relapse after the resolution of all GVHD episodes was about 36% in the long term.

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Fig. 1: Distribution and frequencies of acute and chronic GVHD.
Fig. 2: Cumulative incidences of GVHD.
Fig. 3: Survival outcomes.
Fig. 4: Causes of death among patients with steroid-refractory GVHD.
Fig. 5: Dynamic prediction of each status.
Fig. 6: GVHD risk stratification.

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SP and MR had full access to all of the data in the study and take responsibility for the integrity and the accuracy of the data analysis. Concept and design: SP, GS, and MR. Acquisition, analysis, or interpretation of data: SP and MR. Drafting of the manuscript: SP, MR, and GS. Critical revision of the manuscript for important intellectual content: SP, MR, GS, PHP, ASDG, AB, AX, and ND. Statistical analysis and data interpretation: SP. Final approval of the manuscript: all authors.

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Correspondence to Simona Pagliuca.

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Pagliuca, S., Prata, P.H., Xhaard, A. et al. Long-term outcomes and risk factor analysis of steroid-refractory graft versus host disease after hematopoietic stem cell transplantation. Bone Marrow Transplant 56, 38–49 (2021). https://doi.org/10.1038/s41409-020-0977-3

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