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

Bone Marrow Transplantation volume 56, pages 38–49 (2021)Cite this article

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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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Author notes

  1. These authors contributed equally: Gérard Socié, Marie Robin

Authors and Affiliations

  1. Assistance Publique Hôpitaux des Paris, Saint Louis Hospital, Hematology and Transplantation Unit, Paris, France

    Simona Pagliuca, Pedro Henrique Prata, Aliénor Xhaard, Camilla Frieri, Livia Giannoni, Aurelien Sutra del Galy, Flore Sicre de Fontbrune, David Michonneau, Nathalie Dhedin, Régis Peffault de Latour, Gérard Socié & Marie Robin

  2. Université de Paris, Paris, France

    Simona Pagliuca, Camilla Frieri, Aurelien Sutra del Galy, David Michonneau, Régis Peffault de Latour & Gérard Socié

  3. Department of Translational Hematology and Oncology Research, Cleveland Clinic Foundation, Cleveland, Ohio, United States

    Simona Pagliuca

  4. Department of Hematology and Transplantation, Federico II University, Naples, Italy

    Camilla Frieri

  5. Assistance Publique Hôpitaux des Paris, Saint Louis Hospital, Therapeutic Apheresis Unit, Paris, France

    Anne Brignier

  6. INSERM UMR 976, Paris, France

    David Michonneau & Gérard Socié

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Contributions

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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