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Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP–EBMT analysis on patients with AML in remission

Bone Marrow Transplantation volume 51, pages 610–611 (2016)Cite this article

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Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option to treat patients with high-risk hematological malignancies.1 Transplant procedures have been changed over the years with the possibility of performing transplants from alternative donors, and using reduced intensity conditioning (RIC) regimens. However, transplant-related mortality and disease recurrence remain major obstacles to HSCT success.2 In patients surviving HSCT, long-term complications, particularly chronic GvHD (cGvHD), are associated with high morbidity and impaired quality of life.3 Clinical and biological manifestations of cGvHD4 have a wide range of severity and could involve many tissues and organs including often oral mucosa, eyes, skin, gastrointestinal tract, liver and bone marrow (BM). Incidence of severe chronic GvHD, previously indicated as extensive, affects ~30–70% of HSCT survivors.5, 6

For clinical research on HSCT, the most commonly used end point is disease-free survival (DFS), which reflects a status of survival without relapse or progression. However, the main pitfall of such end point is that it disregards events like severe GvHD. Several publications on retrospective and registry data comparing transplant modalities (according to the type of donor, stem cell source or conditioning intensity) showed major differences in the incidence of chronic GvHD.7 Therefore, a composite end point that combines both DFS and GvHD is needed. Holtan et al. recently proposed use of GvHD-free, relapse-free survival (GRFS) for HSCT outcomes.8 This end point might reflect more precisely health status post transplantation and better quality of life, and has been defined as being alive with neither grade III–IV acute GvHD (aGVHD) nor cGvHD requiring immunosuppressive treatment (IST), and without disease recurrence or death from any cause during the first 1 year after HSCT. The incidence of cGvHD requiring systemic treatment ranges from 30 to 40%, by the National Institute of Health criteria. However, systemic treatment of cGvHD does not always reflect the severity of cGvHD as it could be indicated for patients with moderate disease.9 cGvHD is an event which fluctuates with time, and the initiation of IST may not be a good indicator of the impact of this disabling disease on patients’ long-term outcome and daily life.

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Authors and Affiliations

  1. Service d’Hématologie et Thérapie Cellulaire, Hôpital Saint Antoine, AP-HP, Paris, France

    A Ruggeri, M Labopin & M Mohty

  2. Université Pierre et Marie Curie, Paris, France

    M Labopin, M Mohty & A Nagler

  3. Unità di Ematologia e trapianto di midollo, Ospedale San Raffaele, Milano, Italy

    F Ciceri

  4. Division of Hematology, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    A Nagler

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  1. A Ruggeri
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Correspondence to A Ruggeri.

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Ruggeri, A., Labopin, M., Ciceri, F. et al. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP–EBMT analysis on patients with AML in remission. Bone Marrow Transplant 51, 610–611 (2016). https://doi.org/10.1038/bmt.2015.305

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