Impact of GVHD on lymphoma progression: Nationwide study from Japanese Society for Transplantation and Cellular Therapy

The graft- versus-lymphoma (GVL) effect and its association with acute and chronic GVHD (aGVHD, cGVHD) has not been comprehensively elucidated. We retrospectively analysed 2204 Japanese patients with non-Hodgkin lymphomas (NHLs; indolent B-NHLs, n = 689; aggressive B- NHLs, n = 720; mature T/NK- NHLs, n = 795) receiving a first allo- HSCT in 2003- 2017. Pre-transplant lymphoma control showed complete response (CR) in 759 and non- CR in 1445. We assessed the impact of aGVHD/cGVHD on lymphoma progression and other outcomes. Although aGVHD/ cGVHD showed no statistical impact on lymphoma progression in the overall cohort, their impact was clear in certain groups: Grade I -II aGVHD in CR patients (HR, 0.63; 95% CI, 0.43- 0.91), especially in mature T/NK- NHL (HR, 0.46; 95% CI, 0.26- 0.83) and extensive cGVHD in patients with mature aggressive B- NHLs (HR, 0.55; 95% CI, 0.31- 0.97). In total, limited cGVHD was associated with superior survivals (progression -free survival: HR, 0.71; 95% CI, 0.56- 0.90), whereas severe GVHDs showed negative impacts on them. Our results support the presence of GVL effects differentially associated with GVHD in different lymphoma subtypes/controls. Meanwhile, it was also suggested that we should manage GVHDs within a limited activity, considering the negative impact of severe GVHDs. As pre-transplant lymphoma control remains a strong factor influencing transplant outcomes, improving its management is an important issue to be addressed.