Ikaros Expression in the Graft Is Associated with Chronic Graft Versus Host Disease

Introduction: Hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for several diseases. Immune reconstitution post HSCT is a complex and extremely variable process. Ikaros transcription factor has an important role in hematopoiesis of several cell lines, especially in the lymphoid compartment. We hypothesized that Ikaros expression, both in the graft and in the recipient after transplant, might influence immune reconstitution and, consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD).

Objectives: To correlate Ikaros expression both in the graft and in the recipient’s peripheral blood (PB) after engraftment with the risk of GVHD after allogeneic HSCT outcomes.

Patients and methods: 51 patients were included. Median age was 51 years (19-80), 53% of patients were male, and 57% of them had acute leukemia. Donor were haploidentical in 45% of cases, related identical in 29% and unrelated identical in 26%. Most patients (82%) received reduced-intensity conditioning regimens. Median follow-up was 20 months (10-40 months). Samples were collected from the graft and from the PB of the recipient 3 weeks after neutrophil recovery. Real time polymerase chain reaction (RT-PCR) was performed for analysis of absolute and relative Ikaros expression.

Results: There was no association between Ikaros expression and the risk of acute GVHD, relapse or mortality. However, a significant association was observed in the risk of chronic GVHD. Cumulative incidence (CI) of chronic GVHD and of moderate / severe chronic GVHD (according to National Institute of Health - NIH classification) in two years were 49% and 28%, respectively. Higher Ikaros expression in the graft was associated with a significantly higher risk of moderate/severe chronic GVHD (54% vs. 15%, respectively, P=0.01). Higher Ikaros expression in the recipient’s PB after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P=0.01).

Conclusions: Ikaros expression in the graft and in the PB of the recipient after transplant seems to be correlated with a higher risk of moderate/severe chronic GVHD and might be evaluated in larger and prospective trials as a potential biomarker.