Interferon-gamma in mobilized stem cells: A possible prognostic marker in early post-transplant management in multiple myeloma

Introduction: A complex network of cytokines in the bone marrow microenvironment has been implicated as an important factor in the pathogenesis of multiple myeloma (MM). Different cytokines have been studied in MM, both in peripheral blood and/or bone marrow, but there are few data correlating cytokines in leukapheresis product with post-transplant response depth to treatment. Materials and Methods: In a retrospective cross-sectional study, levels of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta-1 (TGF-beta 1) and interferon gamma (IFN-gamma) in peripheral hematopoietic stem cells/leukapheresis product (PHSC) of patients with MM eligible for transplantation were evaluated. Association of these cytokines with certain factors such as mobilized CD34 + cells/kg, staging, response to treatment and outcome were analyzed. Results: The median baseline IFN-gamma level was 826.4 pg/mL. IFN-gamma levels in the leukapheresis product were significantly lower in patients who achieved complete response (CR) three months post-transplant when compared to patients with very good partial response (VGPR) (674.75 +/- 80.32 pg/mL versus 939.6 +/- 106.8 pg/mL, p = 0.02), respectively. Patients who lost depth of response at the third-month post-transplant had a median level of IFN-gamma 1133, being considered high-expressors of IFN-gamma, while those reaching improved response were called low-expressors (median level IFN-gamma 485 pg/mL). Overall and progression free survival did not have a statistically significant correlation with TNF-alpha, TGF-beta 1 or IFN-gamma, as well as TNF-alpha and TGF-beta 1 levels in post-transplant response assessment. Conclusion: IFN-gamma in PHSC seems to be an important biomarker of loss of response in MM, suggesting a role in early post-transplant therapeutic management.