Calcineurin Inhibitors Replacement By Ruxolitinib As Graft Versus Host Disease Prophylaxis for Patients after Allogeneic Stem Cell Transplantation

Severe graft versus host disease (GVHD) is a leading cause of morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Currently, the most widely used prophylaxis regimen usually includes calcineurin inhibitor (CNI; i.e., tacrolimus and cyclosporine). However, the incidence of aGVHD is about 30%-50%, and a minority of patients have contraindications against CNI. Thus, improved GVHD prevention methods are still needed. This study aimed to determine the prophylactic value of ruxolitinib for graft versus host disease (GVHD) in calcineurin inhibitor (CNI)-intolerant patients after allogeneic stem cell transplantation (SCT). From September 2017 to March 2019, 10 patients intolerant to CNI were enrolled. The regimens were based on the myeloablative BuCy regimen. Thymoglobulin 6 mg/kg was applied to patients with HLA-haploidentical related donors (HRD). All received ruxolitinib to replace CNI as GVHD prophylaxis. Ruxolitinib was initiated at 5-10 mg twice daily, maintained for 2-3 months, and then tapered gradually. Eight patients had acute leukemia, one had myeloproliferative neoplasm, and one had natural killer T-cell (NK/T-cell) lymphoma. The donors were from matched sibling donors (MSD, n = 3) and HRD (n = 7). They received CNI plus short-time methotrexate as GVHD prophylaxis, but all showed intolerance within 45 days after SCT due to transplantation-associated thrombotic microangiopathy (n = 4), CNI-induced pain syndrome (n = 2), and CNI-related renal/hepatic dysfunction (n = 4).After ruxolitinib replacement, only one patient (10%) developed grade II skin aGVHD within 100 days, and only one developed severe aGVHD after 100 days. Among nine patients who survived beyond day +100, two (2/9, %) developed moderate/severe cGVHD after tapering or stopping ruxolitinib, resulting in 1-year accumulative incidence of moderate/severe cGVHD of 23.8%. Cytomegalovirus reactivation occurred in four patients (40%). After a median follow-up of 10.5 (range: 2-14.5) months, two out (20%) relapsed, and seven (70%) were alive in good condition, of whom six (60%) maintained negative MRD.This study showed that the prophylactic application of ruxolitinib for CNI-intolerant patients after allo-SCT was effective in preventing GVHD, with a mild side effect.