Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results.

Ruxolitinib is a promising treatment for steroid refractory graft-vs-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively. Overall response rate (ORR) in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory (EM), and decrease of CD4 central memory percentage. CD4 regulatory T cells percentage decreased significantly. Patients who achieved complete response to ruxolitinib had higher natural killer (NK) cells before ruxolitinib that patients who did not respond. Also there was an increase of CD4 lymphocytes percentage, with decrease of CD8 and NK cells percentage in responders against non-responders. There were 54%, 18% and 13% of infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non-relapse mortality was 19 ± 9%and 28 ± 10%, respectively. Overall survival and disease-free survival rate at 2 years were 62 ± 11% and 58 ± 11%, respectively. Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.