GVHD is a potentially lethal complication after hematopoietic stem cell transplantation [
3]. The absence of response to corticosteroids is associated with an increased risk of death. EP has allowed treating patients who do not respond to corticosteroids, with the advantage of being less immunosuppressive as compared to other strategies such as ATG, imatinib, pentostatin, alemtuzumab, rituximab, etc. However, patients who do not respond to corticosteroids and EP are in a very unfavorable situation. Usually these patients have been treated with different immunosuppressive treatments without a consistent response.
Ruxolitinib has emerged in recent years as an excellent strategy for the control of refractory patients [
9]. Previously, preclinical studies showed that ruxolitinib have a potent immunomodulatory and anti-inflammatory effects with decrease of proinflammatory cytokines [
10]. More recently, a cooperative study [
11] showed a multicentric analysis of 54 patients with aGVHD refractory to corticosteroid treatment and 41 with cGVHD with overall response rate of 81.5% (44/54) in aGVHD including 25 complete responses (46.3%) and an ORR of 85.4% (35/41) in cGVHD, with a low GVHD relapse rate. This outstanding outcomes have also been reported in treatment of sclerotic forms of the disease, a condition that usually has poor response rates [
12,
13]. Not only in adult transplantation has been reported this remarkable response. Recently a pediatric group showed a 45% overall response in 13 children’s with refractory GVHD [
14]. Based on these encouraging results prospective randomized trials are ongoing in order to confirm the efficacy of ruxolitinib in acute and cGVHD. Also, a new JAK2/FLT3 inhibitor, pacritinib, has recently shown promising results in xenograft mouse models of JAK2V617F-driven diseases [
15]. Likewise, there is a growing interest in developing other JAK pathway inhibitors in GVHD, such as momelotinib, bacritinib and itacitinib [
16,
17]. To the best of our knowledge, our report is the first to show experience in the use of ruxolitinib in patients refractory or resistant to corticosteroids and EP. In our patients who have received this agent within a compassionate use, an overall response rate of 90% was observed. Another interesting report from our series is that, even in patients with digestive GVHD responses have been observed, despite the doubts regarding the bioavailability of oral drugs in patients with high-flow diarrhea [
18]. In addition, we observed a favorable response in pulmonary GVHD, the most severe and with the highest mortality [
19]. So far all of our patients continue to use the drug, with good tolerance and without major adverse effects. Only in two of them was it necessary to adjust the dosage due to haematological toxicity, mainly mild neutropenia, which was recovered when establishing the appropriate dose. Our report shows a satisfactory experience in controlling this serious condition among patients failing to corticosteroids and EP. According to our experience, it could be thought that it is better to use ruxolitinib as a second-line medication for the treatment of refractory GVHD. Randomized studies are necessary to answer this and generate a treatment algorithm.