Peritransplantation Ruxolitinib Prevents Acute Graft-versus-Host Disease in Patients with Myelofibrosis Undergoing Allogenic Stem Cell Transplantation

Abstract

JAK inhibition by ruxolitinib is approved for treating myelofibrosis and also has shown efficacy in treating steroid-resistant acute and chronic graft-versus-host disease (GVHD). In 12 patients with myelofibrosis (median age, 63 years; range, 43 to 71 years) who were treated with ruxolitinib and underwent allogeneic stem cell transplantation (ASCT), ruxolitinib was continued (2 × 5 mg daily) until stable engraftment. No graft failure was observed, and leukocyte engraftment was achieved after a median of 12 days (range, 11 to 18 days). One patient developed fever of unknown origin after discontinuation of ruxolitinib; otherwise, no withdrawal syndrome was observed. Overall, only 1 patient each experienced acute GVHD grade I or II, resulting in an 8% incidence of acute GVHD grade II-IV at day +100, with no nonrelapse mortality. Complete chimerism was achieved in 11 patients after a median of 40 days, and molecular clearance of the underlying driver mutation was noted in 10 patients after a median of 32 days. Cytomegalovirus (CMV) reactivation occurred in 5 patients (41%), 1 of whom had CMV colitis as well, but all resolved after ganciclovir treatment. In 2 patients, ruxolitinib had to be discontinued on day 17 and day 18 after ASCT due to cytopenia after engraftment. Levels of inflammatory cytokines IL-8, IL-10, IL-6, TNFR2, INF-α, and INF-β were reduced after ruxolitinib treatment. After day +100, 4 patients developed acute GVHD (1 with grade I, 2 with grade II, and 1 with grade III) after tapering of cyclosporine, and all patients were alive at a median follow-up of 17 months (range, 12 to 18 months).

Impact of ruxolitinib on myelofibrosis patients post allogeneic stem cell transplant—a pilot study

“…Mounting evidence indicated ruxolitinib could shorten the neutrophil engraftment time and reduce GVHD burden via regulation of T cells and cytokine signal transduction pathway (Spoerl et al , ; Kröger et al , ). However, ruxolitinib‐induced cytopenia and CMV reactivation appeared to be a problem (Zeiser et al , ).…”

Selecting patients with primary myelofibrosis for stem cell transplant using clinical, mutational, and transplant‐specific profiles

“…There is preclinical and clinical evidence that JAK signaling plays a major role in graft‐versus‐host disease (GVHD), suggesting a potential role of JAK inhibition in the prevention and treatment of GVHD . A small report on 12 patients with advanced myelofibrosis who were treated with ruxolitinib and scheduled for allo‐HCT as curative treatment investigated the impact on GVHD prevention when ruxolitinib (5 mg twice daily) was not stopped at the time of conditioning and was continued throughout the peritransplantation period until stable engraftment occurred . The authors hypothesized that ruxolitinib may reduce the cytokine storm after ATG and prevent acute GVHD.…”

Viral retinitis: diagnosis and management in the era of biologic immunosuppression: A review

“…Ruxolitinib (Jakafi®) and tofacitinib (Xeljanz®) are Janus associated kinase (JAK) inhibitors which interfere with cell signalling of cytokines and growth factors in the haematopoietic and immune cascades . There have been two reported cases of CMV retinitis in HIV‐negative patients treated with a JAK inhibitor . Both were on other immunosuppressive medications, presumably exacerbating the immunodepression.…”

“…186,187 There have been two reported cases of CMV retinitis in HIV-negative patients treated with a JAK inhibitor. 141,188 Both were on other immunosuppressive medications, presumably exacerbating the immunodepression.…”