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A prospective pilot study was performed to evaluate the effect of reduced-intensity conditioning with busulphan (10 mg/kg), fludarabine (180 mg/qm) and anti-thymocyte globulin followed by allogeneic stem cell transplantation from related (n = 8) and unrelated donors (n = 13) in 21 patients with myelofibrosis. The median age of the patients was 53 years (range, 32–63). No primary graft failure occurred. The median time until leucocyte (>1·0 × 109/l) and platelet (>20 × 109/l) engraftment was 16 (range, 11–26) and 23 d (range, 9–139) respectively. Complete donor chimaerism on day 100 was seen in 20 patients (95%). Acute graft-versus-host disease (GvHD) grades II–IV and III/IV occurred in 48% and 19% of cases and 55% of the patients had chronic GvHD. Treatment-related mortality was 0% at day 100 and 16% [95% confidence interval (CI): 0–32%] at 1 year. Haematological response was seen in 100% and complete histopathological remission was observed in 75% of the patients and 25% of the patients showed partial histopathological remission with a continuing decline in the grade of fibrosis. After a median follow-up of 22 months (range, 4–59), the 3-year estimated overall and disease-free survival was 84% (95% CI: 67–100%). [ABSTRACT FROM AUTHOR]

Summary. Three patients with myelofibrosis received allogeneic stem cell transplantation after a dose-reduced conditioning regimen of busulphan (8 mg/kg), fludarabine (180 mg/m2 ) and antithymocyte globulin (4 × 10 mg/kg). The median age at transplantation was 51 years (range 44–58). All patients engrafted with a leucocyte count > 1·0 × 109 /l after a median of 18 d (range 16–20). Grade II acute skin graft-versus-host disease (GvHD) occurred in one patient. One limited and one extensive chronic GvHD was observed. All patients achieved complete haematological remission. In one patient the fibrosis resolved completely 180 d post transplant. All patients are alive 126, 466 and 764 d after transplantation. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]