Pre-hematopoietic cell transplant Ruxolitinib in patients with primary and secondary myelofibrosis

• Published in: Bone marrow transplantation (Basingstoke) Vol. 55; no. 1; pp. 70 - 76
• Main Authors: Salit, Rachel B., Scott, Bart L., Stevens, Emily A., Baker, Kelsey K., Gooley, Ted A., Deeg, H. Joachim
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2020; Nature Publishing Group
• Subjects: 631/67/1059/602; 631/67/1990/2331; Cell Biology; Cord blood; Graft vs Host Disease; Graft-versus-host reaction; Hematology; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Histocompatibility antigen HLA; Humans; Internal Medicine; Janus kinase; Medicine; Medicine & Public Health; Middle Aged; Mortality; Myelofibrosis; Nitriles; Primary Myelofibrosis - drug therapy; Prospective Studies; Public Health; Pyrazoles; Pyrimidines; Signs and symptoms; Spleen; Stem cell transplantation; Stem Cells; Survival; Survival Analysis; Transplantation; Transplantation Conditioning; Transplants & implants; Treatment Outcome; Umbilical cord
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-019-0523-3

Ruxolitinib (Rux), a Jak1/2 inhibitor, results in reduced spleen size and improvement in constitutional symptoms in the majority of patients with myelofibrosis (MF). Therefore Rux, when given prior to hematopoietic cell transplantation (HCT) in patients with MF was hypothesized to improve engraftment, decrease incidence and severity of graft-versus-host disease, and lower non-relapse mortality (NRM). We conducted a phase II prospective trial to assess the effects of pre-HCT Rux on post-HCT outcomes in patients with MF. The primary endpoint was 2-year overall survival. To date, 28 patients (median age 56 years) have been transplanted. The median time on Rux pre-HCT was 7 months. Twenty-three patients received myeloablative and five reduced intensity conditioning. Donors included 14 HLA-matched siblings, 11 matched unrelated, 1 allele mismatched unrelated, and 3 umbilical cord blood. There have been no episodes of cytokine release syndrome and all patients achieved sustained engraftment. Two patients died from NRM and two patients relapsed. With a median follow-up of 13 months, overall survival is 93% (95% CI: 0.73, 0.98) at 1 year and 86% (95% CI: 0.61, 0.96) at 2 years post-HCT. This study demonstrates that pre-HCT Rux is well tolerated and suggests that pre-HCT Rux may improve post-HCT outcome.