Ruxolitinib Prior to Allogeneic Stem Cell Transplant: The Experience at Mayo Clinic Arizona

Backround:

Primary Myelofibrosis (PMF) and Post  PV/ET MF are a group of myeloproliferative neoplasms that are characterized by marrow fibrosis, cytopenias, constitutional symptoms, and splenomegaly.  Allogeneic stem cell transplant (ASCT) remains the only potential curative modality.  The increased risk of morbidity and mortality warrants careful selection of candidates.  Age, performance status (PS) and HCT-CI scores are all factors that may affect outcomes related to ASCT.   Use of JAK inhibitor therapy prior to HCT may lead to reduction in splenomegaly, decrease in constitutional symptoms, and improved PS.   We report our experience here at Mayo Clinic Arizona using JAK inhibition prior to ASCT.

Methods

 We conducted a retrospective review of all patients from 2011 to current with PMF or post ET/PV-MF who underwent treatment of ruxolitinib followed by ASCT. Patient demographic and transplant data were analyzed from a comprehensive database. The use of such data for reporting purpose was approved by the Mayo Clinic Arizona Institutional Review Board.

Results

Patient characteristics: Eight patients underwent ruxolitinib therapy prior to ASCT. Mean age was 61 yrs. Disease characteristic: DIPSS risk was high risk in 6 and intermediate 2 in 2. The JAK 2 v617 mutation was present in 7 patients. Four patients had PMF and 4 had post PV-MF.  None of the patients underwent splenectomy. The median duration of ruxolitinib was 7.8 months. Improvement in PS was seen 4 pts, stable PS was seen 3 patients and data regarding PS was missing in 1. Six of the 8 patients had reduction in their spleen size prior to ASCT. The median daily dose of Ruxolitinib was 25.6 mg/day.

Transplant characteristics:  One patient underwent myeloablative conditioning (MAC),   5 reduce toxicity, and 2 RIC. All 8 patients had unrelated donors with 1 patient having a mismatch unrelated donor. Graft versus host disease prophylaxis was tacrolimus/methotrexate in 6 patients and tacrolimus/MMF in 2 patients. All 8 patients received in vivo T cell depletion with rabbit ATG and had peripheral stem cells as their graft source.  Of the 8 patients, 1 had primary graft failure 2 had relapsed disease before day 100. All 3 of these patients were conditioned with Bu/Flu RIC regimen.  None of the patients experienced tumor lysis syndrome or cardiogenic shock.

Conclusion

                In our small cohort of patients that received ruxolitinib pre ASCT improvement in performance status and spleen size were seen.  Our data is still immature to make any meaningful comments of outcomes, but all patients tolerated the ruxolitinib and no major adverse outcomes were seen related to the ruxolitinib such as cardiogenic shock or tumor lysis syndrome as seen in a recent French study. Further studies are needed to formally evaluate the impact on JAK inhibitors on transplant both pre and post setting.