Risk Stratification Using DIPSS and Splenomegaly in Myelofibrosis Treated with Pre-Transplant JAK inhibitors.

The Dynamic International Prognostic Scoring System for primary myelofibrosis (DIPSS) has been reported to predict transplant outcomes in myelofibrosis (MF) patients. Recently, the pre-transplant use of JAK inhibitors has become common in clinical practice, but it is unclear whether DIPSS is also useful for predicting transplant outcomes for these patients. In this study, we compared the prognostic impact of DIPSS between MF patients with and without pre-transplant Ruxolitinib therapy. DIPSS stratified overall survival (OS) in patients without pre-transplant Ruxolitinib therapy (P = 0.002), but not in those with it (P = 0.23). In an exploratory analysis, palpable splenomegaly appeared to be a potential prognostic factor among patients who received pre-transplant Ruxolitinib therapy (hazard ratio (HR) 1.53, 95% CI: 0.86-2.72, P = 0.15). Here we propose a modified scoring system, DIPSS with Splenomegaly (DIP3S), and demonstrate that DIP3S high-risk status (defined as DIPSS low-, intermediate-1-, and intermediate-2-risk with splenomegaly, or DIPSS high-risk) is independently associated with inferior OS (HR 2.20, 95% CI: 1.09-4.45, P = 0.027), delayed neutrophil engraftment (HR 0.54, 95% CI: 0.37-0.77, P < 0.001), and delayed platelet engraftment (HR 0.32, 95% CI: 0.20-0.52, P < 0.001). On the other hand, neither DIPSS (HR 0.62, 95% CI: 0.34-1.12, P = 0.11 for low/intermediate-1-risk; HR 0.96, 95% CI: 0.50-1.84, P = 0.90 for high-risk) nor splenomegaly (HR 1.51, 95% CI: 0.83-2.75, P = 0.17) was significantly associated with inferior OS when each factor was independently included in the multivariable analysis. Therefore, the DIP3S risk may be able to identify high-risk patients among those who receive pre-transplant JAK inhibitors. Further validation studies are needed to clarify the prognostic impact of DIP3S.