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JAK1/2 inhibitor ruxolitinib (RUX) is approved in patients with myelofibrosis but the impact of pretreatment with RUX on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) remains to be determined. We evaluated the impact of RUX on outcome in 551 myelofibrosis patients who received HSCT without (n= 274) or with (n= 277) RUX pretreatment. The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs. 85%, p= 0.05). The 1-year non-relapse mortality was 22% without significant difference between the arms. In a multivariate analysis (MVA) RUX pretreated patients with ongoing spleen response at transplant had a significantly lower risk of relapse (8.1% vs. 19.1%; p= 0.04)] and better 2-year event-free survival (68.9% vs. 53.7%; p= 0.02) in comparison to patients without RUX pretreatment. For overall survival the only significant factors were age > 58 years (p= 0.03) and HLA mismatch donor (p= 0.001). RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.

To expand the current knowledge about azacitidine (Aza) and donor lymphocyte infusions (DLI) as salvage therapy for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify predictors for response and survival, we retrospectively analyzed data of 154 patients with acute myeloid leukemia (AML, n = 124), myelodysplastic (MDS, n = 28), or myeloproliferative syndrome (n = 2). All patients received a median number of 4 courses of Aza (range, 4 to 14) and DLI were administered to 105 patients (68%; median number of DLI, 2; range, 1 to 7). Complete and partial remission rates were 27% and 6%, respectively, resulting in an overall response rate of 33%. Multivariate analysis identified molecular-only relapse (hazard ratio [HR], 9.4; 95% confidence interval [CI], 2.0 to 43.5; P = .004) and diagnosis of MDS (HR, 4.1; 95% CI, 1.4 to 12.2; P = .011) as predictors for complete remission. Overall survival (OS) at 2 years was 29% ± 4%. Molecular-only relapse (HR, .14; 95% CI, .03 to .59; P = .007), diagnosis of MDS (HR, .33; 95% CI, .16 to .67; P = .002), and bone marrow blasts <13% (HR, .54; 95% CI, .32 to .91; P = .021) were associated with better OS. Accordingly, 2-year OS rate was higher in MDS patients (66% ± 10%, P = .001) and correlated with disease burden in patients with AML. In summary, Aza and DLI is an effective and well-tolerated treatment option for patients with relapse after allo-HSCT, in particular those with MDS or AML and low disease burden. The latter finding emphasizes the importance of stringent disease monitoring and early intervention.

•Allogeneic hematopoietic cell transplantation (allo-HCT) may provide a long-term survival benefit compared with nontransplantation strategies in higher-risk chronic myelomonocytic leukemia (CMML) according to CMML-specific prognostic scoring system (CPSS).•The CPSS provides only modest utility for risk stratification in the transplantation setting.•Better HCT-specific risk assessment is needed to identify patients who may benefit the most to eventually facilitate patient counseling.

To determine the survival benefit of allogeneic hematopoietic cell transplantation (allo-HCT) in chronic myelomonocytic leukemias (CMML), we assembled a retrospective cohort of CMML patients aged 18-70 years diagnosed between 2000 and 2014 from an International CMML Dataset (ICD, n=730) and from the EBMT registry (n=384). The prognostic impact of allo-HCT was analyzed through univariable and multivariable time-dependent models and with a multi-state model, accounting for age, sex, CMML prognostic scoring system (CPSS low and intermediate-1: lower-risk, intermediate-2 and high: higher-risk) at diagnosis, and AML transformation. In univariable analysis, lower-risk CMMLs had a 5-year OS of 20% (95%CI 12-33%) with allo-HCT versus 42% (95%CI 35-49%) without allo-HCT (P<0.001). In higher-risk patients, 5-year OS was 27% (95%CI 21-34%) with allo-HCT versus 15% (95%CI 11-22%) without allo-HCT (P=0.13). With multi-state models, performing allo-HCT before AML transformation reduced overall survival in patients with lower risk CMML while a survival benefit was predicted for men with higher risk CMML. In a multivariable analysis of lower-risk patients, performing allo-HCT before transformation to AML significantly increased the risk of death within two years of transplantation (HR=3.19, 95%CI 2.30-4.42, P<0.001), with no significant change in long-term survival beyond this time point (HR=0.98, 95%CI 0.58-1.64, P=0.92). In higher risk patients, allo-HCT significantly increased the risk of death in the first two years after transplant (HR=1.46, 95%CI 1.09-1.96, P=0.01), but not beyond (HR=0.60, 95%CI 0.34-1.08, P=0.09). Performing allo-HCT before AML transformation decreases life expectancy in lower risk patients but may be considered in higher risk patients.