The Revised International Prognostic Scoring System (IPSS-R) Predicts Posttransplantation Outcome Of Patients With Myelodysplastic Syndrome Receiving Allogeneic Stem Cell Transplantation: A Basis For Clinical Decision Making

Background The only curative treatment for patients with myelodysplastic syndrome (MDS) is allogeneic stem cell transplantation (allo-SCT). Decision to transplant is currently based on the International Prognostic Scoring System (IPSS), which has limitations. Recently, a revised IPSS (IPSS-R) has been developed (Blood. 2012;120:2454-2465). Aim To identify predictive factors for transplantation outcome, we studied 519 patients with MDS or acute myeloid leukemia (AML) evolving from MDS who received allo-SCT and were reported to the GITMO registry between 2000 and 2010. Results 1 Posttransplantation outcome according to cytogenetics. Cytogenetic abnormalities were classified according to MDS Cytogenetic Scoring System (MCSS) criteria. Four groups of patients with different overall survival (5-year OS ranging from 48% to 15%, P=.003) and probability of relapse (P=.001) after transplantation were identified. In a multivariate model, MCSS significantly affected OS (HR 1.29, P=.001) and probability of relapse (HR 1.40, P<.001). Monosomal karyotype (MK) was found in 76 patients (15%) and was associated with a dismal outcome after allo-SCT (5-year OS 10%; 5-year cumulative incidence of relapse 49%). MK maintained a significant effect on OS and probability of relapse in patients stratified according to MCSS (P<.001 and P=.001, respectively). Results 2 Posttransplantation outcome according to degree of peripheral blood cytopenia and percentage of marrow blasts. No significant effect of neutrophil and platelet count on posttransplantation outcome was noticed. The 5-year OS was 51%, 40% and 33% in patients with hemoglobin >10g/dl, between 8-10 g/dl and <8 g/dl, respectively (P=.001). The 5-year incidence of non-relapse mortality (NRM) was 29%, 37% and 44%, respectively (P=.003). The impact of hemoglobin level on posttransplantation outcome was maintained in a multivariate model (OS: HR 1.37, P=.002; NRM: HR 1.41, P=.009). Marrow blast count as stratified according to IPSS-R criteria significantly predict the probability of relapse (P=.005). Results Posttransplantation outcome of patients stratified according to IPSS-R. Patients were then classified according to IPSS-R criteria: 59 patients had a low risk (11%), 89 patients (17%) an intermediate risk, 207 (40%) a high risk, and 164 (32%) a very high risk. Five-year OS was 71%, 58%, 39% and 23%, respectively ( [Figure 1][1] , P=.001). 5-year cumulative incidence of relapse was 4%, 12%, 23% and 39%, respectively (P=<.001). Compared with the IPSS-based stratification, the IPSS-R risk group would have changed for 65% of patients, 59% of which would have been assigned to a less favourable prognostic group. By applying the Akaike criterion, IPSS-R was more likely to capture prognostic information in this patient setting with respect to IPSS, especially in early stage disease (i.e., low and intermediate-1 IPSS risks). ![Figure 1][2] Figure 1 Overall survival of MDS patients stratified according to IPSS-R criteria We analyzed the prognostic effect of IPSS-R score by a multivariate model. The IPSS-R score significantly affected OS (HR 1.41, P<.001) and probability of relapse (HR 1.81 P<.001) in MDS patients. The effect of IPSS-R on posttransplantation outcome was maintained also when including MDS/AML as well as when stratifying patients according to type of conditioning (P form .006 to <.001). Recipient age (≥50 years) and presence of comorbidity (high risk according to HCT-CI score) were significant risk factors for increased NRM (HR 1.79, P=.02 and HR 1.83 P=.017, respectively), while MK and lack of complete remission after induction chemotherapy showed an independent effect on relapse risk (HR 2.23, P=.001 and HR 1.94, P=.001, respectively). According to the presence of these additional risk factors, the cumulative incidence of NRM among different IPSS-R categories ranged from 13% to 52% in patients receiving standard conditioning (P<.001), and from 9% to 42% in patients receiving reduced-intensity conditioning (P<.001), while the cumulative incidence of relapse ranged from 4% to 39% (P<.001) and from 5% to 57% (P<.001), respectively. Conclusions This study clearly shows that IPSS-R allows a reliable prediction of posttransplantation outcome in MDS patients. Allo-SCT offers optimal survival benefits when the procedure is performed before MDS patients progress to advanced disease stages. Disclosures: Rambaldi: Novartis: Honoraria; Sanofi: Honoraria; Italfarmaco: Honoraria. [1]: #F1 [2]: pending:yes