WHO Classification and WPSS Score Predict Post-Transplant Outcome in Adults with Myelodysplastic Syndrome: A Retrospective Study by GITMO - Gruppo Italiano Trapianto Midollo Osseo.
Authors: Alessandrino Paolo E. , Della Porta Matteo G. , Bacigalupo Andrea , Van Lint Maria Teresa , Falda Michele , Onida Francesco , Bernardi Massimo , Iori Anna P. , Rambaldi Alessandro , Cerretti Raffaella , Marenco Paola , Pioltelli Pietro , Pascutto Cristiana , Oneto Rosi , Fanin Renato , Bosi Alberto 
Published: April 2020

WHO classification and WPSS score (JCO2007;25:3503) have been recently proved to have prognostic significance in myelodysplastic syndromes (MDS), but their impact on the outcome of patients (pts) receiving allogeneic stem-cell transplantation (allo-SCT) is still to be clarified. We retrospectively evaluated the prognostic value of WHO classification and WPSS at the time of transplant in 406 MDS pts who underwent allo-SCT between 1990 and 2006. Patients were reclassified according to the WHO criteria: 30 had refractory anemia (RA/RARS), 54 refractory cytopenia (RCMD/RS), 51 RA with excess blasts (RAEB), type 1 and 95 RAEB type 2. One hundred twenty-seven pts were classified as acute myeloid leukemia (AML). The median recipient age was 48 years (range 17–67). There were 281 HLA-matched sibling and 125 unrelated donor SCT. One hundred forty-three pts (35%) received a reduced intensity regimen (RIC). Considering WHO categories, the probability of OS at 5-years was 0.8 in RA/RARS, 0.52 in RCMD/RS, 0.48 in RAEB-1, 0.26 in RAEB-2 and 0.29 in AML, while the probability of RFS at 5-years was 0.92, 0.78, 0.74, 0.47 and 0.44 respectively. The cumulative probability of TRM was 0.43. We performed a Cox analysis with WHO category, cytogenetics, transfusion dependency, recipient age, disease status, type of donor and type of conditioning as covariates. WHO classification had a significant effect on both OS (P=0.017), and RFS (P=0.01). Cytogenetic risk significantly affected RFS (P=0.04), while had a borderline effect on OS (P=0.09). A regular transfusion dependency before SCT was associated with a reduced OS (P=0.01) and increased TRM (P=0.037), while no significant effect on RFS was noticed. Age and stage of the disease at transplant showed a significant effect on OS (P=0.02 and P=0.04, respectively). RIC and active disease at transplant were associated to a reduced probability of RFS (P=0.02 and P=0.017 respectively). Age and use of myeloablative conditioning were significant risk factors for TRM (P=0.018 and P=0.032 respectively). The WPSS score, based on MDS-WHO category, cytogenetics and transfusion dependency at the time of SCT, was calculated for 171 pts. WPSS showed a prognostic significance on both OS and RFS in a Cox analysis with age of recipient, disease status, type of donor and type of conditioning as covariates (P=0.02 and P=0.01). Focusing the analysis on 84 MDS pts without excess blasts, multilineage dysplasia and regular transfusion-dependency significantly affected post-transplant OS (P=0.005 and P=0.009, respectively), and were associated to an increased TRM. In this clinical setting, WPSS allowed to identify 2 major groups of pts (very-low/low vs. intermediate risk) with significant different OS and TRM (P=0.013 and P=0.039). In conclusion, these data show that WHO classification and WPSS have a relevant prognostic value for the post-transplantation outcome of MDS pts and should be taken into account in transplantation decision-making, especially in subjects with less advanced disease. The independent negative effect of transfusion dependency strengthens the rationale to examine the consequences of iron overload and the potential benefit of chelation therapy in MDS transplant setting.