Analysis Of Transfusion Dependence Development and Disease Evolution In Patients With MDS and Del(5q) and Without Transfusion Needs At Diagnosis
Authors: Rojas Silvia M , Díez-Campelo María , Luño Elisa , Bernal Teresa , Cabrero Monica , Pedro Carme , Calabuig Marisa , Nomdedeu Benet , Cedena Teresa , Arrizabalaga Beatriz , Garcia Marta , Cerveró Carlos , Collado Rosa , Azaceta Gemma , Ardanaz MarÃa Teresa , Muñoz Juan A , Xicoy Blanca , Requena María José , Bargay Joan , Arilla María Jesús , Amigo Luz , Merchan Brayan , Simiele Adriana , Brunet Salut , Gonzalez Bernardo , Ramos Fernando , Solé Francesc , CaÃ‘izo Consuelo Del 
Published: October 2019

Abstract
Myelodysplastic syndrome with 5q- (MDS 5q-) is the only cytogenetically defined MDS category recognized by the world Health Organization (WHO) in 2001 and 2008 and is defined as a MDS with isolated deletion on the long arm of chromosome 5 and less than 5% of blast cells in bone marrow (BM). It is well known that for patients with MDS 5q- and transfusion dependence (TD), Lenalidomide is the first choice treatment. However, as far as we know there are no data regarding factors that may impact on the development of TD in these patients or the disease evolution in patients diagnosed without TD. In the present study a retrospective multicenter analysis on patients with low-int 1 MDS 5q- without TD at diagnosis has been performed in order to answer these questions.

Patients and methods
Data from eighty-four low-Int 1 risk MDS 5q- patients diagnosed between 1980 and 2012 were retrospectively analyzed. Ninety percent of patients had a single 5q deletion and according to IPSS-R 99% were in low and very low risk.

Statistical analysis
The event of TD was defined as the development of TD according to the IWG criteria (2006) and/or the beginning of a treatment which could modify disease course (Lenalidomide or ESA). Patients follow up was updated on March 30, 2013, and all follow up data were censored at that point. Transfusion free survival (TFS), Overall survival (OS) and AML were analyzed using the Kaplan – Meier method. TFS, OS, and Leukemia free survival (LFS) were measured from diagnosis to TD or to last follow up if transfusion free (TFS), death from any cause or last follow up (OS) and evolution to AML or last follow up (LFS). Multivariate analysis was performed using Cox’s proportional hazards regression model. Incidence of progression to AML was analyzed with cumulative incidence competing risk method. For comparison of Kaplan Meier curves the long rank test was used, with statistical significance with p<0.05 statistical analysis was performed using SPSS 15.0 and NCSS V.8, 2010.

Results
During the study 61 (73%) became TD at a median of 1.7 years from diagnosis. The unique factor associated with poorer TFS was Hb level <9 g/dl (p=0.007) and this impact retained statistical significance in the multivariate analysis (table.1) Among the 61 TD patients, 49 received treatment: 19 lenalidomide, 24 ESA and 6 other treatments. Fifteen patients were treated (7 with lenalidomide and 8 with ESA) previous to TD development. In order to know the evolution of this very good prognostic subgroup of patients, OS and LFS analysis were performed. Median follow up was 48 months, 46% of patients are alive at the time of the last follow up and 31% developed secondary AML (sAML). Estimated OS at 2 and 5 y was 92% and 50% respectively. Regarding Univariate analysis, platelet <100.000 x109/L, and IPSS-R intermediate risk group were associated with poorer OS (p=0.001 and 0.019 respectively). On the contrary, patients who had received treatment showed better OS. This benefit is more evident among patients receiving Lenalidomide (p=0.015). In the multivariate analysis platelets <100.000 x109/L and Lenalidomide treatment retained the statistical significant impact on OS (table1). When LFS was analyzed the cumulative incidence of progression into AML was 4,4% after 2 y. and 12,7% after 5 y from diagnosis with median time to sAML of 8.16 years (CI 95%: 6.05-10.27). LFS at 2 and 5 y was 86% and 73% respectively. When univariate analysis was performed variables with impact on sAML were platelet <100.000 x109/L (p=<0,001), and to have received treatment (p=0,02). In the multivariate analysis only thrombocytopenia retained statistical significance (table1).In summary, the present analysis shows that Hb is the only parameter that conditions the TD development in MDS-5q- patients. In this very good prognostic subgroup beginning treatment with lenalidomide improves survival.

Disclosures:
Díez-Campelo: Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen-Cilag: Research Funding. Off Label Use: In the present study we describe Lenalidomide treatment among patients with MDS and del(5q-) receiving this drug, not approval for this use in Europe, patients with anemia and transfusional requirements. Solé:Celgene: Consultancy, Honoraria; Celgene: Consultancy. Consuelo:Celgene Jansen-Cilag Arry Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding.