Should Elderly Patients With Higher-Risk Myelodysplastic Syndromes Undergo Allogeneic Hematopoietic Stem Cell Transplantation?

Amer M Zeidan; Steven D Gore


Expert Rev Hematol. 2013;6(5):539-542. 

In This Article

Abstract and Introduction


Myelodysplastic syndromes (MDS) include a group of hematopoietic malignancies characterized by dysplastic changes, ineffective hematopoiesis and variable risk of leukemic progression. At diagnosis, 86% of MDS patients are ≥60 years. Azacitidine, the only drug that prolongs life in high-risk (HR)-MDS patients, adds a median of only 9.5 months to life. Allogeneic stem cell transplantation (alloSCT) remains the only potentially curative approach. Despite recent improvements including use of reduced intensity conditioning (RIC) that decrease transplant-related mortality, alloSCT continues to be used rarely in elderly MDS. There is paucity of data regarding outcomes of RIC alloSCT in elderly MDS patients, especially in direct comparison with azanucleosides. In this paper, the authors discuss the recent Markov decision analysis by Koreth et al. in which investigators demonstrated superior survival of patients with HR-MDS aged 60–70 years who underwent RIC alloSCT in comparison with those who were treated with azanucleosides.


Myelodysplastic syndromes (MDS) include a group of hematopoietic neoplasms characterized by aberrant myeloid differentiation, dysplasia and ineffective hematopoiesis resulting in cytopenias and increased risk of leukemic progression.[1,2] At diagnosis, 86% of MDS patients are ≥60 years.[3] Reflecting a heterogeneous biology, outcomes are widely variable.[2] The most widely used prognostic instrument to guide therapeutic decisions is the International Prognostic Scoring System (IPSS). The IPSS generally classifies patients into a lower-risk (LR) group (low and intermediate-1 [INT-1]) and a higher-risk (HR) group (intermediate-2 [INT-2] and high).[4]

No drug has proven curative for MDS with only azacitidine proved to prolong overall survival (OS) in HR-MDS by a median of 9.5 months.[5] Allogeneic stem cell transplantation (alloSCT) currently offers the only hope for cure. Recent progress, including use of reduced intensity conditioning (RIC), has reduced transplantation-related mortality (TRM) significantly therefore increasing the applicability of RIC alloSCT for elderly patients.[6,7] Nonetheless, alloSCT is still performed in a small fraction of patients.[8] There are no randomized prospective data comparing alloSCT with azacitidine in MDS, retrospective data are few and conflicting and the two approaches are often used sequentially.[1,9–11]

To address the appropriate choice of treatments for elderly MDS, Koreth et al. used decision analysis (DA); a flexible statistical technique that can assist clinical-decision making by allowing evaluation of potential outcomes given multiple scenarios and assumptions.[10] DA allows for evaluation of results under different sets of assumptions to observe whether the same conclusions are reached.[12] In a previous Markov DA predating the widespread use of AZA, better life expectancy (LE) in IPSS HR-MDS patients was observed among patients who underwent alloSCT soon after diagnosis.[13] By contrast, patients with LR-MDS achieved maximal gain of years of life if alloSCT was delayed.[13] The applicability of these results to elderly HR-MDS patients undergoing RIC alloSCT is not clear as they were based on data from patients younger than 60 years who underwent myeloablative conditioning (MAC) alloSCT from HLA-identical donors before the widespread use of azacitidine.