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Therapy-related myelodysplastic syndromes-specific risk stratification: are we putting the cart before the horse?

Leukemia volume 31, pages 2539–2541 (2017)Cite this article

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In their letter, Calvo et al.1 raise the important question of whether therapy-related (t)-myelodysplastic syndromes (MDS) merit a risk stratification tool distinct from the tools typically used for prognostication in de novo (d)-MDS, such as the International Prognostic Scoring System (IPSS)2 and its revised version (IPSS-R).3 This is a clinically relevant question given the common perception that patients with t-myeloid neoplasms (t-MN) have high-risk disease regardless of how they would score on the IPSS or IPSS-R, and therefore warrant aggressive therapy, such as allogeneic hematopoietic cell transplantation (alloHCT), when medically feasible.4 Earlier reports, limited by small numbers of patients, supported this concept by dismissing the value of previously established prognostic factors, such as the proportion of bone marrow blasts,5 leading the World Health Organization (WHO) to include both t-MDS and t-acute myeloid leukemia (t-AML) under the same entity of t-MN regardless of the blast percentage.6 However, subsequent reports with larger sample sizes, including our study, documented a substantial inter-patient variability in outcomes among patients with t-MDS and validated the prognostic influence of several clinicopathological variables used in conventional MDS risk stratification tools, such as cytogenetics, blood counts, bone marrow blast proportion and transfusion dependency.7, 8, 9 Collectively, these reports suggest that risk stratification remains important in individualized clinical decision making for patients with t-MDS, just as for patients with d-MDS.

Since the importance of risk stratification has been confirmed in patients with t-MDS, research efforts have turned to developing a practical tool that accurately predicts outcomes for these patients. One approach was to examine how prognostic tools already in clinical use for d-MDS perform among patients with t-MDS. We and others demonstrated that the IPSS, IPSS-R, WHO classification-based Prognostic Scoring System (WPSS)10 and the MD Anderson Prognostic Scoring System (MDAS)11 all retained prognostic ability by separating patients with t-MDS into different risk groups with distinct median survivals.7, 8, 9 While survival of patients with t-MDS as a group was, as expected, significantly inferior to that to patients with d-MDS (median, 19 vs 46 months, respectively, P=0.005), within each risk group the survival of patients with t-MDS was lower than that of d-MDS patients regardless of which prognostic tool was used.7 This observation suggested that other factors not captured by the variables used in the existing risk tools, such as co-morbid conditions or molecular genetic changes, might have an important influence on survival. However, we were unable to demonstrate that co-morbidities accounted for the worse survival of patients with t-MDS compared with those with d-MDS. Similarly, the survival of patients with t-MDS who underwent alloHCT was not worse than for their d-MDS counterparts with similar prognostic scores, suggesting that inferior outcomes post alloHCT did not account for the inferior survival of patients with t-MDS compared with d-MDS in similar risk groups.7

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Acknowledgements

Funding for this research has been provided, in part, from the Edward P. Evans Foundation to MAS, DPS, JB and RK.

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Authors and Affiliations

  1. Department of Internal Medicine, Section of Hematology, Yale University, and Yale Comprehensive Cancer Center, New Haven, CT, USA

    A M Zeidan

  2. Leukemia Program, Cleveland Clinic, Cleveland, OH, USA

    M A Sekeres & J Barnard

  3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    D P Steensma

  4. Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    R Komrokji

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  1. A M Zeidan
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Correspondence to A M Zeidan.

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Zeidan, A., Sekeres, M., Barnard, J. et al. Therapy-related myelodysplastic syndromes-specific risk stratification: are we putting the cart before the horse?. Leukemia 31, 2539–2541 (2017). https://doi.org/10.1038/leu.2017.238

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