There’s Risk, and Then There’s RISK: The Latest Clinical Prognostic Risk Stratification Models in Myelodysplastic Syndromes
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Myelodysplastic syndromes (MDS) include a diverse group of clonal hematopoietic disorders characterized by progressive cytopenias and propensity for leukemic progression. The biologic heterogeneity that underlies MDS translates clinically in wide variations of clinical outcomes. Several prognostic schemes were developed to predict the natural course of MDS, counsel patients, and allow evidence-based, risk-adaptive implementation of therapeutic strategies. The prognostic schemes divide patients into subgroups with similar prognosis, but the extent to which the prognostic prediction applies to any individual patient is more variable. None of these instruments was designed to predict the clinical benefit in relation to any specific MDS therapy. The prognostic impact of molecular mutations is being more recognized and attempts at incorporating it into the current prognostic schemes are ongoing.
KeywordsMyelodysplastic syndrome MDS Prognostic scoring systems Prognosis Predictive biomarkers Prognostic schemes Risk stratification IPSS WHO FAB
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Conflict of Interest
A. Zeidan declares that he has no conflict of interest.
R. Komrokji has received grant and payment for development of educational presentations including service on speakers’ bureaus from Celgene.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 2.•• Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364:2496–506. A large genome-wide study of samples from 439 MDS patients in which the authors identified somatic mutations in 18 genes and studied their prognostic effects and relation to specific disease phenotypes.PubMedCrossRefGoogle Scholar
- 6.Zeidan AM, Linhares Y, Gore S. Current therapy of myelodysplastic syndromes. Blood Rev. (In Press).Google Scholar
- 8.Mitchell M, Gore S, Zeidan AM. Iron chelation therapy for myelodysplastic syndromes-associated iron overload: where do we stand? Expert Rev Hematol. (In Press).Google Scholar
- 12.Faltas B, Zeidan AM, Gergis U. Myelodysplastic syndromes: towards a risk-adaptive treatment approach. Expert Rev Hematol. (In Press).Google Scholar
- 15.Bennett JM. The myelodysplastic syndromes: a personal recollection of four decades of classification and prognostic scoring systems. Leuk Lymphoma. 2013. [Epub ahead of print].Google Scholar
- 23.Greenberg PL, Attar E, Bennett JM, et al. NCCN clinical practice guidelines in oncology: myelodysplastic syndromes. J Natl Compr Cancer Netw. 2011;9:30–56.Google Scholar
- 24.Koreth J, Pidala J, Perez WS, et al. Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis. J Clin Oncol. 2013. [Epub ahead of print].Google Scholar
- 25.•• Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454–65. A large study of an international database of 7012 patients that led to the revision of the original international prognostic scoring system (IPSS) and adoption of the revised IPSS (IPSS-R).PubMedCrossRefGoogle Scholar
- 29.Schanz J, Steidl C, Fonatsch C, et al. Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the international prognostic scoring system. J Clin Oncol. 2011;29:1963–70.PubMedCrossRefGoogle Scholar
- 39.Park MJ, Kim HJ, Kim SH, et al. Is International Prognostic Scoring System (IPSS) still standard in predicting prognosis in patients with myelodysplastic syndrome? External validation of the WHO Classification-Based Prognostic Scoring System (WPSS) and comparison with IPSS. Eur J Haematol. 2008;81:364–73.PubMedGoogle Scholar
- 44.Komrokji RS, Padron E, Lancet JE, List AF. Prognostic factors and risk models in myelodysplastic syndromes. Clin Lymphoma Myeloma Leuk. (In Press).Google Scholar
- 47.Komrokji RS, Corrales-Yepez M, Al Ali NH, et al. Validation of the lower risk MD Anderson prognostic scoring system for patients with myelodysplastic syndromes [Abstract 3826]. Presented at the American Society of Hematology 54th Annual Meeting. Atlanta, Georgia; December 2012.Google Scholar
- 48.•• Schanz J, Tuchler H, Sole F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30:820–9. A large study of the cytogenetics of 2,902 patients with de novo MDS treated with supportive care (SC). This study defined 19 cytogenetic groups, thereby allowing cytogenetic classification of 91 % of patients. Based on this study, a novel 5-group cytogenetic prognostic classification system was created and later adopted in the IPSS-R.PubMedCrossRefGoogle Scholar
- 49.Mishra A, Corrales-Yepez M, Ali NA, et al. Validation of the revised International Prognostic Scoring System in treated patients with myelodysplastic syndromes. Am J Hematol. 2013. [Epub ahead of print].Google Scholar
- 52.Voso MT, Fenu S, Latagliata R, et al. Revised International Prognostic Scoring System (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO prognostic scoring system: validation by the Gruppo Romano Mielodisplasie Italian Regional Database. J Clin Oncol. 2013. [Epub ahead of print].Google Scholar
- 59.Gangat N, Patnaik MM, Begna K, et al. Evaluation of revised IPSS cytogenetic risk stratification and prognostic impact of monosomal karyotype in 783 patients with primary myelodysplastic syndromes. Am J Hematol. 2013. [Epub ahead of print].Google Scholar
- 65.Starczynowski DT, Vercauteren S, Telenius A, et al. High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival. Blood. 2008;112:3412–24.PubMedCrossRefGoogle Scholar
- 67.Abdel-Wahab O, Figueroa ME. Interpreting new molecular genetics in myelodysplastic syndromes. Hematol Am Soc Hematol Educ Program. 2012;2012:56–64.Google Scholar
- 69.Bejar R, Stevenson K, Stojanov P, et al. Detection of recurrent mutations by pooled targeted next-generation sequencing in MDS patients prior to treatment with hypomethylating agents or stem cell transplantation [Abstract 311]. Presented at the American Society of Hematology 54th Annual Meeting. Atlanta, Georgia; December 2012.Google Scholar
- 77.Breccia M, Fianchi L, Lunghi M, et al. Newly proposed therapy-related myelodysplastic syndrome prognostic score predicts significant differences in overall survival and leukemia-free survival in patients treated with azacitidine. Leuk Lymphoma. 2012. [Epub ahead of print].Google Scholar
- 93.van der Helm LH, Alhan C, Wijermans PW, et al. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme. Br J Haematol. 2011;155:599–606.PubMedCrossRefGoogle Scholar