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Journal of Clinical Oncology, Vol 26, No 7 (March 1), 2008: pp. 1180 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.2926
Time-Dependent Prognostic Scoring System for Myelodysplastic Syndromes Has Significant Limitations That May Influence Its Reproducibility and Practical ApplicationDepartment of Hematology, Leeds Teaching Hospital, Leeds, United Kingdom
Department of Hematology, Avicenne Hospital, AP-HP, Paris 13 University, Paris, France
Department of Medicine, Karolinska Institutet, Stockholm, Sweden
University Medical Centre, Radboud University, Nijmegen, the Netherlands To the Editor: Malcovati and colleagues report a high-quality study that proposes a new classification-based prognostic system with the advantage of dynamic evaluation.1 The learning cohort of patients from the Pavia database is validated against a cohort of patients from the larger Düsseldorf database. Both centers have a high proportion of patients outside of their catchment population. The authors suggest that this system has greater applicability than the static International Prognostic Scoring System (IPSS), the prognostic value of which has been validated only at diagnosis. This would indeed be the case but for some caveats, some of which are discussed by the authors in the article.
Some concerns must surround the replacement of the IPSS prognostic system based largely on objective criteria with a system based on largely subjective criteria. Two of the three criteria for the WHO classification–based prognostic scoring system (WPSS; transfusion dependence and WHO classification) have a subjective element. Transfusion-dependence—The decision criteria for transfusion of patients with myelodysplatic symdrome (MDS) will vary from clinician to clinician, center to center and country to country. Clinical practice in Leeds and Stockholm is one of fairly aggressive transfusion based on symptoms and not hemoglobin concentration. More than half of our chronically transfused Leeds patients have an interval between transfusion episodes of The study does not indicate a major prognostic advantage for the dynamic WPSS (Fig 1C and 1D)1 over the more objective dynamic IPSS (Fig 2C and 2D).1 The dynamic WPSS better identifies a low-risk group (for both overall survival and acute myeloid leukemia [AML] transformation) while the dynamic IPSS better identifies patients with high cumulative risk of AML transformation and poorer overall survival. Clinically, one could argue that identifying patients at high risk of AML transformation over-rides the confirmation of indolent disease. IPSS and cytogenetics can predict for good outcome in younger patients who should not receive aggressive therapy.3 The age of each cohort is not stated in the manuscript. Previous publications from these groups describe the Pavia cohort with a median age of 66 years,4 and the Düsseldorf cohort with median ages of 70 to 72 years.5,6 Were the learning and validation cohorts comparable for age, including the subsets of patients from whom the dynamic data were derived (noting that these represented < 50% of the patients at diagnosis)? True population-based data indicate a higher median age for MDS patients (77 years),7 thus questioning the extrapolation of data derived from referral centers to MDS patients in most smaller hospitals. The authors are themselves expertly working toward more objective criteria for diagnosis and classification of MDS such as flow cytometry, which may ultimately also have prognostic value. Until such a time as these are standardized and validated, we should persevere with prognostic criteria that are as objective as possible, easily reproducible, and practical. As such, a more thorough evaluation is required to establish the applicability of subjective criteria such as morphology in the smaller centers that manage the vast majority of MDS patients worldwide. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Malcovati L, Germing U, Kuendgen A, et al: Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 25:3503-3510, 2007 2. Howe RB, Porwit-MacDonald A, Wanat R, et al: The WHO classification of MDS does make a difference. Blood 103:3265-3270, 2004 3. Kuendgen A, Strupp C, Aivado M, et al: Myelodysplastic syndromes in patients younger than age 50. J Clin Oncol 24:5358-5365, 2006 4. Malcovati L, Porta MG, Pascutto C, et al: Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: A basis for clinical decision making. J Clin Oncol 23:7594-7603, 2005 5. Germing U, Gattermann N, Strupp C, et al: Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: A retrospective analysis of 1600 patients. Leuk Res 24:983-992, 2000[CrossRef][Medline] 6. Germing U, Strupp C, Kuendgen A, et al: Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica 91:1596-1604, 2006 7. Phekoo KJ, Richards MA, Moller H, et al: The incidence and outcome of myeloid malignancies in 2,112 adult patients in South East-England. Haematologica 91:1400-1404, 2006
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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2 weeks (Leeds Departmental audit, 2007). This will clearly be at variance with the Pavia triggers for transfusion indicated in the manuscript. The evidence base for a red cell transfusion strategy in MDS is weak. The value of transfusion dependence as a surrogate for comorbidity is an interesting and potentially important concept, but this needs a formal prospective study. WHO classification—The reproducibility of the WHO classification is also not known. Limited data from expert morphologists in MDS Centers of Excellence suggest good reproducibility,
