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Journal of Clinical Oncology, Vol 26, No 7 (March 1), 2008: pp. 1181-1182 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.3593
In ReplyFrom the Department of Hematology, University of Pavia & Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy
Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany Dr Bowen et al1 raise concerns regarding the reproducibility of the dynamic scoring system described in our study. We thank our colleagues for their interesting observations, but we also believe that our prognostic scoring system is reproducible and useful for defining the risk of the individual patient with myelodysplastic syndrome (MDS).
The existing evidence- and consensus-based guidelines for treatment of MDS provide reliable criteria for deciding RBC transfusion therapy.2,3 In our study population, regular transfusion dependency identified more than 90% of patients with hemoglobin levels below 9 g/dL (in detail, 100% of patients with hemoglobin levels lower than 8 g/dL and approximately 80% of those with hemoglobin levels from 8 to 8.9 g/dL). By contrast, only 6% of patients with hemoglobin level We defined transfusion dependency as having at least one RBC transfusion every 8 weeks over a period of 4 months (ie, as having received at least two RBC transfusions in the previous 4 months). This threshold was chosen in order to also include patients with low but regular transfusion needs. It should be noted that, in both the Italian and German cohorts, the vast majority of patients had a transfusion frequency of at least one RBC unit per month. Defining the severity of anemia by relying on a single hemoglobin level may introduce a bias in the prognostic stratification of patients with MDS, because of interindividual variability in hemoglobin level due to age and sex. At present, adopting symptomatic anemia as a major criterion for assessing the severity of anemia in the MDS population seems to be a reliable approach to adjust for the variability of hemoglobin values. Indeed, by using transfusion-dependency as a surrogate of symptomatic anemia, we identified a rather homogeneous group of patients with MDS. The second concern raised by Bowen et al deals with the reproducibility of the WHO classification. Morphology is still the mainstay of diagnosis and classification of MDS. However, the reproducibility of morphological analysis is an unsolved issue that concerns not only the WHO classification, but also the criteria included in the French-American-British (FAB) classification, as well as the minimal criteria to formulate a diagnosis of MDS irrespective of the classification system adopted.5 In particular, interobserver agreement among morphologists for recognition of dyserythropoiesis is poor, despite the fact that dyserythropoiesis is mainstay of the morphological diagnosis of MDS, and the same applies to marrow blasts count, which is the backbone of the FAB classification and the International Prognostic Scoring System (IPSS).5 The distinction between uni- or multilineage dysplasia was proven to be of prognostic relevance in MDS patients without excess blasts,6,7 and therefore, though this distinction is difficult, we included it in our prognostic scoring system. Until more reproducible parameters are available, the diagnosis of MDS must rely on the existing morphological criteria, despite their scarce reproducibility. Bowen et al state that our study does not indicate a major advantage of dynamic WHO classification-based Prognostic Scoring System (WPSS) over IPSS, and that dynamic IPSS better identifies patients with high cumulative risk of acute myelogenous leukemia (AML) transformation and poorer overall survival. The WPSS is able to identify five risk groups compared with the four of the IPSS, the most relevant improvement in prognostic ability being observed within MDS patients without excess blasts. In this group of patients, the WPSS is able to identify a subset of patients with a low risk of leukemic evolution and prolonged survival. Using the IPSS, these latter patients are pooled in the less stratified, and therefore more heterogeneous, group of low risk patients. Within patients with a more aggressive disease, the scoring systems show comparable ability to stratify survival and risk of leukemic progression. This suggests that the WPSS provides a more accurate stratification of the patient population diagnosed with the WHO criteria. Two independent cohorts of patients were included in our study, with a median age of 66 and 72 years in the Pavia cohort and the Düsseldorf cohort, respectively. Despite some differences pointed out in the article, the two cohorts of patients were largely comparable, and no significant differences in the characteristics at diagnosis and in overall survival were found between the repeated measures cohort and patients evaluated only at diagnosis. We agree that the median age of the two cohorts is lower than those reported in population-based studies. However, we also believe that relying on patients with a diagnosis of MDS established at a referral center is an important requisite for developing prognostic models. In addition, it should be noted that the median age of the IPSS cohort was 69 years,8 and though it is definitely lower than that of population-based studies, IPSS is currently used worldwide. In conclusion, WPSS provides an accurate prediction of survival and of risk of leukemic evolution in MDS patients as shown by its reproducibility in a completely independent cohort of patients. Nonetheless, we are aware that further validation on different cohorts of MDS patients is warranted to corroborate the validity of our proposal. 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. Alessandrino EP, Amadori S, Barosi G, et al: Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes: A statement from the Italian Society of Hematology. Haematologica 87:1286-1306, 2002 3. Bowen D, Culligan D, Jowitt S, et al: Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol 120:187-200, 2003[CrossRef][Medline] 4. Cheson BD, Greenberg PL, Bennett JM, et al: Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 108:419-425, 2006 5. Vardiman JW: Hematopathological concepts and controversies in the diagnosis and classification of myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program 199-204, 2006 6. 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 7. 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 8. Greenberg P, Cox C, LeBeau MM, et al: International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079-2088, 1997
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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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9 g/dL received regular transfusions. Therefore, the criterion of transfusion-dependency includes all patients with severe anemia, and in addition patients who have moderate but symptomatic anemia. This criterion is in accordance with the definition of clinically relevant transfusion dependency recently proposed in the modified response criteria by the International Working Group (IWG) in MDS.
