Adult; Aged; Bone Marrow/pathology; Female; Humans; Male; Middle Aged; Myelodysplastic Syndromes/mortality/pathology/physiopathology; Predictive Value of Tests; Prognosis; Survival Analysis
Abstract :
[en] Marrow dysplasia is a major characteristic of patients with myelodysplastic syndrome (MDS), along with marrow blastosis, cytopenia and cytogenetic anomalies. However, the impact of the degree of marrow dysplasia on survival has not been fully assessed. In this retrospective analysis of 111 patients selected according to the IPSS criteria of MDS diagnosis, the presence or absence of 21 dysplasia characteristics recognizable in bone marrow smears stained by the May-Grunwald-Giemsa method was correlated with patient survival. Using Cox proportional hazards regression analysis, megaloblastosis (MEGALO), neutrophil agranularity (AGRAN) and hypogranularity (HYPOGRAN) were highly significant predictors (p < 0.005), and Pelger-Huet anomaly (PELGHUET) a significant predictor (p = 0.05), of patient survival. The regression analysis yielded a dysplasia-based risk index (DI) where DI = 1.26 MEGALO + 0.82 AGRAN - 1.08 HYPOGRAN + 0.45 PELGHUET. The two subgroups of 60 and 47 patients with DI < or = 0 and > 0 showed highly significant differences in median survivals (2.6 vs 1.1 yrs; p <0.0001). Multivariate analysis further showed that DI offered additional predictive power that was independent of that provided by the IPSS (p=0.002 and 0.001 respectively). Analysis of survival curves stratified for IPSS and DI showed that the additional predictive power offered by inclusion of the DI essentially concerned the IPSS low/INT-1 risk categories. Further stratification for age did not improve survival prediction. The data indicate that a set of 4 dysplasia parameters can offer some prediction for survival of MDS patients in addition to that provided by the IPSS. Further multicenter studies should aim at including some form of evaluation of the degree of dysplasia in prognostic systems.
Disciplines :
Hematology
Author, co-author :
Tassin, Françoise ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Dewé, Walthère ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments - Département de mathématique
Schaaf-Lafontaine, Nicole ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Herens, Christian ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Ravoet, C.
Albert, Adelin ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique - Département de mathématique
Beguin, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Paulus, Jean-Michel ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Language :
English
Title :
A four-parameter index of marrow dysplasia has predictive value for survival in myelodysplastic syndromes.
Anastasi J. (1996) Molecular cytogenetics and the myelodysplastic syndromes. Leukemia Research, 20, 559-62.
Raza A, Gezer S, Mundle S, et al. (1995) Apoptosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes. Blood, 86, 268-76.
Rajapaksa R, Ginzton N, Rott LS, Greenberg PL. (1996) Altered oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells. Blood, 88, 4275-87.
Barosi G, Cazzola M, Morandi S, Stefanelli M, Perugini S. (1978) Estimation of ferrokinetic parameters by a mathematical model in patients with primary acquired sideroblastic anaemia. British Journal of Haematology, 39, 409-23.
Cazzola M, Barosi G, Berzuini C, et al. (1982) Quantitative evaluation of erythropoietic activity in dysmyelopoietic syndromes. British Journal of Haematology, 50, 55-62.
May SJ, Smith SA, Jacobs A, Williams A, Bailey-Wood R. (1985) The myelodysplastic syndrome : analysis of laboratory characteristics in relation to the FAB classification. British Journal of Haematology, 59, 311-9.
Brada S, de Wolf J, Hendriks D, Louwes H, Van den berg E, Vellenga E. (1998) Characterization of the erythropoiesis in myelodysplasia by means of ferrokinetic studies, in vitro erythroid colony formation and soluble transferrin receptor. Leukemia, 12, 340-5.
Raskind WH, Tirumali N, Jacobson R, Singer J, Fialkow PJ. (1984) Evidence for a multistep pathogenesis of a myelodysplastic syndrome. Blood, 63, 1318-23.
Mufti GJ. (1992) Chromosomal deletions in the myelodysplastic syndrome. Leukemia Research, 16, 35-41.
San Miguel JF, Hernandez JM, Gonzalez-Sarmiento R, et al. (1991) Acute leukemia after a primary myelodysplastic syndrome : immunophenotypic, genotypic, and clinical characteristics. Blood, 78, 768-74.
Greenberg P, Cox C, LeBeau MM, et al. (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood, 89, 2079-88.
Bennett JM, Catovsky D, Daniel MT, et al. (1982) Proposals for the classification of the myelodysplastic syndromes. British Journal of Haematology, 51, 189-99.
Coiffier B, Adeleine P, Viala JJ, et al. (1983) Dysmyelopoietic syndromes. A search for prognostic factors. Cancer, 52, 83-90.
Varela BL, Chuang C, Woll JE, Bennett JM. (1985) Modifications in the classification of primary myelodysplastic syndromes : the addition of a scoring system. Hematological Oncology, 3, 55-63.
Kerkhofs H, Hermans J, Haak HL, Leeksma C. (1987) Utility of the FAB classification for myelodysplastic syndromes: investigation of prognostic factors in 237 cases. British Journal of Haematology, 65, 73-81.
Economopoulos T, Stathakis N, Foudoulakis A, et al. (1987) Myelodysplastic syndromes: analysis of 131 cases according to the FAB classification. European Journal of Haematology, 38, 338-44.
Coiffier B, Adeleine P, Gentilhomme O, Felman P, Treille-Ritouet D, Bryon PA. (1987) Myelodysplastic syndromes. A multiparametric study of prognostic factors in 336 patients. Cancer, 60, 3029-32.
Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D. (1985) Myelodysplastic syndromes: a scoring system with prognostic significance. British Journal of Haematology, 59, 425-33.
Sanz GF, Sanz MA, Vallespi T, et al. (1989) Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes : a multivariate analysis of prognostic factors in 370 patients. Blood, 74, 395-408.
Goasguen JE, Garand R, Bizet M, et al. (1990) Prognostic factors of myelodysplastic syndromes : a simplified 3-D scoring system. Leukemia Research, 14, 255-62.
Second MIC Cooperative Study Group. (1988) Morphologic, immunologic, and cytogenetic (MIC) working classification of the acute myeloid leukemias. Cancer Genetics and Cytogenetics, 30, 1-15.
Yunis JJ, Lobell M, Arnesen MA, et al. (1988) Refined chromosome study helps define prognostic subgroups in most patients with primary myelodysplastic syndrome and acute myelogenous leukaemia. British Journal of Haematology, 68, 189-94.
Suciu S, Kuse R, Weh HJ, Hossfeld DK. (1990) Results of chromosome studies and their relation to morphology, course, and prognosis in 120 patients with de novo myelodysplastic syndrome. Cancer Genetics and Cytogenetics, 44, 15-26.
Toyama K, Ohyashiki K, Yoshida Y, et al. (1993) Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes : a multicentric study in Japan. Leukemia, 7, 499-508.
Morel P, Hebbar M, Lai JL, et al. (1993) Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system : a report on 408 cases. Leukemia, 7, 1315-23.
Jotterand M, Parlier V. (1996) Diagnostic and prognostic significance of cytogenetics in adult primary myelodysplastic syndromes. Leukemia and Lymphoma, 23, 253-66.
Fenaux P, Morel P, Lai JL. (1996) Cytogenetics of myelodysplastic syndromes. Seminars in Hematology, 33, 127-38.
Mufti GJ. (1992) A guide to risk assessment in the primary myelodysplastic syndrome. Hematology and Oncology Clinics of North America, 6, 587-606.
Estey E, Keating M, Pierce S, Beran M. (1997) Application of the international scoring system for myelodysplasia to M.D. Anderson patients. Blood, 90, 2843-4.
Greenberg P, LeBeau MM, Fenaux P, et al. (1997) Application of the international scoring system for myelodysplasia to M.D. Anderson patients : response to Estey et al. Blood, 90, 2844-5.
Langenhuijsen M. (1984) Neutrophils with ring-shaped nuclei in myeloproliferative disease. British Journal of Haematology, 58, 227-30.
Kuriyama K, Tomonaga M, Matsuo T, Ginnai I, Ichimaru M. (1986) Diagnostic significance of detecting pseudo-Pelger-Huët anomalies and micromegakaryocytes in myelodysplastic syndrome. British Journal of Haematology, 63, 665-9.
Teerenhovi L, Lintula R, Ruutu T, Knuutila S. (1987) Correlation between bone marrow karyotype and the occurence of erythroblast micronuclei and nuclear budding in patients with myelodysplastic syndromes. European Journal of Haematology, 39, 237-40.
Felman P, Bryon PA, Gentilhomme O, et al. (1988) The syndrome of abnormal chromatin clumping in leucocytes : a myelodysplastic disorder with proliferative features? British Journal of Haematology, 70, 49-54.
van der Weide M, Sizoo W, Krefft J, Langenhuijsen MM. (1988) Myelodysplastic syndromes : analysis of morphological features related to the FAB-classification. European Journal of Haematology, 41, 58-61.
Garcia S, Sanz MA, Amigo V, et al. (1988) Prognostic factors in chronic myelodysplastic syndromes : a multivariate analysis in 107 cases. American Journal of Hematology, 27, 163-8.
Hast R, Nilsson I, Widell S, Öst A. (1989) Diagnostic significance of dysplastic features of peripheral blood polymorphs in myelodysplastic syndromes. Leukemia Research, 13, 173-8.
Jaen A, Irriguible D, Milla F, et al. (1990) Abnormal chromatin clumping in leucocytes: a clue to a new subtype of myelodysplastic syndrome. European Journal of Haematology, 45, 209-14.
Goasguen JE, Bennett JM, Cox C, Hambley H, Mufti G, Flandrin G. (1991) Prognostic implication and characterization of the blast cell population in the myelodysplastic syndrome. Leukemia Research, 15, 1159-65.
Wong KF, Chan J. (1991) Are "dysplastic" and hypogranular megakaryocytes specific markers for myelodysplastic syndrome? British Journal of Haematology, 77, 509-14.
Aul C, Gattermann N, Heyll A, Germing U, Derigs G, Schneider W. (1992) Primary myelodysplastic syndromes : analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia, 6, 52-9.
Bartl R, Frisch B, Baumgart R. (1992) Morphologic classification of the myelodysplastic syndromes (MDS): combined utilization of bone marrow aspirates and trephine biopsies. Leukemia Research, 16, 15-33.
Widell S, Hellström-Lindberg E, Kock Y, Lindberg M, Öst A, Hast R. (1995) Peripheral blood neutrophil morphology reflects bone marrow dysplasia in myelodysplastic syndromes. American Journal of Hematology, 49, 115-20.
Mazzone A, Porta C, Fossati G, Gritti D, Mazzucchelli I, Ricevuti G. (1996) Granulocyte dysplasia and dysfunction, and CD11/CD18 defects in myelodysplastic syndromes. Leukemia and Lymphoma, 23, 267-75.
Kouides PA, Bennett JM. (1996) Morphology and classification of the myelodysplastic syndromes and their pathologic variants. Seminars in Hematology, 33, 95-110.
Kapff CT and Jandl JH. (1981) Blood: Atlas and Sourcebook of Hematology, 1st edn, p.20. Boston: Little, Brown and Company.
Mitelman F. (ed) (1995) ISCN (1995) An International System for Human Cytogenetic Nomenclature. Basel, Switzerland: Karger.
Cohen J. (1960) A coefficient of agreement for nominal scales. Educational and Psychological Measurement, 20, 37-46.
Cox D. (1972) Regression models and life tables. Journal of the Royal Statistical Society, 34, 187-220.
Flandrin G. (1995) Haematological cytology image bank and teletransmission for microscopic diagnosis. Archives d'Anatomie et de Cytologie Pathologiques, 43, 257-61.