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International scoring system for evaluating prognosis in myelodysplastic syndromes

P Greenberg, C Cox, MM LeBeau, P Fenaux, P Morel, G Sanz, M Sanz, T Vallespi, T Hamblin, D Oscier, K Ohyashiki, K Toyama, C Aul, G Mufti and J Bennett

Hematology Division, Stanford University Medical Center, CA 94305, USA.

Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems. A global analysis was performed on these patients, and critical prognostic variables were re-evaluated to generate a consensus prognostic system, particularly using a more refined bone marrow (BM) cytogenetic classification. Univariate analysis indicated that the major variables having an impact on disease outcome for evolution to acute myeloid leukemia were cytogenetic abnormalities, percentage of BM myeloblasts, and number of cytopenias; for survival, in addition to the above, variables also included age and gender. Cytogenetic subgroups of outcome were as follows: "good" outcomes were normal, -Y alone, del(5q) alone, del(20q) alone; "poor" outcomes were complex (ie, > or = 3 abnormalities) or chromosome 7 anomalies; and "intermediate" outcomes were other abnormalities. Multivariate analysis combined these cytogenetic subgroups with percentage of BM blasts and number of cytopenias to generate a prognostic model. Weighting these variables by their statistical power separated patients into distinctive subgroups of risk for 25% of patients to undergo evolution to acute myeloid leukemia, with: low (31% of patients), 9.4 years; intermediate-1 (INT- 1; 39%), 3.3 years; INT-2 (22%), 1.1 years; and high (8%), 0.2 year. These features also separated patients into similar distinctive risk groups for median survival: low, 5.7 years; INT-1, 3.5 years; INT-2, 1.2 years; and high, 0.4 year. Stratification for age further improved analysis of survival. Compared with prior risk-based classifications, this International Prognostic Scoring System provides an improved method for evaluating prognosis in MDS. This classification system should prove useful for more precise design and analysis of therapeutic trials in this disease.

Volume 89, Issue 6, pp. 2079-2088, 03/15/1997
Copyright © 1997 by The American Society of Hematology


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S. Park, S. Grabar, C. Kelaidi, O. Beyne-Rauzy, F. Picard, V. Bardet, V. Coiteux, G. Leroux, P. Lepelley, M.-T. Daniel, et al.
Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience
Blood, January 15, 2008; 111(2): 574 - 582.
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M. Cazzola, M. G. Della Porta, and L. Malcovati
Clinical Relevance of Anemia and Transfusion Iron Overload in Myelodysplastic Syndromes
Hematology, January 1, 2008; 2008(1): 166 - 175.
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A. Raza, J. A. Reeves, E. J. Feldman, G. W. Dewald, J. M. Bennett, H. J. Deeg, L. Dreisbach, C. A. Schiffer, R. M. Stone, P. L. Greenberg, et al.
Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q
Blood, January 1, 2008; 111(1): 86 - 93.
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BloodHome page
D. Haase, U. Germing, J. Schanz, M. Pfeilstocker, T. Nosslinger, B. Hildebrandt, A. Kundgen, M. Lubbert, R. Kunzmann, A. A. N. Giagounidis, et al.
New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients
Blood, December 15, 2007; 110(13): 4385 - 4395.
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Clin. Cancer Res.Home page
M. Grovdal, R. Khan, A. Aggerholm, P. Antunovic, J. Astermark, P. Bernell, L.-M. Engstrom, L. Kjeldsen, O. Linder, L. Nilsson, et al.
Negative Effect of DNA Hypermethylation on the Outcome of Intensive Chemotherapy in Older Patients with High-Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia following Myelodysplastic Syndrome
Clin. Cancer Res., December 1, 2007; 13(23): 7107 - 7112.
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A. Mohamedali, J. Gaken, N. A. Twine, W. Ingram, N. Westwood, N. C. Lea, J. Hayden, N. Donaldson, C. Aul, N. Gattermann, et al.
Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes
Blood, November 1, 2007; 110(9): 3365 - 3373.
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The OncologistHome page
S. D. Ross, I. E. Allen, C. A. Probst, B. Sercus, S. M. Crean, and G. Ranganathan
Efficacy and Safety of Erythropoiesis-Stimulating Proteins in Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis
Oncologist, October 1, 2007; 12(10): 1264 - 1273.
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JCOHome page
M. L. Sorror, B. M. Sandmaier, B. E. Storer, M. B. Maris, F. Baron, D. G. Maloney, B. L. Scott, H. J. Deeg, F. R. Appelbaum, and R. Storb
Comorbidity and Disease Status Based Risk Stratification of Outcomes Among Patients With Acute Myeloid Leukemia or Myelodysplasia Receiving Allogeneic Hematopoietic Cell Transplantation
J. Clin. Oncol., September 20, 2007; 25(27): 4246 - 4254.
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C. Chang, B. E. Storer, B. L. Scott, E. M. Bryant, H. M. Shulman, M. E. Flowers, B. M. Sandmaier, R. P. Witherspoon, R. A. Nash, J. E. Sanders, et al.
Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders
Blood, August 15, 2007; 110(4): 1379 - 1387.
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L. Malcovati, U. Germing, A. Kuendgen, M. G. Della Porta, C. Pascutto, R. Invernizzi, A. Giagounidis, B. Hildebrandt, P. Bernasconi, S. Knipp, et al.
Time-Dependent Prognostic Scoring System for Predicting Survival and Leukemic Evolution in Myelodysplastic Syndromes
J. Clin. Oncol., August 10, 2007; 25(23): 3503 - 3510.
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T. Siitonen, T. Timonen, E. Juvonen, V. Terava, A. Kutila, T. Honkanen, M. Mikkola, H. Hallman, M. Kauppila, P. Nylanden, et al.
Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes
Haematologica, August 1, 2007; 92(8): 1119 - 1122.
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U. Germing, C. Strupp, S. Knipp, A. Kuendgen, A. Giagounidis, B. Hildebrandt, C. Aul, R. Haas, N. Gattermann, and J. M. Bennett
Chronic myelomonocytic leukemia in the light of the WHO proposals
Haematologica, July 1, 2007; 92(7): 974 - 977.
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D. P. Steensma
The spectrum of molecular aberrations in myelodysplastic syndromes: in the shadow of acute myeloid leukemia
Haematologica, June 1, 2007; 92(6): 723 - 727.
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U. Bacher, T. Haferlach, W. Kern, C. Haferlach, and S. Schnittger
A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia
Haematologica, June 1, 2007; 92(6): 744 - 752.
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P. Fenaux, A. Raza, G. J. Mufti, C. Aul, U. Germing, H. Kantarjian, L. Cripe, R. Kerstens, P. De Porre, and R. Kurzrock
A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome
Blood, May 15, 2007; 109(10): 4158 - 4163.
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E. Estey
Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Patients
J. Clin. Oncol., May 10, 2007; 25(14): 1908 - 1915.
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M. Y. Follo, S. Mongiorgi, C. Bosi, A. Cappellini, C. Finelli, F. Chiarini, V. Papa, M. Libra, G. Martinelli, L. Cocco, et al.
The Akt/Mammalian Target of Rapamycin Signal Transduction Pathway Is Activated in High-Risk Myelodysplastic Syndromes and Influences Cell Survival and Proliferation
Cancer Res., May 1, 2007; 67(9): 4287 - 4294.
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Cancer Res.Home page
Y. A. Boumber, Y. Kondo, X. Chen, L. Shen, V. Gharibyan, K. Konishi, E. Estey, H. Kantarjian, G. Garcia-Manero, and J.-P. J. Issa
RIL, a LIM Gene on 5q31, Is Silenced by Methylation in Cancer and Sensitizes Cancer Cells to Apoptosis
Cancer Res., March 1, 2007; 67(5): 1997 - 2005.
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Proc. Natl. Acad. Sci. USAHome page
M. Aivado, D. Spentzos, U. Germing, G. Alterovitz, X.-Y. Meng, F. Grall, A. A. N. Giagounidis, G. Klement, U. Steidl, H. H. Otu, et al.
From the cover: Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease
PNAS, January 23, 2007; 104(4): 1307 - 1312.
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Proc. Natl. Acad. Sci. USAHome page
A. Ganser, M. A. Morgan, and E. M. Weissinger
Going from genes to proteins in myelodysplastic syndromes
PNAS, January 23, 2007; 104(4): 1109 - 1110.
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W. Barcellini, A. Zaninoni, F. G. Imperiali, C. Boschetti, M. Colombi, A. Iurlo, and A. Zanella
Anti-erythroblast autoimmunity in early myelodysplastic syndromes
Haematologica, January 1, 2007; 92(1): 19 - 26.
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J. Pedersen-Bjergaard, M. T. Andersen, and M. K. Andersen
Genetic Pathways in the Pathogenesis of Therapy-Related Myelodysplasia and Acute Myeloid Leukemia
Hematology, January 1, 2007; 2007(1): 392 - 397.
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M. Melchert and A. F. List
Management of RBC-Transfusion Dependence
Hematology, January 1, 2007; 2007(1): 398 - 404.
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G. Garcia-Manero
Modifying the Epigenome as a Therapeutic Strategy in Myelodysplasia
Hematology, January 1, 2007; 2007(1): 405 - 411.
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K. Shannon and L. R. Silverman
Myelodysplastic syndrome and overlap syndromes
ASH Self-Assessment Program, January 1, 2007; 2007(1): 228 - 242.
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BloodHome page
T. A. Navas, M. Mohindru, M. Estes, J. Y. Ma, L. Sokol, P. Pahanish, S. Parmar, E. Haghnazari, L. Zhou, R. Collins, et al.
Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors
Blood, December 15, 2006; 108(13): 4170 - 4177.
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A. Kuendgen, C. Strupp, M. Aivado, B. Hildebrandt, R. Haas, N. Gattermann, and U. Germing
Myelodysplastic Syndromes in Patients Younger Than Age 50
J. Clin. Oncol., December 1, 2006; 24(34): 5358 - 5365.
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NEJMHome page
A. List, G. Dewald, J. Bennett, A. Giagounidis, A. Raza, E. Feldman, B. Powell, P. Greenberg, D. Thomas, R. Stone, et al.
Lenalidomide in the Myelodysplastic Syndrome with Chromosome 5q Deletion
N. Engl. J. Med., October 5, 2006; 355(14): 1456 - 1465.
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A. Agool, B. W. Schot, P. L. Jager, and E. Vellenga
18F-FLT PET in Hematologic Disorders: A Novel Technique to Analyze the Bone Marrow Compartment
J. Nucl. Med., October 1, 2006; 47(10): 1592 - 1598.
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H. Szpurka, R. Tiu, G. Murugesan, S. Aboudola, E. D. Hsi, K. S. Theil, M. A. Sekeres, and J. P. Maciejewski
Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation
Blood, October 1, 2006; 108(7): 2173 - 2181.
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R. Martino, S. Iacobelli, R. Brand, T. Jansen, A. van Biezen, J. Finke, A. Bacigalupo, D. Beelen, J. Reiffers, A. Devergie, et al.
Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes
Blood, August 1, 2006; 108(3): 836 - 846.
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K. Ogata, Y. Kishikawa, C. Satoh, H. Tamura, K. Dan, and A. Hayashi
Diagnostic application of flow cytometric characteristics of CD34+ cells in low-grade myelodysplastic syndromes
Blood, August 1, 2006; 108(3): 1037 - 1044.
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B. D. Cheson, P. L. Greenberg, J. M. Bennett, B. Lowenberg, P. W. Wijermans, S. D. Nimer, A. Pinto, M. Beran, T. M. de Witte, R. M. Stone, et al.
Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia
Blood, July 15, 2006; 108(2): 419 - 425.
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A. Pellagatti, M. Cazzola, A. A. N. Giagounidis, L. Malcovati, M. G. D. Porta, S. Killick, L. J. Campbell, L. Wang, C. F. Langford, C. Fidler, et al.
Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype
Blood, July 1, 2006; 108(1): 337 - 345.
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Cancer Res.Home page
S. D. Gore, S. Baylin, E. Sugar, H. Carraway, C. B. Miller, M. Carducci, M. Grever, O. Galm, T. Dauses, J. E. Karp, et al.
Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms.
Cancer Res., June 15, 2006; 66(12): 6361 - 6369.
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T. Buchner, W. E. Berdel, C. Schoch, T. Haferlach, H. L. Serve, J. Kienast, S. Schnittger, W. Kern, J. Tchinda, A. Reichle, et al.
Double Induction Containing Either Two Courses or One Course of High-Dose Cytarabine Plus Mitoxantrone and Postremission Therapy by Either Autologous Stem-Cell Transplantation or by Prolonged Maintenance for Acute Myeloid Leukemia
J. Clin. Oncol., June 1, 2006; 24(16): 2480 - 2489.
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R. M. Stone
Is Intravenous Arsenic Trioxide a Useful Therapy in Myelodysplastic Syndromes?
J. Clin. Oncol., June 1, 2006; 24(16): 2414 - 2416.
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J. K. Davies, D. C. Taussig, H. Oakervee, A. J. Davies, S. G. Agrawal, J. G. Gribben, T. A. Lister, and J. D. Cavenagh
Long-Term Follow-Up After Reduced-Intensity Conditioning Allogeneic Transplantation for Acute Myeloid Leukemia/Myelodysplastic Syndrome: Late CNS Relapses Despite Graft-Versus-Host Disease
J. Clin. Oncol., May 10, 2006; 24(14): e23 - e25.
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