Bone marrow blasts level predicts prognosis in patients with refractory cytopenia with multilineage dysplasia
Hong Wang
Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China
Search for more papers by this authorXiao-Qin Wang
Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China
Search for more papers by this authorXiao-Ping Xu
Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China
Search for more papers by this authorGuo-Wei Lin
Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China
Search for more papers by this authorHong Wang
Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China
Search for more papers by this authorXiao-Qin Wang
Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China
Search for more papers by this authorXiao-Ping Xu
Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China
Search for more papers by this authorGuo-Wei Lin
Department of Hematology, Huashan Hospital of Fudan University, Shanghai, China
Search for more papers by this authorAbstract
Objectives: Current prognostic models for myelodysplastic syndrome (MDS) do not consider the prognostic value of a bone marrow blast level that is <5%. Exploring the prognostic value of the International Prognostic Scoring System (IPSS) and a marrow blast level that is <5% may lead to better risk-adapted therapeutic strategies.
Methods: According to the World Health Organization classification, most of our patients (65.5%) fell into the new category ‘refractory cytopenia with multilineage dysplasia’ (RCMD). We evaluated the prognostic value of the IPSS in 435 adult patients with de novo MDS and in the 285 of them that had RCMD in a Chinese population. We also analyzed the prognostic value of bone marrow blast levels in patients with RCMD and in different IPSS risk groups.
Results: We found a significant difference in survival times between RCMD patients with a marrow blast level of 3.5% or higher vs. those with a blast level of <3.5%, with median survival times of 23.7 and 40.8 months, respectively. In addition, application of a marrow blast level cutoff of 3.5% in patients with RCMD could identify patients with a lower IPSS risk but with a potentially worse prognosis. Multivariate analysis showed marrow blast level (using 3.5% as the cutoff) to be an independent factor that impacted survival times of patients with RCMD. Furthermore, we also found that IPSS had strong prognostic value in Chinese RCMD population.
Conclusion: In patients with RCMD, a higher percentage of marrow blasts was associated with a worse prognosis.
References
- 1 Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189–99.
- 2 Boultwood J, Lewis S, Wainscoat JS. The 5q-syndrome. Blood 1994; 84: 3253–60.
- 3 Rosati S, Mick R, Xu F, Stonys E, Le Beau MM, Larson R, Vardiman JW. Refractory cytopenia with multilineage dysplasia: further characterization of an ‘unclassifiable’ myelodysplastic syndrome. Leukemia 1996; 10: 20–6.
- 4 Michaux JL, Martiat P. Chronic myelomonocytic leukaemia (CMML) – a myelodysplastic or myeloproliferative syndrome? Leuk Lymphoma 1993; 9: 35–41.
- 5 Verhoef GE, Pittaluga S, De Wolf-Peeters C, Boogaerts MA. FAB classification of myelodysplastic syndromes: merits and controversies. Ann Hematol 1995; 71: 3–11.
- 6 Chronic myelomonocytic leukemia: single entity or heterogeneous disorder? A prospective multicenter study of 100 patients. Groupe Francais de Cytogenetique Hematologique. Cancer Genet Cytogenet 1991; 55: 57–65.
- 7 Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D. Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 1985; 59: 425–33.
- 8 Sanz GF, Sanz MA, Vallespi T, Canizo MC, Torrabadella M, Garcia S, Irriguible D, San Miguel JF. 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 1989; 74: 395–408.
- 9 Morel P, Hebbar M, Lai JL, Duhamel A, Preudhomme C, Wattel E, Bauters F, Fenaux P. 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 1993; 7: 1315–23.
- 10 Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–88.
- 11 Estey E, Keating M, Pierce S, Beran M. Application of the International Scoring System for myelodysplasia to M.D. Anderson patients. Blood 1997; 90: 2843–6.
- 12 Pfeilstocker M, Reisner R, Nosslinger T, Gruner H, Nowotny H, Tuchler H, Schlogl E, Pittermann E, Heinz R. Cross-validation of prognostic scores in myelodysplastic syndromes on 386 patients from a single institution confirms importance of cytogenetics. Br J Haematol 1999; 106: 455–63.
- 13
Takahashi M,
Takahashi H,
Aizawa Y,
Koike T.
Usefulness of IPSS for the patients with refractory anemia.
Am J Hematol
1998; 58: 250–2.
10.1002/(SICI)1096-8652(199807)58:3<250::AID-AJH23>3.0.CO;2-C CAS PubMed Web of Science® Google Scholar
- 14 Sole F, Espinet B, Sanz GF, et al. Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Espanol de Citogenetica Hematologica. Br J Haematol 2000; 108: 346–56.
- 15 Navarro I, Ruiz MA, Cabello A, et al. Classification and scoring systems in myelodysplastic syndromes: a retrospective analysis of 311 patients. Leuk Res 2006; 30: 971–7.
- 16 ES Jaffe, NL Harris, H Stein, JW Vardiman (eds). Tumours of Haematopoietic and Lymphoid Tissues. World Health Organization Classification of Tumours. Lyon: IARC press, 2001.
- 17 Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002; 100: 2292–302.
- 18 Germing U, Gattermann N, Aivado M, Hildebrandt B, Aul C. Two types of acquired idiopathic sideroblastic anaemia (AISA): a time-tested distinction. Br J Haematol 2000; 108: 724–8.
- 19 Balduini CL, Guarnone R, Pecci A, Centenara E, Ascari E. Multilineage dysplasia without increased blasts identifies a poor prognosis subset of myelodysplastic syndromes. Leukemia 1998; 12: 1655–6.
- 20 Garand R, Gardais J, Bizet M, Bremond JL, Accard F, Callat MP, De Bouchony ET, Goasguen JE. Heterogeneity of acquired idiopathic sideroblastic anaemia (AISA). Leuk Res 1992; 16: 463–8.
- 21 Gattermann N, Aul C, Schneider W. Two types of acquired idiopathic sideroblastic anaemia (AISA). Br J Haematol 1990; 74: 45–52.
- 22 Germing U, Gattermann N, Strupp C, Aivado M, Aul C. Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 2000; 24: 983–92.
- 23 Howe RB, Porwit-MacDonald A, Wanat R, Tehranchi R, Hellstrom-Lindberg E. The WHO classification of MDS does make a difference. Blood 2004; 103: 3265–70.
- 24 Irons RD, Wang X, Gross SA, et al. Prevalence of MDS subtypes in Shanghai, China: a comparison of the World Health Organization and French American British classifications. Leuk Res 2006; 30: 769–75.
- 25 Pozdnyakova O, Miron PM, Tang G, Walter O, Raza A, Woda B, Wang SA. Cytogenetic abnormalities in a series of 1,029 patients with primary myelodysplastic syndromes: a report from the US with a focus on some undefined single chromosomal abnormalities. Cancer 2008; 113: 3331–40.
- 26 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 2005; 23: 7594–603.
- 27 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 2007; 25: 3503–10.
- 28 Sole F, Luno E, Sanzo C, et al. Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes. Haematologica 2005; 90: 1168–78.
- 29 Lorand-Metze I, Pinheiro MP, Ribeiro E, De Paula EV, Metze K. Factors influencing survival in myelodysplastic syndromes in a Brazilian population: comparison of FAB and WHO classifications. Leuk Res 2004; 28: 587–94.
- 30 Bernasconi P, Klersy C, Boni M, et al. World Health Organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes. Br J Haematol 2007; 137: 193–205.
- 31 Mitelman F (ed.). An International System for Human Cytogenetic Nomenclature (ISCN). Basel: S. Karger, 1995.
- 32 Ogata K, Satoh C, Hyodo H, Tamura H, Dan K, Yoshida Y. Association between phenotypic features of blasts and the blast percentage in bone marrow of patients with myelodysplastic syndromes. Leuk Res 2004; 28: 1171–5.
- 33 Fenaux P. Chromosome and molecular abnormalities in myelodysplastic syndromes. Int J Hematol 2001; 73: 429–37.
- 34 Fenaux P, Morel P, Lai JL. Cytogenetics of myelodysplastic syndromes. Semin Hematol 1996; 33: 127–38.
- 35 Haase D, Germing U, Schanz J, 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 2007; 110: 4385–95.
- 36 Lee JH, Shin YR, Lee JS, Kim WK, Chi HS, Park CJ, Seo EJ, Lee KH. Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome. Leukemia 2003; 17: 305–13.
- 37 Matsuda A, Germing U, Jinnai I, et al. Difference in clinical features between Japanese and German patients with refractory anemia in myelodysplastic syndromes. Blood 2005; 106: 2633–40.
- 38 Li L, Liu XP, Nie L, Yu MH, Zhang Y, Qin TJ, Xiao ZJ. Unique cytogenetic features of primary myelodysplastic syndromes in Chinese patients. Leuk Res 2009; 33: 1194–8.
- 39 Chen B, Zhao WL, Jin J, et al. Clinical and cytogenetic features of 508 Chinese patients with myelodysplastic syndrome and comparison with those in Western countries. Leukemia 2005; 19: 767–75.
- 40 Bernasconi P, Klersy C, Boni M, et al. Incidence and prognostic significance of karyotype abnormalities in de novo primary myelodysplastic syndromes: a study on 331 patients from a single institution. Leukemia 2005; 19: 1424–31.
- 41 Liu YC, Ito Y, Hsiao HH, Sashida G, Kodama A, Ohyashiki JH, Ohyashiki K. Risk factor analysis in myelodysplastic syndrome patients with del(20q): prognosis revisited. Cancer Genet Cytogenet 2006; 171: 9–16.
- 42 De Souza Fernandez T, Ornellas MH, Otero de Carvalho L, Tabak D, Abdelhay E. Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia. Leuk Res 2000; 24: 839–48.
- 43 Wang XQ, Chen ZX, Chen SC, Lin GW, Ji MR, Liang JY, Liu DD, Li DG, Ma Y. Prognostic analysis of refractory anaemia in adult myelodysplastic syndromes. Chin Med J (Engl) 2008; 121: 1787–91.
- 44 Smith SM, Le Beau MM, Huo D, Karrison T, Sobecks RM, Anastasi J, Vardiman JW, Rowley JD, Larson RA. Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood 2003; 102: 43–52.
- 45 Pedersen-Bjergaard J, Pedersen M, Roulston D, Philip P. Different genetic pathways in leukemogenesis for patients presenting with therapy-related myelodysplasia and therapy-related acute myeloid leukemia. Blood 1995; 86: 3542–52.
- 46 Mauritzson N, Albin M, Rylander L, et al. Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001. Leukemia 2002; 16: 2366–78.
- 47 Le Beau MM, Albain KS, Larson RA, Vardiman JW, Davis EM, Blough RR, Golomb HM, Rowley JD. Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7. J Clin Oncol 1986; 4: 325–45.