Significance of cytogenetic-risk categories and refined international prognostic scoring system for overall survival in primary myelofibrosis: A single-center experience

Vesna Djordjević; Marija  Denčić-Fekete; Jelica  Jovanović; Ivan  Soldatović; Gradimir  Janković; Andrija  Bogdanović

doi:10.2298/VSP171129117D

Vesna Djordjević Clinical Center of Serbia, Clinic of Hematology
Marija Denčić-Fekete Clinical Center of Serbia, Clinic of Hematology
Jelica Jovanović Clinical Center of Serbia, Clinic of Hematology
Ivan Soldatović University of Belgrade, Faculty of Medicine, Institute for Medical Statistics and Informatics
Gradimir Janković Clinical Center of Serbia, Clinic of Hematology
Andrija Bogdanović Clinical Center of Serbia, Clinic of Hematology

DOI: https://doi.org/10.2298/VSP171129117D

Keywords: chromosome aberrations;, cytogenetics;, primary myelofibrosis;, prognosis

Abstract

Background/Aim. Primary myelofibrosis (PMF) is a chronic, malignant hematological disease characterized by a leucoerythroblastic blood picture, anisopoikilocytosis teardrop-shaped erythrocytes, different degrees of bone marrow fibrosis and hepatosplenomegaly due to extramedullary hematopoiesis. Among genetic specificities of the disease, those that stand out are chromosomal aberrations in pathological, myeloid blood cells. The aim of this study was to examine the prognostic significance of clinical, hematologic and cytogenetic parameters in PMF. Methods. A retrospective study included 144 patients with PMF. Karyotypes were analyzed using conventional cytogenetic methods. Results. The chromosome examinations were successful in 126 (88%) patients and failed in the remainder ones (12%). Karyotype was abnormal in 36/126 (29%) subjects at presentation. The most frequent changes included +9, 13q- and 20q- (28%). Other abnormalities were: aberrations of chromosome 18 and 16, deletions (9q-, 12p-, 7q-, 5q-, 6q-, 8q-), trisomies (+1q, +8, +10, +21), monosomies (-7, -11), 3q inversion and loss of Y chromosome. We detected four novel balanced translocations in PMF: t(17;22)(q11;q13), t(15;17)(q22;q25), t(9;12)(q22;q24) and t(2;4)(q21;p16), one constitutional translocation-rob(13;14)(q10;q10) and some new karyotype anomalies ˗ deletion of both homologues, hyperdiploidy and the coexistence of unrelated pathological clones. Conclusion. Chromosomal aberrations had a significant influence on overall survival of patients with PMF according to the refined cytogenetic-risk of the International Prognostic Scoring System (Refined CIPSS) (p = 0.004). Our patients matched the pattern of chromosome aberrations usually observed in PMF but some newly registered, balanced translocations and other rare karyotype anomalies were recorded as well.

References

Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organi-zation criteria and point-of-care diagnostic algorithms. Leu-kemia 2008; 22(1): 14‒22.

Barosi G, Mesa RA, Thiele J, Cervantes F, Campbell PJ, Ver-stovsek S, et al. Proposed criteria for the diagnosis of post- pol-ycythemia vera and post-essential thrombocythemia myelofi-brosis: a consensus statement from International Working Group for myelofibrosis research and treatment. Leukemia 2008; 22(2): 437‒8.

Dupriez B, Morel P, Demory JL, Lai JL, Simon M, Plantier I, et al. Prognostic factors in agnogenic myeloid metaplasia: a re-port on 195 cases with a new scoring system. Blood 1996; 88(3): 1013‒8.

Cervantes F, Pereira A, Esteve J, Rafel M, Cobo F, Rozman C, et al. Identification of ‘short-lived’ and ‘long-lived’ patients at presentation of idiopathic myelofibrosis. Br J Haematol 1997; 97(3): 635‒40.

Djordjevic V, Dencic-Fekete M, Jovanovic J, Bizic S, Jankovic G, Bogdanovic A, et al. Cytogenetics of agnogenic myeloid meta-plasia: a study of 61 patients. Cancer Genet Cytogenet 2007; 173(1): 57‒62.

Reilly JT, Snowden JA, Spearing RL, Fitzgerald PM, Jones N, Watmore A, et al. Cytogenetic abnormalities and their prog-nostic significance in idiopathic myelofibrosis: a study of 106 cases. Br J Haematol 1997; 98(1): 96‒102.

Tefferi A, Dingli D, Li CY, Dewald GW. Prognostic diversity among cytogenetic abnormalities in myelofibrosis with mye-loid metaplasia. Cancer 2005; 104(8): 1656‒60.

Hussein K, Pardanani AD, Van Dyke DL, Hanson CA, Tefferi A. International Prognostic Scoring System-independent cytoge-netic risk categorization in primary myelofibrosis. Blood 2010; 115(3): 496‒9.

Caramazza D, Begna KH, GangatN, Vaidya R, Siragusa S, Van Dyke DL, et al. Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients. Leukemia 2011; 25(1): 82‒8.

Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, et al. New prognostic scoring system for primary myelofi-brosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009; 113(13): 2895‒901.

Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pe-reira A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (Interna-tional Working Group for Myeloproliferative Neoplasms Re-search and Treatment). Blood 2010; 115(9): 1703‒8.

Tefferi A, Huang J, Schwager S, Li CY, Wu W, Pardanani A, et al. Validation and comparison of contemporary prognostic models in primary myelofibrosis: analysis based on 334 pa-tients from a single institution. Cancer 2007; 109(10): 2083‒8.

Elliott MA, Verstovsek S, Dingli D, Schwager SM, Mesa RA, Li CY, et al. Monocytosis is an adverse prognostic factor for sur-vival in younger patients with primary myelofibrosis. Leuk Res 2007; 31(11): 1503‒9.

Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002; 100(7): 2292‒302.

Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organ-ization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114(5): 937–51.

Novak A, Kruškić M, Ludoški M, Jurukovski V. Rapid method for obtaining high-quality chromosome banding in the study of hematopoietic neoplasia. Cancer Genet Cytogenet 1994; 74(2): 109‒14.

Shaffer LG, McGowan-Jordan J, Schmid M. ISCN (2013): An In-ternational System for Human Cytogenetic Nomenclature. Ba-sel, Switzerland: S. Karger; 2013.

Tefferi A, Mesa RA, Schroeder G, Hanson CA, Li CY, Dewald GW. Cytogenetic findings and their clinical relevance in myelofibrosis with myeloid metaplasia. Br J Haematol 2001; 113(3): 763‒71.

Dingli D, Grand FH, Mahaffey V, Spurbeck J, Ross FM, Watmore AE, et al. Der(6)t(1;6)(q21-23;p21.3): a specific cytogenetic abnormality in myelofibrosis with myeloid metaplasia. Br J Haematol 2005; 130(2): 229‒32.

Wassie E, Finke C, Gangat N, Lasho TL, Pardanani A, Hanson CA, et al. A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 pa-tients. Br J Haematol 2015; 169(1): 71‒6.

Hussein K, Van Dyke DL, Tefferi A. Conventional cytogenetics in myelofibrosis: literature review and discussion. Eur J Hae-matol 2009; 82(5): 329‒38.

Djordjević V, Dencić-Fekete M, Jovanović J, Drakulić D, Stevanović M, Janković G, et al. Pattern of trisomy 1q in hematological malignancies: a single institution experience. Cancer Genet Cytogenet 2008; 186(1): 12‒8.

Vardiman JW, Brunning RD, Arber DA, Le Beau MM, Porwit A, Tefferi A, et al. Introduction and overview of the classification of the myeloid neoplasms. In: Swerdlow SH, Campo E, Lee Har-ris N, Jaffe ES, Pileri SA, Stein H, et al, editors. In: World Health Organization (WHO) classification of tumors of haematopoietic and lymphoid tissues. 4th ed. Lyon: Interna-tional agency for research on cancer (IARC); 2008. p. 18‒30.

Sreekantaiah C, Baer MR, Preisler HD, Sandberg AA. Involve-ment of bands 9q21-q22 in five cases of acute nonlymphocyt-ic leukemia. Cancer Genet Cytogenet 1989; 39(1): 55‒64.

Wiktor A, Rybicki BA, Piao ZS, Shurafa M, Barthel B, Maeda K, et al. Clinical significance of Y chromosome loss in hemato-logic disease. Genes Chromosomes Cancer 2000; 27(1): 11‒6.

Welborn J. Constitutional chromosome aberrations as pathoge-netic events in hematologic malignancies. Cancer Genet Cyto-genet 2004; 149(2): 137‒53.

Gilbert HS. Long term treatment of myeloproliferative disease with interferon-alpha-2b: feasibility and efficacy. Cancer 1998; 83(6): 1205‒13.