Impact of unbalanced minor route versus major route karyotypes at diagnosis on prognosis of CML

被引:56
作者
Fabarius, Alice [1 ]
Kalmanti, Lida [1 ]
Dietz, Christian T. [1 ]
Lauseker, Michael [2 ]
Rinaldetti, Sebastien [1 ]
Haferlach, Claudia [3 ]
Goehring, Gudrun [4 ]
Schlegelberger, Brigitte [4 ]
Jotterand, Martine [5 ]
Hanfstein, Benjamin [1 ]
Seifarth, Wolfgang [1 ]
Haenel, Mathias [6 ]
Koehne, Claus-Henning [7 ]
Lindemann, Hans W. [8 ]
Berdel, Wolfgang E. [9 ]
Staib, Peter [10 ]
Mueller, Martin C. [1 ]
Proetel, Ulrike [1 ]
Balleisen, Leopold [11 ]
Goebeler, Maria-Elisabeth [12 ]
Dengler, Jolanta [13 ]
Falge, Christiane [14 ]
Kanz, Lothar [15 ]
Burchert, Andreas [16 ]
Kneba, Michael [17 ]
Stegelmann, Frank [18 ]
Pfreundschuh, Michael [19 ]
Waller, Cornelius F. [20 ]
Spiekermann, Karsten [21 ]
Bruemmendorf, Tim H. [22 ]
Edinger, Matthias [23 ]
Hofmann, Wolf-Karsten [1 ]
Pfirrmann, Markus [2 ]
Hasford, Joerg [2 ]
Krause, Stefan [24 ]
Hochhaus, Andreas [25 ]
Saussele, Susanne [1 ]
Hehlmann, Ruediger [1 ]
机构
[1] Heidelberg Univ, Med Fak Mannheim, Med Univ Klin 3, D-68169 Mannheim, Germany
[2] Univ Munich, Inst Med Informat Verarbeitung Biometrie & Epidem, Munich, Germany
[3] MLL Munchner Leukamielab, Munich, Germany
[4] Hannover Med Sch, Inst Human Genet, D-30623 Hannover, Germany
[5] CHU Vaudois, Serv Genet Med, CH-1011 Lausanne, Switzerland
[6] Klinikum Chemnitz, Innere Med Klin 3, Chemnitz, Germany
[7] Klinikum Oldenburg, Klin Onkol & Hamatol, Oldenburg, Germany
[8] St Marien Hosp Hagen, Klin Hamatol & Onkol, Hagen, Germany
[9] Univ Klinikum Munster, Med Klin A, Munster, Germany
[10] St Antonius Hosp, Klin Hamatol & Onkol, Eschweiler, Germany
[11] Evangel Krankenhaus Hamm, Hamatol Onkol Abt, Hamm, Germany
[12] Univ Klinikum Wurzburg, Med Klin & Poliklin 2, Wurzburg, Germany
[13] Univ Klinikum Heidelberg, Med Klin, Abt Innere Med 5, Heidelberg, Germany
[14] Klinikum Nurnberg Nord, Med Klin 5, Nord, Germany
[15] Univ Klinikum Tubingen, Abt 2, Med Klin, Tubingen, Germany
[16] Univ Klinikum Marburg, Klin Innere Med Schwerpunkt Hamatol Onkol & Immun, Marburg, Germany
[17] Univ Klinikum Schleswig Holstein, Med Klin & Poliklin 2, Kiel, Germany
[18] Univ Ulm Klinikum, Innere Med Klin 3, Ulm, Germany
[19] Univ Klinikum Saarlandes, Innere Med Klin 1, Homburg, Germany
[20] Univ Freiburg Klinikum, Innere Med Abt 1, Freiburg, Germany
[21] Univ Klinikum Munchen, Med Klin & Poliklin 3, Munich, Germany
[22] Uniklin RWTH Aachen, Med Klin 4, D-52062 Aachen, Germany
[23] Univ Kliniken Regensburg, Klin & Poliklin Innere Med 3, Regensburg, Germany
[24] Univ Klinikum Erlangen, Med Klin 5, Erlangen, Germany
[25] Univ Klinikum Jena, Hamatol Onkol Abt, Jena, Germany
关键词
Chronic myeloid leukaemia; Balanced and unbalanced karyotypes; Cytogenetics; Prognosis; Outcome; CHRONIC MYELOID-LEUKEMIA; CLONAL EVOLUTION; CYTOGENETIC RESPONSE; SURVIVAL; RECOMMENDATIONS; ABERRATIONS; ANEUPLOIDY;
D O I
10.1007/s00277-015-2494-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Major route additional cytogenetic aberrations (ACA) at diagnosis of chronic myeloid leukaemia (CML) indicate an increased risk of progression and shorter survival. Since major route ACA are almost always unbalanced, it is unclear whether other unbalanced ACA at diagnosis also confer an unfavourable prognosis. On the basis of 1348 Philadelphia chromosome-positive chronic phase patients of the randomized CML study IV, we examined the impact of unbalanced minor route ACA at diagnosis versus major route ACA on prognosis. At diagnosis, 1175 patients (87.2 %) had a translocation t(9;22)(q34;q11) and 74 (5.5 %) a variant translocation t(v;22) only, while a loss of the Y chromosome (-Y) was present in addition in 44 (3.3 %), balanced or unbalanced minor route ACA each in 17 (1.3 %) and major route ACA in 21 (1.6 %) cases. Patients with unbalanced minor route ACA had no significantly different cumulative incidences of complete cytogenetic remission or major molecular remission and no significantly different progression-free survival (PFS) or overall survival (OS) than patients with t(9;22), t(v;22), -Y and balanced minor route karyotypes. In contrast, patients with major route ACA had a shorter OS and PFS than all other groups (all pairwise comparisons to each of the other groups: p a parts per thousand currency signaEuro parts per thousand 0.015). Five-year survival probabilities were for t(9;22) 91.4 % (95 % CI 89.5-93.1), t(v; 22) 87 % (77.2-94.3), -Y 89.0 % (76.7-97.0), balanced 100 %, unbalanced minor route 92.3 % (72.4-100) and major route 52.2 % (28.2-75.5). We conclude that only major route, but not balanced or unbalanced minor route ACA at diagnosis, has a negative impact on prognosis of CML.
引用
收藏
页码:2015 / 2024
页数:10
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