High-risk additional chromosomal abnormalities at low blast counts herald death by CML
Rüdiger Hehlmann, Astghik Voskanyan, Michael Lauseker, Markus Pfirrmann, Lida Kalmanti, Sébastien Rinaldetti, Katharina Kohlbrenner, Claudia Haferlach, Brigitte Schlegelberger, Alice Fabarius, Wolfgang Seifarth, Birgit Spieß, Patrick Wuchter, Stefan W. Krause, Hans‐Jochem Kolb, Andreas Neubauer, Dieter K. Hossfeld, Christoph Nerl, Aloïs Gratwohl, Gabriela M. Baerlocher, Andreas Burchert, Tim H. Brümmendorf, Jörg Hasford, Andreas Hochhaus, Susanne Saußele, Michele Baccarani, for the SAKK and the German CML Study Group, Ludwig Fischer von Weikersthal, Markus Hahn, Günter Schlimok, Dietmar Reichert, Jan Janßen, Uwe M. Martens, Peter Majunke, Peter Reichert, Kai Neben, Stefan Korsten, Ch. Scholz, Bernd Oldenkott, Jörg Heßling, D. Kingreen, Christian Sperling, C. Schelenz, I. W. Blau, A. Urmersbach, W. D. Ludwig, Philipp le Coutre, R. Arnold, Maike de Wit, Antonio Pezzutto, E. Schäfer, Roland Schroers, A. Lochter, Dirk Behringer, Y. Ko, St. Weidenhöfer, Walter Verbeek, Peter Brossart, Guido Trenn, W Pommerien, J. Krauter, G. Döering, H. Munzinger, C. Diekmann, Bernd Hertenstein, Sebastian Stier, F. Möller-Faßbender, Mathias Hänel, T. Zöller, C. Lamberti, Babette Koch, A. Henzel, Siegfried Wagner, A. Schmalenbach, M. Hoffknecht, Gerhard Ehninger, Alexander Kiani, Thomas Illmer, Carlo Aul, Michael Flaßhove, F. Henneke, M. Simon, Lothar Müller, Heiko Becker, R. F. Janz, Michael J. Eckart, Roland J. Fuchs, Frank Schlegel, Mohammad Amen Wattad, R. Rudolph, Dietrich W. Beelen, A Lindemann, D. Linck, Wassman, Elke Jäger, Salah‐Eddin Al‐Batran, T Reiber, Cornelius F. Waller, Heinz‐Gert Hoeffkes, L.S. Schulz
Abstract
Blast crisis is one of the remaining challenges in chronic myeloid leukemia (CML). Whether additional chromosomal abnormalities (ACAs) enable an earlier recognition of imminent blastic proliferation and a timelier change of treatment is unknown. One thousand five hundred and ten imatinib-treated patients with Philadelphia-chromosome-positive (Ph+) CML randomized in CML-study IV were analyzed for ACA/Ph+ and blast increase. By impact on survival, ACAs were grouped into high risk (+8, +Ph, i(17q), +17, +19, +21, 3q26.2, 11q23, -7/7q abnormalities; complex) and low risk (all other). The presence of high- and low-risk ACAs was linked to six cohorts with different blast levels (1%, 5%, 10%, 15%, 20%, and 30%) in a Cox model. One hundred and twenty-three patients displayed ACA/Ph+ (8.1%), 91 were high risk. At low blast levels (1-15%), high-risk ACA showed an increased hazard to die compared to no ACA (ratios: 3.65 in blood; 6.12 in marrow) in contrast to low-risk ACA. No effect was observed at blast levels of 20-30%. Sixty-three patients with high-risk ACA (69%) died (n = 37) or were alive after progression or progression-related transplantation (n = 26). High-risk ACA at low blast counts identify end-phase CML earlier than current diagnostic systems. Mortality was lower with earlier treatment. Cytogenetic monitoring is indicated when signs of progression surface or response to therapy is unsatisfactory.