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High-risk additional chromosomal abnormalities at low blast counts herald death by CML

2020; Springer Nature; Volume: 34; Issue: 8 Linguagem: Inglês

10.1038/s41375-020-0826-9

1476-5551

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, Joerg Hasford, Andreas Hochhaus, Susanne Saußele, Michele Baccarani, 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, K. Tajrobehkar, J. Mittermüller, H. Pralle, V. Runde, Annika Hoyer, H. Tessen, Lorenz Trümper, Christian Schmidt, M. Sieber, H. Eschenburg, Reinhard Depenbusch, Siegfried Rösel, H. W. Lindemann, H. Wolf, C. Spohn, Regina Moeller, D. K. Hossfeld, A. Zander, Philippe Schafhausen, Harry Koster, Wiebke Hollburg, Norbert Schmitz, Heinz Dürk, M. Hemeier, A. Grote-Metke, H. Weischer, Benjamin Bechtel, L. Balleisen, Markus Sosada, Anthony D. Ho, Volker Petersen, Jolanta Dengler, Stephan Bildat, Lars Hahn, Hermann Dietzfelbinger, W. Gröschel, A. Bartholomäus, W. Freier, B Sievers, I.-M. Pfreundschuh, Tressie Herrmann, A. A. Fauser, J. Menzel, M. Kemmerling, Richard M. Hansen, Hartmut Link, Michael Schatz, Martin Bentz, Otto Prümmer, Michael Kneba, Jochen Heymanns, S. Schmitz, C. Scheid, André Lollert, Michael Neise, M. Planker, Martina Stauch, M. Schröder, B. Kempf, Ursula Vehling‐Kaiser, Stephan Kremers, Georg Köchling, Lothar Müller, Frank Hartmann, T. Neuhaus, Sebastian Fetscher, D. Kämpfe, Gerhard Heil, M. Uppenkamp, Bernhard Goldmann, T. Fischer Huber, U. Hieber, Christoph Plöger, Martin Grießhammer, Christopher S. Lange, B. Göttler, C. Lunscken, Xaver Schiel, Claude Scheidegger, Oliver Stötzer, H. Hitz, H. Schick, S. Völkl, Karsten Spiekermann, W Berdel, Holger Hebart, Ekkehart Ladda, P. Schmidt, U. Burkhardt, S. Hentschke, Christiane Falge, D. Reschke, Claus-Henning Köhne, C. Müller-Naendrup, Maik Sauer, S. Frühauf, K Ranft, Y. Dencausse, Bettina Sandritter, G. Baake, M. Hofknecht, Robert Dengler, Matthias Edinger, Michael Schenk, A. Wehmeier, H.-P. Weidelich, Rudolf Pihusch, Kerstin Stahlhut, M. Baldus, Axel Matzdorff, Thomas Geer, Stefan Schanz, G. Käfer, W. Gaßmann, C. Priebe-Richter, M. Demandt, Gayle Springer, Heinrich Fiechtner, Claudio Denzlinger, Jan Schleicher, D. Assman, R. Gaeckler, Gina E. Adam, Ali Reza Waladkhani, Bernhard Rendenbach, Helmut Forstbauer, Lothar Kanz, Swen Jacki, Frank Stegelmann, Niakan Kalhori, Arud Nusch, W. Langer, F. Müller, Stefan Brettner, B. Uebelmesser, T. Kamp, C. Schadeck-Gressel, K. Josten, Ophir D. Klein, Rainer Schwerdtfeger, H. Baurmann, H. Strotkötter, W. Fett, Aruna Raghavachar, Christoph Maintz, M. C. Goebler, Rudolf Schlag, W. Elsel, Martin Wernli, Dominik Heim, Walter A. Wuillemin, U Hess, J Gmür, Jiří Mayer,

Chronic Lymphocytic Leukemia Research

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.