Younger patients with chronic myeloid leukemia do well in spite of poor prognostic indicators: results from the randomized CML study IV

Lida Kalmanti, Susanne Saussele, Michael Lauseker, Ulrike Proetel, Martin C Müller, Benjamin Hanfstein, Annette Schreiber, Alice Fabarius, Markus Pfirrmann, Susanne Schnittger, Jolanta Dengler, Christiane Falge, Lothar Kanz, Andreas Neubauer, Frank Stegelmann, Michael Pfreundschuh, Cornelius F Waller, Karsten Spiekermann, Stefan W Krause, Dominik Heim, Christoph Nerl, Dieter K Hossfeld, Hans-Jochem Kolb, Andreas Hochhaus, Joerg Hasford, Rüdiger Hehlmann, German Chronic Myeloid Leukemia Study Group, Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK), Lida Kalmanti, Susanne Saussele, Michael Lauseker, Ulrike Proetel, Martin C Müller, Benjamin Hanfstein, Annette Schreiber, Alice Fabarius, Markus Pfirrmann, Susanne Schnittger, Jolanta Dengler, Christiane Falge, Lothar Kanz, Andreas Neubauer, Frank Stegelmann, Michael Pfreundschuh, Cornelius F Waller, Karsten Spiekermann, Stefan W Krause, Dominik Heim, Christoph Nerl, Dieter K Hossfeld, Hans-Jochem Kolb, Andreas Hochhaus, Joerg Hasford, Rüdiger Hehlmann, German Chronic Myeloid Leukemia Study Group, Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK)

Abstract

Since the advent of tyrosine kinase inhibitors, the impact of age on outcome of chronic myeloid leukemia (CML) patients has changed. We therefore analyzed patients from the randomized CML study IV to investigate disease manifestations and outcome in different age groups. One thousand five hundred twenty-four patients with BCR-ABL-positive chronic phase CML were divided into four age groups: (1) 16-29 years, n = 120; (2) 30-44 years, n = 383; (3) 45-59 years, n = 495; and (4) ≥60 years, n = 526. Group 1 (adolescents and young adults (AYAs)) presented with more aggressive disease features (larger spleen size, more frequent symptoms of organomegaly, higher white blood count, higher percentage of peripheral blasts and lower hemoglobin levels) than the other age groups. In addition, a higher rate of patients with BCR-ABL transcript levels >10 % on the international scale (IS) at 3 months was observed. After a median observation time of 67.5 months, no inferior survival and no differences in cytogenetic and molecular remissions or progression rates were observed. We conclude that AYAs show more aggressive features and poor prognostic indicators possibly indicating differences in disease biology. This, however, does not affect outcome.

Trial registration: ClinicalTrials.gov NCT00055874.

Figures

Fig. 1
Fig. 1
Overview of evaluable patients according to age groups. n Number of patients, CML chronic myeloid leukemia, CP chronic phase, OS overall survival, CCR complete cytogenetic remission, MMR major molecular remission, MR4 molecular remission ≤0.01 % on the international scale
Fig. 2
Fig. 2
a–c Cumulative incidences of a CCR, b MMR, and c MR4 according to the four age groups determined under consideration of competing risks. n Number of patients, CCR complete cytogenetic, remission, MMR major molecular remission, MR4 molecular remission ≤0.01 % on the international scale. p refers to level of significance between AYAs and the other three age groups
Fig. 3
Fig. 3
Rates of progression to AP and BC according to age group. No statistical difference was observed between the four age groups. n Number of patients, AP accelerated phase, BC blast crisis, CI cumulative incidence. p refers to level of significance between AYAs and the other three age groups

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