Therapy-associated genetic aberrations in patients treated for non-Hodgkin lymphoma |
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Authors: | Basecke Jorg Podleschny Martina Becker Annegret Seiffert Edda Schwiers Ivonne Schwiers Roman Haase Detlef Glass Bertram Schmitz Norbert Trumper Lorenz Griesinger Frank |
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Institution: | Department of Haematology and Oncology, University of Goettingen, Goettingen;, and Department of Haematology, Allgemeines Krankenhaus St. Georg, Hamburg, Germany |
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Abstract: | Therapy-associated myelodysplastic syndromes and acute myeloid leukaemia (t-AML/MDS) following high dose chemotherapy are significant problems, with a cumulative incidence of 20% or more in myeloablative treatment regimen. Retrospective findings indicated that t-AML/MDS associated genetic aberrations can be observed directly after exposure to chemotherapy and can precede t-AML by several months. To determine the incidence of post-therapeutic aberrations and their predictive value, we prospectively investigated 316 samples of 95 patients with non-Hodgkin lymphoma (NHL) who were treated with intermediate and high dose chemotherapy (Arm A and B of the megaCHOEP (cyclophosphamide, doxorubicin, etoposide, vincristine, prednisolone) trial of the German High Grade NHL study group). Molecular aberrations ( RUNX1/RUNX1T1, PML-RARA, CBFB-MYH11, MLL-MLLT1, BCR-ABL1 ) were observed in 33·3% (Arm A) and 55·4% (Arm B) of patients and in 14·9% and 28·7% of respective samples. Cytogenetic analysis of 53 NHL patients after high dose therapy showed frequent chromosomal breakage. Clonal aberrations were found in three patients. None of these patients developed a t-AML/MDS during a 3-year clinical follow up period. We concluded that the high incidence of genetic aberrations reflected a dose-dependent, transient therapy-induced genetic damage which is not predictive of a t-AML/MDS. |
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Keywords: | non-Hodgkin lymphoma chemotherapy genetic aberrations therapy-associated acute myeloid leukaemia |
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