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Therapy‐associated genetic aberrations in patients treated for non‐Hodgkin lymphoma
Author(s) -
Basecke Jorg,
Podleschny Martina,
Becker Annegret,
Seiffert Edda,
Schwiers Ivonne,
Schwiers Roman,
Haase Detlef,
Glass Bertram,
Schmitz Norbert,
Trumper Lorenz,
Griesinger Frank
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07023.x
Subject(s) - medicine , cumulative incidence , vincristine , chemotherapy , cyclophosphamide , oncology , lymphoma , incidence (geometry) , myeloid leukemia , etoposide , prednisolone , gastroenterology , transplantation , physics , optics
Summary 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.