title: Therapy-associated genetic aberrations in patients treated for non-Hodgkin lymphoma.
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.
authors.affiliation: Department of Haematology and Oncology, University of Goettingen, Goettingen, Germany. jbaesec@gwdg.de
authors.forename: Jorg
authors.initials: J
authors.lastname: Basecke
authors.forename: Martina
authors.initials: M
authors.lastname: Podleschny
authors.forename: Annegret
authors.initials: A
authors.lastname: Becker
authors.forename: Edda
authors.initials: E
authors.lastname: Seiffert
authors.forename: Ivonne
authors.initials: I
authors.lastname: Schwiers
authors.forename: Roman
authors.initials: R
authors.lastname: Schwiers
authors.forename: Detlef
authors.initials: D
authors.lastname: Haase
authors.forename: Bertram
authors.initials: B
authors.lastname: Glass
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trumper
authors.forename: Frank
authors.initials: F
authors.lastname: Griesinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002869:Chromosome Aberrations / Q000187:drug effects*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014178:Translocation, Genetic; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone