Basecke Jorg, Podleschny Martina, Becker Annegret, Seiffert Edda, Schwiers Ivonne, Schwiers Roman, Haase Detlef, Glass Bertram, Schmitz Norbert, Trumper Lorenz, Griesinger Frank
Department of Haematology and Oncology, University of Goettingen, Goettingen, Germany.
Br J Haematol. 2008 Apr;141(1):52-9. doi: 10.1111/j.1365-2141.2008.07023.x.
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.
大剂量化疗后出现的治疗相关骨髓增生异常综合征和急性髓系白血病（t-AML/MDS）是严重问题，在清髓性治疗方案中的累积发生率达20%或更高。回顾性研究结果表明，t-AML/MDS相关的基因畸变在接触化疗后可直接观察到，且可在t-AML出现前数月就已存在。为确定治疗后畸变的发生率及其预测价值，我们前瞻性地研究了95例接受中高剂量化疗的非霍奇金淋巴瘤（NHL）患者的316份样本（德国高级别NHL研究组的megaCHOEP（环磷酰胺、阿霉素、依托泊苷、长春新碱、泼尼松龙）试验的A组和B组）。在33.3%（A组）和55.4%（B组）的患者以及14.9%和28.7%的相应样本中观察到分子畸变（RUNX1/RUNX1T1、PML-RARA、CBFB-MYH11、MLL-MLLT1、BCR-ABL1）。对53例接受高剂量治疗的NHL患者进行的细胞遗传学分析显示频繁的染色体断裂。在3例患者中发现了克隆性畸变。在3年的临床随访期内，这些患者均未发生t-AML/MDS。我们得出结论，基因畸变的高发生率反映了一种剂量依赖性、短暂的治疗诱导的基因损伤，其不能预测t-AML/MDS。
