Pedersen-Bjergaard J, Pedersen M, Myhre J, Geisler C
Department of Hematology, Laboratory for Cancer Genetics and Cytogenetics, Finsen Center, Rigshospitalet, Copenhagen, Denmark.
Leukemia. 1997 Oct;11(10):1654-60. doi: 10.1038/sj.leu.2400809.
A cohort of 76 patients with previous chemotherapy for Hodgkin's disease and non-Hodgkin lymphomas received high-dose carmustine, etoposide, cytosine-arabinoside and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) and was followed for relapse and development of leukemic complications. Six patients, four with Hodgkin's disease and two with non-Hodgkin lymphomas, developed leukemic complications, myelodysplasia (MDS) in four cases and overt acute myeloid leukemia (AML) in two. All six showed an abnormal karyotype, in four of them highly characteristic of therapy-related MDS (t-MDS) and therapy-related AML (t-AML). The cumulative risk of t-MDS and t-AML increased from 16 months after start of the primary chemotherapy for lymphoma and reached 17.3% (s.e. 8.5%) after 74 months. If calculated from start of BEAM and ASCT, the cumulative risk increased as early as 4 months and reached 24.3% (s.e. 12.9%) after 43 months. For the whole course of the disease, the relative risk (RR) of AML was 357 (95% CI: 43-1290), as two overt leukemias were observed vs 0.0056 expected cases of de novo AML. In the present cohort the risk of t-MDS and t-AML although high, did not differ from our previous experience in patients treated conventionally for Hodgkin's disease and non-Hodgkin lymphomas, and did not differ for patients receiving stem cells isolated from the bone marrow as compared to patients receiving stem cells isolated from peripheral blood. Antecedent chemotherapy seems to be the critical factor for the development of t-MDS and t-AML rather than the BEAM and ASCT regimen, which however may accelerate the evolution of the disease.
一组76例曾接受过霍奇金淋巴瘤和非霍奇金淋巴瘤化疗的患者接受了大剂量卡莫司汀、依托泊苷、阿糖胞苷和美法仑（BEAM方案），随后进行自体干细胞移植（ASCT），并随访观察复发情况及白血病并发症的发生。6例患者出现白血病并发症，其中4例为霍奇金淋巴瘤患者，2例为非霍奇金淋巴瘤患者，4例发生骨髓增生异常综合征（MDS），2例发生明显的急性髓系白血病（AML）。所有6例患者均显示核型异常，其中4例具有与治疗相关的MDS（t-MDS）和与治疗相关的AML（t-AML）的高度特征性。t-MDS和t-AML的累积风险从淋巴瘤初始化疗开始后16个月起增加，74个月后达到17.3%（标准误8.5%）。如果从BEAM方案和ASCT开始计算，累积风险早在4个月时就开始增加，43个月后达到24.3%（标准误12.9%）。在疾病的整个过程中，AML的相对风险（RR）为357（95%可信区间：43-1290），因为观察到2例明显的白血病，而预期的新发AML病例为0.0056例。在本队列中，t-MDS和t-AML的风险虽然很高，但与我们之前对接受传统治疗的霍奇金淋巴瘤和非霍奇金淋巴瘤患者的经验并无差异，并且与接受从外周血分离的干细胞的患者相比，接受从骨髓分离的干细胞的患者的风险也没有差异。先前的化疗似乎是t-MDS和t-AML发生的关键因素，而不是BEAM方案和ASCT方案，不过后者可能会加速疾病的进展。
