Nichols G, de Castro K, Wei L-X, Griffin M, Lin N, Oratzi A, Murty V V V S, Troxel A, Vahdat L, Hesdorffer C
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Leukemia. 2002 Sep;16(9):1673-9. doi: 10.1038/sj.leu.2402631.
Therapy-related myelodysplastic syndrome and acute myelogenous leukemia (t-MDS/AML) are serious complications of chemotherapy and radiotherapy for cancer. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) may be associated with an increased incidence of these complications. The frequency of t-MDS/AML after ASCT for breast cancer is uncertain. We reviewed our database of 379 consecutive breast cancer ASCT patients treated with alkylator-based chemotherapy, followed for a median of 1.52 years (range 0-8.97), with a median survival of 6.16 years. Three patients have developed tMDS/AML. The probability of developing this complication at 5 years is 0.032 in our series. We have used pathologic, cytogenetic and molecular methods to evaluate which portions of therapy may have predisposed to the development of this complication. Cytogenetic abnormalities were not found in the stem cell harvests of these patients by metaphase analysis or by fluorescence in situ hybridization (FISH). One patient demonstrated a clonal X chromosome inactivation pattern in her stem cell harvest, indicating pre-transplant chemotherapy may have been responsible for the development of her leukemia. As two of our patients developed this complication at greater than 4 years post-transplant, the number of cases may increase with longer follow-up. While the incidence appears to be low, further prospective and retrospective analysis will be necessary to determine which portions of therapy predispose to the development of t-MDS/AML in patients undergoing ASCT for treatment of breast cancer.
治疗相关的骨髓增生异常综合征和急性髓系白血病（t-MDS/AML）是癌症化疗和放疗的严重并发症。高剂量化疗后进行自体干细胞移植（ASCT）可能会增加这些并发症的发生率。乳腺癌患者ASCT后发生t-MDS/AML的频率尚不确定。我们回顾了我们的数据库，其中379例接受基于烷化剂化疗的连续乳腺癌ASCT患者，中位随访时间为1.52年（范围0-8.97年），中位生存期为6.16年。有3例患者发生了tMDS/AML。在我们的系列研究中，5年时发生这种并发症的概率为0.032。我们使用了病理、细胞遗传学和分子方法来评估治疗的哪些部分可能易引发这种并发症。通过中期分析或荧光原位杂交（FISH）在这些患者的干细胞采集物中未发现细胞遗传学异常。一名患者在其干细胞采集中表现出克隆性X染色体失活模式，表明移植前化疗可能是其白血病发生的原因。由于我们的两名患者在移植后4年以上发生了这种并发症，随着随访时间延长，病例数可能会增加。虽然发病率似乎较低，但需要进一步的前瞻性和回顾性分析来确定在接受ASCT治疗乳腺癌的患者中，治疗的哪些部分易引发t-MDS/AML的发生。
