Myeloma Institute for Research & Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
Mediterr J Hematol Infect Dis. 2011;3(1):e2011047. doi: 10.4084/MJHID.2011.047. Epub 2011 Oct 24.
Therapy related myeloid malignancies are an increasingly recognized treatment complication in patients undergoing therapy for multiple myeloma. The main predisposing factors are the alkylating agents, topoisomerase II inhibitors and radiotherapy, but recently questions have been raised regarding the immunomodulatory agent lenalidomide. Little is known about the new antimyeloma agents in the context of therapy related myeloid malignancies. The duration of treatment and the time from diagnosis are the main contributing factors in alkylating induced myeloid malignancies which occur 5-10 years after treatment, chromosome 5 and 7 abnormalities being the characteristic finding. High dose therapy (HDT) does not seem to be a major contributing factor per se in multiple myeloma. In a number of large published series, all the factors related with therapy-induced myelodysplasia were defined prior to HDT. Topoisomerase II inhibitors induce mainly acute leukemias which invariably correlate with dysregulation of the MLL gene. Radiotherapy causes therapy related myelodysplasia if applied in bone marrow producing areas, especially if combined with chemotherapy. Therapy related myeloid malignancies generally herald a poor prognosis. Karyotypic abnormalities seem to be the main prognostic factor. In all cases the risk for therapy related myeloid malignancies drops sharply by 10 years after the treatment.
治疗相关髓系恶性肿瘤是多发性骨髓瘤患者接受治疗时越来越被认识到的治疗并发症。主要的诱发因素是烷化剂、拓扑异构酶 II 抑制剂和放疗，但最近人们对免疫调节剂来那度胺提出了质疑。关于治疗相关髓系恶性肿瘤中的新型抗骨髓瘤药物，人们知之甚少。烷化剂诱导的髓系恶性肿瘤的发生时间是治疗后 5-10 年，与治疗时间和从诊断到治疗的时间有关，其特征性发现是 5 号和 7 号染色体异常。高剂量治疗（HDT）本身似乎并不是多发性骨髓瘤的主要诱发因素。在许多已发表的大型系列研究中，所有与治疗诱导的骨髓发育不良相关的因素都是在 HDT 之前定义的。拓扑异构酶 II 抑制剂主要诱导急性白血病，这与 MLL 基因的失调有必然联系。如果放疗应用于骨髓产生区域，特别是与化疗联合应用，会导致治疗相关的骨髓发育不良。治疗相关髓系恶性肿瘤通常预示着预后不良。细胞遗传学异常似乎是主要的预后因素。在所有情况下，治疗后 10 年，治疗相关髓系恶性肿瘤的风险急剧下降。
