Levine E G, Bloomfield C D
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.
Semin Oncol. 1992 Feb;19(1):47-84.
The median latency of 2 degrees MDS/AL is 4 to 5 years. A high percentage of patients with 2 degrees MDS/AL convert to 2 degrees AL. Survival of either is less than 1 year. A constellation of morphologic abnormalities from all 3 cell lines produces a unique appearance. Both 2 degrees MDS and 2 degrees AL are difficult to classify by the FAB system. With the exception of the identification of karyotypic abnormalities, the biology of 2 degrees MDS/AL remains largely unexplored. Alterations of chromosomes 5 and 7 predominate, but other associated cytogenetic abnormalities are being increasingly recognized. A synthesis of data regarding 2 degrees MDS/AL resulting from the treatment of several primary malignancies generates the tentative conclusions that (a) many of the alkylating agents, and the nonclassic alkylating agent procarbazine, are leukemogens; (b) melphalan is a more potent leukemogen than cyclophosphamide. None of the other alkylating agents has been clearly established to be more or less potent than another; (c) increasing duration or amount of alkylator-based chemotherapy increases the risk of leukemogenesis; (d) low doses of radiation delivered to large volumes of bone marrow are weakly leukemogenic. High doses of radiation delivered to small volumes are not. Due to the latter, there is minimal additive risk for 2 degrees MDS/AL among studies using alkylator-based chemotherapy and radiotherapy, either concurrently or sequentially; (e) the older patient (greater than 40) is at increased risk for 2 degrees MDS/AL, at least in Hodgkin's disease. Children may be at lesser risk than adults, and younger children at lesser risk than older children; (f) the risk of 2 degrees MDS/AL peaks within the first decade after treatment for the primary malignancy. The incidence rates during the second decade are low. Identified occupational/environmental risks for 2 degrees MDS/AL include benzene, ambient and diagnostic radiation exposure, and perhaps ethylene oxide. The similarities in karyotype abnormalities among leukemic cells of those whose occupations expose them to chemical hazard, and those who are exposed to cytotoxic agents, suggest that many more environmental leukemogens have yet to be discovered. Karyotype is an important prognostic factor for both achievement of CR and for survival. Nonaggressive treatment approaches have not proven useful, although the use of hematopoietic growth factors offers promise in this area. Combination chemotherapy is justified in patients with adequate performance statuses and "favorable" karyotypes. Allogeneic bone marrow transplantation is currently the only curative approach, and can be applied without attempts to first reduce the leukemic burden.
二度骨髓增生异常综合征/急性白血病（MDS/AL）的中位潜伏期为4至5年。高比例的二度MDS/AL患者会转化为二度急性白血病（AL）。二者的生存期均不足1年。所有3种细胞系的一系列形态学异常产生了独特的表现。二度MDS和二度AL都难以用FAB系统进行分类。除了核型异常的鉴定外，二度MDS/AL的生物学特性在很大程度上仍未被探索。5号和7号染色体的改变最为常见，但其他相关的细胞遗传学异常也越来越受到认可。对几种原发性恶性肿瘤治疗后产生的二度MDS/AL的数据进行综合分析得出了初步结论：（a）许多烷化剂以及非经典烷化剂丙卡巴肼都是致白血病物质；（b）美法仑比环磷酰胺是更强效的致白血病物质。没有明确确定其他烷化剂的效力比另一种更强或更弱；（c）基于烷化剂的化疗时间延长或剂量增加会增加白血病发生的风险；（d）对大量骨髓进行低剂量辐射具有弱致白血病性。对小体积进行高剂量辐射则不然。由于后者，在同时或相继使用基于烷化剂的化疗和放疗的研究中，二度MDS/AL的附加风险极小；（e）老年患者（大于40岁）患二度MDS/AL的风险增加，至少在霍奇金病中如此。儿童的风险可能低于成人，幼儿的风险低于大龄儿童；（f）二度MDS/AL的风险在原发性恶性肿瘤治疗后的第一个十年内达到峰值。第二个十年的发病率较低。已确定的二度MDS/AL的职业/环境风险包括苯、环境辐射和诊断性辐射暴露，可能还有环氧乙烷。职业暴露于化学危害的人群以及暴露于细胞毒性药物的人群的白血病细胞核型异常相似，这表明还有更多的环境致白血病物质有待发现。核型是实现完全缓解（CR）和生存的重要预后因素。尽管使用造血生长因子在这一领域有前景，但非积极的治疗方法尚未被证明有效。对于身体状况良好且核型“良好”的患者，联合化疗是合理的。异基因骨髓移植目前是唯一的治愈方法，且无需先尝试减轻白血病负担即可应用。
