Slovak Marilyn L, Bedell Victoria, Popplewell Leslie, Arber Daniel A, Schoch Claudia, Slater Rosalyn
Department of Cytogenetics, City of Hope National Medical Center, Duarte, California 91010, USA.
Genes Chromosomes Cancer. 2002 Apr;33(4):379-94. doi: 10.1002/gcc.10042.
The International Workshop on the relationship between prior therapy and balanced chromosome aberrations in therapy-related myelodysplastic syndromes (t-MDS) and therapy-related acute leukemia (t-AL) identified 79 of 511 (15.5%) patients with balanced 21q22 translocations. Patients were treated for their primary disease, including solid tumors (56%), hematologic malignancy (43%), and juvenile rheumatoid arthritis (single case), by radiation therapy (5 patients), chemotherapy (36 patients), or combined-modality therapy (38 patients). 21q translocations involved common partner chromosomes in 81% of cases: t(8;21) (n = 44; 56%), t(3;21) (n = 16; 20%), and t(16;21) (n = 4; 5%). Translocations involving 15 other partner chromosomes were also documented with involvement of AML1(CBFA2/RUNX1), identifying a total of 23 different 21q22/AML1 translocations. The data analysis was carried out on the basis of five subsets of 21q22 cases, that is, t(8;21) with and without additional aberrations, t(3;21), t(16;21), and other 21q22 translocations. Dysplastic features were present in all 21q22 cases. Therapy-related acute myeloid leukemia (t-AML) at presentation was highest in t(8;21) (82%) and lowest in t(3;21) (37.5%) patients. Cumulative drug dose exposure scores for alkylating agents (AAs) and topoisomerase II inhibitors indicated that t(3;21) patients received the most intensive therapy among the five 21q22 subsets, and the median AA score for patients with secondary chromosome 7 aberrations was double the AA score for the entire 21q22 group. All five patients who received only radiation therapy had t(8;21) t-AML. The median latency and overall survival (OS) for 21q22 patients were 39 and 14 months (mo), compared to 26 and 8 mo for 11q23 patients, 22 and 28 mo for inv(16), 69 and 7 mo for Rare recurring aberrations, and 59 and 7 mo for Unique (nonrecurring) balanced aberration (latency P < or = 0.016 for all pairwise comparisons; OS, P < or = 0.018 for all pairwise comparisons). The percentages of 21q22 patients surviving 1 year, 2 years, and 5 years were 58%, 33%, and 18%, respectively. Noticeable differences were observed in median OS between 21q22 patients (n = 7) receiving transplant (BMT) (31 mo) compared to 21q22 patients who received intensive non-BMT therapy (n = 46) (17 mo); however, this was nonsignificant because of the small sample size (log-rank, P = 0.33). t-MDS/t-AML with balanced 21q22 aberrations was associated with prior exposure to radiation, epipodophyllotoxins, and anthracyclines, dysplastic morphologic features, multiple partner chromosomes, and longer latency periods when compared to 11q23 and inv(16) t-MDS/AML Workshop subgroups. In general, patients could be divided into two prognostic risk groups, those with t(8;21) (median OS, 19 mo) and those without t(8;21) (median OS, 7 mo) leukemia (log-rank, P = 0.0007).
关于既往治疗与治疗相关的骨髓增生异常综合征（t-MDS）和治疗相关的急性白血病（t-AL）中平衡染色体畸变之间关系的国际研讨会，在511例患者中识别出79例（15.5%）存在21q22平衡易位。患者因原发性疾病接受治疗，包括实体瘤（56%）、血液系统恶性肿瘤（43%）和青少年类风湿关节炎（1例），治疗方式有放射治疗（5例）、化疗（36例）或综合治疗（38例）。81%的21q易位病例涉及常见的伙伴染色体：t(8;21)（n = 44；56%）、t(3;21)（n = 16；20%）和t(16;21)（n = 4；5%）。还记录了涉及其他15条伙伴染色体的易位，均累及AML1（CBFA2/RUNX1），共识别出23种不同的21q22/AML1易位。数据分析基于21q22病例的五个亚组进行，即有或无其他畸变的t(8;21)、t(3;21)、t(16;21)以及其他21q22易位。所有21q22病例均有发育异常特征。初诊时治疗相关的急性髓系白血病（t-AML）在t(8;21)患者中发生率最高（82%），在t(3;21)患者中最低（37.5%）。烷化剂（AAs）和拓扑异构酶II抑制剂的累积药物剂量暴露评分表明，在21q22的五个亚组中，t(3;21)患者接受的治疗强度最大，继发染色体7畸变患者的AAs评分中位数是整个21q22组的两倍。仅接受放射治疗的5例患者均为t(8;21) t-AML。21q22患者的中位潜伏期和总生存期（OS）分别为39个月和14个月，而11q23患者为26个月和8个月，inv(16)患者为22个月和28个月，罕见复发性畸变患者为69个月和7个月，独特（非复发性）平衡畸变患者为59个月和7个月（潜伏期所有成对比较P≤0.016；OS，所有成对比较P≤0.018）。21q22患者1年、2年和5年生存率分别为58%、33%和18%。接受移植（BMT）的21q22患者（n = 7）中位OS为31个月，接受强化非BMT治疗的21q22患者（n = 46）中位OS为17个月，二者存在显著差异；然而，由于样本量小，差异无统计学意义（对数秩检验，P = 0.33）。与11q23和inv(16) t-MDS/AML研讨会亚组相比，具有21q22平衡畸变的t-MDS/t-AML与既往暴露于放射、表鬼臼毒素和蒽环类药物、发育异常形态学特征、多个伙伴染色体以及更长潜伏期相关。总体而言，患者可分为两个预后风险组，即患有t(8;21)的患者（中位OS，19个月）和未患t(8;21)白血病的患者（中位OS，7个月）（对数秩检验，P = 0.0007）。
