Traweek S T, Slovak M L, Nademanee A P, Brynes R K, Niland J C, Forman S J
James Irvine Center for the study of Leukemia and Lymphoma, City of Hope National Medical Center, Duarte, CA.
Blood. 1994 Aug 1;84(3):957-63.
Over a 6-year period, 275 patients were treated with autologous bone marrow transplantation (auto-BMT) for advanced-stage malignant lymphoma. After BMT, clonal chromosomal abnormalities were detected in hematopoietic cells from 10 patients. All 10 had morphologically and cytogenetically normal BMs at the time of stem cell harvest. The cytogenetic changes were first detected 1.8 to 6.5 years (mean, 3.9) after induction chemotherapy, and 0.5 to 3.1 years (mean, 1.4) after transplantation, and were characteristic of those reported for therapy-related myelodysplastic syndrome (MDS) in 9 of the patients: abnormalities of chromosome 5 or 7 (classical-form) were present in 4, 11q23 or 21q22 abnormalities (topoisomerase II-related form) were detected in 3, and a combination of both forms was seen in 2 patients. Clonal 2p abnormalities were found in the 1 remaining patient. The abnormal karyotypes were associated with morphologically recognizable MDS in 3 patients and with acute myeloid leukemia (AML) arising in MDS in 2. Four of these patients have died: 3 of AML and 1 of infection. One patient is still alive with cytopenia. The clonal cytogenetic abnormalities were not associated with MDS in 5 patients: 1 has died of recurrent lymphoma, 2 have cytopenia, and 2 still have no morphologic or clinical evidence of MDS after short follow-up (4 and 13 months). Compared with a control group matched for disease, length of follow-up, and treatment with auto-BMT, there were no statistically significant associations between the development of clonal chromosomal abnormalities and age, number of chemotherapeutic regimens, prior local radiation, BMT conditioning regimen (with or without total body irradiation), or type of lymphoma. These studies show that the risk of developing clonal cytogenetic changes after auto-BMT for malignant lymphoma is approximately 9% at 3 years, even when pre-BMT karyotypic studies are normal. The exact significance of these cytogenetic abnormalities in the absence of MDS or AML is unclear.
在6年期间，275例晚期恶性淋巴瘤患者接受了自体骨髓移植（auto-BMT）治疗。骨髓移植后，在10例患者的造血细胞中检测到克隆性染色体异常。所有10例患者在干细胞采集时骨髓形态学和细胞遗传学均正常。细胞遗传学改变首次在诱导化疗后1.8至6.5年（平均3.9年）以及移植后0.5至3.1年（平均1.4年）被检测到，9例患者的改变具有治疗相关骨髓增生异常综合征（MDS）的特征：4例存在5号或7号染色体异常（经典型），3例检测到11q23或21q22异常（拓扑异构酶II相关型），2例患者同时出现这两种类型。剩余1例患者发现克隆性2号染色体异常。异常核型在3例患者中与形态学上可识别的MDS相关，2例与MDS中发生的急性髓系白血病（AML）相关。这些患者中有4例死亡：3例死于AML，1例死于感染。1例患者仍存活，伴有血细胞减少。5例患者的克隆性细胞遗传学异常与MDS无关：1例死于复发性淋巴瘤，2例有血细胞减少，2例在短期随访（4个月和13个月）后仍无MDS的形态学或临床证据。与在疾病、随访时间和auto-BMT治疗方面相匹配的对照组相比，克隆性染色体异常的发生与年龄、化疗方案数量、既往局部放疗、BMT预处理方案（有无全身照射）或淋巴瘤类型之间无统计学显著关联。这些研究表明，恶性淋巴瘤自体骨髓移植后发生克隆性细胞遗传学改变的风险在3年时约为9%，即使移植前核型研究正常。这些细胞遗传学异常在无MDS或AML情况下的确切意义尚不清楚。
