Mohamed Anwar N, Pemberton Pamela, Zonder Jeffrey, Schiffer Charles A
Department of Pathology and the Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Clin Cancer Res. 2003 Apr;9(4):1333-7.
The acquisition of secondary chromosomal aberrations in chronic myeloid leukemia (CML) patients with Philadelphia chromosome-positive (Ph+) karyotype signifies clonal evolution associated with disease progression to accelerated/blastic phase. Therefore, these aberrations are of clinical and biological importance. We identified 58 cases with secondary abnormalities in addition to t(9;22)(q34;q11.2) or its variants in a review of 137 CML patients treated with imatinib mesylate (STI571). Clinically 13 patients were in chronic phase, 24 in accelerated phase, and 21 in blastic phase.
More than 50% of cases showed the major routes of CML clonal evolution [+8, i(17q), +Ph, and/or +19]. The remainder exhibited minor routes of secondary abnormalities with -17/17p-, 11p-/rearr(11p), and -7/rearr(7) as the most frequent abnormalities. Of particular interest, one case developed an inv(16)(p13q22) as a secondary anomaly during blastic transformation. The bone marrow was consistent with myelomonocytic morphology with eosinophilia. Cytogenetic responses to imatinib mesylate occurred in 15 of 58 (26%) patients; 12 achieved complete cytogenetic remission, 2 had a major response, and 1 had a minor response, with most responses noted within 3-6 months. Seven patients remain in remission >17-30 months, 2 patients relapsed between 12 and 19 months on therapy, and 1 patient was treated by bone marrow transplantation.
Although some Ph+ CML patients with clonal evolution can have a complete cytogenetic response to imatinib mesylate, responses tend to be brief, and such patients may benefit from subsequent stem cell transplantation. Therefore, CML patients with clonal evolution may require therapy additional to imatinib mesylate for maximal eradication of the Ph+ leukemic cells.
在费城染色体阳性（Ph+）核型的慢性髓性白血病（CML）患者中，继发性染色体畸变的出现标志着与疾病进展至加速期/急变期相关的克隆进化。因此，这些畸变具有临床和生物学重要性。在对137例接受甲磺酸伊马替尼（STI571）治疗的CML患者进行回顾时，我们识别出58例除t(9;22)(q34;q11.2)或其变异型外还存在继发性异常的病例。临床上，13例患者处于慢性期，24例处于加速期，21例处于急变期。
超过50%的病例显示出CML克隆进化的主要途径[+8、i(17q)、+Ph和/或+19]。其余病例表现为继发性异常的次要途径，-17/17p-、11p-/重排(11p)和-7/重排(7)为最常见的异常。特别值得注意的是，1例患者在急变转化期间出现inv(16)(p13q22)作为继发性异常。骨髓符合伴有嗜酸性粒细胞增多的粒单核细胞形态。58例患者中有15例（26%）对甲磺酸伊马替尼产生细胞遗传学反应；12例达到完全细胞遗传学缓解，2例有主要反应，1例有轻微反应，大多数反应在3 - 6个月内出现。7例患者缓解超过17 - 30个月，2例患者在治疗12至19个月之间复发，1例患者接受了骨髓移植。
尽管一些具有克隆进化的Ph+ CML患者对甲磺酸伊马替尼可产生完全细胞遗传学反应，但反应往往短暂，此类患者可能从后续干细胞移植中获益。因此，具有克隆进化的CML患者可能需要在甲磺酸伊马替尼治疗之外进行额外治疗，以最大程度根除Ph+白血病细胞。
