Jabbour Elias, Cortes Jorge, Kantarjian Hagop M, Giralt Sergio, Jones Dan, Jones Roy, Giles Francis, Andersson Borje S, Champlin Richard, de Lima Marcos
Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Blood. 2006 Aug 15;108(4):1421-3. doi: 10.1182/blood-2006-02-001933. Epub 2006 Apr 6.
Resistance to imatinib mesylate is an emerging problem in the treatment of chronic myeloid leukemia (CML), often associated with point mutations in the Bcr-Abl kinase domain. Outcome of patients with such mutations after allogeneic stem cell transplantation (Allo-SCT) is unknown. Ten imatinib-resistant patients with Bcr-Abl kinase mutations received a transplant: 9 had CML (3 in chronic phase, 4 in accelerated phase, and 2 in blast phase) and 1 had Philadelphia-positive acute lymphocytic leukemia (ALL). Patients harbored 9 different protein kinase mutations (T315I mutation, n = 2). Preparative regimens were ablative (n = 7) and nonablative (n = 3). All patients engrafted; there were no treatment-related deaths. Disease response was complete molecular (CMR; n = 7), major molecular (n = 2), and no response (n = 1). Three patients (mutations Q252H, E255K, and T315I) died of relapse after Allo-SCT. Seven patients are alive (6 in CMR) for a median of 19 months. Allo-SCT remains an important salvage option for patients who develop resistance to imatinib through Bcr-Abl mutations.
对甲磺酸伊马替尼耐药是慢性髓性白血病（CML）治疗中一个新出现的问题，常与Bcr-Abl激酶结构域的点突变相关。异基因干细胞移植（Allo-SCT）后发生此类突变的患者的预后尚不清楚。10例存在Bcr-Abl激酶突变的伊马替尼耐药患者接受了移植：9例为CML（3例处于慢性期，4例处于加速期，2例处于急变期），1例为费城染色体阳性的急性淋巴细胞白血病（ALL）。患者存在9种不同的蛋白激酶突变（T315I突变，n = 2）。预处理方案为清髓性（n = 7）和非清髓性（n = 3）。所有患者均植入成功；无治疗相关死亡。疾病反应为完全分子学缓解（CMR；n = 7）、主要分子学缓解（n = 2）和无反应（n = 1）。3例患者（Q252H、E255K和T315I突变）在Allo-SCT后死于复发。7例患者存活（6例处于CMR状态），中位存活时间为19个月。对于因Bcr-Abl突变而对伊马替尼产生耐药的患者，Allo-SCT仍然是一种重要的挽救治疗选择。
