伊马替尼联合异基因造血干细胞移植治疗Ph染色体阳性急性淋巴细胞白血病的对照研究

Efficacies of hematopoietic stem cell transplantation plus imatinib in the treatment of Philadelphiachromosome-positive acute lymphoblastic leukemia： a comparative study

目的探讨伊马替尼联合应用异基因造血干细胞移植治疗费城染色体（Ph染色体）阳性的急性淋巴细胞白血病（ALL）的疗效，判断其是否有助于延长移植后生存期，改善生活质量。方法回顾性分析自2003--2011年苏州大学附属第一医院行异基因造血干细胞移植的Ph染色体阳性ALL患者，可评价病例共35例。其中联合应用伊马替尼的移植患者23例（观察组），未联合应用者12例（对照组）。通过比较两组患者的移植物抗宿主病（GVHD）发生率、总生存（OS）率、无病生存（DFS）率及非复发死亡（NRM）率，从而分析联合治疗是否具有优越性。结果两组患者年龄、性别、细胞遗传学改变、供体来源、预处理方案、干细胞计数等基本匹配。观察组中处于第1次缓解期（CRl）的患者比例高于对照组（20／23比6／12，P=0．038），但单因素分析显示其并非为OS、DFS的影响因素（P=0．884、0．924）。观察组与对照组预期急性GVHD发生率分别为45．5％和66．7％（P=0．386），其中Ⅱ度以上急性GVHD发生率分别为26．1％和41．7％（P=0．349）；预期的5年0s率分别为62．6％和41．7％（P=0．028）；预期5年DFS率分别为53．7％和33．3％（P=0．054）；5年NRM率分别为22．7％和41．7％（P=0．084）。观察组NRM的主要原因是感染，而对照组的主要原因是感染与重度GVHD并存。观察组白细胞与血小板植入时间均晚于对照组（白细胞植入中位时间：13比11d，P=0．008；血小板植入中位时间：14比11d，P=0．002）。结论伊马替尼联合异基因造血干细胞移植有助于提高Ph染色体阳性ALL患者的长期生存，而不增加急性GVHD和NRM的发生率。

Objective To compare the efficacies of hematopoietic stem cell transplantation with and without imatinib in the treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia by evaluating the post-transplantation survival and quality-of-life. Methods A total of 35 acute lymphoblastic leukemia patients with Philadelphia chromosome-positive underwent hematopoietic stem cell transplantation from 2003 to 2011. They were divided into the imatinib （rt = 23 ） and control （n = 12） groups. The incidence of graft-versus-host disease （GVHD） , overall survival （ OS）, disease-free survival （DFS） and non-relapse mortality （NRM） of two groups were compared to identify the superiority of combined treatment. Results Age, gender, cytogenetic classification, donor type, proposed regimen and counts of infused stem cells were comparable between two groups. The proportion of patients in the first remission （ CR1 ） in the imatinib group was higher than that in control group （20/23 vs 6/12, P = 0. 038）. However, single factor analysis showed that it did not affect the survival significantly （ P = 0. 884, 0.924 ）. The estimated incidence of acute GVHD was 45.5% in the imatinib group versus 66. 7% in the control group （P =0. 386）. And the incidence of acute GVHD of Grades Ⅱ - Ⅳ were 26. 1% and 41.7% （P =0. 349）respectively. The estimated 5-year OS of two groups showed statistical difference （62. 6% vs 41.7%, P = 0. 028） and estimated 5-year DFS were 53.7% and 33.3% respectively （P =0. 054）. The 5-year NRM was 41.7% in the control group and the main causes were infection and severe GVHD versus 22. 7% in the imatinib group （P = 0. 084） and the main cause was infection. The engraftment of white blood cell （median time： 13 vs 11 days, P =0. 008） and platelet （median time： 14 vs 11 days, P =0. 002） was delayed in imatinib group compared with control group. Conclusions The patients of Philadelphia chromosome- positive acute lymphoblastic leukemia may acquire a better survival from the combined regimen of hematopoietic stem cell transplantation and imatinib, without increasing the hazard of acute GVHD and NRM.