Comparison of haploidentical versus matched sibling donor stem cell transplantation in patients with chronic myelomonocytic leukemia
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摘要: 目的 比较单倍型造血干细胞移植(haplo-HSCT)与同胞相合造血干细胞移植(MSD-HSCT)治疗慢性粒-单核细胞白血病(CMML)的疗效，为患者移植方式的选择提供依据。方法 回顾性分析2004年1月—2020年1月于北京大学血液病研究所行haplo-HSCT(29例)及MSD-HSCT(16例)的45例CMML患者的临床特征，分析不同移植方式患者的累积复发率、移植相关死亡率、总生存率及无白血病生存率等，比较不同移植方式的临床疗效。结果 29例haplo-HSCT患者中，男15例，女14例；中位年龄42(12~63)岁；中位移植年度2016年。16例MSD-HSCT患者中，男10例，女6例；中位年龄50(33~59)岁；中位移植年度2013年。haplo-HSCT患者、MSD-HSCT患者粒细胞植入中位时间分别为15(10~22) d、17(13~21) d；血小板植入中位时间分别为17(10~157) d、14(10~20) d；Ⅱ~Ⅳ度急性移植物抗宿主病累积发生率分别为48.3%、31.3%(χ2=1.225，P=0.268)，Ⅲ~Ⅳ度急性移植物抗宿主病累积发生率分别为10.3%、12.5%(χ2＜0.001，P=1.000)；慢性移植物抗宿主病2年累积发生率分别为28.6%、47.8%(χ2=1.239，P=0.266)，中重度慢性移植物抗宿主病发生率分别为10.9%、23.6%(χ2=0.326，P=0.568)；4年累积复发率[(26.8±10.2)% vs (52.0±19.3)%，P=0.265]、4年总生存率[(51.6±10.2)% vs (35.5±18.1)%，P=0.886]、4年无白血病生存率[(41.1±10.8)% vs (20.7±16.9)%，P=0.908]和4年累积移植相关死亡率[(32.1±9.8)% vs (27.4±23.3)%，P=0.272]比较，差异均无统计学意义。结论 haplo-HSCT是CMML患者可行、有效的治疗手段，可作为缺乏全相合移植物来源患者的替代性治疗。
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关键词:
- 慢性粒-单核细胞白血病 /
- 异基因造血干细胞移植 /
- 单倍型移植
Abstract: Objective To compare the efficacy of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)with matched sibling donor hematopoietic stem cell transplantation(MSD-HSCT)in chronic myelomonocytic leukemia(CMML)and provide a basis for the choice of transplantation method.Methods Clinical data of 45 patients with CMML who underwent haplo-HSCT(29 cases)and MSD-HSCT(16 cases)in Peking University Institute of Hematology from January 2004 to January 2020 were retrospectively analyzed. The cumulative incidence of relapse, transplantation-related death rate, overall survival rate and leukemia-free survival rate of patients with different transplantation methods were analyzed, and the clinical efficacy of different transplantation methods were compared.Results Among 29 patients with haplo-HSCT, there were 15 males and 14 females; The median age was 42(12-63) years; The median transplant year was 2016.Among 16 patients with MSD-HSCT, there were 10 males and 6 females; The median age was 50(33-59) years; The median transplant year was 2013.The median time of granulocyte implantation in patients with haplo-HSCT and MSD-HSCT were 15(10-22) days and 17(13-21) days, respectively; The median time of platelet implantation were 17(10-157) days and 14(10-20) days, respectively; The cumulative incidence of grade Ⅱ-Ⅳ and Ⅲ-Ⅳ acute graft-versus-host disease were 48.3% vs 31.3%(χ2=1.225,P=0.268) and 10.3% vs 12.5%(χ2 < 0.001,P=1.000), respectively.The 2-year cumulative incidence of chronic graft-versus-host disease in patients with haplo-HSCT and MSD-HSCT were 28.6% and 47.8%(χ2=1.239,P=0.266), respectively; The incidence of moderate to severe chronic graft-versus-host disease were 10.9% and 23.6%(χ2=0.326,P=0.568), respectively.There was no significant difference in 4-year cumulative recurrence rate([26.8±10.2]% vs [52.0±19.3]%,P=0.265), 4-year overall survival rate([51.6±10.2]% vs [35.5±18.1]%,P=0.886), 4-year leukemia free survival rate([41.1±10.8]% vs [20.7±16.9]%,P=0.908) and 4-year cumulative transplantation related mortality([32.1±9.8]% vs [27.4±23.3%],P=0.272)between the 2 groups.Conclusion Haplo-HSCT is a feasible and effective treatment for CMML patients and serves as an alternative treatment for patients with a lack of matched sibling donor. -
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表 1 2组患者基线特征比较
指标 单倍型移植
(29例)全相合移植
(16例)P 中位年龄/岁 42(12~63) 50(33~59) 0.097 性别/例 0.486 男 15 10 女 14 6 WHO分型/例 0.687 CMML-0 6 3 CMML-1 9 7 CMML-2 14 6 移植前病程/月 6(1~24) 4.5(1~17) 0.082 染色体核型/例 0.645 低危 18 12 中危 2 1 高危 9 3 CPSS评分△/例 0.264 低危 0 0 中危-1 1 1 中危-2 21 14 高危 7 1 MDAPS评分▲/例 0.144 低危 5 4 中危-1 9 5 中危-2 5 6 高危 9 1 未知 1 0 治疗/例 0.912 去甲基化药物或其他化疗 15 8 无 14 8 移植前疾病完全缓解/例 5 4 0.815 回输单个核细胞/(×108·kg-1) 8.32
(4.67~12.00)7.93
(6.73~12.09)0.393 回输CD34+细胞/(×106·kg-1) 2.87
(1.01~8.87)2.66
(1.09~4.44)0.090 △CPSS评分：CMML特定预后积分系统；▲MDAPS评分：MD Anderson预后评分。 
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表 2 影响CMML患者allo-HSCT后生存和复发的危险因素
分析因素 复发 OS LFS 单因素P 多因素P 单因素P 多因素P 单因素P 多因素P 性别(男性vs女性) N - N - N - 中位年龄(>46岁vs ≤46岁) 0.070 0.004 0.093 0.016 0.021 0.001 初始WHO分型(CMML-0 vs CMML-1/2) 0.010 0.004 0.021 0.003 0.013 < 0.001 CPSS分期(低危/中危-1 vs中危-2/高危) N - N - N - MDAPS分期(低危/中危-1 vs中危-2/高危) N - N - N - 染色体核型(低/中危vs高危) N - 0.036 0.132 N - 移植前治疗(治疗vs未治疗) N - N - N - 移植前状态(完全缓解vs未达完全缓解) N - N - 0.073 0.024 诊断距移植中位时间(>5个月vs ≤5个月) N - N - N - aGVHD(发生vs未发生) N - N - N - cGVHD(发生vs未发生) N - N - N -
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