刘利, 刘强, 陈任安, 何华, 蒋姗姗, 杜娟, 梁英民. 7例格列卫联合非清髓造血干细胞移植治疗加速期、急变期CML的临床观察[J]. 中国肿瘤临床, 2006, 33(17): 1008-1011.
引用本文: 刘利, 刘强, 陈任安, 何华, 蒋姗姗, 杜娟, 梁英民. 7例格列卫联合非清髓造血干细胞移植治疗加速期、急变期CML的临床观察[J]. 中国肿瘤临床, 2006, 33(17): 1008-1011.
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Liu Li, Liu Qiang, Hao Miaowang, . Clinical Observation of Gleevec Combined with Non-myeloablative Transplantation of Allogeneic Peripheral Blood Stem Cells for Treatment of Accelerated or Blast-Crisis Phase Chronic Myeloid Leukemia[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2006, 33(17): 1008-1011.
Citation: Liu Li, Liu Qiang, Hao Miaowang, . Clinical Observation of Gleevec Combined with Non-myeloablative Transplantation of Allogeneic Peripheral Blood Stem Cells for Treatment of Accelerated or Blast-Crisis Phase Chronic Myeloid Leukemia[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2006, 33(17): 1008-1011.
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7例格列卫联合非清髓造血干细胞移植治疗加速期、急变期CML的临床观察

Clinical Observation of Gleevec Combined with Non-myeloablative Transplantation of Allogeneic Peripheral Blood Stem Cells for Treatment of Accelerated or Blast-Crisis Phase Chronic Myeloid Leukemia

    摘要
  • 摘要: 目的 :探讨非清髓造血干细胞移植联合格列卫在治疗慢性粒细胞性白血病(CML)中的作用。 方法 :7例CML患者(4例为AP,3例为BP),移植前、后口服格列卫(400～1500mg/d)治疗,预处理方案为福达华氟达拉宾、环磷酰胺和阿糖胞苷联合ATG和(或)CD3单抗。供者HLA配型2例完全相合,2例一个位点不相合,1例3个位点不相合的同胞及2例半匹配的母亲供者,干细胞来源为G-CSF动员的外周血造血干细胞(P结果:7例患者均获得不同程度的嵌合状态,3例获得完全嵌合(FC<95%),4例获得44%～95%的混合嵌合,经调整免疫抑制剂、供者淋巴细胞/PBSC输注,格列卫治疗后,2例患者在移植后1.5～10个月转变为完全嵌合。移植后中性粒细胞<0.5×109/L天数,16d(范围10～21d);血小板大于20×109/L天数,10d(范围4～15d)。移植期间1例患者移植后45天因肠道感染,颅内出血死亡。另1例患者移植后27天因多脏器衰竭死亡。5例患者随访7～23个月,3例发生Ⅰ～ⅡGVHD,2例发生Ⅲ～ⅣGVHD,1例因cGVHD死于感染,余4例仍生存,平均无病生存12.2个月(7～17个月),Bcr/abl转阴时间33～130天,巡访期间无1例复发。 结论 :非清髓造血干细胞移植前、后联合格列卫治疗CML,具有降低移植前白血病细胞负荷,抑制残留白血病细胞增殖,促进供者完全嵌合状态的转变,增强GVL效应的作用,是一种安全有效的治疗方法,值得进一步临床研究。

     

    Abstract: Objective : To study the effect of transplantation of non-myeloablative allogeneic peripheral blood stem cells (NST) combined with Gleevec for treatment of the accelerated or blast-crisis (acute-transformation) phase of chronic myeloid leukemia (CML). Methods : Seven patients with CML were treated with Gleevec before (n=7) and after (n=5) transplantation of NST, with 4 in the accelerated phase (AP) and 3 in the blast-crisis phase (BP). The donors were matched as HLA-identical (n=2), a 5/6 antigen-match (n=2) or haplo-identical siblings (n=1) or mother (n=2). All of the patients took Gleevec before and after transplantation. The pretreatment regimen included CTX, Ara-C and Fludarabine, and in some cases, ATG, or Anti-CD3 monoclonal antibody. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine (CSA) and mycophenolate mofetil (MMF), in some cases with low-dose methotrexate (MTX) or Zenapax. Results : All 7 patients had a variable percent of donor cell chimerism: 3 had full chimerism, and 4 had mixed chimerism (44~95%). Full chimerism was transformed from the mixed chimerisms during the 1.5 to 10 months following NST through the withdrawal of the immunosuppressive agents, donor peripheral blood stem cell/donor lymphocyte infusions or treatment with Gleevec in 2 patients. Neutrophil levels reached 0.5×109/L within 16 days. Platelet levels reached 20×109/L within 10 days (range 4-15 days). Three cases had acute or chronic GVHD grade Ⅰ-Ⅱof skin. Two cases had chronic GVHD grade Ⅲ-Ⅳ. Two cases died of transplantation-related complications on day 27 and day 45 after transplantation. One patient died of cGVHD grade Ⅲ-Ⅳ. Four patients remain alive after a median follow-up of 12.2 months (range 7-17 months). The bcr/abl fusion was no longer detected within 33 to 130 days. No cases relapsed during follow-up. Conclusion : The treatment for CML consisting of NST combined with Gleevec before and after transplantation reduced leukemic cell load, inhibited the proliferation of residual leukemic cells, promoted full chimerism and enhanced the effect of the graft-versus-leukemia (GVL) immune response. It provided an effective and safe method for treating CML, especially advanced CML.

     

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