Roddie H, Klammer M, Thomas C, Thomson R, Atkinson A, Sproul A, Waterfall M, Samuel K, Yin J, Johnson P, Turner M
Haematology Department, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
Br J Haematol. 2006 Apr;133(2):152-7. doi: 10.1111/j.1365-2141.2006.05997.x.
Twenty-two patients with acute myeloid leukaemia were recruited into a phase I/II clinical trial investigating the vaccination of patients in complete remission (CR) with autologous dendritic-like leukaemia cells (DLLC). At trial entry, leukaemia cells were harvested and tested for their ability to undergo cytokine-induced dendritic cell differentiation. Patients were then treated with intensive chemotherapy. Five patients achieved both CR and had leukaemia cells that successfully underwent differentiation and therefore proceeded to vaccination. Four escalating doses of DLLC were administered weekly by subcutaneous injection. Vaccination was generally well tolerated although one patient developed extensive eczema and an increased antinuclear factor titre possibly indicating induction of autoimmunity. Development of anti-leukaemic T-cell responses was assessed by enzyme-linked immunospot analysis of gamma-interferon secreting T lymphocytes and by human leucocyte antigen tetramer analysis for WT1-specific T cells. Increases in anti-leukaemic T-cell responses were demonstrated in four patients, but only two of the five remained in remission more than 12 months postvaccination. The study has demonstrated that generation of DLLC is feasible in only a subgroup of patients and is currently neither broadly applicable or clinically effective.
22例急性髓系白血病患者被纳入一项I/II期临床试验，该试验旨在研究用自体树突状样白血病细胞（DLLC）对完全缓解（CR）的患者进行疫苗接种。在试验开始时，采集白血病细胞并检测其进行细胞因子诱导的树突状细胞分化的能力。然后患者接受强化化疗。5例患者达到CR且白血病细胞成功分化，因此进入疫苗接种阶段。通过皮下注射每周给予4个递增剂量的DLLC。疫苗接种一般耐受性良好，尽管有1例患者出现广泛湿疹且抗核因子滴度升高，这可能表明诱发了自身免疫。通过对分泌γ-干扰素的T淋巴细胞进行酶联免疫斑点分析以及对WT1特异性T细胞进行人类白细胞抗原四聚体分析来评估抗白血病T细胞反应的发展。4例患者显示抗白血病T细胞反应增加，但5例患者中只有2例在接种疫苗后12个月以上仍处于缓解状态。该研究表明，仅在部分患者亚组中生成DLLC是可行的，目前既没有广泛适用性也没有临床有效性。
