Schaap N, Schattenberg A, Bär B, Mensink E, de Man A, Geurts van Kessel A, de Witte T
Department of Haematology, University Hospital Nijmegen, The Netherlands.
Br J Haematol. 2000 Jan;108(1):116-25. doi: 10.1046/j.1365-2141.2000.01803.x.
Fifteen consecutive patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukaemia (CML) who relapsed from T-cell-depleted bone marrow transplantation (BMT) were successfully treated with donor leucocyte infusions (DLIs). Chimaerism was analysed using red blood cell phenotyping (RCP), and the results were compared with cytogenetic analysis and outcome of qualitative and quantitative polymerase chain reaction (PCR) for breakpoint molecules. In all patients, an increase in autologous erythrocytes and/or a decrease in donor red cells indicated relapse. Donor erythrocytes started to increase from 4 to 20 (median 12) weeks after DLI. At 6 and 12 months after DLI, complete donor chimaerism was found in 11 and 15 patients, respectively, and all patients were in cytogenic remission. A high percentage of autologous red cells at the time of DLI predicted pancytopenia. During relapse and after DLI, the percentage of autologous red cells was strongly correlated with the reappearance and disappearance of Ph-positive metaphases (r = 0.90; P < 0.001 and r = 0.96; P < 0.001 respectively). The same was true for the correlation between the percentage of autologous red cells and positivity/negativity in PCR for Bcr-Abl breakpoint molecules (r = 0.94; P < 0.001). A normalized Bcr-Abl dose of greater than 10-3 in real-time quantitative PCR correlated well with relapse and the presence of autologous red blood cells (r = 0.77; P < 0.001). We conclude that RCP is a sensitive, easy to perform and fast technique for the prediction of pending relapse after BMT for CML. RCP also predicts the response to DLI and the occurrence of bone marrow aplasia after DLI.
15例费城染色体(Ph)阳性的慢性粒细胞白血病(CML)患者在接受去除T细胞的骨髓移植(BMT)后复发,通过供体白细胞输注(DLI)成功得到治疗。采用红细胞表型分析(RCP)检测嵌合体,并将结果与细胞遗传学分析以及断裂点分子的定性和定量聚合酶链反应(PCR)结果进行比较。在所有患者中,自体红细胞增加和/或供体红细胞减少均提示复发。供体红细胞在DLI后4至20周(中位数为12周)开始增加。在DLI后6个月和12个月时,分别有11例和15例患者实现完全供体嵌合,所有患者均处于细胞遗传学缓解状态。DLI时自体红细胞比例高预示全血细胞减少。在复发期间及DLI后,自体红细胞比例与Ph阳性中期相的再现和消失密切相关(分别为r = 0.90;P < 0.001和r = 0.96;P < 0.001)。自体红细胞比例与Bcr-Abl断裂点分子PCR阳性/阴性之间的相关性也是如此(r = 0.94;P < 0.001)。实时定量PCR中标准化的Bcr-Abl剂量大于10^-3与复发及自体红细胞的存在密切相关(r = 0.77;P < 0.001)。我们得出结论,RCP是一种敏感、易于操作且快速的技术,可用于预测CML患者BMT后即将发生的复发。RCP还可预测对DLI的反应以及DLI后骨髓再生障碍的发生。