Gardiner N, Lawler M, O'Riordan J M, Duggan C, De Arce M, McCann S R
Department of Haematology, St James Hospital, Dublin, Ireland.
Bone Marrow Transplant. 1998 Apr;21(7):711-9. doi: 10.1038/sj.bmt.1701154.
Donor lymphocyte infusions (DLI) have been shown to enhance the graft-versus-leukaemia (GVL) effect and induce haematological and molecular remission in patients with relapsed CML following allogeneic bone marrow transplantation (BMT). The potent donor cell-mediated cytolysis following DLI may lead to a short period of aplasia before the re-establishment of donor haematopoiesis. The absence of detectable donor cells in patients prior to DLI infusion may result in permanent aplasia in certain patients. We report on four patients who relapsed 1, 3, 6.5 and 7 years post-BMT for chronic phase CML and were treated with DLI from their original BMT donor. Polymorphic short tandem repeats (STRs) were used to assess haematological chimaerism both prior to and following DLI. At the time of relapse, STR-PCR indicated the presence of donor cells in all four patients, at levels ranging from 1-40%. A clinical and molecular response was seen in 4/4 patients following a short period of cytopenia and all patients remain in clinical remission with a follow-up of 2 months-3 years post-DLI. STR-PCR indicated that a response was occurring during the period of pancytopenia when metaphase analysis was unsuccessful. Lineage-specific analysis of the cellular response to DLI was monitored using STR-PCR of peripheral blood (PB) and bone marrow (BM) lymphocyte-enriched fractions and CD2-positive and -negative T cell fractions. In one patient BM and PB CD34-positive and -negative fractions were also assessed. A change in the ratio of donor:recipient cells in the PB lymphocyte fraction was the earliest molecular indication of an anti-leukaemic response. Subsequent conversion to donor chimaerism occurred in the other lineages and the granulocyte fraction was the last lineage to convert. In conclusion, lineage-specific STR-PCR permits detailed monitoring of subtle changes in donor/recipient cell dynamics in specific lineages following DLI during the crucial pancytopenic phase and may be a useful predictor of haematological response to DLI therapy.
供体淋巴细胞输注（DLI）已被证明可增强异基因骨髓移植（BMT）后复发慢性粒细胞白血病（CML）患者的移植物抗白血病（GVL）效应，并诱导血液学和分子学缓解。DLI后强大的供体细胞介导的细胞溶解可能会在供体造血重建之前导致短期的再生障碍。在输注DLI之前患者体内未检测到供体细胞可能会导致某些患者永久性再生障碍。我们报告了4例慢性期CML患者，他们在BMT后1、3、6.5和7年复发，并接受了来自其原始BMT供体的DLI治疗。多态性短串联重复序列（STR）用于评估DLI前后的血液学嵌合情况。复发时，STR-PCR表明所有4例患者均存在供体细胞，水平范围为1%-40%。4例患者在短期血细胞减少后出现临床和分子反应，所有患者在DLI后2个月至3年的随访中均保持临床缓解。STR-PCR表明，在中期分析不成功的全血细胞减少期正在发生反应。使用外周血（PB）和骨髓（BM）淋巴细胞富集部分以及CD2阳性和阴性T细胞部分的STR-PCR监测对DLI的细胞反应的谱系特异性分析。在1例患者中，还评估了BM和PB CD34阳性和阴性部分。PB淋巴细胞部分中供体：受体细胞比例的变化是抗白血病反应的最早分子迹象。随后在其他谱系中转化为供体嵌合，粒细胞部分是最后转化的谱系。总之，谱系特异性STR-PCR允许在关键的全血细胞减少期详细监测DLI后特定谱系中供体/受体细胞动态的细微变化，并且可能是DLI治疗血液学反应的有用预测指标。
