Gardiner N, Lawler M, O'Riordan J, DeArce M, Humphries P, McCann S R
Department of Haematology/Oncology, St James Hospital, Dublin, Ireland.
Bone Marrow Transplant. 1997 Aug;20(3):235-41. doi: 10.1038/sj.bmt.1700861.
Chronic myeloid leukaemia (CML) can be treated successfully with allogeneic bone marrow transplantation (BMT) leading to long-term disease-free survival. Leukemia relapse, however, remains a significant clinical problem. Relapse following BMT presumably results from the expansion of small numbers of recipient leukaemic cells which have survived the conditioning therapy. In order to define patients who are at a high risk of leukaemia relapse, a variety of techniques have been employed to detect persistence of host haemopoiesis (mixed chimaerism, MC) or residual leukaemia (minimal residual disease, MRD). However, the precise relationship between the detection of MC and MRD post-BMT is unknown. We have investigated chimaerism and MRD status in 22 patients who were in clinical and haematological remission post-allogeneic BMT for chronic phase CML. Chimaerism was assessed using short tandem repeat PCR (STR-PCR) while BCR-ABL mRNA detection using reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect the presence of MRD. Seventeen patients received unmanipulated marrow (non-TCD) while in five patients a T cell-depleted transplant (TCD) was performed as additional GVHD prophylaxis. Chimaerism was evaluated in 18 patients (14 non-TCD, four TCD). Mixed chimaerism was an uncommon finding in recipients of unmanipulated BMT (21%) when compared to TCD BMT (100%). No evidence of MRD, as identified using the BCR-ABL mRNA RT-PCR assay, was detected in those patients who were donor chimaeras. Early and transient MC and MRD was detected in four patients (two non-TCD, two TCD) who have subsequently converted to a donor profile. One patient has stable low-level MC but remains MRD negative 4 years post-BMT. Late MC and MRD was observed in two patients who relapsed >6 years after TCD BMT for CML. We conclude that mixed chimaerism is a rare event in recipients of unmanipulated BMT and that donor chimaerism as detected by STR-PCR assay is consistent with disease-free survival and identifies patients with a low risk of leukaemic relapse post-BMT for CML.
慢性粒细胞白血病（CML）可通过异基因骨髓移植（BMT）成功治疗，从而实现长期无病生存。然而，白血病复发仍然是一个重大的临床问题。BMT后复发可能是由于少量在预处理治疗中存活下来的受者白血病细胞扩增所致。为了确定白血病复发风险高的患者，已采用多种技术来检测宿主造血的持续性（混合嵌合体，MC）或残留白血病（微小残留病，MRD）。然而，BMT后MC和MRD检测之间的确切关系尚不清楚。我们调查了22例慢性期CML异基因BMT后处于临床和血液学缓解期的患者的嵌合体和MRD状态。使用短串联重复序列PCR（STR-PCR）评估嵌合体，同时使用逆转录聚合酶链反应（RT-PCR）检测BCR-ABL mRNA以检测MRD的存在。17例患者接受了未处理的骨髓（非T细胞去除，non-TCD），而5例患者进行了T细胞去除移植（TCD）作为额外的移植物抗宿主病（GVHD）预防措施。对18例患者（14例non-TCD，4例TCD）进行了嵌合体评估。与TCD BMT（100%）相比，混合嵌合体在未处理BMT受者中是一个不常见的发现（21%）。在那些为供体嵌合体的患者中，未检测到使用BCR-ABL mRNA RT-PCR检测法确定的MRD证据。在4例患者（2例non-TCD，2例TCD）中检测到早期和短暂的MC和MRD，这些患者随后已转变为供体状态。1例患者有稳定的低水平MC，但在BMT后4年仍为MRD阴性。在2例CML患者TCD BMT后6年以上复发的患者中观察到晚期MC和MRD。我们得出结论，混合嵌合体在未处理BMT受者中是罕见事件，并且通过STR-PCR检测法检测到的供体嵌合体与无病生存一致，并识别出CML患者BMT后白血病复发风险低的患者。
