Knechtli C J, Goulden N J, Hancock J P, Grandage V L, Harris E L, Garland R J, Jones C G, Rowbottom A W, Hunt L P, Green A F, Clarke E, Lankester A W, Cornish J M, Pamphilon D H, Steward C G, Oakhill A
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, UK.
Blood. 1998 Dec 1;92(11):4072-9.
The efficacy of allografting in acute lymphoblastic leukemia (ALL) is heavily influenced by remission status at the time of transplant. Using polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis, we have investigated retrospectively the impact of submicroscopic leukemia on outcome in 64 patients receiving allogeneic bone marrow transplantation (BMT) for childhood ALL. Remission BM specimens were taken 6 to 81 days (median, 23) before transplant. All patients received similar conditioning therapy; 50 received grafts from unrelated donors and 14 from related donors. Nineteen patients were transplanted in first complete remission (CR1) and 45 in second or subsequent CR. MRD was analyzed by PCR of Ig or T-cell receptor delta or gamma rearrangements, electrophoresis, and allele-specific oligoprobing. Samples were rated high-level positive (clonal band evident after electrophoresis; sensitivity 10(-2) to 10(-3)), low-level positive (MRD detected only after oligoprobing; sensitivity 10(-3) to 10(-5)), or negative. Excluding 8 patients transplanted in CR2 for isolated extramedullary relapse (all MRD-), MRD was detected at high level in 12 patients, low level in 11, and was undetectable in 33. Two-year event-free survival for these groups was 0%, 36%, and 73%, respectively (P <.001). Follow-up in patients remaining in continuing remission is 20 to 96 months (median, 35). These results suggest that MRD analysis could be used routinely in this setting. This would allow identification of patients with resistant leukemia (who may benefit from innovative BMT protocols) and of those with more responsive disease (who may be candidates for randomized trials of BMT versus modern intensive relapse chemotherapy).
同种异体移植治疗急性淋巴细胞白血病（ALL）的疗效在很大程度上受移植时缓解状态的影响。我们采用基于聚合酶链反应（PCR）的微小残留病（MRD）分析方法，对64例接受异基因骨髓移植（BMT）治疗儿童ALL的患者进行回顾性研究，以探讨亚显微镜下白血病对预后的影响。在移植前6至81天（中位数为23天）采集缓解期骨髓标本。所有患者均接受相似的预处理方案；50例接受无关供者的移植物，14例接受相关供者的移植物。19例患者在首次完全缓解（CR1）期接受移植，45例在第二次或后续缓解期接受移植。通过对免疫球蛋白或T细胞受体δ或γ重排进行PCR、电泳及等位基因特异性寡核苷酸探针杂交分析MRD。样本分为高水平阳性（电泳后可见克隆条带；灵敏度为10^(-2)至10^(-3)）、低水平阳性（仅在寡核苷酸探针杂交后检测到MRD；灵敏度为10^(-3)至10^(-5)）或阴性。排除8例因孤立髓外复发在CR2期接受移植的患者（均为MRD阴性），12例患者检测到高水平MRD，11例检测到低水平MRD，33例未检测到MRD。这些组的两年无事件生存率分别为0%、36%和73%（P<.001）。仍处于持续缓解状态的患者随访时间为20至96个月（中位数为35个月）。这些结果表明，MRD分析可在此情况下常规使用。这将有助于识别白血病耐药患者（可能从创新的BMT方案中获益）以及疾病反应性更强的患者（可能成为BMT与现代强化复发化疗随机试验的候选者）。
