Gruhn B, Hongeng S, Yi H, Hancock M L, Rubnitz J E, Neale G A, Kitchingman G R
Department of Virology and Molecular Biology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Leukemia. 1998 May;12(5):675-81. doi: 10.1038/sj.leu.2400985.
We investigated the level of minimal residual disease (MRD) in 26 children with B-lineage acute lymphoblastic leukemia (ALL) after intensive induction therapy. A quantitative semi-nested polymerase chain reaction (PCR) detecting the clone-specific rearranged immunoglobulin heavy chain genes was developed to improve sensitivity and specificity of amplification. In all patients, one leukemic cell could be detected in a background of 10(5) normal blood mononuclear cells. All patients investigated were in complete remission at the end of induction therapy as evaluated by morphologic criteria. Nineteen patients (73%) had no detectable residual leukemic cells using the sensitive semi-nested PCR. Seven patients (27%) were PCR positive. Three had a low level (<2 x 10(-5) leukemic cells per bone marrow cell), while four patients had a high level (>2 x 10(5)) of detectable residual leukemic cells. All patients with low or undetectable levels of residual leukemia remained in complete remission at a median of 63 months from diagnosis (range 40-80 months), while all four patients with a high level of residual leukemia subsequently relapsed at a median of 21 months from diagnosis (range 13-37 months). The patient groups with undetectable or low, and high level of MRD did not differ significantly in other clinical or genetic features with prognostic significance. We conclude that the level of MRD at the end of the intensive induction therapy period is predictive of outcome in childhood B lineage ALL. If confirmed by large prospective studies, the level of MRD might be useful in stratifying patients into high and low risk categories.
我们调查了26例B系急性淋巴细胞白血病（ALL）患儿在强化诱导治疗后的微小残留病（MRD）水平。开发了一种定量半巢式聚合酶链反应（PCR）来检测克隆特异性重排的免疫球蛋白重链基因，以提高扩增的敏感性和特异性。在所有患者中，在10⁵个正常血液单核细胞的背景下可检测到一个白血病细胞。根据形态学标准评估，所有接受调查的患者在诱导治疗结束时均处于完全缓解状态。使用敏感的半巢式PCR，19例患者（73%）未检测到残留白血病细胞。7例患者（27%）PCR呈阳性。3例患者残留白血病细胞水平较低（每骨髓细胞<2×10⁻⁵个白血病细胞），而4例患者残留白血病细胞水平较高（>2×10⁻⁵）。所有残留白血病水平低或未检测到的患者自诊断起中位63个月（范围40 - 80个月）仍处于完全缓解状态，而所有4例残留白血病水平高的患者随后自诊断起中位21个月（范围13 - 37个月）复发。MRD水平不可检测或低水平组与高水平组在其他具有预后意义的临床或遗传特征方面无显著差异。我们得出结论，强化诱导治疗期结束时的MRD水平可预测儿童B系ALL的预后。如果大型前瞻性研究证实，MRD水平可能有助于将患者分为高风险和低风险类别。
