Minimal residual disease in childhood B-lineage lymphoblastic leukemia. Persistence of leukemic cells during the first 18 months of treatment.
Minimal residual disease in childhood B-lineage lymphoblastic leukemia. Persistence of leukemic cells during the first 18 months of treatment.
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DOI：
10.1056/nejm199008163230705
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发表时间：
1990-08
期刊：
影响因子：
--
通讯作者：
Masao Yamada;R. Wasserman;Beverly J. Lange;B. A. Reichard;R. Womer;Giovanni Rovera
中科院分区：
文献类型：
--
作者：
Masao Yamada;R. Wasserman;Beverly J. Lange;B. A. Reichard;R. Womer;Giovanni Rovera
急性淋巴细胞白血病（ALL）临床缓解期患者是否继续携带白血病细胞尚不清楚，因为检测残留恶性细胞的方法还不够敏感。这些信息可能有助于预测复发和确定治疗的持续时间。方法采用一种敏感的新方法--聚合酶链反应鉴定互补决定区III序列--我们估计了8例B系淋巴细胞白血病患儿缓解前后骨髓中残留白血病细胞的数量。结果诱导化疗使白血病细胞数量减少3-4-log。然而，在诊断后18个月内获得的所有样本中，0.004%至2.6%的骨髓有核细胞是残留的白血病细胞。在诊断后超过18个月的四名患者中，三名患者的骨髓样本中没有检测到白血病细胞。尽管如此，其中一人不再接受治疗，中枢神经系统复发。在一名接受维持化疗的患者中，骨髓复发前三个月白血病细胞增加了60倍。结论：白血病细胞的完全消失（或减少到我们方法的检测阈值以下，10万分之一）可能是治愈ALL所必需的。在治疗过程中连续骨髓抽吸物中残留白血病细胞的定量可以早期检测复发。
BACKGROUND Whether patients in clinical remission for acute lymphoblastic leukemia (ALL) continue to harbor leukemic cells is not known, because methods of detecting residual malignant cells have not been sufficiently sensitive. This information might be useful for predicting recurrence and determining the duration of therapy. METHODS Using a sensitive new method--identifying complementarity-determining region III sequences with the polymerase chain reaction--we estimated the number of residual leukemic cells in the bone marrow of eight children with B-lineage lymphoblastic leukemia before and after remission. RESULTS Induction chemotherapy produced a 3-to-4-log reduction in the number of leukemic cells. In all samples obtained up to 18 months after diagnosis, however, 0.004 to 2.6 percent of bone marrow nucleated cells were residual leukemic cells. Among the four patients studied more than 18 months after diagnosis, three had no detectable leukemic cells in marrow samples. Despite this, one of them, who was no longer receiving therapy, had a central nervous system relapse. In one patient receiving maintenance chemotherapy, there was a 60-fold increase in leukemic cells three months before bone marrow relapse. CONCLUSIONS The complete disappearance of leukemic cells (or their reduction below our method's threshold of detection, 1 in 100,000 cells) may be necessary to achieve a cure of ALL. The quantification of residual leukemic cells in serial marrow aspirates during therapy may allow the early detection of relapse.