Vora A, Frost L, Goodeve A, Wilson G, Ireland R M, Lilleyman J, Eden T, Peake I, Richards S
Molecular Haematology Unit, Children's and Royal Hallamshire Hospital, Sheffield, UK.
Blood. 1998 Oct 1;92(7):2334-7.
Childhood lymphoblastic leukemia (ALL) is usually assumed to have been permanently eradicated in patients in long-term remission, but occasionally can recur after many years. To learn more about the problem, we studied a group of children whose leukemia had been in remission for 10 or more years before relapse and tried to determine whether they had true recurrences or second malignancies. We studied children treated on Medical Research Council ALL protocols between 1970 and 1984 and followed up by the Clinical Trial Service Unit in Oxford. Detailed clinical and laboratory data was collected from the centers concerned on all who were reported to have had a recurrence of their leukemia after 10 or more years from the time of achieving first complete remission (CR1). To prove that the relapse was a true recurrence rather than a second or secondary leukemia, DNA extracted from archived marrow smears was subjected to polymerase chain reaction (PCR) analysis for the presence of an identical Ig heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement at initial diagnosis and subsequent relapse. A total of 1,134 of 2,746 children had survived 10 years or more (range, 10 to 24 years) in CR1 and of those, 12 (approximately 1%) had subsequently relapsed. Relapse blast cells were shown to express the common ALL antigen (CD 10) in all cases and an identical clonal IgH or TCR gene rearrangement was found on PCR analysis of DNA from diagnosis and relapse in all eight cases where DNA extraction was successful. A further program of therapy was successful in inducing a second CR in all patients, four of whom have succumbed to a second relapse after 12 to 27 months. The remaining eight are in continuing CR2 at a follow-up of 12 to 108 months (median, 52) from relapse. Although the risk of relapse of childhood ALL after 10 years in remission appears to be small (around 1%), it persists. This raises questions about how blasts can survive quiescent for so long and when we can truly be confident of cure, if ever.
儿童淋巴细胞白血病（ALL）通常被认为在长期缓解的患者中已被永久根除，但偶尔会在多年后复发。为了更多地了解这个问题，我们研究了一组白血病在复发前已缓解10年或更长时间的儿童，并试图确定他们是真正复发还是发生了第二原发性恶性肿瘤。我们研究了1970年至1984年间按照医学研究委员会ALL方案接受治疗并由牛津临床试验服务部进行随访的儿童。从相关中心收集了所有在首次完全缓解（CR1）后10年或更长时间报告白血病复发者的详细临床和实验室数据。为了证明复发是真正的复发而非第二原发性或继发性白血病，对从存档骨髓涂片提取的DNA进行聚合酶链反应（PCR）分析，以检测初始诊断和随后复发时是否存在相同的免疫球蛋白重链（IgH）或T细胞受体（TCR）基因重排。2746名儿童中有1134名在CR1状态下存活了10年或更长时间（范围为10至24年），其中12名（约1%）随后复发。所有病例的复发原始细胞均显示表达常见的ALL抗原（CD10），在DNA提取成功的所有8例病例中，PCR分析诊断和复发时的DNA发现了相同的克隆性IgH或TCR基因重排。进一步的治疗方案成功诱导所有患者再次达到CR，其中4例在12至27个月后死于第二次复发。其余8例在复发后12至108个月（中位数为52个月）的随访中处于持续的CR2状态。尽管儿童ALL缓解10年后复发的风险似乎较小（约1%），但这种风险仍然存在。这引发了关于原始细胞如何能长期处于静止状态存活以及我们何时才能真正确信治愈（如果能治愈的话）的问题。
