Gameiro Paula, Mortuza Forida Y, Hoffbrand A Victor, Foroni Letizia
Department of Hematology, Royal Free and University College School of Medicine, Rowland Hill Street, London, UK.
Haematologica. 2002 Nov;87(11):1126-34.
Minimal residual disease (MRD) is important in the measurement of response to treatment in childhood B- and T-cell acute lymphoblastic leukemia (ALL) and in adult B-cell ALL. Little is known about MRD evaluation in adult T-cell ALL. This study aimed to determine the prognostic significance of MRD measurements in adult T-cell ALL.
T-cell receptor (TCR) gamma (G) and TCR delta (D) gene analyses were carried out at presentation in 49 patients with de novo T-ALL using a polymerase chain reaction (PCR) approach. In 26 of the patients bone marrow (BM) samples were collected at sequential time points (0-2, 3-5, 6-9, 10-24 months) after diagnosis for MRD investigation. The relationship between MRD status and clinical outcome was investigated and correlated with age, gender and white blood cell count at presentation.
TCRG clonal gene rearrangements were found in 40 patients (82%). Eleven patients showed TCRD rearrangements (22%), in one of them as the sole molecular marker. V(gamma)I family rearrangements predominated (45 of 65 alleles) together with V(delta)1-J(delta)1/2 (9 of 13 alleles). Continuous clinical remission (CCR) occurred in 17 patients while nine patients relapsed. MRD analysis showed that negative tests during the first 6 months post-induction, and persisting negative MRD after induction were the best predictors of CCR. A positive test after 5 months was better at predicting relapse. In only four of seven patients was relapse preceded by a positive test the 5 months preceding relapse.
Overall the ability of positive and negative tests to predict relapse or CCR was weaker in this cohort of adult T-ALL patients than in T- and B-lineage childhood ALL and B-lineage adult ALL. TCRG and TCRD gene analysis provides a clonal marker in the majority of adult T-ALL. These results suggest that caution should be taken in using MRD data based on TCR gene rearrangements to predict prognosis in adult T-ALL. Biological reasons may underlie differences between the performance of MRD tests in B- and T-lineage ALL. Further studies in a larger cohort of patients are needed to determine the exact role that MRD determination has in the management of T-ALL in adults.
微小残留病（MRD）对于儿童B细胞和T细胞急性淋巴细胞白血病（ALL）以及成人B细胞ALL治疗反应的评估至关重要。关于成人T细胞ALL的MRD评估知之甚少。本研究旨在确定MRD检测在成人T细胞ALL中的预后意义。
采用聚合酶链反应（PCR）方法，对49例初发T-ALL患者就诊时进行T细胞受体（TCR）γ（G）和TCRδ（D）基因分析。26例患者在诊断后的连续时间点（0 - 2、3 - 5、6 - 9、10 - 24个月）采集骨髓（BM）样本进行MRD研究。研究MRD状态与临床结局之间的关系，并与就诊时的年龄、性别和白细胞计数进行关联分析。
40例患者（82%）发现TCRG克隆基因重排。11例患者出现TCRD重排（22%），其中1例为唯一的分子标志物。V（γ）I家族重排占主导（65个等位基因中的45个），同时V（δ）1 - J（δ）1/2重排（13个等位基因中的9个）。17例患者持续临床缓解（CCR），9例患者复发。MRD分析表明，诱导后前6个月检测为阴性，且诱导后持续MRD阴性是CCR的最佳预测指标。诱导后5个月检测为阳性对复发的预测效果更好。在7例复发患者中，仅有4例在复发前5个月检测为阳性。
总体而言，在该成人T-ALL患者队列中，阳性和阴性检测预测复发或CCR的能力比儿童T细胞和B细胞ALL以及成人B细胞ALL队列中的弱。TCRG和TCRD基因分析在大多数成人T-ALL中提供了一个克隆标志物。这些结果表明，在使用基于TCR基因重排的MRD数据预测成人T-ALL预后时应谨慎。生物学原因可能是B细胞和T细胞ALL中MRD检测性能差异的基础。需要对更大患者队列进行进一步研究，以确定MRD检测在成人T-ALL管理中的确切作用。
