Stark Batia, Avigad Smadar, Luria Drorit, Manor Sigal, Reshef-Ronen Tali, Avrahami Gali, Yaniv Isaac
Center of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel.
Pediatr Blood Cancer. 2009 Jan;52(1):20-5. doi: 10.1002/pbc.21823.
Despite overlapping features of T-cell lymphoblastic lymphoma (T-LLy) and T-cell acute lymphoblastic leukemia (T-ALL), which respond favorably to T-ALL treatment, clinical and biological differences exist. We retrospectively assessed the prevalence of submicroscopic bone marrow (BM) minimal disseminated disease (MDD) at diagnosis and the early response to treatment (minimal residual disease--MRD) and their prognostic significance in 17 children with stage III T-LLy treated according to Berlin-Frankfurt-Munster (BFM) non-Hodgkin lymphoma protocols.
Four-color flow cytometry (FC) was used for lymphoma associated immunophenotype and real-time quantitative polymerase chain reaction (RQ-PCR) for T-cell receptor (TCR beta/delta/gamma) gene rearrangements with at least 0.01% sensitivity.
Two markers per patient were identified in all cases using FC and in 80% using RQ-PCR. BM MDD at diagnosis of >or=0.01% was detected by FC and RQ-PCR in 88% and 80% of patients, respectively, and by at least one of the methods in all patients. A significant correlation was achieved between the methods by Pearson correlation analysis (P = 0.004). MRD levels significantly decreased to very low levels on day 33 in 9 out of 10 patients studied. The only patient that remained positive relapsed.
MDD was prevalent in stage III T-LLy, for which we could not prove a prognostic significance in the context of ALL-like treatment. This study shows that both FC and RQ-PCR methods are efficient for MDD and MRD analyses in T-LLy.
尽管T细胞淋巴母细胞淋巴瘤(T-LLy)和T细胞急性淋巴细胞白血病(T-ALL)具有重叠特征,且对T-ALL治疗反应良好,但它们在临床和生物学上存在差异。我们回顾性评估了17例根据柏林-法兰克福-明斯特(BFM)非霍奇金淋巴瘤方案治疗的III期T-LLy患儿在诊断时亚显微镜下骨髓(BM)微小播散性疾病(MDD)的患病率以及对治疗的早期反应(微小残留病-MRD)及其预后意义。
采用四色流式细胞术(FC)检测淋巴瘤相关免疫表型,采用实时定量聚合酶链反应(RQ-PCR)检测T细胞受体(TCRβ/δ/γ)基因重排,灵敏度至少为0.01%。
所有病例均通过FC鉴定出每位患者两个标志物,80%的病例通过RQ-PCR鉴定出。分别有88%和80%的患者通过FC和RQ-PCR检测到诊断时BM MDD≥0.01%,所有患者中至少有一种方法检测到。通过Pearson相关分析,两种方法之间具有显著相关性(P = 0.004)。在研究的10例患者中,有9例在第33天时MRD水平显著降至极低水平。唯一仍为阳性的患者复发。
MDD在III期T-LLy中普遍存在,在类似ALL的治疗背景下,我们无法证明其具有预后意义。本研究表明,FC和RQ-PCR方法在T-LLy的MDD和MRD分析中均有效。