Toubai Tomomi, Tanaka Junji, Ota Shuichi, Fukuhara Takashi, Hashino Satoshi, Kondo Takeshi, Kasai Masaharu, Kakinoki Yasutaka, Masauzi Nobuo, Morioka Masanobu, Kawamura Tsugumichi, Iwasaki Hiroshi, Asaka Masahiro, Imamura Masahiro
Department of Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Am J Hematol. 2005 Nov;80(3):181-7. doi: 10.1002/ajh.20461.
We evaluate whether molecular monitoring of minimal residual disease (MRD) using TCR delta (TCRD), TCR gamma (TCRG), and immunoglobulin H (IgH) gene rearrangements in the bone marrow (BM) is correlated with clinical events in ALL patients. The 14 patients enrolled in this study included 6 males and 8 females with a median age of 53 years (range, 25-79 years), and the median duration of follow-up was 417 days (range, 57-617 days). The median WBC count was 11.3 x 10(9)/L at diagnosis. All patients had L2 type ALL. Eleven patients had a monoclonal pattern of IgH (7), TCRD (3) and TCRG (1), and 3 patients had two clonal patterns. Eleven of the 14 patients achieved the first complete remission (CR) after the first induction chemotherapy. We analyzed 9 of 11 CR patients who could be examined immediately after induction chemotherapy (including re-induction therapy). Event-free survival (EFS, 0%) and disease-free survival (DFS, 0%) at 1 year in CR patients with MRD level >or=10(-3) (n = 3) were significantly lower than those in CR patients with MRD level <10(-3) (n = 6) (log-rank test, P = 0.013, 0.013). A lower MRD in BM value after induction chemotherapy was associated significantly with longer survival in the log-rank test. Our data provide evidence that molecular MRD status of BM is a strong predictor of outcome in adult ALL.
我们评估了采用骨髓（BM）中TCRδ（TCRD）、TCRγ（TCRG）和免疫球蛋白H（IgH）基因重排对微小残留病（MRD）进行分子监测是否与急性淋巴细胞白血病（ALL）患者的临床事件相关。本研究纳入的14例患者中，男性6例，女性8例，中位年龄53岁（范围25 - 79岁），中位随访时间为417天（范围57 - 617天）。诊断时白细胞计数中位数为11.3×10⁹/L。所有患者均为L2型ALL。11例患者具有IgH（7例）、TCRD（3例）和TCRG（1例）的单克隆模式，3例患者具有两种克隆模式。14例患者中有11例在首次诱导化疗后达到首次完全缓解（CR）。我们分析了11例CR患者中的9例，这些患者在诱导化疗后（包括再诱导治疗）可立即进行检测。MRD水平≥10⁻³的CR患者（n = 3）1年时的无事件生存期（EFS，0%）和无病生存期（DFS，0%）显著低于MRD水平<10⁻³的CR患者（n = 6）（对数秩检验，P = 0.013，0.013）。诱导化疗后BM值中较低的MRD与对数秩检验中较长的生存期显著相关。我们的数据表明，BM的分子MRD状态是成人ALL预后的有力预测指标。
