Tallman M S, Hakimian D, Kopecky K J, Wheaton S, Wollins E, Foucar K, Cassileth P A, Habermann T, Grever M, Rowe J M, Peterson L C
Northwestern University Medical School, Robert H. Lurie Comprehensive Cancer Center of Northwestern University Chicago, Illinois 60611, USA.
Clin Cancer Res. 1999 Jul;5(7):1665-70.
The purine nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) induce complete remission (CR) in the majority of patients with hairy cell leukemia. However, minimal residual disease (MRD) has been detected in bone marrow core biopsies using immunohistochemical techniques in patients achieving CR by conventional criteria. This study was designed to compare the prevalence of MRD with each agent in patients in CR by using conventional criteria and the relapse-free survival for patients with and without MRD. Bone marrow biopsies from 39 patients treated with a single cycle of 2-CdA and 27 patients treated with multiple cycles of 2'-DCF were studied. The monoclonal antibodies anti-CD20, DBA.44, and anti-CD45RO were used to evaluate the paraffin-embedded bone marrow core biopsies for MRD. Five of 39 patients (13%) treated with 2-CdA had MRD, as compared to 7 of 27 patients (26%) treated with 2'-DCF (two-tailed P = 0.21). Relapse has occurred in two of the five patients with MRD after 2-CdA treatment and in four of the seven patients with MRD after 2'-DCF treatment. In total, 6 of the 12 patients (50%) with MRD have relapsed, whereas 3 of 54 patients (6%) without MRD have relapsed, and 2 patients have died without evidence of relapse. The estimated 4-year relapse-free survival among patients with MRD is 55% (+/- 15%, SE), compared to 88% (+/- 5%, SE) among patients without MRD (two-tailed P = 0.0023). The prevalence of MRD detected in a subset of patients in CR after either 2-CdA or 2'-DCF treatment did not differ significantly. However, the presence of MRD is associated with an increased risk of relapse.
嘌呤核苷类似物2-氯脱氧腺苷(2-CdA)和2'-脱氧助间型霉素(2'-DCF)可使大多数毛细胞白血病患者获得完全缓解(CR)。然而,在通过传统标准达到CR的患者中,使用免疫组织化学技术在骨髓芯活检中检测到了微小残留病(MRD)。本研究旨在比较采用传统标准达到CR的患者中,每种药物治疗后MRD的发生率,以及有和无MRD患者的无复发生存率。对39例接受单周期2-CdA治疗的患者和27例接受多周期2'-DCF治疗的患者的骨髓活检进行了研究。使用抗CD20、DBA.44和抗CD45RO单克隆抗体评估石蜡包埋的骨髓芯活检中的MRD。接受2-CdA治疗的39例患者中有5例(13%)存在MRD,而接受2'-DCF治疗的27例患者中有7例(26%)存在MRD(双侧P = 0.21)。2-CdA治疗后,5例有MRD的患者中有2例复发;2'-DCF治疗后,7例有MRD的患者中有4例复发。总体而言,12例有MRD的患者中有6例(50%)复发,而54例无MRD的患者中有3例(6%)复发,2例患者未复发死亡。有MRD患者的估计4年无复发生存率为55%(±15%,SE),无MRD患者为88%(±5%,SE)(双侧P = 0.0023)。在接受2-CdA或2'-DCF治疗后达到CR的部分患者中检测到的MRD发生率无显著差异。然而,MRD的存在与复发风险增加相关。