Sawyers C L, Timson L, Kawasaki E S, Clark S S, Witte O N, Champlin R
Department of Medicine, University of California, Los Angeles Center for the Health Sciences.
Proc Natl Acad Sci U S A. 1990 Jan;87(2):563-7. doi: 10.1073/pnas.87.2.563.
Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. We prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. We used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment (median, 15 months; range, 6-45 months) and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. In 2 patients BCR-ABL mRNA was detected in all samples, and both have developed cytogenetic relapse. In 1 patient BCR-ABL mRNA was detected transiently during the first month after transplant but was undetectable thereafter. The fourth patient had BCR-ABL mRNA 6 months after bone marrow transplantation but not in prior samples. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. We recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction.
慢性粒细胞白血病骨髓移植后复发可通过临床、细胞遗传学或分子手段检测出来。聚合酶链反应的一种改良方法可用于患者,以检测低水平的BCR-ABL编码的mRNA转录本,这是慢性粒细胞白血病的一种特异性标志物。骨髓移植后复发的早期检测可能会改变治疗决策。我们前瞻性地评估了19例骨髓移植后的患者,以寻找分子复发、细胞遗传学复发和临床复发的证据。我们使用聚合酶链反应检测治疗后随访长达45个月(中位时间为15个月;范围为6-45个月)的患者体内残留的BCR-ABL mRNA,发现4例患者在骨髓移植后有BCR-ABL mRNA表达。在2例患者中,所有样本均检测到BCR-ABL mRNA,且这2例患者均已出现细胞遗传学复发。在1例患者中,移植后第一个月短暂检测到BCR-ABL mRNA,但此后未检测到。第4例患者在骨髓移植后6个月检测到BCR-ABL mRNA,但之前的样本中未检测到。15例患者未表达可检测到的BCR-ABL mRNA。所有19例患者均处于临床缓解状态。在这项对接受骨髓移植治疗的慢性粒细胞白血病患者的前瞻性研究中,持续表达BCR-ABL mRNA的患者分子复发先于细胞遗传学复发。我们建议在进一步随访确定通过聚合酶链反应检测到残留BCR-ABL mRNA转录本的患者的临床结局之前,使用标准的临床和细胞遗传学检测来做出患者护理决策。