Laczika K, Mitterbauer G, Korninger L, Knöbl P, Schwarzinger I, Kapiotis S, Haas O A, Kyrle P A, Pont J, Oehler L
Department of Medicine, University of Vienna, Austria.
Leukemia. 1994 Jan;8(1):1-5.
The reverse transcriptase-polymerase chain reaction (RT-PCR) for the fusion transcript of PML-RAR alpha can be used to detect minimal residual disease (MRD) in acute promyelocytic leukemia (APL). We have applied a semi-quantitative two-step PCR assay (sensitivity: step 1 = 1 in 10(3) cells; step 2 = 1 in 10(6) cells) to monitor the dynamics of MRD after combined therapy with all-trans-retinoic acid (ATRA) and chemotherapy (CT) in 5 patients in whom complete clinical remission (CR) was achieved. The patients received an induction treatment with ATRA for 47, 40, 38, 14 or 10 days. In three patients ATRA was followed by CT. Two patients with hyperleukocytosis at diagnosis or after ATRA received an overlapping CT starting from day 3 or 7. Four of the five patients became two-step PCR-negative in their bone marrow within 43 to 82 days after onset of therapy. Two-step PCR-negatively was achieved with ATRA plus one course of CT in these four patients who are still in continuous complete remission after 19, 18, 7 and 5 months. One of these patients did not even receive consolidation CT because of congestive heart failure. The fifth patient remained second-step PCR-positive and relapsed after 5 months. Our results indicate that the combined regimen can rapidly reduce MRD below a detection limit of 1 in 10(6) cells within 1-3 months and that these results can even by achieved by a short course of ATRA together with only one cycle of CT.
用于检测PML-RARα融合转录本的逆转录聚合酶链反应（RT-PCR）可用于检测急性早幼粒细胞白血病（APL）中的微小残留病（MRD）。我们应用了一种半定量两步PCR检测法（灵敏度：第一步为1/10³细胞；第二步为1/10⁶细胞）来监测5例实现完全临床缓解（CR）的患者在接受全反式维甲酸（ATRA）和化疗（CT）联合治疗后MRD的动态变化。这些患者接受了47、40、38、14或10天的ATRA诱导治疗。3例患者在ATRA治疗后接受了CT治疗。2例诊断时或ATRA治疗后出现白细胞增多症的患者从第3天或第7天开始接受重叠CT治疗。5例患者中有4例在治疗开始后43至82天内骨髓两步PCR检测呈阴性。这4例患者通过ATRA加一个疗程的CT治疗实现了两步PCR阴性，在19、18、7和5个月后仍处于持续完全缓解状态。其中1例患者因充血性心力衰竭甚至未接受巩固性CT治疗。第5例患者两步PCR检测仍为阳性，5个月后复发。我们的结果表明，联合治疗方案可在1至3个月内迅速将MRD降至1/10⁶细胞的检测限以下，而且仅通过短疗程的ATRA加一个周期的CT治疗就能取得这些结果。
