Laczika K, Mitterbauer G, Mitterbauer M, Knöbl P, Schwarzinger I, Greinix H T, Rabitsch W, Fonatsch C, Mannhalter C, Lechner K, Jaeger U
Department of Medicine I, University of Vienna, Austria.
Leuk Lymphoma. 2001 Sep-Oct;42(5):923-31. doi: 10.3109/10428190109097711.
Minimal residual disease in patients with acute myeloid leukemia (AML) with inversion(16) can be monitored by CBFbeta/MYH11 RT-PCR. While the association between molecular remission (MR) in bone marrow (BM) and peripheral blood (PB) and long-term clinical remission (CR) seems to be established, there are insufficient data on the kinetics of CBFbeta/MYH11. We have performed a prospective study in order to generate a reasonable and sufficient schedule for PCR-monitoring. 11 patients with AML and inversion (16) in complete hematological remission have been prospectively monitored by CBFbeta/MYH11 RT-PCR in their BM and PB during an observation period of 7 to 67 months (median 32 months). Patients were followed during consolidation chemotherapy with repetitive cycles of high-dose Ara-C and after autologous or allogeneic stem cell transplantation in 2nd CR or refractory AML. MR never coincided with achievement of CR but occurred between 2 and 8 months after hematological remission. All patients in continuous CR were PCR-negative after 1-8 (median 4) months. Two patients relapsed despite MR for 10 to 15 months. Molecular relapse preceded hematological relapse by 3 to 5 months. Three out of four patients who were not in MR after 8 months relapsed. Allogeneic stem cell transplantation was able to eradicate minimal residual disease in 4/4 patients. In 2 patients a temporary reconversion to PCR-positivity was reversed by reduction of immunosuppression. 1 patient did not become PCR-negative until compete withdrawal of immunosuppression. We suggest that BM and PB should be examined after the last consolidation treatment. In case of MR, PB should be examined every 1 to 2 months and BM examination should be done only in case of PCR-positivity in PB in order to confirm the molecular relapse and to identify an impending cytogenetic and/or hematological relapse. CBFbeta/MYH11 RT-PCR monitoring is able to predict relapse 3 to 5 months prior to overt hematological relapse, offers a window of opportunity for preemptive therapy of molecular relapse and confers implications for immunotherapy in the setting of allografting.
伴有16号染色体倒位的急性髓系白血病（AML）患者的微小残留病可通过CBFβ/MYH11逆转录聚合酶链反应（RT-PCR）进行监测。虽然骨髓（BM）和外周血（PB）中的分子缓解（MR）与长期临床缓解（CR）之间的关联似乎已经确立，但关于CBFβ/MYH11动力学的数据不足。我们进行了一项前瞻性研究，以制定合理且充分的PCR监测方案。11例伴有16号染色体倒位且处于完全血液学缓解的AML患者在7至67个月（中位时间32个月）的观察期内接受了BM和PB的CBFβ/MYH11 RT-PCR前瞻性监测。患者在接受大剂量阿糖胞苷重复周期的巩固化疗期间以及在第二次完全缓解（CR）或难治性AML患者接受自体或异基因干细胞移植后接受随访。MR从未与CR的实现同时出现，而是发生在血液学缓解后的2至8个月之间。所有持续CR的患者在1至8个月（中位时间4个月）后PCR检测为阴性。2例患者尽管MR持续10至15个月仍复发。分子复发比血液学复发早3至5个月。8个月后未达到MR的4例患者中有3例复发。异基因干细胞移植能够在4/4例患者中根除微小残留病。2例患者通过降低免疫抑制使暂时恢复为PCR阳性的情况得到逆转。1例患者直到完全停用免疫抑制才变为PCR阴性。我们建议在最后一次巩固治疗后检查BM和PB。如果出现MR，应每1至2个月检查PB，仅在PB中PCR检测为阳性时才进行BM检查，以确认分子复发并识别即将发生的细胞遗传学和/或血液学复发。CBFβ/MYH11 RT-PCR监测能够在明显血液学复发前3至5个月预测复发，为分子复发的抢先治疗提供了机会窗口，并对同种异体移植中的免疫治疗具有启示意义。
