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慢性粒细胞白血病患者接受α-干扰素治疗后完全细胞遗传学缓解者的分子异质性:微小残留病低水平与持续缓解相关。德国慢性粒细胞白血病研究组和英国医学研究理事会慢性粒细胞白血病研究组

Molecular heterogeneity in complete cytogenetic responders after interferon-alpha therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission. German CML Study Group and the UK MRC CML Study Group.

作者信息

Hochhaus A, Reiter A, Saussele S, Reichert A, Emig M, Kaeda J, Schultheis B, Berger U, Shepherd P C, Allan N C, Hehlmann R, Goldman J M, Cross N C

机构信息

III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin, Mannheim der Universität Heidelberg, Mannheim, Germany.

出版信息

Blood. 2000 Jan 1;95(1):62-6.

Abstract

A substantial minority of patients with chronic myelogenous leukemia (CML) achieve a complete response (CR) to treatment with interferon-alpha (IFN), defined as the disappearance of Philadelphia chromosome-positive metaphases. Currently it is unclear how long IFN treatment should be continued for such patients. We used a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify levels of BCR-ABL transcripts in 297 peripheral blood specimens collected from 54 patients who had achieved CR with IFN. The median duration of observation was 1.9 years (range, 0.3-11.0 years). Total ABL transcripts were quantified as internal control and results were expressed as the ratio BCR-ABL/ABL. All 54 patients had molecular evidence of residual disease, although 3 patients were intermittently PCR negative. The median BCR-ABL/ABL ratio at the time of maximal response for each patient was 0.045% (range, 0%-3. 6%). During the period of observation 14 patients relapsed, 11 cytogenetically to chronic phase disease and 3 directly to blastic phase. The median ratio of BCR-ABL/ABL at maximal response was significantly higher in patients who relapsed than in those who remained in CR (0.49% versus 0.021%, P < 0.0001). Our findings show that the level of residual disease falls with time in complete responders to IFN, but molecular evidence of disease is rarely if ever eliminated. The actual level of minimal residual disease correlates with the probability of relapse. We suggest that for patients who reach CR, IFN should be continued at least until relatively low levels of residual leukemia are achieved. (Blood. 2000;95:62-66)

摘要

相当一部分慢性粒细胞白血病(CML)患者对α干扰素(IFN)治疗可获得完全缓解(CR),完全缓解定义为费城染色体阳性中期相消失。目前尚不清楚此类患者应持续接受IFN治疗多长时间。我们采用竞争性逆转录聚合酶链反应(RT-PCR)对54例接受IFN治疗达到CR的患者所采集的297份外周血标本中的BCR-ABL转录本水平进行定量。观察的中位持续时间为1.9年(范围0.3 - 11.0年)。将总ABL转录本定量作为内对照,结果以BCR-ABL/ABL比值表示。所有54例患者均有残留疾病的分子学证据,尽管有3例患者PCR结果呈间歇性阴性。每位患者最大反应时的BCR-ABL/ABL比值中位数为0.045%(范围0% - 3.6%)。在观察期间,14例患者复发,11例细胞遗传学复发至慢性期疾病,3例直接复发至急变期。复发患者最大反应时的BCR-ABL/ABL比值中位数显著高于仍处于CR状态的患者(0.49%对0.021%,P < 0.0001)。我们的研究结果表明,对IFN治疗达到完全缓解的患者,残留疾病水平随时间下降,但疾病的分子学证据极少被清除。最小残留疾病的实际水平与复发概率相关。我们建议,对于达到CR的患者,应持续使用IFN至少至获得相对低水平的残留白血病。(《血液》。2000年;95:62 - 66)

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