Martinelli G, Montefusco V, Testoni N, Amabile M, Saglio G, Ottaviani E, Terragna C, Bonifazi F, Rosti G, Bandini G, Tura S
Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, via Massarenti 9, 40138 Bologna, Italy.
Haematologica. 2000 Jun;85(6):653-8.
For purposes of therapeutic decision making, we used quantitative polymerase chain reaction (PCR) for molecular follow-up of 55 patients with chronic myeloid leukemia (CML) in complete remission (CR) after allogeneic bone marrow transplantation (BMT) from HLA compatible donors.
A total of 402 bone marrow samples from 40 patients transplanted in chronic phase (group 1) and 15 in accelerated/blastic phase (group 2) were analyzed by qualitative and quantitative PCR.
Regarding clinical outcome, 34/40 (85%) group 1 vs. 8/15 (54%) group 2 patients are alive. Only 1/40 (2.5%) group 1 patient relapsed, as against 6/15 (40%) in group 2 (p = 0. 0002). At qualitative PCR, 8/40 (19%) group 1 vs. 9/15 (60%) group 2 patients were positive, with a significantly greater total number of positive samples in group 2 (33/129, 27% vs. 16/273, 5%; p<0.001). The probability of qualitative PCR positivity >1 year after BMT was significantly lower in group 1 patients (4/40 pts, 10% vs. 9/15 pts, 60%; p = 0.01). At quantitative PCR, 4/8 (50%) group 1 patients were positive only once (< 400 transcripts/microg RNA). In group 2, 9/15 (60%) patients had 3 or more positive samples (always with >4,000 copies/mg RNA); therapeutic interventions (cyclosporin A discontinuation, temporary a-interferon or donor lymphocyte infusion) restored molecular remission in 4/9 (44%) cases.
This study indicates that quantitative PCR could provide practical indications capable of directing therapeutic interventions for transplanted CML patients, especially those transplanted in accelerated/blastic phase, for whom intensive monitoring is required.
为了进行治疗决策，我们采用定量聚合酶链反应（PCR）对55例接受来自HLA相合同胞供者的异基因骨髓移植（BMT）且处于完全缓解（CR）期的慢性髓性白血病（CML）患者进行分子学随访。
对40例处于慢性期（第1组）和15例处于加速期/急变期（第2组）的移植患者共402份骨髓样本进行定性和定量PCR分析。
关于临床结局，第1组40例患者中有34例（85%）存活，第2组15例患者中有8例（54%）存活。第1组仅1例（2.5%）患者复发，而第2组有6例（40%）复发（p = 0.0002）。在定性PCR检测中，第1组40例患者中有8例（19%）呈阳性，第2组15例患者中有9例（60%）呈阳性，第2组阳性样本总数显著更多（33/129，27%对16/273，5%；p<0.001）。BMT后1年以上定性PCR呈阳性的概率在第1组患者中显著更低（4/40例患者，10%对9/15例患者，60%；p = 0.01）。在定量PCR检测中，第1组8例患者中有4例（50%）仅出现一次阳性（<400个转录本/微克RNA）。在第2组中，15例患者中有9例（60%）有3次或更多次阳性样本（总是>4000拷贝/毫克RNA）；治疗干预（停用环孢素A、短期使用α干扰素或供者淋巴细胞输注）使4/9（44%）的病例恢复分子学缓解。
本研究表明，定量PCR可为移植的CML患者，尤其是处于加速期/急变期的患者（这类患者需要密切监测）指导治疗干预提供实用的指标。
