Ha C S, Tucker S L, Lee M S, McLaughlin P, Cabanillas F, Cox J D
Department of Radiation Oncology, Box 97, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Int J Radiat Oncol Biol Phys. 2001 Mar 1;49(3):727-32. doi: 10.1016/s0360-3016(00)01416-4.
More than 80% of the patients with follicular lymphoma have a characteristic chromosomal translocation, t(14;18)(q32;q21), at the major breakpoint region (MBR) or minor cluster region (MCR) involving the bcl-2 oncogene. This study was undertaken to assess the significance of the molecular response rate measured by the polymerase chain reaction (PCR) evidence of translocation among patients with Stage I to III follicular lymphoma treated with central lymphatic irradiation (CLI).
Thirty-three patients with Stage I-III follicular lymphoma were treated with CLI on a prospective protocol. Bone marrow and peripheral blood samples were obtained before CLI for PCR analysis of t(14;18)(q32; q21). PCR-positive patients were followed by PCR analysis at regular intervals during and after CLI, and the results were correlated with clinical outcome. The following pretreatment factors were also investigated for their relationship to relapse and molecular response: gender, age, lactate dehydrogenase (LDH) and beta-2 microglobulin (beta2M) levels, Ann Arbor stage, and International Prognostic Index (IPI) for malignant lymphoma.
The subjects were 19 men and 14 women, with a median age of 52 years (range 30-69), who started CLI between January 1993 and February 1998. Median follow-up was 44 months (range 12-67), and all but 2 patients were still alive at the last follow-up. Four patients were Stage IA, 8 were Stage IIA, 19 were Stage IIIA, and 2 were Stage IIIB. Two patients had abnormal LDH levels (> 618 U/dL) and 7 patients had abnormal beta2M levels (> 2 mg/dL). Nine patients had IPI = 0, 16 had IPI = 1, and 8 had IPI = 2. All patients achieved complete response (CR). Twelve patients have relapsed to date. The median overall time to relapse was 54 months. The actuarial proportion of patients free from relapse at 3 years was 87% (95% confidence interval [CI] 69-95%). A total of 287 PCR results were available, 64 from bone marrow and 223 from peripheral blood. Pretreatment PCR data were available for 27 patients, of whom 21 were positive and 3 were unambiguously negative (in blood and bone marrow for both MBR and MCR). For the 19 PCR positive patients for whom we had post-treatment results, there was a clear and steady decreasing trend toward loss of PCR positivity (49% positive for bone marrow and 32% positive for peripheral blood at 3 years). There was a clear trend for increasing PCR positivity with increasing IPI: 10% for IPI = 0, 31% for IPI = 1, and 63% for IPI = 2 at 3 years for blood. The same trend was also observed for bone marrow. The IPI was the only statistically significant predictor for relapse with a relapse-free survival of 91% at 3 years for IPI < 2 and 75% for IPI = 2 (p = 0.024, log-rank test).
Molecular response to CLI occurs gradually over years. High IPI is a negative predictor for molecular response and relapse-free survival.
超过80%的滤泡性淋巴瘤患者在主要断裂点区域（MBR）或次要簇区域（MCR）存在特征性染色体易位t(14;18)(q32;q21)，涉及bcl-2癌基因。本研究旨在评估在接受中枢淋巴照射（CLI）治疗的I至III期滤泡性淋巴瘤患者中，通过聚合酶链反应（PCR）检测到的易位证据所衡量的分子反应率的意义。
33例I - III期滤泡性淋巴瘤患者按照前瞻性方案接受CLI治疗。在CLI治疗前采集骨髓和外周血样本，进行t(14;18)(q32;q21)的PCR分析。PCR阳性患者在CLI治疗期间及治疗后定期进行PCR分析，结果与临床结局相关。还研究了以下预处理因素与复发和分子反应的关系：性别、年龄、乳酸脱氢酶（LDH）和β2微球蛋白（β2M）水平、Ann Arbor分期以及恶性淋巴瘤的国际预后指数（IPI）。
研究对象为19名男性和14名女性，中位年龄52岁（范围30 - 69岁），于1993年1月至1998年2月开始接受CLI治疗。中位随访时间为44个月（范围12 - 67个月），除2例患者外，所有患者在最后一次随访时仍存活。4例为IA期，8例为IIA期，19例为IIIA期，2例为IIIB期。2例患者LDH水平异常（> 618 U/dL），7例患者β2M水平异常（> 2 mg/dL）。9例患者IPI = 0，16例患者IPI = 1，8例患者IPI = 2。所有患者均达到完全缓解（CR）。截至目前，12例患者复发。复发的中位总时间为54个月。3年时无复发患者的精算比例为87%（95%置信区间[CI] 69 - 95%）。共获得287份PCR结果，其中64份来自骨髓，223份来自外周血。27例患者有治疗前PCR数据，其中21例阳性，3例明确阴性（MBR和MCR的血液和骨髓样本均为阴性）。对于19例有治疗后结果的PCR阳性患者，PCR阳性率呈明显且稳定的下降趋势（3年时骨髓阳性率为49%，外周血阳性率为32%）。随着IPI增加，PCR阳性率有明显上升趋势：3年时血液中IPI = 0为10%，IPI = 1为31%，IPI = 2为63%。骨髓中也观察到相同趋势。IPI是复发的唯一具有统计学意义的预测因素，IPI < 2时3年无复发生存率为91%，IPI = 2时为75%（p = 0.024，对数秩检验）。
CLI的分子反应在数年内逐渐发生。高IPI是分子反应和无复发生存的负性预测因素。
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