Risk of leukemia following treatment for non-Hodgkin's lymphoma.
Risk of leukemia following treatment for non-Hodgkin's lymphoma.
复制标题
非霍奇金淋巴瘤治疗后患白血病的风险。
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
J. Boice
中科院分区：
文献类型：
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作者：
L. Travis;R. Curtis;M. Stovall;E. Holowaty;F. Leeuwen;B. Glimelius;Charles F. Lynch;A. Hagenbeek;chin;P. Banks;M. Gospodarowicz;J. Adami;S. Wacholder;P. Inskip;M. Tucker;J. Boice
背景
对非霍奇金淋巴瘤（NHL）治疗后发生急性非淋巴细胞白血病（ANLL）的风险评价很少。此外，细胞毒性药物的累积剂量、活性骨髓的辐射剂量和NHL后ANLL风险之间的关系尚未得到很好的描述。
目的
我们的目的是研究ANLL的风险与所有既往NHL治疗的关系。
方法
在一项队列研究中，11,386名2年生存的NHL患者中，确定了35例继发性ANLL患者，并与140名未发生ANLL的NHL对照组进行了匹配。该队列的主要合格标准包括：1965年1月1日至1989年12月31日期间NHL诊断为第一原发性癌症;初次诊断时年龄为18至70岁;生存2年或更长时间，未发生第二种浸润性原发性恶性肿瘤。收集所有患者化疗药物和放疗的详细信息。通过比较病例患者与个体匹配对照的暴露史，使用标准条件Logistic回归程序估计与特定治疗相关的ANLL的相对风险（RR）。
结果
使用泼尼松治疗（RR = 13.4; 95%可信区间[CI] = 1.1-156; P剂量趋势<0.05）或含氮芥和丙卡巴肼的方案（RR = 12.6; 95% CI = 2.0-79; P <0.05）后ANLL显著过量。苯丁酸氮芥治疗后白血病风险升高仅限于累积剂量≥ 1300 mg的患者（RR = 6.5; 95% CI = 1.6-26; P <0.05）。环磷酰胺方案与ANLL风险的小幅、非显著性增加相关（RR = 1.8;95% CI = 0.7-4.9），大多数患者接受相对较低的累积剂量（<20，000 mg）。与低剂量放疗或无放疗相比，无烷化剂的高剂量放疗与ANLL风险的3倍无显著性相关。
结论
我们的研究结果表明，泼尼松可能是一种人类致癌物，与ANLL风险的正剂量反应梯度明显。与环磷酰胺相关的低、非显著性白血病风险令人放心，因为这种药物今天被广泛使用。尽管与特定治疗相关的ANLL过度，继发性白血病仍然是NHL后罕见的事件。在10，000名NHL患者中，使用包括低累积剂量环磷酰胺在内的选定方案治疗6个月，并随访10年，预计可能会出现4例白血病。
BACKGROUND
There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between cumulative dose of cytotoxic drug, radiation dose to active bone marrow, and the risk of ANLL following NHL have not been well described.
PURPOSE
Our purpose was to examine the risk of ANLL in relationship to all prior treatment for NHL.
METHODS
Within a cohort study of 11,386 2-year survivors of NHL, 35 case patients with secondary ANLL were identified and matched to 140 controls with NHL who did not develop ANLL. The primary eligibility criteria for the cohort included a diagnosis of NHL as a first primary cancer from January 1, 1965, through December 31, 1989; age 18 through 70 years at the time of initial diagnosis; and survival for 2 or more years without the development of a second invasive primary malignancy. Detailed information on chemotherapeutic drugs and radiotherapy was collected for all patients. Standard conditional logistic regression programs were used to estimate the relative risk (RR) of ANLL associated with specific therapies by comparing the exposure histories of case patients with individually matched controls.
RESULTS
Significant excesses of ANLL followed therapy with either prednimustine (RR = 13.4; 95% confidence interval [CI] = 1.1-156; P trend for dose < .05) or regimens containing mechlorethamine and procarbazine (RR = 12.6; 95% CI = 2.0-79; P < .05). Elevated risks of leukemia following therapy with chlorambucil were restricted to patients given cumulative doses of 1300 mg or more (RR = 6.5; 95% CI = 1.6-26; P < .05). Cyclophosphamide regimens were associated with a small, nonsignificant increased risk of ANLL (RR = 1.8;95% CI = 0.7-4.9), with most patients receiving relatively low cumulative doses (< 20,000 mg). Radiotherapy given at higher doses without alkylating agents was linked to a nonsignificant threefold risk of ANLL compared with lower dose radiation or no radiotherapy.
CONCLUSIONS
Our results suggest that prednimustine may be a human carcinogen, with a positive dose-response gradient evident for ANLL risk. The low, nonsignificant risk of leukemia associated with cyclophosphamide was reassuring because this drug is commonly used today. Despite the excesses of ANLL associated with specific therapies, secondary leukemia remains a rare occurrence following NHL. Of 10,000 NHL patients treated for 6 months with selected regimens including low cumulative doses of cyclophosphamide and followed for 10 years, an excess of four leukemias might be expected.