Stanford University Medical Center, 875 Blake Wilbur Dr, CC-2338, Stanford, CA 94305, USA.
J Clin Oncol. 2013 Feb 10;31(5):592-8. doi: 10.1200/JCO.2012.44.5791. Epub 2013 Jan 7.
To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials.
Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS.
Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy.
Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).
评估斯坦福临床试验中连续几代治疗霍奇金淋巴瘤（HL）的患者的治疗相关急性髓系白血病/骨髓增生异常综合征（t-AML/MDS）风险。
从我们的数据库中确定了至少在完成治疗后有 5 年以上随访记录的斯坦福治疗 HL 患者。回顾记录以了解结局和 t-AML/MDS 的发展情况。
共确定了 754 例 1974 年至 2003 年接受治疗的患者。各研究中治疗方法不同。放射治疗从扩展野（S 和 C 研究）演变为受累野（G 研究）。S 研究中的初级化疗为氮芥、长春新碱、丙卡巴肼和泼尼松（MOPP）或丙卡巴肼、氮芥和长春新碱（PAVe）；C 研究中的 MOPP、PAVe、长春新碱、博来霉素和甲氨蝶呤（VBM），或多柔比星、博来霉素、长春新碱和达卡巴嗪（ABVD）；G 研究中的 VbM（与 VBM 相比，博来霉素剂量减少）或氮芥、多柔比星、长春新碱、长春新碱、博来霉素、依托泊苷和泼尼松（斯坦福 V）。与 S 和 C 研究相比，G 研究中累积接触烷化剂（AA）显著降低，氮芥剂量降低 75%至 83%，此外还省略了丙卡巴肼和苯丁酸氮芥。754 例患者中 24 例（3.2%）发生 t-AML/MDS，15 例发生于原发性化疗后，9 例发生于 HL 复发后的挽救性化疗后。G 研究中的 t-AML/MDS 发生率明显低于 S（5.7%）或 C（5.2%）研究（P<.001）。此外，在 G 研究中，原发性治疗后未发现 t-AML/MDS，唯一发生 t-AML/MDS 的患者是在二线治疗后发生的。
我们的数据表明 AA 累积剂量与 t-AML/MDS 之间存在相关性。限制 AA 剂量和减少对二线治疗的需求显著降低了 t-AML/MDS 的发生率，G 研究（斯坦福 V 时代）中 t-AML/MDS 极为罕见。
