氟达拉滨、环磷酰胺和利妥昔单抗（FCR）化疗免疫疗法可实现持久缓解，对于带有突变IGHV基因（IGHV-M）的患者，可通过改变无进展生存（PFS）曲线的趋势。我们更新了M.D. Anderson 1999年开始的原始300名FCR研究的长期随访结果。目前的中位随访时间为19.0年。借助这个长期随访，我们发现IGHV-M患者的中位PFS为14.6年，而未突变IGHV患者（IGHV-UM）的中位PFS为4.2年。超过10年的疾病进展很少见。与我们2015年的报告相比，10年处于缓解状态的94名患者中，随后有16人（17%）在额外的随访中进展。IGHV-M患者中只有45人中有4人（9%）在10年后进展。剔除转化布赖特氏白血病后，300名患者中有96人（32%）出现了106种其他恶性肿瘤，其中19人（6.3%）发展为与治疗相关的髓性肿瘤（tMNs），其中16人（84%）致命。没有预治疗患者特征能预测tMNs的风险。总而言之，FCR仍然是IGHV-M慢性淋巴细胞白血病患者的一种选择，其中有相当一部分患者实现了功能性治愈。在与患者咨询时，应根据潜在的功能性治愈与晚期复发和严重继发恶性肿瘤风险之间的平衡进行风险-获益评估。Copyright © 2023美国血液学学会。

Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) achieves durable remissions, with flattening of the progression-free survival (PFS) curve in patients with mutated IGHV gene (IGHV-M). We updated long-term follow-up results from the original 300 patient FCR study initiated at M.D. Anderson in 1999. Current median follow-up is 19.0 years. With this extended follow-up, the median PFS for patients with IGHV-M was 14.6 years vs 4.2 years for patients with unmutated IGHV (IGHV-UM). Disease progression beyond 10 years was uncommon. Sixteen of 94 (17%) patients in remission at 10 years subsequently progressed with the additional follow-up compared to our prior report in 2015. Only 4 of 45 (9%) of patients with IGHV-M progressed beyond 10 years. Excluding Richter transformation, 96 of 300 (32%) patients developed 106 other malignancies, with 19/300 (6.3%) developing therapy-related myeloid neoplasms (tMNs), which were fatal in 16/19 (84%). No pre-treatment patient characteristics predicted for risk of tMNs. In summary, FCR remains an option for patients with IGHV-M CLL, with a significant fraction achieving functional cure of CLL. A risk-benefit assessment is warranted when counseling patients, balancing potential functional cure with the risk of late relapses and serious secondary malignancies.Copyright © 2023 American Society of Hematology.