Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
Am J Hematol. 2018 Feb;93(2):187-194. doi: 10.1002/ajh.24955. Epub 2017 Nov 17.
Waldenström macroglobulinemia (WM) is an immunoglobulin M-associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88 . Owing to low prevalence of the wild-type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10-fold increased risk of mortality in this subgroup compared to patients with MYD88 mutation. We studied a large cohort of patients with MYD88 and MYD88 WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016, to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88 mutation status, as determined by allele-specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88 , 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88 genotype, 44 had active disease. The estimated median follow-up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4-16.5) for MYD88 versus 13.9 years (95% CI: 6.4-29.3) for the MYD88 (P = 0.86). The time-to-next therapy from frontline treatment and the presenting features were similar in the two patient populations. For patients with smoldering WM at diagnosis, the median time-to-progression to active disease was 2.8 years (95% CI: 2.2-3.8) in the MYD88 cohort and 1.9 years (95% CI: 0.7-3.1) in the MYD88 cohort (P = 0.21). The frequency of transformation to high-grade lymphoma, or the development of therapy-elated myelodysplastic syndrome was higher in the MYD88 cohort (16% versus 4% in the MYD88 , P = 0.009). In conclusion, MYD88 mutation does not appear to be a determinant of outcome, and its presence may not be a disease-defining feature in WM. Our findings warrant external validation, preferably through prospective studies.
华氏巨球蛋白血症（WM）是一种与免疫球蛋白 M 相关的淋巴瘤，大多数病例表现出 MYD88 基因座改变，最常见的是 MYD88 。由于 WM 中野生型（WT）MYD88 基因型的患病率较低，因此在该患者人群中临床相关数据很少，一项研究表明，与 MYD88 突变患者相比，该亚组的死亡率几乎增加了 10 倍。我们研究了在梅奥诊所罗切斯特分校就诊的 1995 年至 2016 年间的大量 MYD88 和 MYD88 WM 患者，以专门评估这些基因型对临床病程的影响。在 557 例患者中，通过等位基因特异性聚合酶链反应确定了 219 例 MYD88 突变状态，其中 174 例（79%）表现出 MYD88 ，157 例 174 例患者患有活动性疾病。在 45 例（21%） MYD88 基因型患者中，44 例患有活动性疾病。估计中位随访时间为 7.0 年；中位总生存期为 MYD88 为 10.2 年（95%CI：8.4-16.5），而 MYD88 为 13.9 年（95%CI：6.4-29.3）（P = 0.86）。在前一线治疗时，从下一治疗方案开始的时间和表现出的特征在这两个患者群体中相似。对于诊断为冒烟型 WM 的患者，在 MYD88 队列中，从一线治疗到活动性疾病的中位进展时间为 2.8 年（95%CI：2.2-3.8），而在 MYD88 队列中为 1.9 年（95%CI：0.7-3.1）（P = 0.21）。MYD88 队列中转化为高级别淋巴瘤或发生治疗相关骨髓增生异常综合征的频率更高（16%比 MYD88 中的 4%，P = 0.009）。总之，MYD88 突变似乎不是结局的决定因素，其存在可能不是 WM 的疾病定义特征。我们的研究结果需要外部验证，最好通过前瞻性研究来验证。
