背景:接受大剂量化疗和自体造血细胞移植(Auto-HCT)的多发性骨髓瘤(MM)患者发生治疗相关骨髓增生异常综合征和急性髓细胞白血病(t-MDS/AML)的风险增加。
方法:我们回顾性审查了2000年1月1日至2018年12月31日在我们机构接受Auto-HCT并随后发展为t-MDS/AML的所有MM患者的病历。
结果:在接受至少一次Auto-HCT的2982名患者中,55(2%)发展为t-MDS/AML(MDS,n=52;AML,n=3)。诊断为t-MDS/AML的中位年龄为66岁(范围,43-83岁),从Auto-HCT到t-MDS/AML诊断的中位时间为58.5个月(范围,6-206个月)。诊断时,所有3名tAML患者和65%的tMDS患者都有高风险疾病,根据ELN2022和R-IPSS,分别,62%有TP53基因突变。发展为t-MDS/AML的患者在MM诊断时年龄较大(中位数:61vs.59年;p=0.06),更常见的是男性(73%vs.58%;p=0.029),接受了2年以上的来那度胺维护(57%vs.39%;p=0.014),与未发生t-MDS/AML的患者相比,Auto-HCT后更频繁地经历了完全缓解(56%vs.40%;p=0.012)。在多变量模型中,男性,在MM诊断时高龄,Auto-HCT后经历完全缓解,和来那度胺维持治疗是发生t-MDS/AML的独立预测因子。在发展为t-MDS/AML的患者中,14人(25%)接受了异基因造血干细胞移植(Allo-HCT)。在t-MDS/AML诊断后,中位随访9.9个月,所有患者诊断为t-MDS/AML后的中位总生存期(OS)为11.8个月,和18.2个月vs.Allo-HCT接受者的11.1个月与非收件人,分别(P=0.25)。在单变量分析中,接受烷化剂作为MM的诱导(危险比[95%CI]:2.9[1.3-6.3];P=0.009),年龄>60岁(3.1[1.2-8.2];P=0.025),和较高风险的R-IPSS(2.7[1.3-6.0];P=0.011)预测t-MDS/AML诊断后OS恶化。这些在多变量分析中都没有保留显著性。
结论:自动HCT治疗MM后的T-MDS/AML与侵袭性疾病特征相关,包括高危细胞遗传学和TP53突变。患者的预后仍然很差,即使是Allo-HCT.有必要更好地了解疾病生物学和新的治疗方法。
Patients with multiple myeloma (MM) who undergo high-dose chemotherapy and autologous hematopoietic cell transplantation (Auto-HCT) have an increased risk of developing therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML). We retrospectively reviewed the medical records of all MM patients who underwent an Auto-HCT at our institution between 1 January and 31 December 2018 and later developed t-MDS/AML. Among the 2982 patients who underwent at least 1 Auto-HCT, 55 (2%) developed t-MDS/AML (MDS, n = 52; AML, n = 3). The median age at t-MDS/AML diagnosis was 66 years (range 43-83 years), and the median time from Auto-HCT to t-MDS/AML diagnosis was 58.5 months (range 6-206 months). At diagnosis, all 3 patients with tAML and 65% of those with therapy-related myelodysplastic syndrome (tMDS) had high-risk disease, per 2022 European LeukemiaNet and R-IPSS, respectively, and 62% had TP53 gene mutations. Patients who developed tMDS/AML were older at MM diagnosis (median 61 versus 59 years; P = .06), more often were male (73% versus 58%; P = .029), received more than 2 years of lenalidomide maintenance (57% versus 39%; P = .014), and experienced complete remission more frequently after Auto-HCT compared to those who did not develop t-MDS/AML (56% versus 40%; P = .012). In a multivariable model, male gender, advanced age at MM diagnosis, experiencing complete remission after Auto-HCT, and lenalidomide maintenance were independent predictors of developing t-MDS/AML. Among the patients who developed t-MDS/AML, 14 (25%) underwent allogeneic hematopoietic stem transplantation (Allo-HCT). After a median follow-up of 9.9 months from t-MDS/AML diagnosis, the median overall survival (OS) after t-MDS/AML diagnosis was 11.8 months for all patients, and 18.2 months versus 11.1 months for Allo-HCT recipients versus nonrecipients, respectively (P = .25). On univariate analysis, receiving an alkylator as induction for MM (hazard ratio [95% confidence interval]: 2.9 [1.3-6.3]; P = .009), age > 60 years (3.1 [1.2-8.2]; P = .025), and higher-risk R-IPSS (2.7 [1.3-6.0]; P=0.011) predicted worse OS after t-MDS/AML diagnosis. None of these retained significance in the multivariable analysis. T-MDS/AML after Auto-HCT for MM is associated with aggressive disease characteristics, including high-risk cytogenetics and TP53 mutations. The outcomes of patients remain poor, even with Allo-HCT. A better understanding of disease biology and novel therapeutic approaches is warranted.