Hematology, University Hospital, Basel, Switzerland.
EBMT Paris Study Office/CEREST-TC, Hôpital Saint Antoine, Paris, France.
JAMA Oncol. 2019 Feb 1;5(2):229-235. doi: 10.1001/jamaoncol.2018.4934.
Incidence and risk factors of second solid cancers (SSCs) that occur after hematopoietic stem cell transplantation (HSCT) are well documented. However, clinical outcome data of patients who developed an SSC after HSCT are limited.
To assess the outcome of patients with an SSC occurring after HSCT from the time of SSC diagnosis.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data of 4065 patients from 26 countries registered with the European Society for Blood and Marrow Transplantation, which has maintained clinical data since 1977 of patients who received a transplant. Information from all patients who underwent a transplant in Europe and had an SSC diagnosis between January 1, 2000, and December 31, 2014, was extracted. The cohort included patients with 18 different cancers. Data analysis was conducted from September 3, 2017, to March 17, 2018.
Median and 5-year age-standardized overall survival, causes of death, risk factor multivariate analysis using a clustered Cox proportional hazard regression model, and standardized mortality ratio were calculated for each of the 18 types of SSC.
In total, 220 617 patients underwent a transplant, of whom only 4065 (1.8%) patients with a second solid cancer after HSCT were included in the study. Among the 4065 patients, 2321 (57.1%) were men and 1744 (42.9%) were women, with a mean (range) age of 59.1 (3.2-82.3) years at diagnosis of second solid cancer. The 5-year age-standardized overall survival was 47% (95% CI, 45%-49%). The 5-year overall survival rate after SSC diagnosis was poor for pancreas, lung, hepatobiliary, esophageal, brain, and gastric cancers, with a median survival between 0.6 and 1 year. The 5-year overall survival was intermediate for endometrial, colorectal, sarcomas, ovarian, bladder, oropharyngeal, and kidney cancers, with a median survival between 2 and 10 years. The 5-year overall survival was more favorable for melanoma, breast, prostate, cervix, and thyroid cancers, with a median survival of 10 or more years. Additional transplant-associated factors for mortality for patients treated with allogeneic HSCT were age at transplant, donor type, conditioning regimen, and graft-vs-host disease. In total, 1777 patients (43.7%) died, of which 1256 (74.8%) were from SSC, 344 (20.5%) from primary disease, and 79 (4.7%) from other causes. Standardized mortality ratio was higher, compared with de novo solid cancers, for melanoma, prostate, breast, kidney, bladder, colorectal, and endometrial cancers but not for the other cancers.
The outcome of SSC is mainly dependent on the type of second cancer; thus, future studies should investigate the reasons the standardized mortality ratio is higher for some cancers to identify whether patients with these cancers should be treated differently and to help in screening and counseling patients who developed an SSC after HSCT.
造血干细胞移植（HSCT）后发生的第二实体癌（SSC）的发病率和风险因素已有充分记录。然而，接受 HSCT 后发生 SSC 的患者的临床结果数据有限。
评估从 SSC 诊断时间起，接受 HSCT 后发生 SSC 的患者的结局。
设计、地点和参与者：这项队列研究使用了来自 26 个国家的 4065 名患者的数据，这些患者来自自 1977 年以来接受移植的欧洲血液和骨髓移植学会注册的患者。从 2000 年 1 月 1 日至 2014 年 12 月 31 日，从欧洲接受移植并诊断出 SSC 的所有患者中提取了信息。该队列包括 18 种不同癌症的患者。数据分析于 2017 年 9 月 3 日至 2018 年 3 月 17 日进行。
计算了每一种 18 种 SSC 的中位年龄标准化总体生存率、死亡原因、使用聚类 Cox 比例风险回归模型进行的风险因素多变量分析以及标准化死亡率。
共有 220617 名患者接受了移植，其中只有 4065 名（1.8%）接受 HSCT 后的第二实体癌患者被纳入研究。在这 4065 名患者中，2321 名（57.1%）为男性，1744 名（42.9%）为女性，诊断第二实体癌时的平均（范围）年龄为 59.1（3.2-82.3）岁。5 年年龄标准化总体生存率为 47%（95%CI，45%-49%）。SSC 诊断后 5 年的总体生存率对于胰腺、肺、肝胆、食管、脑和胃癌较差，中位生存时间为 0.6 至 1 年。子宫内膜癌、结直肠癌、肉瘤、卵巢癌、膀胱癌、口咽癌和肾癌的 5 年总体生存率为中等，中位生存时间为 2 至 10 年。黑色素瘤、乳腺癌、前列腺癌、宫颈癌和甲状腺癌的 5 年总体生存率较好，中位生存时间为 10 年或更长。对于接受同种异体 HSCT 治疗的患者，与移植相关的额外死亡因素包括移植时的年龄、供体类型、预处理方案和移植物抗宿主病。共有 1777 名患者（43.7%）死亡，其中 1256 名（74.8%）死于 SSC，344 名（20.5%）死于原发性疾病，79 名（4.7%）死于其他原因。与新发实体癌相比，黑色素瘤、前列腺癌、乳腺癌、肾癌、膀胱癌、结直肠癌和子宫内膜癌的标准化死亡率较高，但其他癌症则不是。
SSC 的结果主要取决于第二癌症的类型；因此，未来的研究应调查标准化死亡率较高的原因，以确定是否应对这些癌症患者进行不同的治疗，并帮助对接受 HSCT 后发生 SSC 的患者进行筛查和咨询。
