Vo Phuong, Onstad Lynn, Flowers Mary E, Storb Rainer
Division of Clinical Research, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
Department of Medicine, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
Bone Marrow Transplant. 2022 Jan;57(1):83-88. doi: 10.1038/s41409-021-01498-1. Epub 2021 Oct 16.
We analyzed subsequent cancers in 329 patients with aplastic anemia given HLA-matched related marrow grafts. Median follow-up: 26 (range 1-47) years. Conditioning: cyclophosphamide ± antithymocyte globulin; graft-vs.-host disease (GVHD) prevention: methotrexate ± cyclosporine. The long follow-up and homogeneous treatment allowed definitive analyses of incidence, nature, time of onset, and potential causes of cancers. Fifty-three cancers occurred in 46 patients, 42 had solid tumors and 4 blood cancers. Of the 42, 22 had non-melanoma skin and 7 oropharyngeal cancers. The remainder had a spectrum of other cancers including two liver cancers from pre-transplant hepatitis C. The 26-year cumulative incidence (CI) of cancer was 11% and mortality 5%. Excluding non-melanoma skin cancers, the 26-year CI of cancer was 7%. Cancers were 2.03-fold more than expected from SEER data; that number was 1.89-fold after excluding liver cancers. Nearly all cancers developed between 14 and 34 years. Skin and oropharyngeal cancers showed significant association with chronic GVHD, whereby GVHD had resolved in most patients within 7 years of transplantation. Thus, tumors evolved after a lag time of 7-27 years. Other cancers showed no clear associations with chronic GVHD or drugs used for transplantation. Results reemphasize the importance of preventing chronic GVHD.
我们分析了329例接受人类白细胞抗原（HLA）匹配的相关骨髓移植的再生障碍性贫血患者后续发生癌症的情况。中位随访时间：26年（范围1 - 47年）。预处理方案：环磷酰胺±抗胸腺细胞球蛋白；移植物抗宿主病（GVHD）预防方案：甲氨蝶呤±环孢素。长时间的随访和统一的治疗使得能够对癌症的发病率、性质、发病时间及潜在病因进行确定性分析。46例患者发生了53例癌症，其中42例为实体瘤，4例为血液系统癌症。在这42例实体瘤患者中，22例为非黑色素瘤皮肤癌，7例为口咽癌。其余患者患有一系列其他癌症，包括2例因移植前丙型肝炎导致的肝癌。26年的癌症累积发病率（CI）为11%，死亡率为5%。排除非黑色素瘤皮肤癌后，26年的癌症CI为7%。癌症发生率比监测、流行病学与最终结果（SEER）数据预期的高2.03倍；排除肝癌后该数字为1.89倍。几乎所有癌症都在14至34岁之间发生。皮肤癌和口咽癌与慢性GVHD显著相关，而在大多数患者中，GVHD在移植后7年内已缓解。因此，肿瘤在7至27年的滞后时间后发生。其他癌症与慢性GVHD或移植所用药物无明显关联。结果再次强调了预防慢性GVHD的重要性。
