Cancers after HLA-matched related bone marrow transplantation for aplastic anemia

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.