MALIGNANT-TUMORS OCCURRING AFTER TREATMENT OF APLASTIC-ANEMIA

Background and Methods. Recent studies have shown that long-term survi vors of acquired aplastic anemia may be at high risk for malignant dis eases. We assessed the risk of cancer after aplastic anemia was treate d with immunosuppression or bone marrow transplantation and sought to identify risk factors according to treatment. The study population con sisted of 860 patients treated by immunosuppression and 748 patients w ho had received bone marrow transplants for the treatment of severe ap lastic anemia. The risk of cancer was analyzed overall and according t o treatment relative to the risk in the general population. In calcula ting relative risk, we excluded patients with myelodysplastic syndrome s or acute leukemias arising less than 6 months after treatment, and s olid cancers arising less than 12 months after treatment, because of a possible association with aplastic anemia itself rather than with the treatment received. Results. Forty-two malignant conditions were repo rted in the 860 patients who received immunosuppressive therapy: 19 ca ses of myelodysplastic syndrome, 15 cases of acute leukemia, 1 case of non-Hodgkin's lymphoma, and 7 solid tumors. Nine were reported in the 748 patients who received bone marrow transplants: two cases of acute leukemia and seven solid tumors. After the exclusions listed above, t he overall relative risk of cancer was 5.50 (P<0.001) as compared with that in the general European population; the risk was 5.15 (P<0.001) after immunosuppressive therapy and 6.67 (P<0.001) after transplantati on. The 10-year cumulative incidence rate of cancer was 18.8 percent a fter immunosuppressive therapy and 3.1 percent after transplantation. The risk factors for myelodysplastic syndrome or acute leukemia after immunosuppressive therapy included the addition of androgens to the im munosuppressive treatment (relative risk = 0.28), older age (relative risk = 1.03), treatment in 1982 or later, as compared with 1981 or ear lier (relative risk = 3.01), splenectomy (relative risk = 3.65), and t reatment with multiple courses of immunosuppression (relative risk = 2 .26). Risk factors for solid tumors after bone marrow transplantation were age (relative risk = 1.11 per year) and the use of radiation as a conditioning regimen before transplantation (relative risk = 9.56); s uch tumors occurred only in male patients. Conclusions. Survivors of a plastic anemia are at high risk for subsequent malignant conditions. M yelodysplastic syndrome and acute leukemia tend to follow immunosuppre ssive therapy, whereas the incidence of solid tumors is similar after immunosuppression and after bone marrow transplantation.