Life expectancy of thalassemic patients, appropriately transfused and adequately iron-chelated, has been substantially extended the last decades. However, these patients are subjected to particular risks which might favor the development of neoplasia, such as transfusional iron overload, high prevalence of viral diseases, particularly HCV infection, and transfusion-associated alteration of their immune status. The occurrence of neoplastic diseases has not been extensively investigated in this patient population.
We sought to investigate the occurrence of neoplastic diseases during a 16.5 year-period, in a large cohort of 1972 thalassemic patients (homozygous beta-thalassemia N=1448, thalassemia intermedia N=352 and sickle-cell/beta thalassemia N=172), followed-up in 6 large Greek Thalassemic Units. All documented cases of neoplastic diseases, diagnosed during the period between 1.1.1996 and 30.6.2012 were collected and analyzed. The frequency of each type of neoplasia was then correlated with specific factors, potentially influencing the occurrence of these disorders, and particularly age at first transfusion, frequency of transfusions, previous splenectomy, smoking, use of hydroxyurea, previous autoimmune disorders, presence of HBV, HCV and HIV infection, adequacy of iron chelation and the degree of hepatic siderosis.
Totally 38 cases of neoplastic disorders were documented among the 1972 patients. These were Hepatocellular carcinoma (10 cases), non-Hodgkin's Lymphoma (6 cases in total: Marginal-zone lymphoma N=2, Mantle-cell lymphoma N=1, Diffuse large B-cell lymphoma N=1, Burkitt's lymphoma N=1, T-cell lymphoblastic lymphoma N=1), Thyroid carcinoma (3 cases in total: papillary N=2, follicular N=1), Hodgkin's lymphoma (3 cases in total, classical N=2, LPHD N=1), Renal cell cancer (N=3), Colon cancer (N=3), Breast cancer (N=2), Cholangiocarcinoma (N=2), Pre-B Acute Lymphoblastic Leukemia (N=2), Testicular cancer (2 cases in total, seminoma N=1, teratoma N=1), melanoma (N=1), and Renal oncocytoma (N=1). Twenty-eight cases were diagnosed among patients with homozygous beta-thalassemia, 6 among patients with thalassemia intermedia and 4 among patients with sickle-cell/beta thalassemia. Median age at diagnosis of the neoplastic disease was 39 years (age range 21 to 63 years). Twenty-nine cases (76.3%) were diagnosed among previously splenectomized patients, although splenectomy had been performed in 41% of the total cohort of patients. All patients were HIV-negative, 3/31 (9.7%) were HBsAg-positive, whereas 22/37 (59.5%) had HCV infection. Patients were then classified according to the level of liver siderosis and the effectiveness of their iron chelation treatment, estimated by their annual median serum ferritin levels. Eleven patients were found to be adequately chelated (median serum ferritin 310 ng/ml), 16 were moderately-effectively chelated (median serum ferritin 1240 ng/ml) and 11 were inadequately chelated (median serum ferritin 2552 ng/ml). There was no difference in patient's age or in the type of neoplastic disorders occurred in each of the 3 categories, however 3/11 poorly chelated patients were long term survivors, versus 8/16 moderately chelated and 9/11 adequately chelated patients.
In conclusion, the prolongation of overall survival of thalassemic patients results in increasing occurrence of neoplastic diseases among this patient population. Splenectomized and HCV-infected patients appear to represent higher-risk groups, whereas the role of iron overload appears not to influence the occurrence of neoplastic diseases but may have an impact on the long-term outcome and clearly deserves further investigation.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.