BACKROUND: Survival of patients with transfusion dependent (TD) beta thalassemia major (TM) has improved significantly over the past few decades as better treatment became available. However, due to ineffective erythropoiesis, reduced red blood cell (RBC) survival, and subsequent continuous hemolytic anemia, these patients are regularly and heavily transfused since early childhood. Exposure to multi transfusions is associated with significant risks including development of antibodies against RBC antigens, both alloantibodies and autoantibodies, which in turn complicate RBC cross matching, shorten in vivo survival of transfused RBC, and may accelerate tissue iron loading. Anti-K, anti-E and other Rh blood group system alloantibodies are the most frequently detected.AIMS: Assessment of RBC alloimmunization and autoimmunization rate in adult patients with TD TM followed and treated in our center.PATIENTS and METHODS: The study included a total of 40 patients with TD TM, >18 years of age. Clinical and transfusion records, including age, gender, ethnicity, history of pregnancies, blood group, history of splenectomy, age at first transfusion and lifelong cumulative number of blood units transfused, were retrieved from patients' files and from the blood bank database.RESULTS: Twenty one (52.5%) patients were males, 19 (47.5%) were females, the mean ±SD (range) age was 31.8 ± 6.9 (20-47) years, 29 patients (72.5%) were of Muslim Arab origin, 11 (27.5%) were Jewish. Thirty (75.0%) of the patients were splenectomized (SPX). The median (mean) ±SD (range) age at first transfusion was 0.71 (1.07) ± 0.93 (0.25-4.0) years, and the mean ±SD (range) of lifelong cumulative number of blood units transfused was 828.5 ± 239.3 (439-1363).Alloimmunization was demonstrated in 17 (42.5%) patients; 10 of 21 (47.6%) males and 7 of 19 (36.8%) females; 11 of 29 (37.9%) of Muslim Arab origin, 6 of 11 (54.5%) of Jewish origin; 11 (64.7%) had >1 alloantibody. Among female patients, alloimmunization was demonstrated in 4 (31.0%) of 13 with no history of pregnancy and in 3 (50.0%) of 6 with history of pregnancy. Twelve (40.0%) of 30 SPX patients had alloantibodies, compared to 5 (50.0%) of 10 patients with intact spleen.Anti-Rh antibodies were the most prevalent, detected in 10/17 (58.8%) patients having 12 alloantibodies (8 anti-E, 2 anti-D, 1 anti-C and 1 anti-Cw), followed by Anti-Kell antibodies detected in 7/17 (41.2%) patients having 8 alloantibodies (6 anti-K, 2 anti-Kpa). One patient had anti-Jkb, and 3 patients had alloantibodies against low frequency antigens. Autoimmunization was demonstrated in 2 (5.0%) patients (Figure 1).Significant inverse correlation was found between age at first transfusion and rate of alloimmunization. Thirty (75.0%) patients started blood transfusions before 1 year; 9 (30.0%) of them had alloantibodies. Ten (25.0%) patients started blood transfusions after the first year; 8 (80.0%) of them had alloantibodies (p=0.009).There was no significant association between alloimmunization and patients' age, gender, ethnicity, history of pregnancies, blood group, splenectomy status, and lifelong cumulative number of blood units transfused (p >0.05).CONCLUSIONS: We have found a high rate (42.5%) of alloimmunization in adult TD TM patients, which might be attributed to multi transfusions over many years without RBC antigen matching beyond ABO and Rh. Alloimmunization rate was lower in those who began transfusions before 1 year of age, similar to previous studies, supporting the concept of immune tolerance developing in young children who begin transfusions before 1 year of age. Based on our study results, transfusion policies, especially extended antigen matching for Rh and K, should be considered in order to reduce alloimmunization. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.