TRANSFUSION PRACTICE Hematopoietic peripheral circulating blood stem cells as an independent marker of good transfusion management in patients with b-thalassemia: results from a preliminary study Mariasanta Napolitano, 1 Calogera Gerardi, 2 Anna Di Lucia, 2 Pietro Andrea Accardo, 3 Luigi Rizzuto, 3 Maria Ferraro, 3 Sergio Siragusa, 1 and Filippo Buscemi 3 BACKGROUND: Beyond hemoglobin (Hb) levels and performance status, further surrogate markers of appropriate transfusion management should improve the quality of thalassemia care. We investigated the levels of peripheral circulating CD341 stem cells as an independent marker of appropriate hematopoietic balance in patients with thalassemia. STUDY DESIGN AND METHODS: Peripheral circulating CD341 stem cells, colony-forming unit– granulocyte, erythrocyte, macrophage, magakaryocyte (CF-GEMM), colony-forming unit–granulocyte/macrophage (CFU-GM), and erythroid-burst-forming units (BFU-E) were assayed, according to standard procedures. Patients with thalassemia major (TM) and thalassemia intermedia (TI) were tested and compared to healthy controls. Demographic and clinical data were recorded. RESULTS: Overall, 56 patients with TM (median age, 35 years; range, 13-52 years) and 13 with TI (median age, 44 years; range, 27-67 years) were evaluated. Annual red blood cell (RBC) transfusion requirements ranged from 10 to 65 units in all patients except four nontransfused cases. A significant increase in peripheral circulating stem cells was observed in patients, in comparison with healthy controls. Nontransfused patients showed the mean highest levels of stem cells (CD34, 32.5 6 14.8/lL; BFU-E, 41.3 6 22.8/mL; CFU-GM, 19.6 6 5.6/ mL; CFU-GEMM, 9.0 6 6.1/mL). CD341 cell count was 6.9 6 4.5/lL in TM (p = 0.014) and 11.8 6 14.8/lL (p 5 0.051) in TI. Furthermore, only in patients with TI was a significant increase in CFU-GEMM (3.0 6 4.8 vs. 0.75 6 2.05/mL, p 5 0.0001) observed. At multivariate analysis, peripheral circulating CD341 stem cells did not correlate with age, sex, smoking habit, number of RBCs units transfused, Hb levels, iron chelation therapy, history of splenectomy, and hypothyroidism. CONCLUSION: Circulating peripheral CD34 1 stem cells are increased in b-thalassemia, in particular in nontransfused patients, compared to healthy controls. b -Thalassemias are determined by a reduced or absent b-globin synthesis, ineffective erythropoi- esis, and compensatory erythroid hyperplasia. b- Thalassemia is characterized by a wide range of clinical severity, from high transfusion dependency (in b- thalassemia major [TM]) to partially less severe anemia (in b-thalassemia intermedia [TI]). TM is treated with reg- ular blood transfusion and iron chelation therapy since infancy, while patients with TI are usually transfusion independent and their clinical phenotype is intermediate between TM and asymptomatic heterozygous. 1 Little is known about the effects of blood transfusions on circulating hemopoietic progenitors in b-thalassemia patients. Circulating myeloid stem cells (CFU-c) in the peripheral blood of children with TM have been assessed in the early 1980s with culture techniques. 2 CFU-c were actively proliferating and higher in number in splenec- tomized patients than in controls; their amount was posi- tively related with the time elapsed since the last transfusion. Mean higher hemoglobin (Hb) levels were associated with a marked reduction in the number of CFU-c. Authors of this seminal work hypothesized that an ABBREVIATIONS: TI 5 thalassemia intermedia; TM 5 thalassemia major. From the 1 UOC Ematologia con Trapianto, Universit a di Palermo, Palermo, Italy; and the 2 Banca del Sangue da Cordone Ombelicale and the 3 UOS Talassemia, UOC Medicina Trasfusionale, PO “Giovanni Paolo II,” Sciacca, Italy. Address reprint requests to: Napolitano Mariasanta, MD, PhD, UOC Ematologia, Policlinico “P. Giaccone,” Universit a di Palermo, Via del Vespro 127, I-90127 Palermo, Italy; e-mail: mariasanta.napolitano@unipa.it. Received for publication August 26, 2015; revision received November 8, 2015; and accepted November 13, 2015. doi:10.1111/trf.13452 V C 2016 AABB TRANSFUSION 2016;56;827–830 Volume 56, April 2016 TRANSFUSION 827