Castaldo Alice, Cimbalo Chiara, Fevola Cristina, Carnovale Vincenzo, Iacotucci Paola, Raia Valeria, Terlizzi Vito, Gelzo Monica, Sepe Angela, Tosco Antonella
Unità Di Pediatria, Centro Di Riferimento Regionale Pediatrico FC Campania, AOU Federico II, DAI Materno-Infantile, Napoli, Italy.
SC Di Pneumologia E UTSIR, AORN Santobono-Pausilipon, Napoli, Italy.
Sci Rep. 2025 Jul 29;15(1):27571. doi: 10.1038/s41598-025-12333-8.
The elexacaftor/tezacaftor/ivacaftor (ETI) combination for cystic fibrosis transmembrane regulator modulators is a safe and effective treatment in both adults and children who are homozygous or compound heterozygous for the F508del variant. However, few cases involving a significant reduction in blood platelets and an increase in the alanine aminotransferase/platelet ratio have been described in adult and pediatric patients receiving ETI therapy. In the present study, we describe 272 people with cystic fibrosis (pwCF) (166 adult and 106 pediatric pwCF) who were independently followed at two centers; moreover, these individuals were homozygous or compound heterozygous for the F508del variant, were treated with ETI for at least one year, and exhibited monitored platelet and leukocyte counts (together with liver and inflammatory biochemical indices). As controls, 272 healthy subjects (HCs) matched for sex and age were evaluated. At baseline, both adult and pediatric pwCF demonstrated significantly (p < 0.01) greater blood platelet and leukocyte counts compared with HCs. One year of treatment significantly reduced blood platelet counts (adults: 24810/mmc vs. 28810/mmc, p < 0.01; children: 28310/mmc vs. 32010/mmc, p < 0.01) and leukocyte counts (adults: 6.510/mmc vs. 7.610/mmc, p < 0.01; children: 6.810/mmc vs. 7.910/mmc, p < 0.01). In addition, the serum C-reactive protein (CRP) level was significantly (p < 0.01) decreased after therapy, whereas the alanine aminotransferase (ALT) level and the ALT/platelet ratio were significantly increased (p < 0.01). After the second year of therapy, the laboratory parameters were not further altered in approximately half of the patients. The reduction in platelets was significantly correlated with a decrease in leukocytes (r: 0.352, p < 0.001), serum CRP levels (r: 0.392, p < 0.001) and exacerbations (oral antibiotic cycles, r: 0.241, p = 0.002; intravenous antibiotic cycles, r: 0.153, p = 0.049). These findings suggest that the normalization of platelets may be dependent on the reduction in systemic inflammation induced by ETI therapy.
用于囊性纤维化跨膜传导调节因子调节剂的依列卡福/替扎卡福/艾伐卡福（ETI）组合，对于F508del变体纯合子或复合杂合子的成人和儿童而言，是一种安全有效的治疗方法。然而，在接受ETI治疗的成人和儿科患者中，很少有病例描述血小板显著减少以及丙氨酸转氨酶/血小板比率增加。在本研究中，我们描述了272例囊性纤维化患者（pwCF）（166例成人和106例儿科pwCF），他们在两个中心独立接受随访；此外，这些个体为F508del变体的纯合子或复合杂合子，接受ETI治疗至少一年，并展示了监测的血小板和白细胞计数（以及肝脏和炎症生化指标）。作为对照，评估了272名年龄和性别匹配的健康受试者（HCs）。在基线时，与HCs相比，成人和儿科pwCF的血小板和白细胞计数均显著更高（p < 0.01）。一年的治疗显著降低了血小板计数（成人：248×10⁹/mm³ 对 288×10⁹/mm³，p < 0.01；儿童：283×10⁹/mm³ 对 320×10⁹/mm³，p < 0.01）和白细胞计数（成人：6·5×10⁹/mm³ 对 7·6×10⁹/mm³，p < 0.01；儿童：6·8×10⁹/mm³ 对 7·9×10⁹/mm³，p < 0.01）。此外，治疗后血清C反应蛋白（CRP）水平显著降低（p < 0.01），而丙氨酸转氨酶（ALT）水平和ALT/血小板比率显著升高（p < 0.01）。在治疗的第二年之后，大约一半患者的实验室参数没有进一步改变。血小板减少与白细胞减少（r：0.352，p < 0.001）、血清CRP水平降低（r：0.392，p < 0.001）以及病情加重（口服抗生素疗程，r：0.241，p = 0.002；静脉抗生素疗程，r：0.153，p = 0.049）显著相关。这些发现表明，血小板的正常化可能取决于ETI治疗引起的全身炎症的减轻。
