Totadri Sidharth, Bansal Deepak, Bhatia Prateek, Attri Savita V, Trehan Amita, Marwaha R K
Department of Pediatrics, Hematology-Oncology Unit and Biochemistry, Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Pediatr Blood Cancer. 2015 Sep;62(9):1592-6. doi: 10.1002/pbc.25533. Epub 2015 Mar 28.
The high cost, coupled with the need for continuous infusion, renders Desferrioxamine (DFO), a non-feasible option for iron-chelation in a large majority of patients with β-thalassemia major in developing countries. Monotherapy with deferiprone (DFP) or deferasirox (DFX) may not always attain optimal control, particularly in heavily iron-loaded patients. Combination of DFP and DFX is a potential alternative.
A prospective, single-center, open-label, uncontrolled study was conducted to evaluate the safety and efficacy of the combination in patients with β-thalassemia major. Patients who had received either DFP or DFX for >1 year and a serum ferritin >2,000 μg/L were enrolled. Blood counts, liver/renal functions, and serum ferritin were monitored during the 1-year study period. Facilities for cardiac T2*-MRI were unavailable.
Thirty-six patients with a mean age of 13 ± 6.9 years (range: 4-29) and a ferritin of 6,768 ± 4,145 μg/L formed the study cohort. Eight (22%) patients had transient gastrointestinal adverse effects. DFX was discontinued in one patient for persistent abdominal pain/diarrhea. Eight (22%) had joint symptoms; DFP was discontinued in two. Four (11%) patients had elevation in AST/ALT levels, managed with temporary interruption of DFX. Nine (25%) had an inconsistent elevation of creatinine to >33% of baseline; no intervention was done. One had transient proteinuria. None had neutropenia. At the end of 1 year, the serum ferritin reduced by a mean value of 3,275.3 ± 618.2 μg/L (P < 0.001).
The oral combination was found to be safe, efficacious, and a feasible option in patients with suboptimal response to monotherapy.
去铁胺（DFO）成本高昂，且需要持续输注，这使得在大多数发展中国家的重型β地中海贫血患者中，它并非铁螯合的可行选择。单独使用去铁酮（DFP）或地拉罗司（DFX）进行治疗可能无法始终实现最佳控制，尤其是在铁负荷严重的患者中。DFP与DFX联合使用是一种潜在的替代方案。
开展了一项前瞻性、单中心、开放标签、非对照研究，以评估该联合用药方案对重型β地中海贫血患者的安全性和有效性。纳入了接受DFP或DFX治疗超过1年且血清铁蛋白>2000μg/L的患者。在为期1年的研究期间监测血细胞计数、肝/肾功能和血清铁蛋白。无法进行心脏T2*磁共振成像检查。
36例患者构成了研究队列，平均年龄为13±6.9岁（范围：4 - 29岁），铁蛋白水平为6768±4145μg/L。8例（22%）患者出现短暂的胃肠道不良反应。1例患者因持续性腹痛/腹泻停用DFX。8例（22%）有关节症状；2例停用DFP。4例（11%）患者的谷草转氨酶/谷丙转氨酶水平升高，通过暂时中断DFX进行处理。9例（25%）患者的肌酐水平不一致地升高至超过基线的33%；未采取干预措施。1例出现短暂性蛋白尿。无人出现中性粒细胞减少。1年后，血清铁蛋白平均降低了3275.3±618.2μg/L（P<0.001）。
对于单药治疗反应欠佳的患者，发现该口服联合用药方案安全、有效且可行。
