Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon and Claude Bernard Lyon 1 University, Lyon, France; Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM) EA7424, Team "Vascular Biology and Red Blood Cell", Université Claude Bernard Lyon 1, Lyon, France; Laboratoire d'Excellence du Globule Rouge (Labex GR-Ex), PRES Sorbonne, Paris, France.
Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon and Claude Bernard Lyon 1 University, Lyon, France; Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France; EMR 3738 Ciblage Thérapeutique, Lyon-Sud Hospital, Pierre-Bénite, France.
Biol Blood Marrow Transplant. 2020 Dec;26(12):2285-2291. doi: 10.1016/j.bbmt.2020.01.016. Epub 2020 Jan 31.
Graft-versus-host disease (GVHD) is an important challenge and a major cause of morbidity and mortality in children after hematopoietic stem cell transplant (HSCT). Herein we report our institution's experience of goal-oriented Bayesian monitoring for cyclosporine (CsA) used alone as GVHD prophylaxis during the post-transplant period in pediatric patients with thalassemia major (TM) or sickle cell anemia (SCA) undergoing HLA-matched HSCT. We also studied evolution of chimerism. Twenty-six consecutive patients (SCA, 14; TM, 12) underwent matched sibling donor (MSD) HSCT from 2004 to 2014. All patients received a myeloablative conditioning regimen. GVHD prophylaxis consisted of 20 mg/kg antithymocyte globulin in the conditioning regimens and then CsA alone in the post-transplant period. Target CsA trough blood concentration (TBC) was 150 ± 20 ng/mL. At last follow-up, all patients were alive and free of disease, even in cases of mixed chimerism. Engraftment occurred in all patients. No patient developed grades II to IV acute GVHD, 4 patients developed acute grade I skin GVHD, and only 1 presented with chronic pulmonary GVHD. A better control of GVHD and immunosuppression by a strict monitoring of CsA TBC as described herein is promising and could play a crucial role. Further investigations are required, but this study opens new perspectives to improve survival and safety of HSCT from alternative donors in TM and SCA to levels compatible with that obtained with MSDs.
移植物抗宿主病（GVHD）是造血干细胞移植（HSCT）后儿童发病率和死亡率的重要挑战和主要原因。在此，我们报告了我们机构在接受 HLA 匹配 HSCT 的重型地中海贫血（TM）或镰状细胞贫血（SCA）患儿中，单独使用环孢素（CsA）作为 GVHD 预防的目标导向贝叶斯监测的经验。我们还研究了嵌合体的演变。26 例连续患者（SCA14 例；TM12 例）于 2004 年至 2014 年接受同胞供体（MSD）HSCT。所有患者均接受清髓性预处理方案。GVHD 预防包括预处理方案中的 20mg/kg 抗胸腺细胞球蛋白，然后在移植后单独使用 CsA。目标 CsA 谷浓度（TBC）为 150±20ng/ml。在最后一次随访时，所有患者均存活且无疾病，即使存在混合嵌合体。所有患者均发生植入。无患者发生 II 至 IV 级急性 GVHD，4 例患者发生急性 I 级皮肤 GVHD，仅 1 例患者发生慢性肺 GVHD。通过严格监测 CsA TBC 对 GVHD 和免疫抑制的更好控制是有希望的，并可能发挥关键作用。需要进一步研究，但这项研究为 TM 和 SCA 中从替代供体进行 HSCT 以获得与 MSD 相当的生存率和安全性开辟了新的前景。
