Single-Agent High-Dose Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Human Leukocyte Antigen-Matched Reduced-Intensity Peripheral Blood Stem Cell Transplantation Results in an Unacceptably High Rate of Severe Acute Graft-versus-Host Disease
Single-Agent High-Dose Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Human Leukocyte Antigen-Matched Reduced-Intensity Peripheral Blood Stem Cell Transplantation Results in an Unacceptably High Rate of Severe Acute Graft-versus-Host Disease
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DOI：
10.1016/j.bbmt.2015.01.020
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发表时间：
2015-05-01
影响因子：
4.3
通讯作者：
Gottlieb, David
中科院分区：
文献类型：
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作者：
Bradstock, Kenneth F.;Bilmon, Ian;Gottlieb, David
在HLA匹配的清髓性骨髓移植中，异基因造血细胞移植后早期给予高剂量环磷酰胺已被证明是有效预防移植物抗宿主病（GVHD）的方法，可避免某些患者使用钙调磷酸酶抑制剂进行长期免疫抑制。使用粒细胞集落刺激因子（G-CSF）动员的外周血干细胞移植物是否可行尚不清楚。我们进行了一项探索性II期试验，在移植后第3天和第4天静脉注射环磷酰胺50 mg/kg，作为HLA匹配的相关或无关供体的G-CSF动员外周血干细胞移植物接受者中唯一的GVHD预防，接受者接受氟达拉滨、卡莫司汀和美法仑的低强度预处理治疗。5例患者，年龄在52至67岁之间，患有高风险血液恶性肿瘤。5例中有4例发生了3 - 4级严重急性GVHD，需要甲基强的松龙和环孢素治疗; 3例为类固醇难治性，接受了挽救治疗。其中1例死于肝移植物抗宿主病，1例死于败血症，2例存活。我们的结论是，移植后环磷酰胺是不够的，作为唯一的GVHD预防的背景下，外周血降低强度的条件移植HLA匹配的捐助者。本试验注册于ACTRN 12613001154796。
High-dose cyclophosphamide given early after allogeneic hemopoietic cell transplantation has been shown to be effective prophylaxis against graft-versus-host disease (GVHD) in the setting of HLA-matched myeloablative bone marrow grafts, allowing avoidance of long-term immunosuppression with calcineurin inhibitors in some patients. Whether this approach is feasible using granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell grafts is unknown. We conducted an exploratory phase 2 trial of cyclophosphamide given at 50 mg/kg i.v. on days 3 and 4 after transplantation as sole GVHD prophylaxis in recipients of G-CSF-mobilized peripheral blood stem cell grafts from HLA-matched related or unrelated donors after reduced-intensity conditioning therapy with fludarabine, carmustine, and melphalan. Five patients, ages 52 to 67 years, with high-risk hematologic malignancies were enrolled. Four of the 5 developed severe acute GVHD of grades 3 to 4, requiring treatment with methylprednisolone and cyclosporine; 3 were steroid refractory and were given salvage therapy. One of these 4 patients died of hepatic GVHD, one died of sepsis, and 2 survived. We conclude that post-transplantation cyclophosphamide is inadequate as sole GVHD prophylaxis in the context of peripheral blood reduced-intensity conditioning transplantations from HLA-matched donors. This trial is registered at ACTRN12613001154796.