Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)
Phase 1/2 randomized, placebo-control trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)
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DOI：
10.1182/blood-2006-04-017780
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发表时间：
2006-11-01
期刊：
影响因子：
20.3
通讯作者：
Ferrara, James L. M.
中科院分区：
文献类型：
--
作者：
Blazar, Bruce R.;Weisdorf, Daniel J.;Ferrara, James L. M.
Palifermin是一种重组人角质形成细胞生长因子，在异基因造血干细胞移植（HSCT）受者中测试其对急性移植物抗宿主病（GVHD）和造血恢复的潜在益处。这项随机、双盲、安慰剂对照、剂量递增研究在接受环磷酰胺和分次全身照射（Cy/TBI）或白消安和环磷酰胺（Bu/Cy）并接受甲氨蝶呤沿着钙调磷酸酶抑制剂（环孢素A，他克莫司）预防GVHD的患者中评估了帕利佛明（n = 69）与安慰剂（n = 31）相比的安全性和耐受性。所有患者在预处理前接受了3剂，在HSCT后接受了3剂（队列1）、6剂（队列2）或9剂（队列3）。帕利弗明剂量为每天40 μ g/kg（仅队列I）或每天60 μ g/kg（所有队列）。6例患者（安慰剂组= 2例，帕利弗明组= 4例）共发生11例剂量限制性毒性（最常见的是皮肤、呼吸道或口腔粘膜炎）。最常见的不良反应包括水肿、感染、皮肤疼痛或皮疹。至中性粒细胞和血小板植入的时间相似。两组间急性GVHD发生率或严重程度、存活率或第100天复发率无显著差异。帕利弗明与Cy/TBI条件治疗患者的粘膜炎发生率和平均严重程度降低相关，但与Bu/Cy无关。我们得出结论，帕利弗明在同种异体造血干细胞移植中一般是安全的，但在本试验中对移植、急性GVHD或存活率无显著影响。
Palifermin, a recombinant human keratinocyte growth factor, was tested for potential benefits on acute graft-versus-host disease (GVHD) and hematopoletic recovery in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. This randomized, double-blind, placebo-controlled, dose-escalation study assessed the safety and tolerability of palifermin (n = 69) as compared with placebo (n = 31) in patients conditioned with cyclophosphamide and fractionated total-body irradiation (Cy/TBI) or busulfan and cyclophosphamide, (Bu/Cy) and given methotrexate along with a calcineurin inhibitor (cyclosporine A, tacrolimus) for GVHD prophylaxis. All patients received 3 doses before conditioning and either 3 (cohort 1), 6 (cohort 2), or 9 (cohort 3) doses after HSCT. Palifermin doses were 40 mu g/kg per day (cohort I only) or 60 mu g/kg per day (all cohorts). Six patients (placebo = 2, palifermin = 4) experienced a total of 11 dose-limiting toxicities (most often skin, respiratory, or oral mucositis). The most common adverse events included edema, infection, skin pain, or rash. Times to neutrophil and platelet engraftment were similar. No significant differences in acute GVHD incidence or severity, survival, or day 100 relapse rates were observed between groups. Palifermin was associated with reduced incidence and mean severity of mucositis in patients conditioned with Cy/TBI but not Bu/Cy. We conclude that palifermin was generally safe in allogeneic HSCTs but had no significant effect on engraftment, acute GVHD, or survival in this trial.