PDF(Pubmed)
Abstract：
Graft-versus-host disease (GVHD) is a common complication in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized as either acute or chronic based on symptomatology and histopathological findings. Despite advancements in disease-targeting therapeutics, steroid-refractory GVHD remains a significant contributor to mortality in HSCT recipients, highlighting the gaps in our understanding of its pathophysiology and treatment strategies. We present the case of a 46-year-old woman diagnosed with acute undifferentiated leukemia, who exhibited persistently elevated levels of serum total bilirubin (T.Bili), alkaline phosphatase (ALP), and liver function tests (LFTs) beginning on [day +201] post-haploidentical peripheral blood stem cell (PBSC) transplantation. The patient received fludarabine/total body irradiation (Flu/TBI) as a myeloablative conditioning regimen and post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (PTCy/Tac/MMF) as GVHD prophylaxis. A liver biopsy confirmed the diagnosis of GVHD, while other possible etiologies were excluded by corresponding tests. Initial treatment with prednisone and tacrolimus, and the later addition of ruxolitinib, all showed poor response indicated by worsening T.Bili, ALP, and LFTs at the same time. Based on a multidisciplinary comprehensive assessment, we decided to administer 1,000 mg/m2 (1,600 mg) of cyclophosphamide (\"pulse Cy\"), which resulted in a dramatic improvement in T.Bili and transaminases starting from the very next day. A durable response to pulse cyclophosphamide was observed, as all indicators normalized (\"complete response\") within 55 days without relapses. The patient remains in good health with no recurrence of hepatic GVHD. To our knowledge, this is the first case in which Grade IV hepatic GVHD, refractory to multiple agents including steroids, tacrolimus, and ruxolitinib, demonstrated a complete response to pulse cyclophosphamide. The success highlights the potential therapeutic role of cyclophosphamide, a potent and cost-effective chemotherapy agent, in treating multi-agent-refractory GVHD. Large-scale clinical trials are warranted to validate its efficacy in this setting.
摘要：
移植物抗宿主病（GVHD）是接受异基因造血干细胞移植（HSCT）的患者的常见并发症。根据症状学和组织病理学发现，GVHD的特征为急性或慢性。尽管疾病靶向疗法取得了进展，激素难治性GVHD仍然是HSCT受者死亡率的重要因素，强调我们对其病理生理学和治疗策略的理解存在差距。我们介绍了一名46岁的女性，被诊断患有急性未分化白血病，谁表现出持续升高的血清总胆红素水平（T。Bili),碱性磷酸酶(ALP),和肝功能检查（LFTs）从单倍型外周血干细胞（PBSC）移植后[第201天]开始。患者接受氟达拉滨/全身照射（Flu/TBI）作为清髓预处理方案，移植后环磷酰胺/他克莫司/霉酚酸酯（PTCy/Tac/MMF）作为GVHD预防。肝活检证实了GVHD的诊断，而其他可能的病因被相应的测试排除。最初用泼尼松和他克莫司治疗，和后来加入的鲁索利替尼，都表现出反应不佳，表明T.Bili恶化，ALP,和LFTs在同一时间。基于多学科综合评估，我们决定服用1,000毫克/平方米（1,600毫克）的环磷酰胺（“脉冲Cy”），从第二天开始，T.Bili和转氨酶的显着改善。观察到脉冲环磷酰胺的持久反应，所有指标在55天内恢复正常（“完全缓解”），无复发。患者身体健康，无肝脏GVHD复发。据我们所知,这是首例IV级肝GVHD,对包括类固醇在内的多种药物难以治疗，他克莫司,和鲁索替尼,表现出对脉冲环磷酰胺的完全反应。成功凸显了环磷酰胺的潜在治疗作用，一种有效且具有成本效益的化疗药物，治疗多剂难治性GVHD。有必要进行大规模的临床试验以验证其在这种情况下的疗效。
