PD-1 blockader-associated atypical hemophagocytic lymphohistiocytosis: A cautionary case report

Hemophagocytic lymphohistiocytosis (HLH) is a fatal immune hyperactivity syndrome with high mortality. It seriously endangers human health. HLH associated with immune checkpoint inhibitors is rare, and no particular diagnostic guidelines or treatment regimens exist. A 36-year-old patient with metastatic right atrial angiosarcoma was treated with programmed cell death-1 (PD-1) blockader toripalimab and pazopanib, a vascular endothelial growth factor receptor blockader. However, the patient presented to our center with HLH, and he accepted combination therapy of therapeutic plasma exchange (TPE) and immunotherapy. The patient improved quickly, after only one TPE procedure. Finally, he was discharged after completing two TPE procedures. We summarize a case of PD-1 blocker associated atypical HLH that was successfully treated with TPE. Further evidence is needed to elucidate whether TPE has therapeutic potential for immunotherapy associated HLH.     

Prognostic factors in patients with bone marrow hemophagocytosis and its association with hematologic malignancies

Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous group of hyperinflammatory statuses that are difficult to diagnose and can be life-threatening. Bone marrow (BM) hemophagocytosis is one of the diagnostic criteria according to HLH 2004 diagnostic criteria and HS score. Limited studies have focused on the prognostic factors of BM hemophagocytosis and its association with hematologic malignancies. We aimed to analyze the clinical significance of BM hemophagocytosis. Patients with BM hemophagocytosis, either by cytology or pathology, were enrolled at Taipei Veterans General Hospital from January 2002 to July 2021. Relevant clinical and laboratory data were extracted from medical records. Of 119 patients with BM hemophagocytosis, 57 were diagnosed with hematologic malignancies. The median age of the patients was 58, ranging from 21 to 90. Splenomegaly (adjusted odds ratio [aOR] 2.96; 95% confidence interval [CI] 1.13–7.79) was a risk factor for hematologic malignancies, while autoimmune disease (aOR 0.07; 95% CI 0.01–0.39) and increased D-dimer (aOR 0.25; 95% CI 0.07–0.92) were protective factors. Risk factors for mortality in patients with BM hemophagocytosis were hematologic malignancies (adjusted hazard ratio [aHR] 2.34; 95% CI 1.24–4.44), Eastern Cooperative Oncology Group score ≥3 (aHR 2.42; 95% CI 1.20–4.89) and thrombocytopenia (aHR 3.09; 95% CI 1.04–9.16). In conclusion, among patients with BM hemophagocytosis, splenomegaly was a predictor of hematologic malignancies. Patients with hematologic malignancies, poor performance status, or thrombocytopenia had a higher mortality risk. Further validation studies are warranted.     

Combined IFN-γ and JAK inhibition to treat hemophagocytic lymphohistiocytosis in mice

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Case report of unrelated cord blood transplantation for the treatment of recurrent refractory Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with intestinal perforation and literature review北大核心CSCD

目的探讨非血缘脐带血移植(UCBT)治疗儿童复发难治性EB病毒相关噬血细胞综合征(EBV-HLH)的临床经验及疗效。方法回顾性分析2015年9月郑州大学第一附属医院儿科诊治的1例复发难治性EBV-HLH合并肠穿孔,最终接受UCBT治愈患儿的临床资料,并进行文献复习。结果患儿,男,1岁6个月,因"发热15 d,皮疹9 d"为主诉入院,主要表现为高热,肝、脾、淋巴结大,快速进展的全血细胞减少、肝功能损害,骨髓涂片可见吞噬血细胞,2015年9月确诊为EBV-HLH,按国际组织细胞协会制定的HLH-2004方案化疗,维持期间2次复发,给予挽救性二线方案"培门冬酰胺酶、阿霉素脂质体、依托泊苷、甲泼尼龙"(L-DEP方案)化疗,化疗后评估噬血细胞综合征指标完全缓解,突发肠穿孔,紧急外科手术行小肠造瘘术,病情稳定后,给予"氟达拉滨+白消安+环磷酰胺"方案(Flu+BU+CY方案)预处理后行UCBT,全程静脉营养支持,移植后第13天中性粒细胞植入,第35天血小板植入,嵌合率为100%,植入成功;移植后第15天出现肝小静脉闭塞征,移植后第22天出现真菌性肺炎,移植后第26天出现皮肤移植物抗宿主病(GVHD)Ⅱ度,给予相应治疗好转;移植后第49天行二期肠造瘘关瘘术;现随访至移植后70个月,患儿一般状况良好,病情持续缓解,无慢性GVHD及其他合并症。结论异基因造血干细胞移植可能是治疗儿童复发难治性EBV-HLH的唯一有效手段;无合适同胞或非血缘供者时,非血缘脐带血干细胞可作为移植物来源;肠穿孔术后肠造瘘不是移植禁忌。     

皮肤T细胞淋巴瘤继发噬血细胞性淋巴组织细胞增多症7例临床分析

目的探讨皮肤T细胞淋巴瘤(CTCL)合并继发性噬血细胞性淋巴组织细胞增多症(sHLH)的临床及实验室特征。方法回顾性分析2016年6月至2021年10月武汉市第一医院血液内科收治的CTCL并拟诊sHLH患者, 按照HLH-2004标准和HScore评分对患者进行评估。结果 7例CTCL患者确诊合并sHLH, 分别为2例原发性皮肤γδT细胞淋巴瘤(PC-GDTCL), 3例皮肤结外NK/T细胞淋巴瘤(C-ENKTCL), 2例原发皮肤间变大细胞淋巴瘤(PC-ALCL)。7例患者均接受化疗, 6例死亡, 确诊CTCL合并sHLH后生存期14 ～ 60 d (中位生存期26.5 d)。2例检出HLH相关基因突变(PRF1、LYST突变), 2例PC-GDTCL患者分别检出淋巴瘤相关基因突变(KRAS、KMT2D和JAK3 、SAMHD1突变)。结论 CTCL合并sHLH临床进展迅速, 需早期诊断及干预, 初诊及病情进展时行骨穿检查及淋巴瘤、HLH相关基因突变检测有助于早期诊断。