Hu Qin, Li Yunfei, Zhang Ying, Sun Shusen, Wang Hui, Jiang Zhiping, Deng Sheng
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2022 May 6;12:824393. doi: 10.3389/fonc.2022.824393. eCollection 2022.
T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder that starts in T cells and is usually indolent. Long-term use of immunosuppressants, combined with agranulocytosis, is a double-edged sword, as both can lead to serious infections, especially in patients with combined hematologic malignancies and immune defects.
A 30-year-old female patient was admitted to the hospital because of agranulocytosis for five years, with chest tightness, fatigue, and fever for two days. Pathology and metagenomic next-generation sequencing (mNGS) detected Aspergillus. Although she received cyclosporine and methylprednisolone, the patient showed drug intolerance and progression with invasive pulmonary fungal infections. After a bone marrow aspiration biopsy and other related examinations, she was diagnosed with T-LGLL and invasive pulmonary aspergillosis (IPA). T-cell immunophenotype was CD45+CD3dim+CD5-CD4-CD8+CD7+CD57p+CD25-CD30-, TCRγδ+, transducer and activator of transcripton-3 (STAT3) Y640F mutation and fusion gene NPL-DHX9 rearrangement were confirmed, which has never been reported in hematological diseases. After voriconazole regimen adjustment during treatment based on therapeutic drug concentration monitoring (TDM) and improvement in lung infection, the patient finally treated with purine nucleoside analogues (PNA) cladribine as a single agent at 0.14 mg/kg/d for 5 days. Complete response was achieved after four-cycles cladribine treatment (WBC 2.1109/L, HGB 117 g/L, PLT 196109/L, ANC 1.6109/L, and ALC 0.2109/L).
To our knowledge, this is the first case of T-LGLL with a rare γδ type and fusion gene NPL-DHX9 rearrangement. The patient was successfully treated with cladribine, suggesting that this regimen could be a promising therapeutic strategy for patients with aggressive T-LGLL.
T 细胞大颗粒淋巴细胞白血病（T-LGLL）是一种罕见的淋巴细胞增殖性疾病，起源于 T 细胞，通常进展缓慢。长期使用免疫抑制剂并伴有粒细胞缺乏症，犹如一把双刃剑，因为两者都可能导致严重感染，尤其是在合并血液系统恶性肿瘤和免疫缺陷的患者中。
一名 30 岁女性患者因粒细胞缺乏症五年入院，伴有两天的胸闷、乏力和发热。病理及宏基因组下一代测序（mNGS）检测到曲霉菌。尽管她接受了环孢素和甲泼尼龙治疗，但患者出现药物不耐受且侵袭性肺部真菌感染病情进展。经过骨髓穿刺活检及其他相关检查，她被诊断为 T-LGLL 和侵袭性肺曲霉病（IPA）。确认 T 细胞免疫表型为 CD45+CD3dim+CD5-CD4-CD8+CD7+CD57p+CD25-CD30-，TCRγδ+，转录信号调节因子 3（STAT3）Y640F 突变以及融合基因 NPL-DHX9 重排，这在血液系统疾病中从未有过报道。治疗期间基于治疗药物浓度监测（TDM）调整伏立康唑治疗方案并改善肺部感染后，患者最终接受嘌呤核苷类似物（PNA）克拉屈滨单药治疗，剂量为 0.14 mg/kg/d，持续 5 天。克拉屈滨治疗四个周期后达到完全缓解（白细胞计数 2.1×10⁹/L，血红蛋白 117 g/L，血小板计数 196×10⁹/L，中性粒细胞计数 1.6×10⁹/L，淋巴细胞计数 0.2×10⁹/L）。
据我们所知，这是首例具有罕见γδ型和融合基因 NPL-DHX9 重排的 T-LGLL 病例。患者接受克拉屈滨治疗成功，表明该方案可能是侵袭性 T-LGLL 患者一种有前景的治疗策略。
