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 2.1*109/L, HGB 117 g/L, PLT 196*109/L, ANC 1.6*109/L, and ALC 0.2*109/L).
Conclusions: 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.