LAUSR

Dear editor, Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a distinctive and extremely aggressive subtype of T-ALL. It is characterized by the aberrant expression of myeloid/stem cell antigens and the lack of Tlymphoid antigens including CD1a, CD4, CD5, and CD8. Clinically, relapses/refractoriness frequently occur in ETP-ALL. Therefore, re-achievement of complete remission (CR) for further hematopoietic stem cell transplantation (HSCT) is essential for relapsed/refractory ETP-ALL. However, the best re-induction regimen remains unestablished. Here, we reported a case in which relapsed/refractory ETP-ALL was successfully salvaged by venetoclax plus HAG regimen. A 25-year-old male ETP-ALL patient experienced the relapse of disease after being in complete remission (CR) for 22 months with the manifestation of cytopenia (WBC: 1.1 × 10/L, HB: 102 g/L, PLT: 16 × 10/L). Bone marrow biopsy revealed a hypercellular bone marrow with 84% lymphoid blasts, negative for MPO staining (Fig. 1A). The flow cytometry showed the immunophenotype of the lymphoid blasts (CD1a-CD2-sCD3-CD4-CD5-CD7 + CD8 -CD33 + CD34 + CD117 + CD123 -CD200+ (F i g . 1C ) ) , w h i c h w e r e c o n s i s t e n t w i t h t h e immunophenotype of the ETP-leukemic cells at primary diagnosis (CD1a-CD2-sCD3-cytoCD3 + CD4-CD5CD7 + CD8-CD10-CD13-CD16-CD19-CD20-CD33CD34 + CD38 + CD56 + CD117 + CD200 + HLADR + TCRα/β-TCRγ/δ-MPO(Fig. 1B)). Cytogenetics showed a normal karyotype, and the next generation sequencing revealed mutations in JAK3, KRAS, and RPS15 (Fig. 1D). Therefore, relapsed ETP-ALL was diagnosed. Initially, he received two cycles of CAG regimen (aclacinomycin 20 mg qd d1–4; cytarabine 37 mg q12h d1–7; G-CSF 300 μg q12h d1–14), an effective regimen for relapsed/refractory T-ALL [1], but no response was observed. Then, he switched to receive venetoclax plus HAG regimen (venetoclax, 100 mg d1, 200 mg d2, 400 mg qd d3–28; homoharringtonine 2 mg qd d1–8; cytarabine 37.4 mg qd d1–10; G-CSF 300 μg qd d1–8) [2 ] and CR was ach ieved th i s t ime (F ig . 1E) . Subsequently, he underwent hematopoietic stem cell transplantation (HSCT) successfully, and CR was still maintained at now 5 months after HSCT. In preclinical studies, the BCL2 inhibitor venetoclax was shown to be an effective agent for T-ALL treatment [3]. Compared to mature T-ALL, immature T-ALL, especially ETP-ALL, is much more sensitive to venetoclax due to the contribution of high BCL-2/BCL-XL ratio and the addiction to BCL2 overexpression in ETP-ALL [4]. Besides, T-ALL with RPL10 mutation is also sensitive to venetoclax due to the activation of IRES-dependent BCL2 translation [5]. Except for monotherapy, venetoclax can be combined with different types of drugs used in T-ALL treatment, e.g., with doxorubicin or L-asparaginase to treat different subtypes of TALL [3]. However, when combined with cytarabine or dexamethasone, the synergistic effects could only be observed in ETP-ALL [3, 6]. What’s more, venetoclax showed promising synergistic effects when used in combination with targeted therapy agents, including MCL-1 inhibitor S63845 [7], BET bromodomain inhibitor JQ1 [8], JAK inhibitor ruxolitinib [9], and hypomethylation agent decitabine [10]. Above all, we demonstrated that ETP-ALL is the best indication for * Wenjuan Yu [email protected]