Daratumumab, Venetoclax, and Azacitidine in Combination with HAA Regimen as Consolidation Chemotherapy for T-cell Acute Lymphoblastic Leukemia with High CD38 Expression

To the EditorThe combination of Venetoclax (Ven) and Azacitidine (Aza) may be effective for relapsed or refractory T-ALL (R/R T-ALL) [i,ii] .Researchers are exploring the use of Ven and/or Aza with AML-like chemotherapy regimens (e.g., HAG, CAG, FAI) for R/R T-ALL, including ETP and non-ETP subtypes [iii,iv,v] .The HAA regimen, composed of homoharringtonine (HHT), cytarabine (Ara-C), and Aclarubicin (Acla), has been commonly used in AML induction and salvage chemotherapy [vi,vii,viii] .We hypothesize that combining Ven and Aza with the HAA regimen (VA-HAA) may also exhibit therapeutic effects on T-ALL.In addition, the therapeutic potential of the CD38 monoclonal antibody for T-ALL has gradually attracted attention [ix] .Biologically, CD38 expression is nearly ubiquitous in T-ALL cells.Up to 98% of T-ALL patients exhibit CD38-positive cells, and as many as 89% of patients display a CD38 positive expression rate exceeding 80%, which is significantly higher compared to B-ALL [x] .The frequent and stable expression of CD38 suggests that CD38-targeted therapy may offer significant potential in the treatment strategy for T-ALL [xi,xii,xiii] .Therefore, we exploratively employed a combination therapy consisting of Daratumumab (Dara) in conjunction with VA-HAA (Dara-VA-HAA) for a newly diagnosed (ND) T-ALL patient with high CD38 expression.The patient was a 60-year-old female who was newly diagnosed with non-ETP-ALL in February 2024.This patient achieved complete remission (CR) after one cycle of VDLP induction chemotherapy but remained minimal residual disease (MRD) positive, with persistent high CD38 expression.Given the patient's insufficient depth of disease remission, there is a significant risk of relapse and a less favorable prognosis.After thorough discussion and comprehensive disclosure of the patient's condition by the physician, and following the acquisition of the patient's written informed consent, consolidation chemotherapy was initiated in April 2024 using the Dara-VA-HAA regimen (see Supplementary Material).The patient experienced grade I/II adverse reactions, including headache, nausea, vomiting, and infusion-related reactions, all of which were fully resolved with appropriate symptomatic treatment.On day 11 of consolidation chemotherapy, chemotherapy-associated neutropenia, severe anemia, and thrombocytopenia were observed.To manage these complications, the patient received granulocyte colony-stimulating factor, recombinant human thrombopoietin, suspended red blood cell transfusions, and platelet apheresis transfusions for supportive care.By day 31, the ANC had recovered to greater than 1.010 9 /L; by day 37, the PLT had recovered to greater than 10010 9 /L.