First report of clinical response to Venetoclax in Early T-cell Precursor Acute Lymphoblastic Leukemia.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized, highrisk subgroup of ALL characterized by early differentiation arrest and distinct genetic and transcriptional features. ETP-ALL represents 10% to 30% of T-cell ALL (T-ALL) cases in adults and 10% to 15% of cases in children, exhibits inferior response rates to chemotherapy, and is characterized by high relapse rates with dismal outcomes in the relapsed/refractory setting.1 Recent insights into the biology of ETPALL using BH3 profiling have revealed BCL-2 dependence2 with exquisite in vitro sensitivity to the BCL-2–selective antagonist venetoclax.3 Herein, we report a patient with refractory ETP-ALL and another with T-ALL and some features suggestive of the ETP subtype who had excellent responses to venetoclax given in combination with cytotoxic chemotherapy. Both patients received venetoclax off-label and provided written informed consent after receiving counseling about the unapproved nature of this treatment, the rationale for its use, and possible adverse effects from the medication.