Ataxia Telangiectasia (AT) is an autosomal recessive disorder which is associated with progressive neurodegeneration, immunodeficiency, and predisposition to cancer. Specifically, around 40% of patients with AT will develop malignancy during their lifetime, most commonly lymphoid malignancies. Patients with AT have increased toxicity to chemotherapy and radiation, which necessitates modified and individualized therapy approaches.
Early T-cell precursor ALL (ETP-ALL) is considered high risk and venetoclax has emerged as potential therapy combined with other chemotherapy to help achieve remission but there have been no reports of venetoclax use in patients with AT.
Here, we present a case of an 18-year-old male with Ataxia Telangiectasia diagnosed with ETP-ALL, who achieved remission after therapy was augmented with venetoclax during consolidation phase of chemotherapy. The patient initially presented with lower limb swelling, fatigue and nose bleeds and found to have a white cell count (WBC) of 107 K/uL with 72% peripheral blasts. He was treated with steroid monotherapy for 38 days prior to presentation to our institution. On arrival to our institution he had a WBC count of 42 K/uL with 75 % blasts in peripheral blood. His bone marrow evaluation had 83% blasts. Flow cytometry was positive for CD3, CD5 (partial), CD7, CD38, CD45, CD54, CD56, CD 117 (partial), negative for MPO, TdT, HLA-DR. This confirmed the diagnosis of ETP-ALL. An 81 gene panel testing was positive for NOTCH 1, SRSF2, EZH2, CREBBP. No abnormal fusions or translocations were present, and cytogenetics did not reveal a clonal abnormality.
Induction chemotherapy was given as per COG AALL1231 protocol with dose modifications including 50% decrease in vincristine and cyclophosphamide. His end of induction (EOI) bone marrow evaluation was positive for 32% MRD. Molecular diagnosis positive for NOTCH1, SRSF2 and EZH2. As it is not uncommon for patients with ETP-ALL to have persistent disease after induction chemotherapy cycle, we proceeded with consolidation per AALL0434 protocol with Nelarabine. Unfortunately, even with dose reduced vincristine he developed vocal cord paralysis, lower extremity neuropathy and urinary retention, hence vincristine was omitted. Bone marrow evaluation was repeated mid consolidation and was still positive for 20% MRD. Due to significant modifications in therapy as well as persistent disease midway through consolidation, venetoclax was added to augment therapy during the consolidation phase. He was given 150 mg/m2 for 7 days directly followed by nelarabine. End of consolidation marrow was negative for MRD, and molecular testing (81 gene panel) was also negative. He tolerated venetoclax well without any significant toxicities and remains in remission 4 months post therapy with venetoclax.
This report indicates that venetoclax can be used safely in patients with AT. This patient showed persistent MRD positive mid-way through consolidation with negativity after augmentation with venetoclax. Patients with AT have increased risk of toxicity from chemotherapy agents which requires dose modifications in their chemotherapy regimen. Venetoclax augmentation may be a viable approach for patients with AT or DNA repair disorders.
Disclosures
No relevant conflicts of interest to declare.
