Crossing our Ts: An unusual presentation of infantile T‐cell leukemia

Abstract

To the Editor, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy comprising 10–15% of pediatric leukemia diagnoses.1,2 T-ALL is rarely reported in children less than 12 months of age with only two cases in the literature.3,4 The paucity of data regarding clinical presentation,management, genomics, and outcomes of infantile T-ALL results in difficult treatment decisions. We present the case of a previously healthy 4-month-old Caucasian female with hepatomegaly and lab work significant for pancytopenia and 94% peripheral blasts. Peripheral flow was obtained and demonstrated dim CD45 expression, CD34+, dim CD38+, CD7+, CD3+, and TDT+, confirming a diagnosis of T-ALL. Lumbar puncture indicated a CNS1 status. She received induction therapy per Children’s Oncology Group protocol AALL0631.5 Induction was complicated by bacteremia and mucositis; end of Induction minimal residual disease (MRD) was 4.1%. She subsequently tolerated induction intensification well, resulting in an MRD of 3.1%. Due to disease persistence at the end of two cycles of chemotherapy, the decision wasmade that she would benefit from a stem cell transplant once her disease was controlled. Consideringher continueddiseaseburden, she received an individualized treatment plan based on AALL0434 consisting of nelarabine followed by Capizzi methotrexate (Figure 1). Due to continued neutropenia, methotrexate dosing was not escalated. She tolerated the cycle well with no identifiable side effects or neurological toxicity associated with nelarabine.MRDwas0.02%and shewas successfully transitioned to stem cell transplant. This suggests that infant T-ALL may be more responsive to T-cell ALL-based therapy as opposed to standard infant ALL therapy. Nelarabine as management for T-ALL is well established due to the cytotoxic effect to T-lymphoblasts through accumulation of ara-GTP, which is found in high levels in T-cells, and has been found to have a 55% response rate with relapsed/refractory T-ALL.1,6 There is infrequent use of nelarabine in infants. AALL0434 found that high-dose methotrexate had lower 5-year disease-free survival (DFS) and overall survival when compared to Capizzi methotrexate (85.3% and 89.4%, respectively, versus 91.5% and 93.7%).7,8 Analysis of T-ALL patients who received Capizzi methotrexatewith versuswithout nelarabine found4-yearDFSof 92.2 ± 2.8% compared to 89.8± 3%.8 A diverse spectrum of genetic and epigenetic mutations comprise T-ALL, with several well-documented, targetable pathways including Notch, JAK/STAT, P13K/Akt/mTOR, andMAPK.1 FoundationOne testing identified a LIM-domain-only 2 (LMO2) overexpression, noted in ∼9% of patients with T-ALL,1 as well as a unique colony stimulation factor 3 receptor (CSF3R) R698H mutation, which is associated with promotion of neutrophil differentiation through granulocyte colonystimulation factor binding.9,10 CSF3R mutation has been identified in chronic neutrophilic leukemia andatypical chronicmyeloid leukemia.11 The use of GCSF during induction intensification was taken into context with our patients CSF3R mutation; as this is a variant of unknown significance, it was determined that keepingGCSF in her treatment did not present significant risk of changing the effect of GCSF on her neutrophils. This case highlights the specialized management, outcome, and unique genomic findings in a rare diagnosis of infantile T-ALL. Future research should focus on reporting rare infantile T-ALL leukemia cases to help guide management and successful remissions for these patients.