CASE PRESENTATION
We present the case of a previously healthy 4-month-old Caucasian female with hepatomegaly at a routine 4-month-old well child visit. She was found to have lab work significant for a leukocytosis of 770 K/mm3 comprised of 94% peripheral blasts, hemoglobin of 6.3GM/dL, and platelets 43k/mm3. Physical exam was notable for marked hepatosplenomegaly, and ~1cm subcutaneous nodule of the right thigh. Initial management consisted of hyperhydration and rasburicase for an elevated uric acid of 12.9mg/dL.
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. Foundation One testing demonstrated non-MLL-rearranged, a LIM-domain-only 2 (LM02 ) rearrangement, and variants of unknown significance, most uniquely Colony Stimulation Factor 3 Receptor (CSF3R ) R698H mutation.
She received induction therapy per Children’s Oncology Group (COG) protocol AALL06315. Induction included Prednisone for the first week followed by Dexamethasone, Vincristine, Daunorubicin, Pegasparaginase, Cytarabine and triple intrathecal chemotherapy. During Induction she had complications including bacteremia (Staphylococcus epidermidis, Staphylococcus Hominis, Streptococcus Viridans, and Klebsiella Pneumoniae ) and mucositis for which she required parenteral nutritional support. End of Induction bone marrow aspirate demonstrated a minimal residual disease (MRD) of 4.1%. She continued AALL0631 and tolerated Induction Intensification without infections, minimal mucositis or nutritional support. Induction Intensification included high dose methotrexate, etoposide, cyclophosphamide, triple intrathecal chemotherapy, with filgrastim until absolute neutrophil count (ANC) > 1500/uL for two days. MRD at end of Induction Intensification was 3.1%.
Considering her continued disease burden, we changed protocols and she received an individualized treatment plan based off AALL0434 with a course of nelarabine followed by Capizzi methotrexate (Figure 1). This included five days of nelarabine, vincristine, Capizzi methotrexate, PEG-asparaginase, and concluded in triple intrathecal methotrexate. Due to continued neutropenia, we were unable to escalate methotrexate beyond the starting dose. Her MRD at the end of this cycle was 0.02% and she was successfully transitioned to stem cell transplant (SCT). Summary of our patient’s treatment course can be seen in Figure 1.
She received a 10/10 matched sibling donor SCT and tolerated therapy well with anticipated supportive care and engrafted on day +20. On day +22 she met the European Society for Blood and Marrow Transplantation criteria for veno-occlusive disease and was started on treatment with Defibrotide6. Her clinical course declined rapidly, and she developed transplant associated thrombotic microangiopathy on day +23. She required circulatory and ventilator support for multiple days with blood product, dialysis, one dose of tocilizumab for elevated IL-6, and eculizumab. On day +55 she had improvement in her organ function and subsequently was successfully extubated and weaned off vasopressor support.