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.