Patient 3: J.P.
A 17-year-old Caucasian male presented with pancytopenia and proctitis
and was diagnosed with T-ALL and treated per COG-AALL1231. [6] His
course was complicated by bacteremia, fungemia, severe myelosuppression,
and persistent fevers. He ultimately met HLH criteria and was treated
per HLH-2004. Due to his myelosuppression, adjustments were made to both
his chemotherapy and his HLH treatment. Reduced doses of dexamethasone
were used, and etoposide was not introduced initially. Trials of IVIG
and hydrocortisone showed minimal response. We then trialed ruxolitinib,
a JAK 1/2 inhibitor shown to improve the inflammatory status of patients
with HLH. [7] Although laboratory markers did not indicate
resolution of his HLH, while our patient was on ruxolitinib, he had an
overall improved quality of life. He had more energy, improved wound
healing, and significantly fewer admissions for flares for 3 months. The
effects of ruxolitinib eventually waned and our patient showed signs of
hyperinflammation. Abdominal imaging demonstrated diffuse hepatic fungal
micro-abscesses confirmed with biopsy. He was previously treated with
courses of voriconazole and micafungin, but doses were adjusted due to
incompatibility with his chemotherapy and concurrent toxicities.
Treatment with a course of high dose fluconazole and repeat imaging
showed resolution of the hepatic nodules. For his HLH, we trialed a
course of etoposide, which was not used before due to his
myelosuppression, but HLH did not improve. With our patient’s fungal
infection controlled, we began a trial of emapalumab for 2 months and
resulted in progressive improvement of his inflammation, which has
allowed for progression of his treatment for his T-ALL. Currently, his
HLH and T-ALL both remain in remission and he has begun maintenance
therapy for his leukemia while remaining on low-dose hydrocortisone and
ruxolitinib.