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.