Successful Treatment Of Toxoplasma Induced Hemophagocytic Lymphohistiocytosis (Hlh) After Undergoing Allogenic Stem Cell Transplantation (Hsct)

IntroductionToxoplasmosis is a well-known intracellular protozoan parasite with seroprevalence varying geographically. Relatively asymptomatic in healthy individuals, it's reactivation can be a devastating opportunistic infection in HSCT patients with rare documentation of associated HLH.CaseA 25-year-old woman with Hodgkin lymphoma, refractory to multiple chemotherapies, autologous transplant and Nivolumab, who underwent haploidentical HSCT, was admitted on day +33 with persistent high-grade fevers. Blood counts were unremarkable, except for eosinophilia. She received broad spectrum antibiotics. PET/CT on day +36 demonstrated resolution of metabolic activity in multiple lymph nodes, but revealed ‘revved-up’ bone marrow(Image 1). CT-chest (day +41) demonstrated widespread centrilobular nodules. Blood, urine, enteric cultures, HIV, Histoplasma studies, and respiratory viral panel PCR were negative. Pre-transplant serologies noted a positive toxoplasma IgG. Toxoplasma DNA was detected in blood on day +41; she received clindamycin, pyrimethamine, and atovaquone due to sulfa allergy but successfully underwent rapid sulfa desensitization. She developed progressive pancytopenia and hypoxemia (day +43) requiring intubation in the ICU. Ferritin was >50,000 ng/mL, and triglycerides 931 mg/dL. Bone marrow biopsy showed activated macrophages and hemophagocytosis (Image 2). She met 6/8 criteria described in HLH-2004 trial. She received dexamethasone and tocilizumab for HLH, leading to prompt reversal of HLH physiology within 72 hours of HLH-directed therapy initiation. She was extubated on day +48. She was discharged on sulfadiazine and pyrimethamine (day +60) with almost normal ferritin levels and transfusion-independency.DiscussionHLH is characterized by cytopenias, extreme systemic inflammatory response, and high mortality. HLH can be triggered by infections, such as toxoplasmosis. Disseminated toxoplasmosis has a high mortality itself (>60 % treated, and 99% untreated), and HSCT recipients appear to have the highest risk. Early detection and treatment of the underlying infection is essential. Novel drugs, such as Tocilizumab, should be prospectively studied in HLH. In conclusion, HLH after HSCT should be suspected in cases of unexplained inflammatory response and cytopenias after successful engraftment; secondary causes must be explored and promptly treated.