Hemophagocytic Lymphohistiocytosis and Fibroblast Growth Factor 23 (FGF23)-Induced Hypophosphatemia.

Abstract

Hypophosphatemia is a frequent complication of chimeric antigen receptor T-cell therapy. In this setting, hypophosphatemia has been previously associated with cytokine release syndrome. The mechanisms underlying this electrolyte derangement are not fully understood. Extracellular phosphate consumption by chimeric antigen receptor T cells was demonstrated in vitro, but inflammation is also thought to play a contributing role. We present a case of severe, refractory hypophosphatemia with renal phosphate wasting triggered by hemophagocytic lymphohistiocytosis in acute lymphoblastic leukemia. The diagnosis of phosphate wasting was made at the onset of leukemia and a clinical exacerbation occurred after chimeric antigen receptor T-cell therapy. Diagnostic workup revealed very high fibroblast growth factor 23 (FGF23) levels in the absence of recognized acquired or genetic causes of impaired FGF23 cleavage. This case suggests that inflammation associated with hemophagocytic lymphohistiocytosis may induce FGF23 as a potential mechanism for hypophosphatemia. In this context, we recommend evaluation of renal phosphate wasting and subsequently FGF23 in patients with persistent hypophosphatemia despite standard supplementation.