Vitamin D Deficiency Is Prevalent and Resistant to Correction in Patients with Hemophagocytic Lymphohistiocytosis

Background Vitamin D plays a key role in immunoregulatory functions, and many patients are deficient prior to hematopoietic cell transplant (HCT), which is associated with poor outcome. Worsening nutrient deficiencies can occur during HCT secondary to increased nutritional requirements, inflammation, and mucosal barrier breakdown affecting absorption, potentially leading to endothelial injury and post-HCT complications. Standard repletion often does not sufficiently replete vitamin D levels in patients undergoing HCT which has led to the implementation of high-dose replacement regimens, such as Stoss dosing (one-time dose of ∼7,000 U/kg). Objective We sought to characterize the incidence and impact of vitamin D insufficiency in patients with HLH undergoing HCT. Additionally, we investigated the use of standard repletion versus Stoss therapy on the ability to achieve sufficient levels pre-HCT. Methods A retrospective chart review was performed on 135 patients with a diagnosis of HLH undergoing their first HCT at Cincinnati Children’s Hospital Medical Center from 2010 to 2023. Demographic data, vitamin D levels at predetermined time points, vitamin D supplementation received (Stoss and/or standard therapy), length of supplementation, and post-transplant outcomes were recorded. Results Eighty-four patients met inclusion criteria and had documented vitamin D levels pre-HSCT. Of these, 76 (90%) were identified as vitamin D deficient (<30 ng/mL). At the time of transplant, 34 patients (45%) were corrected to sufficient levels (>30 ng/mL; 24 with standard therapy, 9 with Stoss therapy). Three patients who failed to correct with standard supplementation subsequently corrected with Stoss dosing and 1 patient corrected after receiving both standard and Stoss supplementation. The other 42 patients (55%) remained vitamin D deficient at HCT (22 were not on any supplementation, 19 received standard therapy, and 1 received Stoss therapy). Conclusion We show that there is a very high incidence of vitamin D deficiency in HLH patients, which may worsen outcomes. Many patients do not correct with standard therapy and often require aggressive repletion to achieve sufficient levels. Future analyses will include examining the impact of steroid exposure on vitamin D levels, describing optimal timing and degree of vitamin D supplementation needed to achieve and maintain sufficiency, and correlation with outcomes post-HCT.