Vitamin D Deficiency and Survival in Children after Hematopoietic Stem Cell Transplant

Abstract

Vitamin D has endocrine function as a key regulator of calcium absorption and bone homeostasis and also has intracrine function as an immunomodulator. Vitamin D deficiency before hematopoietic stem cell transplantation (HSCT) has been variably associated with higher risks of graft-versus-host disease (GVHD) and mortality. Children are at particular risk of growth impairment and bony abnormalities in the face of prolonged deficiency. There are few longitudinal studies of vitamin D deficient children receiving HSCT, and the prevalence and consequences of vitamin D deficiency 100 days after transplant has been poorly studied. Serum samples from 134 consecutive HSCT patients prospectively enrolled into an HSCT sample repository were tested for 25-hydroxy (25 OH) vitamin D levels before starting HSCT (baseline) and at 100 days after transplantation. Ninety-four of 134 patients (70%) had a vitamin D level < 30 ng/mL before HSCT, despite supplemental therapy in 16% of subjects. Post-transplant samples were available in 129 patients who survived to day 100 post-transplant. Vitamin D deficiency persisted in 66 of 87 patients (76%) who were already deficient before HSCT. Moreover, 24 patients with normal vitamin D levels before HSCT were vitamin D deficient by day 100. Overall, 68% of patients were vitamin D deficient (<30 ng/mL) at day 100, and one third of these cases had severe vitamin D deficiency (<20 ng/mL). Low vitamin D levels before HSCT were not associated with subsequent acute or chronic GVHD, contrary to some prior reports. However, severe vitamin D deficiency (<20 ng/mL) at 100 days post-HSCT was associated with decreased overall survival after transplantation (P = .044, 1-year rate of overall survival: 70% versus 84.1%). We conclude that all pediatric transplant recipients should be screened for vitamin D deficiency before HSCT and at day 100 post-transplant and that aggressive supplementation is needed to maintain sufficient levels.

A Functional Bioluminescent Zebrafish Screen for Enhancing Hematopoietic Cell Homing

“…Vitamin D-sufficient children with malignancy also had improved overall survival (87% versus 50%, p = 0.01). Other groups have shown that severe vitamin D deficiency at HCT was associated with reduced survival after transplant in pediatric patients (Wallace et al., 2015). These reports suggest that vitamin D positively affects engraftment and overall HCT outcome.…”

Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation Patients Despite Both Standard and Aggressive Supplementation

“…Standard doses of multivitamins delivered in TPN are inadequate to maintain sufficient VD levels in HSCT recipients. In addition, many patients are already VD-deficient at the start of the transplantation process [1,11]. The cushingoid body habitus often observed in a HSCT population also increases VD supplementation needs [12].…”

“…Importantly, all children with sufficient VD before HSCT became VD-deficient in the first 100 days after transplantation, despite receiving current standard recommended vitamin supplementation via total parenteral nutrition (TPN) and vitamins present in food and enteral formulas. Children who were VD-deficient before HSCT generally remained deficient, despite supervision by a registered dietician prescribing currently recommended supplementation [1]. …”

Salud ósea en pacientes sometidos a trasplante de precursores hematopoyéticos: un nuevo problema a considerar

“…Este alto porcentaje es concordante con la literatura internacional que muestra una frecuencia de insuficiencia de vitamina D entre 70 y 100% en pacientes sometidos a TPH 7,16,17 . Este hecho es de especial relevancia clínica considerando que, como ya fue mencionado, datos recientemente publicados muestran que el déficit de vitamina D puede impactar negativamente en la respuesta a tratamiento, así como en la sobrevida en algunas neoplasias hematológicas [8][9][10][11][12] . Encontramos también una alta frecuencia de hiperparatiroidismo secundario que en parte puede ser explicado por el déficit de vitamina D, pero deben considerarse otros factores tales como alteraciones de absorción intestinal de calcio, alteraciones de hidroxilación renal de la vitamina D, procesos inflamatorios sistémicos, entre otros.…”

“…Concordante a lo anterior Wallace et al encontró que el déficit de Vitamina D (< 20 ng/mL) 100 días post TPH en niños se asociaba a disminución significativa en la sobrevida global 10 . Glotzbecker et al demostró en pacientes evaluados pre TPH alogénico, que aquellos con déficit de vitamina D (< 25 ng/mL) tenían incidencia acumulada de GVHD crónico a dos años significativamente mayor que aquellos con niveles sobre 25 ng/mL 11 .…”