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1.
Biol Blood Marrow Transplant ; 24(9): 1856-1860, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29782992

RESUMO

Vitamin D deficiency is prevalent among childhood hematopoietic stem cell transplantation (HSCT) recipients and associated with inferior survival at 100 days after transplantation. Achieving and maintaining therapeutic vitamin D levels in HSCT recipients is extremely challenging in the first 3 to 6 months after transplantation due to poor compliance in the setting of mucositis and the concomitant use of critical transplantation drugs that interfere with vitamin D absorption. We sought to evaluate the safety and efficacy of a single, ultra-high-dose of vitamin D given before childhood HSCT to maintain levels in a therapeutic range during the peritransplantation period. Ten HSCT recipients with pretransplantation 25-OH vitamin D (25OHD) level <50 ng/mL and with no history of hypercalcemia, nephrolithiasis, or pathological fractures were enrolled on this pilot study. A single enteral vitamin D dose (maximum 600,000 IU) was administered to each patient based on weight and pretransplantation vitamin D level before the day of HSCT. Vitamin D levels between 30 and 150 ng/mL were considered therapeutic. All patients received close clinical observation and monitoring of 25OHD levels, calcium, phosphate, parathyroid hormone, urine calcium/creatinine ratio, and n-telopeptide for safety and efficacy assessment. The mean age of the study subjects was 5.8 ± 4.9 years, and the mean pretransplantation 25OHD level was 28.9 ± 13.1 ng/mL. All patients tolerated single, ultra-high-oral dose of vitamin D under direct medical supervision. No other oral vitamin D supplements were administered during the observation window of 8 weeks. Three of 10 patients received 400 IU/day of vitamin D in parenteral nutrition only for 5 days during the study window. A mean peak serum vitamin D level of 80.4 ± 28.6 ng/mL was reached at a median of 9 days after the vitamin D dose. All patients achieved a therapeutic vitamin D level of >30 ng/mL. Mean vitamin D levels were sustained at or above 30 ng/mL during the 8-week observation window. There were no electrolyte abnormalities attributed to the ultra-high-dose of vitamin D. Most patients had mildly elevated urine calcium/creatinine ratios during treatment, but none showed clinical or radiologic signs of nephrocalcinosis or nephrolithiasis. Our findings indicate that single ultra-high-oral dose vitamin D treatment given just before HSCT is safe and well tolerated in the immediate peritransplant period in children. Patients in our study were able to achieve and sustain therapeutic vitamin D levels throughout the critical period during which vitamin D insufficiency is associated with decreased overall survival. Larger prospective studies are needed to address the impact of single ultra-high-dose vitamin D treatment on HSCT outcomes.


Assuntos
Hormônios e Agentes Reguladores de Cálcio/uso terapêutico , Colecalciferol/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Deficiência de Vitamina D/tratamento farmacológico , Adolescente , Hormônios e Agentes Reguladores de Cálcio/farmacologia , Criança , Pré-Escolar , Colecalciferol/farmacologia , Feminino , Humanos , Lactente , Masculino , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/patologia
2.
Biol Blood Marrow Transplant ; 22(7): 1271-1274, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27044905

RESUMO

We recently reported that more than 70% of pediatric and young adult patients had a vitamin D (VD) deficiency at the time of their hematopoietic stem cell transplantation (HSCT). Moreover, VD deficiency was associated with inferior survival at 100 days after transplantation. The goal of the present study was to evaluate the VD requirements needed to maintain an optimal VD level (30 to 60 ng/mL) during the first 3 months after transplantation using real-time VD monitoring and personalized VD supplementation. We examined 2 cohorts in this study: cohort 1, the "preintervention" cohort (n = 35), who were treated according to National Kidney Foundation guidelines for VD therapy, and cohort 2, the "intervention" cohort (n = 25) who were treated with high-dose VD with an aggressive dosage increase in those who remained VD-insufficient. Results from cohort 1 showed that despite aggressive monitoring and VD supplementation, therapeutic vitamin D levels were difficult to achieve and maintain in HSCT recipients during the early post-transplantation period. Only 43% of cohort 1 achieved a therapeutic VD level, leading to our intervention in cohort 2. Outcomes improved in cohort 2, but still only 64% of cohort 2 patients achieved a therapeutic VD level despite receiving >200 IU/kg/day of VD enterally. The median VD level in patients who did achieve sufficient levels was 40 ng/mL, with only 1 patient in each cohort achieving a supratherapeutic but nontoxic level. These data indicate that standard guidelines for VD replacement are inadequate in HSCT recipients, and further work is needed to define more appropriate dosing in this clinical setting.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Deficiência de Vitamina D/etiologia , Vitamina D/administração & dosagem , Adolescente , Criança , Pré-Escolar , Suplementos Nutricionais , Monitoramento de Medicamentos , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Transplantados , Vitamina D/sangue , Vitamina D/farmacocinética , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/mortalidade
3.
Biol Blood Marrow Transplant ; 21(9): 1627-31, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26093045

RESUMO

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.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Vitamina D/análogos & derivados , Adolescente , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Taxa de Sobrevida , Fatores de Tempo , Vitamina D/sangue , Deficiência de Vitamina D/etiologia
4.
Biol Blood Marrow Transplant ; 21(2): 379-81, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25300869

RESUMO

Veno-occlusive disease (VOD) of the liver is a well-described and significant complication of hematopoietic stem cell transplantation (HSCT), with limited successful therapeutic options in severe cases. Prompt diagnosis and initiation of treatment is crucial to restrict the extent of disease. However, a subset of patients may not meet all current diagnostic criteria at presentation, and waiting for these to be met may delay therapy. We retrospectively reviewed 794 HSCT patients treated at our institution between 2003 and 2013, identifying 17 (2.1%) who developed VOD. Of these, 5 (29%) were noted to have an absence of elevated bilirubin at the time of VOD diagnosis and reversal of portal venous flow on ultrasound. Median total and conjugated bilirubin at VOD diagnosis were 1.0 and 0.2 mg/dL, respectively. All 5 patients were subsequently diagnosed with multiorgan failure associated with VOD, including 1 with encephalopathy. Four were treated with intravenous high-dose methylprednisolone (500 mg/m(2) per dose every 12 hours for 6 doses). One patient received defibrotide therapy in addition to steroids and another supportive care alone. VOD resolved in 4 of 5 patients, with median time to resolution of VOD, defined as recovery of all organ function and normalization of bilirubin and portal venous flow, of 8 days. Two patients died later from progressive primary disease and chronic graft-versus-host disease, respectively. We conclude that a high index of suspicion for VOD should be maintained in patients despite lack of bilirubin elevation in the presence of other diagnostic criteria such as hepatomegaly, abdominal pain, ascites, or weight gain. Early ultrasound evaluation in these patients may lead to more timely diagnosis and therapeutic interventions.


Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico , Insuficiência de Múltiplos Órgãos/diagnóstico , Adolescente , Anti-Inflamatórios/uso terapêutico , Bilirrubina/sangue , Criança , Pré-Escolar , Feminino , Fibrinolíticos/uso terapêutico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/patologia , Humanos , Imunossupressores/uso terapêutico , Leucemia/imunologia , Leucemia/patologia , Leucemia/terapia , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Metilprednisolona/uso terapêutico , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/patologia , Neuroblastoma/imunologia , Neuroblastoma/patologia , Neuroblastoma/terapia , Polidesoxirribonucleotídeos/uso terapêutico , Estudos Retrospectivos , Transplante Homólogo
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