Immunomodulatory Effect of Vitamin D after Allogeneic Stem Cell Transplantation: Results of a Prospective Multicenter Clinical Trial

Caballero‐Velázquez, Teresa; Montero, Isabel; Sánchez‐Guijo, Fermín; Parody, Rocío; Saldaña, Raquel; Valcárcel, David; López‐Godino, Oriana; Coll, Christelle Ferra i; Cuesta, Marian; Carrillo-Vico, Antonio; Sánchez‐Abarca, Luis Ignacio; López-Corral, Lucía; Márquez-Malaver, Francisco J.; Pérez-Simón, Josè Antonio

doi:10.1158/1078-0432.ccr-16-0238

Cited by 43 publications

(41 citation statements)

References 45 publications

(50 reference statements)

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“…A number of reports has described insufficiency for 25-hydroxyvitamin-D3 in patients undergoing allogeneic HSCT [2,5,6,19]. As a consequence, we and others used different approaches to increase vitamin D levels in patients undergoing HSCT [7,12,[20][21][22]. At present, the role of 25-hydroxyvitamin-D3 for survival after HSCT has been examined in eight studies [3-5, 7, 18, 23-25].…”

Section: Discussionmentioning

confidence: 99%

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1,25-dihydroxyvitamin-D3 but not the clinically applied marker 25-hydroxyvitamin-D3 predicts survival after stem cell transplantation

Peter

Siska

Roider

et al. 2020

Bone Marrow Transplant

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The serum level of 25-hydroxyvitamin-D3 is accepted as marker for a person’s vitamin D status but its role for the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is controversially discussed. The impact of 1,25-dihydroxyvitamin-D3 on HSCT outcome, however, has never been studied. In a discovery cohort of 143 HSCT patients we repeatedly (day −16 to 100) measured 1,25-dihydroxyvitamin-D3 and in comparison the well-established marker for serum vitamin D status 25-hydroxyvitamin-D3. Only lower 1,25-dihydroxyvitamin-D3 levels around HSCT (day −2 to 7, peritransplant) were significantly associated with higher 1-year treatment-related mortality (TRM) risk (Mann–Whitney U test, P = 0.001). This was confirmed by Cox-model regression without and with adjustment for baseline risk factors and severe acute Graft-versus-Host disease (aGvHD; unadjusted P = 0.001, adjusted P = 0.005). The optimal threshold for 1,25-dihydroxyvitamin-D3 to identify patients at high risk was 139.5 pM. Also in three replication cohorts consisting of altogether 365 patients 1,25-dihydroxyvitamin-D3 levels below 139.5 pM had a 3.3-fold increased risk of TRM independent of severe aGvHD compared to patients above 139.5 pM (Cox-model unadjusted P < 0.0005, adjusted P = 0.001). Our data highlight peritransplant 1,25-dihydroxyvitamin-D3 levels but not the commonly monitored 25-hydroxyvitamin-D3 levels as potent predictor of 1-year TRM and suggest to monitor both vitamin D metabolites in HSCT patients.

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Section: Discussionmentioning

confidence: 99%

“…In some studies, the impact of 25-hydroxyvitamin-D3 serum levels on adverse events of allogeneic HSCT was evaluated, but results are inconsistent [2][3][4][5][6]. In one prospective trial, safety and efficacy of vitamin D3 supplementation after HSCT was evaluated and no significant impact on overall survival was found [7].…”

Section: Introductionmentioning

confidence: 99%

1,25-dihydroxyvitamin-D3 but not the clinically applied marker 25-hydroxyvitamin-D3 predicts survival after stem cell transplantation

Peter

Siska

Roider

et al. 2020

Bone Marrow Transplant

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“…There were no adverse events attributed to the vitamin D, more specifically, no case of hypercalcemia was observed. With this low toxicity profile, a prospective randomized trial would be required to confirm the potential efficacy of vitamin D as immune-modulatory agent after HSCT [ 182 ].…”

Section: Clinical Applicationsmentioning

confidence: 99%

Vitamin D: Effect on Haematopoiesis and Immune System and Clinical Applications

Medrano

Carrillo‐Cruz

Montero

et al. 2018

IJMS

Self Cite

146

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Vitamin D is a steroid-like hormone which acts by binding to vitamin D receptor (VDR). It plays a main role in the calcium homeostasis and metabolism. In addition, vitamin D display other important effects called “non-classical actions.” Among them, vitamin D regulates immune cells function and hematopoietic cells differentiation and proliferation. Based on these effects, it is currently being evaluated for the treatment of hematologic malignancies. In addition, vitamin D levels have been correlated with patients’ outcome after allogeneic stem cell transplantation, where it might regulate immune response and, accordingly, might influence the risk of graft-versus-host disease. Here, we present recent advances regarding its clinical applications both in the treatment of hematologic malignancies and in the transplant setting.

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“…Velazquez ve arkadaşları, değişen dozlarda vitamin D replasmanı yaparak değerlendirdikleri hasta gruplarında nüks ve akut GVHH üzerine etki gösterememişler fakat kronik GVHH riskini azalttığını göstermişlerdir (7).…”

Section: Tartişma Ve Sonuçunclassified

Vitamin D Deficiency and Outcomes in Adult Acute Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Soydan¹,

Gökmen²,

Özkumur³

et al. 2020

LLM Dergi

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ÖZAmaç: Vitamin D eksikliği, kalp damar sistemi, immün sistem ve kemik metabolizması gibi pek çok farklı sistemde olumsuz etkilere sebep olabilecek, toplum sağlığı açısından önemli bir metabolik sorun olarak değerlendirilmektedir. Vitamin D etkilerini, doğuştan ve adaptif immün sistem hücrelerinde bulunan vitamin D reseptörleri aracılığıyla gösterir. İnflamasyonu durdururken aynı zamanda tolerans oluşturarak immün dengelenme oluşturur. Hematopoietik kök hücre nakli sonrası ortaya çıkan graft versus host hastalığı (GVHH) gibi komplikasyonları etkileyebilir. Son çalışmalar, düşük D vitamin düzeylerinin akut ve kronik GVHH ile ilişkili olduğunu göstermiştir. Hastalar ve Yöntem:Bu retrospektif çalışmada, 128 akut lösemi olgusunda vitamin D düzeylerinin nakil sonuçlarına etkisi değerlendirildi. Hastaların 67'si erkek, 61'i kadın, yaş ortalaması 45 (19-73 yıl) yıldı. Doksan beş hasta akut miyeloid lösemi, 33 hasta akut lenfoblastik lösemi idi. Elli beş histokompatibilite antijeni (HLA) tam uygun kardeş, 51 HLA tam ya da iyi uygun akraba dışı ve 22 haploidentik verici mevcuttu. Vitamin D düzeyleri beş hasta dışında tüm hastalarda düşük (30 ng/mL'nin altında), 65 hastada çok düşük (10 ng/mL'nin altında) bulundu. Hastalar, vitamin D düzeyi 10 ng/mL'nin altında ve üstünde olarak iki gruba ayrılarak değerlendirildi.Bulgular: İki grup yaş, verici tipi, hazırlık rejimi, cinsiyet ve kan grubu açısından benzer bulunmuştur. Remisyonda ve refrakter olan hasta oranları da iki grup arasında farklılık göstermemiştir. Çok düşük vitamin D düzeyi olan grupta akut ve kronik GVHH artışı gözlenmemiş, aynı zamanda sitomegalovirüs reaktivasyonu da bu grupta daha fazla saptanmamıştır.Sonuç: Bu sonuçlara bakılarak, çok düşük vitamin D düzeylerinin akut lösemili hastalarda GVHH ve sitomegalovirüs reaktivasyonu için bir dezavantaj oluşturmadığını söyleyebiliriz. Bu verilerin vitamin D düzeyi normal olan olgularla karşılaştırılarak değerlendirilme yapılması daha anlamlı olacaktır.Anahtar Kelimeler: Vitamin D eksikliği; Graft versus host hastalığı; Allojeneik kök hücre nakli ABSTRACT Objective: Vitamin D deficiency is one of the public health concerns which has multiple effects on different systems such as cardiovascular system, immune system and bone metabolism. Vitamin D exerts its biologic function through the vitamin D receptor, located in cells from the innate and adaptive immunity. It blunts inflammation while enhancing a tolerogenic status, mediating in immune homeostasis. It can also affect post-hematopoietic stem cell transplantation (HSCT) complications such as graft-versus-host disease (GVHD). Recent studies have proved the association between chronic and acute GVHD and low levels of serum vitamin D in allogeneic HSCT patients.

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Immunomodulatory Effect of Vitamin D after Allogeneic Stem Cell Transplantation: Results of a Prospective Multicenter Clinical Trial

Abstract: This is the first prospective trial that analyzes the effect of VitD postransplant. We observed a significantly lower incidence of cGVHD among patients receiving VitD. Interestingly, VitD modified the immune response after allo-SCT. Clin Cancer Res; 22(23); 5673-81. ©2016 AACR.

Cited by 43 publications

References 45 publications

1,25-dihydroxyvitamin-D3 but not the clinically applied marker 25-hydroxyvitamin-D3 predicts survival after stem cell transplantation

1,25-dihydroxyvitamin-D3 but not the clinically applied marker 25-hydroxyvitamin-D3 predicts survival after stem cell transplantation

Vitamin D: Effect on Haematopoiesis and Immune System and Clinical Applications

Vitamin D Deficiency and Outcomes in Adult Acute Leukemia Patients After Allogeneic Hematopoietic Stem Cell Transplantation

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