High-dose zinc oral supplementation after stem cell transplantation causes an increase of TRECs and CD4+ naïve lymphocytes and prevents TTV reactivation

Lorenzo Iovino; Francesco Mazziotta; Giovanni Carulli; Francesca Guerrini; Riccardo Morganti; Valentina Mazzotti; Fabrizio Maggi; Lisa Macera; Enrico Orciuolo; Gabriele Buda; Edoardo Benedetti; Francesco Caracciolo; Sara Galimberti; Mauro Pistello; Mario Petrini

doi:10.1016/j.leukres.2018.04.016

High-dose zinc oral supplementation after stem cell transplantation causes an increase of TRECs and CD4+ naïve lymphocytes and prevents TTV reactivation

Leuk Res. 2018 Jul:70:20-24. doi: 10.1016/j.leukres.2018.04.016. Epub 2018 May 2.

Authors

Affiliations

¹ Hematology Division, Pisa University Hospital, Pisa, Italy; Dudakov Lab, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Electronic address: iovino-lorenzo@tiscali.it.
² Hematology Division, Pisa University Hospital, Pisa, Italy.
³ Biostatistical Consulting, Pisa University Hospital, University of Pisa, Pisa, Italy.
⁴ Virology Unit and Retrovirus Centre, Pisa University Hospital, Pisa, Italy.

PMID: 29747074
DOI: 10.1016/j.leukres.2018.04.016

Abstract

Introduction: Zinc plays an important role in thymic function and immune homeostasis. We performed a prospective clinical trial using a high-dose zinc oral supplementation to improve the immune reconstitution after hematopoietic stem cell transplant (HSCT).

Patients and methods: We enrolled 18 patients undergoing autologous HSCT for multiple myeloma. Nine patients were randomized to receive only a standard antimicrobial prophylaxis; whereas, nine patients received in addition 150 mg/day of zinc from day +5 to day +100 after transplant.

Results: CD4+ naïve lymphocytes and TRECs showed a significant increase from day +30 until day +100 only in the zinc-treated group. Moreover, the load of Torquetenovirus, a harmless virus that replicates in course of immunedepression, increased at day +100 only in the control group. No severe adverse events were reported during the zinc consumption.

Conclusion: First data from the ZENITH trial suggest that high-dose zinc supplementation is safe and may enhance the thymic reconstitution after HSCT. Registered: http://Clinicaltrials.gov (NCT03159845); and EUDRACT: 2014-28 004499-47.

Keywords: Bone marrow transplant; Digital PCR; Immune reconstitution; Immunesenescence; T cell; TTV; Thymus; Zinc.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism*
DNA Virus Infections / etiology*
Dietary Supplements*
Female
Hematopoietic Stem Cell Transplantation / adverse effects
Hematopoietic Stem Cell Transplantation / methods
Humans
Male
Middle Aged
Receptors, Antigen, T-Cell / metabolism*
Stem Cell Transplantation / adverse effects*
Torque teno virus / physiology*
Transplantation, Autologous
Transplantation, Homologous
Virus Activation* / drug effects
Virus Activation* / immunology
Zinc / administration & dosage*

Substances

Receptors, Antigen, T-Cell
Zinc

Associated data

ClinicalTrials.gov/NCT03159845
EudraCT/2014-28 004499-47