Comparison of Oral Zinc Supplement and Placebo Effect in Improving the T-cells Regeneration in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: Clinical Trial Study

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2024 Dec 20

PMID 39705427

Authors

Maryam Nikoonezhad

Ahmad Zavaran Hosseini

Abbas Hajifathali

Sayeh Parkhideh

Mahdi Shadnoush

Yadollah Shakiba

Hoda Zahedi

Affiliations

Soon will be listed here.

Abstract

Background: Immune reconstitution is a significant factor in the success of "hematopoietic stem cell transplantation" (HSCT). Delaying the immune reconstitution increases the risk of infections and relapse after transplantation. T-cell recovery after HSCT is mainly thymus-dependent, and thymic atrophy is associated with various clinical conditions that correlate with HSCT outcomes. Thymus rejuvenation can improve immune reconstitution after transplantation.Zinc (Zn) plays a pivotal role in thymus rejuvenation. Zn deficiency can lead to thymic atrophy, which increases susceptibility to infections. Zn supplementation restores the immune system by increasing thymus output and T-cell repertoire production.We designed this protocol to investigate the effect of oral Zn supplementation on T-cell recovery in patients undergoing HSCT.

Methods: Forty eligible candidates for autologous-HSCT will be selected. They will be randomly divided into Zn and placebo groups. Subsequently, they will receive 3 Zn or placebo tablets for the first 30 days post-HSCT (+1 to +30), followed by 1 pill or placebo for days (+31 to +90). The copy numbers of "recent thymic emigrants" T cells and "T cell Receptor Excision Circles" (TREC) will be assessed before and after the intervention in peripheral blood mononuclear cells (PBMCs). All patients will be followed up 365 days post-HSCT for relapse and infection.

Conclusion: This clinical trial is the first to determine the efficiency of "Zn gluconate" as daily Supplementation in T cell recovery post-HSCT.If successful, an available and inexpensive drug will improve immune system reconstruction after HSCT, reduce the risk of infection, particularly viral infections, and increase patient survival.

Citing Articles

The Possible Impact of Zinc-Enriched Multivitamins on Treatment-Naïve Recurrent Aphthous Stomatitis Patients.

Seo H, Chung K, Kim D J Clin Med. 2025; 14(1.

PMID: 39797342 PMC: 11721099. DOI: 10.3390/jcm14010260.

References

Gammoh N, Rink L . Zinc in Infection and Inflammation. Nutrients. 2017; 9(6). PMC: 5490603. DOI: 10.3390/nu9060624. View

Sottini A, Ghidini C, Zanotti C, Chiarini M, Caimi L, Lanfranchi A . Simultaneous quantification of recent thymic T-cell and bone marrow B-cell emigrants in patients with primary immunodeficiency undergone to stem cell transplantation. Clin Immunol. 2010; 136(2):217-27. DOI: 10.1016/j.clim.2010.04.005. View

da Rocha L, de Barros S, Bandeira F, Bollini A, Testa L, Simione A . Thymopoiesis in Pre- and Post-Hematopoietic Stem Cell Transplantation. Front Immunol. 2018; 9:1889. PMC: 6137257. DOI: 10.3389/fimmu.2018.01889. View

Iovino L, Cooper K, deRoos P, Kinsella S, Evandy C, Ugrai T . Activation of the zinc-sensing receptor GPR39 promotes T-cell reconstitution after hematopoietic cell transplant in mice. Blood. 2022; 139(25):3655-3666. PMC: 9227099. DOI: 10.1182/blood.2021013950. View

Gombart A, Pierre A, Maggini S . A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients. 2020; 12(1). PMC: 7019735. DOI: 10.3390/nu12010236. View

Wessels I, Fischer H, Rink L . Dietary and Physiological Effects of Zinc on the Immune System. Annu Rev Nutr. 2021; 41:133-175. DOI: 10.1146/annurev-nutr-122019-120635. View

Drozdov D, Petermann K, Dougoud S, Oberholzer S, Held L, Gungor T . Dynamics of recent thymic emigrants in pediatric recipients of allogeneic hematopoetic stem cell transplantation. Bone Marrow Transplant. 2022; 57(4):620-626. DOI: 10.1038/s41409-022-01594-w. View

Simons L, Cavazzana M, Andre I . Concise Review: Boosting T-Cell Reconstitution Following Allogeneic Transplantation-Current Concepts and Future Perspectives. Stem Cells Transl Med. 2019; 8(7):650-657. PMC: 6591542. DOI: 10.1002/sctm.18-0248. View

Urbalejo-Ceniceros V, Rocha-Gonzalez H, Acosta-Maldonado B, Valero-Saldana L, Hernandez-Alcantara A, Perez-Camargo D . Effect of vitamin C on immune reconstitution after bone marrow transplantation. Int J Clin Pharmacol Ther. 2022; 60(9):384-391. DOI: 10.5414/CP204182. View

10.

Mansouri A, Hadjibabaie M, Iravani M, Shamshiri A, Hayatshahi A, Javadi M . The effect of zinc sulfate in the prevention of high-dose chemotherapy-induced mucositis: a double-blind, randomized, placebo-controlled study. Hematol Oncol. 2011; 30(1):22-6. DOI: 10.1002/hon.999. View

11.

Velardi E, Clave E, Arruda L, Benini F, Locatelli F, Toubert A . The role of the thymus in allogeneic bone marrow transplantation and the recovery of the peripheral T-cell compartment. Semin Immunopathol. 2021; 43(1):101-117. DOI: 10.1007/s00281-020-00828-7. View

12.

Majumdar S, Nandi D . Thymic Atrophy: Experimental Studies and Therapeutic Interventions. Scand J Immunol. 2017; 87(1):4-14. DOI: 10.1111/sji.12618. View

13.

Lei Y, Chen X, Jiang S, Guo M, Yu C, Qiao J . Mechanisms of Thymic Repair of In Vitro-Induced Precursor T Cells as a Haploidentical Hematopoietic Stem Cell Transplantation Regimen. Transplant Cell Ther. 2023; 29(6):382.e1-382.e11. DOI: 10.1016/j.jtct.2023.03.015. View

14.

Wessels I, Maywald M, Rink L . Zinc as a Gatekeeper of Immune Function. Nutrients. 2017; 9(12). PMC: 5748737. DOI: 10.3390/nu9121286. View

15.

Maywald M, Wessels I, Rink L . Zinc Signals and Immunity. Int J Mol Sci. 2017; 18(10). PMC: 5666901. DOI: 10.3390/ijms18102222. View

16.

Fan Z, Han T, Zuo W, Zhao X, Chang Y, Lv M . CMV infection combined with acute GVHD associated with poor CD8+ T-cell immune reconstitution and poor prognosis post-HLA-matched allo-HSCT. Clin Exp Immunol. 2022; 208(3):332-339. PMC: 9226149. DOI: 10.1093/cei/uxac047. View

17.

Andrlova H, van den Brink M, Markey K . An Unconventional View of T Cell Reconstitution After Allogeneic Hematopoietic Cell Transplantation. Front Oncol. 2021; 10:608923. PMC: 7930482. DOI: 10.3389/fonc.2020.608923. View

18.

Gaballa A, Clave E, Uhlin M, Toubert A, Arruda L . Evaluating Thymic Function After Human Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era. Front Immunol. 2020; 11:1341. PMC: 7412601. DOI: 10.3389/fimmu.2020.01341. View

19.

Gupta V, Braun T, Chowdhury M, Tewari M, Choi S . A Systematic Review of Machine Learning Techniques in Hematopoietic Stem Cell Transplantation (HSCT). Sensors (Basel). 2020; 20(21). PMC: 7663237. DOI: 10.3390/s20216100. View

20.

Spadea M, Saglio F, Tripodi S, Menconi M, Zecca M, Fagioli F . Multivariate Analysis of Immune Reconstitution and Relapse Risk Scoring in Children Receiving Allogeneic Stem Cell Transplantation for Acute Leukemias. Transplant Direct. 2021; 7(11):e774. PMC: 8500617. DOI: 10.1097/TXD.0000000000001226. View