Novel Insights into GVHD and Immune Reconstitution After Allogeneic Hematopoietic Cell Transplantation

Overview

Journal Blood Cell Ther

Date 2023 Jun 21

PMID 37342354

Authors

Takanori Teshima

Jaap Jan Boelens

Ken-Ichi Matsuoka

Affiliations

Soon will be listed here.

Abstract

Effective control of the graft-versus-host disease (GVHD) and immune reconstitution are crucial in improving the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) as well as the quality of life of the transplant survivors. Recent basic and clinical studies have deepened our understanding of the mechanisms of the immunological sequelae of HSCT, GVHD, and compromised immune systems. Based on the findings, various novel approaches have also been developed and tested clinically. However, further studies are necessary to develop therapeutic strategies with significant clinical benefits.

References

Admiraal R, Nierkens S, Bierings M, Bredius R, van Vliet I, Jiang Y . Individualised dosing of anti-thymocyte globulin in paediatric unrelated allogeneic haematopoietic stem-cell transplantation (PARACHUTE): a single-arm, phase 2 clinical trial. Lancet Haematol. 2022; 9(2):e111-e120. DOI: 10.1016/S2352-3026(21)00375-6. View

Zeiser R, Blazar B . Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. N Engl J Med. 2017; 377(22):2167-2179. PMC: 6034180. DOI: 10.1056/NEJMra1609337. View

Norona J, Apostolova P, Schmidt D, Ihlemann R, Reischmann N, Taylor G . Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. Blood. 2020; 136(12):1442-1455. PMC: 7498363. DOI: 10.1182/blood.2020005957. View

Cutler C, Kim H, Bindra B, Sarantopoulos S, Ho V, Chen Y . Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial. Blood. 2013; 122(8):1510-7. PMC: 3750344. DOI: 10.1182/blood-2013-04-495895. View

Lindemans C, Calafiore M, Mertelsmann A, OConnor M, Dudakov J, Jenq R . Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature. 2015; 528(7583):560-564. PMC: 4720437. DOI: 10.1038/nature16460. View

Lakkaraja M, Scordo M, Mauguen A, Cho C, Devlin S, Ruiz J . Antithymocyte globulin exposure in CD34+ T-cell-depleted allogeneic hematopoietic cell transplantation. Blood Adv. 2021; 6(3):1054-1063. PMC: 8945304. DOI: 10.1182/bloodadvances.2021005584. View

Mehta R, Holtan S, Wang T, Hemmer M, Spellman S, Arora M . Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT. J Clin Oncol. 2020; 38(18):2062-2076. PMC: 7302955. DOI: 10.1200/JCO.19.00396. View

Ishaqi M, Afzal S, Dupuis A, Doyle J, Gassas A . Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia. Bone Marrow Transplant. 2007; 41(3):245-52. DOI: 10.1038/sj.bmt.1705891. View

Eriguchi Y, Takashima S, Oka H, Shimoji S, Nakamura K, Uryu H . Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins. Blood. 2012; 120(1):223-31. DOI: 10.1182/blood-2011-12-401166. View

10.

Langenhorst J, van Kesteren C, van Maarseveen E, Dorlo T, Nierkens S, Lindemans C . Fludarabine exposure in the conditioning prior to allogeneic hematopoietic cell transplantation predicts outcomes. Blood Adv. 2019; 3(14):2179-2187. PMC: 6650734. DOI: 10.1182/bloodadvances.2018029421. View

11.

Hayase E, Hashimoto D, Nakamura K, Noizat C, Ogasawara R, Takahashi S . R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease. J Exp Med. 2017; 214(12):3507-3518. PMC: 5716036. DOI: 10.1084/jem.20170418. View

12.

Le Blanc K, Barrett A, Schaffer M, Hagglund H, Ljungman P, Ringden O . Lymphocyte recovery is a major determinant of outcome after matched unrelated myeloablative transplantation for myelogenous malignancies. Biol Blood Marrow Transplant. 2009; 15(9):1108-15. PMC: 3793397. DOI: 10.1016/j.bbmt.2009.05.015. View

13.

Takashima S, Kadowaki M, Aoyama K, Koyama M, Oshima T, Tomizuka K . The Wnt agonist R-spondin1 regulates systemic graft-versus-host disease by protecting intestinal stem cells. J Exp Med. 2011; 208(2):285-94. PMC: 3039850. DOI: 10.1084/jem.20101559. View

14.

Ogasawara R, Hashimoto D, Kimura S, Hayase E, Ara T, Takahashi S . Intestinal Lymphatic Endothelial Cells Produce R-Spondin3. Sci Rep. 2018; 8(1):10719. PMC: 6048029. DOI: 10.1038/s41598-018-29100-7. View

15.

Forcade E, Kim H, Cutler C, Wang K, Alho A, Nikiforow S . Circulating T follicular helper cells with increased function during chronic graft-versus-host disease. Blood. 2016; 127(20):2489-97. PMC: 4874229. DOI: 10.1182/blood-2015-12-688895. View

16.

Toubert A, Glauzy S, Douay C, Clave E . Thymus and immune reconstitution after allogeneic hematopoietic stem cell transplantation in humans: never say never again. Tissue Antigens. 2012; 79(2):83-9. DOI: 10.1111/j.1399-0039.2011.01820.x. View

17.

Soiffer R, Kim H, McGuirk J, Horwitz M, Johnston L, Patnaik M . Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell.... J Clin Oncol. 2017; 35(36):4003-4011. PMC: 8462523. DOI: 10.1200/JCO.2017.75.8177. View

18.

Khoder A, Sarvaria A, Alsuliman A, Chew C, Sekine T, Cooper N . Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD. Blood. 2014; 124(13):2034-45. PMC: 4186534. DOI: 10.1182/blood-2014-04-571125. View

19.

Savani B, Mielke S, Rezvani K, Montero A, Yong A, Wish L . Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2007; 13(10):1216-23. PMC: 3426353. DOI: 10.1016/j.bbmt.2007.07.005. View

20.

Wu S, Reddy P . Tissue tolerance: a distinct concept to control acute GVHD severity. Blood. 2017; 129(13):1747-1752. PMC: 5374290. DOI: 10.1182/blood-2016-09-740431. View