High Proportions of CD3 T Cells in Grafts Delayed Lymphocyte Recovery and Reduced Overall Survival in Haploidentical Peripheral Blood Stem Cell Transplantation

Overview

Journal Mol Clin Oncol

Specialty Oncology

Date 2020 Apr 28

PMID 32337040

Citations 5

Authors

Ying Zhang

Caili Guo

Chunhong Sun

Ying Chen

Huachao Zhu

Jieying Xi

Mei Zhang

Pengcheng He

Xiaoning Wang

Affiliations

Soon will be listed here.

Abstract

T cells in grafts serve an important role in the pathogenesis of graft versus host disease (GVHD) and immune recovery during HLA matched allogeneic stem cell transplantation. However, the role of T cells in the haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT) is yet to be determined. In the present study, the role of CD3 T cells in grafts and impact on hematopoietic and immune recovery, cytomegalovirus (CMV) reactivation, GVHD, relapse, progress free survival and overall survival (OS) were evaluated and analyzed. A total of 30 patients who underwent haplo-PBSCT were included in the present study. CD3 T cells accounted for a median of 23.1% (range 8-47.4%) with a median dose of 299.7x10/kg (range 104-623.4). Patients were divided into two groups according to the CD3 T cell count: Above the median (high T cell group) and below the median CD3 T cell (low T cell group). No significant difference was identified between neutrophil and platelet recovery time between two groups (P>0.05). The mean lymphocyte recovery time of high T cell group and low T cell group were 107.07 days (95% CI 79.88-134.25), and 50.4 days (95% CI 41.42-59.38), respectively. The lymphocyte recovery time of high T cell group was higher that of low T cell group (P<0.05). No significant difference between CMV reactivation, chronic GVHD and primary disease relapse rates was observed between two groups (P>0.05). The cumulative incidence of grade II or above acute GVHD was higher in the high T groups compared with low T groups (P<0.05). The overall survival and progress free survival rates were higher in the low T cell group compared with the high T cell group (P<0.05). In conclusion, high levels of CD3 T cells in the grafts were associated with delayed lymphocyte recovery and an increased risk of acute GVHD and decreased overall survival.

Citing Articles

High levels of NK Cells in graft are associated with reduced febrile neutropenia after haploidentical peripheral blood stem cell transplantation.

Guo C, Li X, Li M, He P, Wang W, Wang X J Int Med Res. 2023; 51(7):3000605231187932.

PMID: 37480280 PMC: 10363871. DOI: 10.1177/03000605231187932.

The Impact of Graft CD3 T-Cell Dose on the Outcome of T-Cell Replete Human Leukocyte Antigen-Mismatched Allogeneic Hematopoietic Peripheral Blood Stem Cells Transplantation.

Halahleh K, Mustafa R, Sarhan D, Al Rimawi D, Abdelkhaleq H, Muradi I J Hematol. 2023; 12(1):27-36.

PMID: 36895292 PMC: 9990716. DOI: 10.14740/jh1071.

A Prospective Study of an HLA-Haploidentical Peripheral Blood Stem Cell Transplantation Regimen Based on Modification of the Dose of Posttransplant Cyclophosphamide for Poor Prognosis or Refractory Hematological Malignancies.

Nakamae H, Okamura H, Hirose A, Koh H, Nakashima Y, Nakamae M Cell Transplant. 2022; 31:9636897221112098.

PMID: 35906755 PMC: 9340897. DOI: 10.1177/09636897221112098.

Addition of a Single Low Dose of Anti T-Lymphocyte Globulin to Post-Transplant Cyclophosphamide after Allogeneic Hematopoietic Stem Cell Transplant: A Pilot Study.

Xue E, Lorentino F, Lupo Stanghellini M, Giglio F, Piemontese S, Clerici D J Clin Med. 2022; 11(4).

PMID: 35207379 PMC: 8879643. DOI: 10.3390/jcm11041106.

Late Effects After Haematopoietic Stem Cell Transplantation in ALL, Long-Term Follow-Up and Transition: A Step Into Adult Life.

Diesch-Furlanetto T, Gabriel M, Zajac-Spychala O, Cattoni A, Hoeben B, Balduzzi A Front Pediatr. 2021; 9:773895.

PMID: 34900873 PMC: 8652149. DOI: 10.3389/fped.2021.773895.

References

Chang Y, Zhao X, Huo M, Huang X . Expression of CD62L on donor CD4(+) T cells in allografts: correlation with graft-versus-host disease after unmanipulated allogeneic blood and marrow transplantation. J Clin Immunol. 2009; 29(5):696-704. DOI: 10.1007/s10875-009-9293-9. View

Prentice H, Blacklock H, Janossy G, Gilmore M, Tidman N, Trejdosiewicz L . Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukaemic marrow transplant recipients. Lancet. 1984; 1(8375):472-6. DOI: 10.1016/s0140-6736(84)92848-4. View

Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, De La Rubia J, Brunet S . The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings. Blood. 2001; 97(2):383-7. DOI: 10.1182/blood.v97.2.383. View

Sakiyama M, Kami M, Hori A, Imataki O, Hamaki T, Murashige N . Regimen-related toxicity following reduced-intensity stem-cell transplantation (RIST): comparison between Seattle criteria and National Cancer Center Common Toxicity Criteria (NCI-CTC) version 2.0. Bone Marrow Transplant. 2004; 34(9):787-94. DOI: 10.1038/sj.bmt.1704673. View

Pabst C, Schirutschke H, Ehninger G, Bornhauser M, Platzbecker U . The graft content of donor T cells expressing gamma delta TCR+ and CD4+foxp3+ predicts the risk of acute graft versus host disease after transplantation of allogeneic peripheral blood stem cells from unrelated donors. Clin Cancer Res. 2007; 13(10):2916-22. DOI: 10.1158/1078-0432.CCR-06-2602. View

Mohty M, Bagattini S, Chabannon C, Faucher C, Bardou V, Bilger K . CD8+ T cell dose affects development of acute graft-vs-host disease following reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Exp Hematol. 2004; 32(11):1097-102. DOI: 10.1016/j.exphem.2004.07.020. View

Kosugi-Kanaya M, Ueha S, Abe J, Shichino S, Shand F, Morikawa T . Long-Lasting Graft-Derived Donor T Cells Contribute to the Pathogenesis of Chronic Graft-versus-Host Disease in Mice. Front Immunol. 2018; 8:1842. PMC: 5741650. DOI: 10.3389/fimmu.2017.01842. View

Anderson B, Taylor P, McNiff J, Jain D, Demetris A, Panoskaltsis-Mortari A . Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells. Blood. 2008; 111(10):5242-51. PMC: 2384145. DOI: 10.1182/blood-2007-09-107953. View

Vadakekolathu J, Rutella S . T-Cell Manipulation Strategies to Prevent Graft-Versus-Host Disease in Haploidentical Stem Cell Transplantation. Biomedicines. 2017; 5(2). PMC: 5489819. DOI: 10.3390/biomedicines5020033. View

10.

Pastore D, Delia M, Mestice A, Carluccio P, Perrone T, Gaudio F . CD3+/Tregs ratio in donor grafts is linked to acute graft-versus-host disease and immunologic recovery after allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2011; 18(6):887-93. DOI: 10.1016/j.bbmt.2011.10.039. View

11.

Gu G, Yang J, Sun L . Correlation of graft immune composition with outcomes after allogeneic stem cell transplantation: Moving towards a perfect transplant. Cell Immunol. 2017; 323:1-8. DOI: 10.1016/j.cellimm.2017.11.002. View

12.

Saad A, Lamb L . Ex vivo T-cell depletion in allogeneic hematopoietic stem cell transplant: past, present and future. Bone Marrow Transplant. 2017; 52(9):1241-1248. PMC: 5589981. DOI: 10.1038/bmt.2017.22. View

13.

Handgretinger R . New approaches to graft engineering for haploidentical bone marrow transplantation. Semin Oncol. 2012; 39(6):664-73. DOI: 10.1053/j.seminoncol.2012.09.007. View

14.

Kalwak K, Porwolik J, Mielcarek M, Gorczynska E, Owoc-Lempach J, Ussowicz M . Higher CD34(+) and CD3(+) cell doses in the graft promote long-term survival, and have no impact on the incidence of severe acute or chronic graft-versus-host disease after in vivo T cell-depleted unrelated donor hematopoietic stem cell.... Biol Blood Marrow Transplant. 2010; 16(10):1388-401. DOI: 10.1016/j.bbmt.2010.04.001. View

15.

Gaziev J, Isgro A, Marziali M, Daniele N, Gallucci C, Sodani P . Higher CD3(+) and CD34(+) cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia. Bone Marrow Transplant. 2011; 47(1):107-14. DOI: 10.1038/bmt.2011.3. View

16.

Oevermann L, Handgretinger R . New strategies for haploidentical transplantation. Pediatr Res. 2012; 71(4 Pt 2):418-26. DOI: 10.1038/pr.2011.60. View

17.

Li Pira G, Malaspina D, Girolami E, Biagini S, Cicchetti E, Conflitti G . Selective Depletion of αβ T Cells and B Cells for Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation. A Three-Year Follow-Up of Procedure Efficiency. Biol Blood Marrow Transplant. 2016; 22(11):2056-2064. DOI: 10.1016/j.bbmt.2016.08.006. View

18.

Czerw T, Labopin M, Schmid C, Cornelissen J, Chevallier P, Blaise D . High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched.... Oncotarget. 2016; 7(19):27255-66. PMC: 5053647. DOI: 10.18632/oncotarget.8463. View

19.

Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, Rubia J, Brunet S . Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings. Blood. 2002; 100(2):724-7. DOI: 10.1182/blood-2001-11-0057. View

20.

Oevermann L, Lang P, Feuchtinger T, Schumm M, Teltschik H, Schlegel P . Immune reconstitution and strategies for rebuilding the immune system after haploidentical stem cell transplantation. Ann N Y Acad Sci. 2012; 1266:161-70. DOI: 10.1111/j.1749-6632.2012.06606.x. View