Mechanism of separation of graft-versus-host disease and graft versus leukemia in unrelated cord blood transplantation for hematological malignancies

doi:10.12307/2022.323

Abstract

Abstract: BACKGROUND: Numerous clinical studies in and outside China have shown that unrelated cord blood transplantation has a lower incidence of graft-versus-host disease compared with peripheral blood stem cell or bone marrow transplantation, and the recurrence rate of the disease is also markedly reduced. It has a strong graft versus leukemia effect and is one of the models for clinically separating graft-versus-host disease and graft versus leukemia effect. How the immune cells differentiate after unrelated cord blood transplantation and why the transplant has a strong graft versus leukemia effect; the mechanism is still unclear.
OBJECTIVE: To retrospectively analyze the long-term clinical follow-up data of unrelated cord blood transplantation patients, investigate dominant cell subsets and differentiation, related activation and expression of inhibitory molecules after unrelated cord blood transplantation, and further explore the mechanism of graft-versus-host disease and graft versus leukemia separation of unrelated cord blood transplantation.
METHODS: From July 1, 2012 to June 31, 2017, 154 adult patients with hematologic malignancies received hematopoietic stem cell transplantation, including 93 cases of unrelated cord blood transplantation and 61 cases of sibling peripheral blood stem cell transplantation. The immune characteristics of T cells in patients with unrelated cord blood transplantation were studied by collecting bone marrow samples from patients with unrelated cord blood transplantation and peripheral blood stem cell transplantation, and the separation of clinical graft-versus-host disease and graft versus leukemia effect in unrelated cord blood transplantation was investigated.
RESULTS AND CONCLUSION: (1) After a median follow-up of 61 months (42-99 months), the 5-year prevalence of chronic graft-versus-host disease and five year-relapse in unrelated cord blood transplantation group were significantly lower than those in peripheral blood stem cell transplantation group (P=0.003). Integration of III-IV graft-versus-host disease, extensive chronic graft-versus-host disease and disease recurrence, 5-year graft-versus-host disease-free and disease-free survival were significantly higher in the unrelated cord blood transplantation group than those in the peripheral blood stem cell transplantation group (P=0.038). (2) The percentage of CD3+ T cells was significantly higher in unrelated cord blood transplantation group than that in the peripheral blood stem cell transplantation group (P=0.04). The percentage of CD3+CD4+ T cell subsets in unrelated cord blood transplantation group was lower than that in the peripheral blood stem cell transplantation group. The percentage of CD3+CD8+ cell subsets in unrelated cord blood transplantation group was higher than that in the peripheral blood stem cell transplantation group. The percentage of CD4+CD80+ T cells in unrelated cord blood transplantation group was lower than that in the peripheral blood stem cell transplantation group (P=0.089). The percentage of CD4+PD-1+ T cells in the unrelated cord blood transplantation group was higher than that in the peripheral blood stem cell transplantation group. The percentage of CD8+CD80+ T cells in the unrelated cord blood transplantation group was higher than that in the peripheral blood stem cell transplantation group. (3) The results suggest that unrelated cord blood transplantation patients not only have lower chronic graft-versus-host disease, but also have lower disease recurrence rate, showing the separation of graft-versus-host disease and graft versus leukemia. Immune function test showed that the proportion of T cells in unrelated cord blood transplantation group was relatively high, and CD8+ T cells were the dominant subset, which may be one of the mechanisms of strong graft versus leukemia effect of unrelated cord blood transplantation.

Key words: cord blood, peripheral blood stem cell, transplantation, graft-versus-host disease, graft versus leukemia, T cells, immune function

CLC Number:

Xu Anhui, Lin Xiuxiu, Zhang Xuhan, Song Kaidi, Sun Guangyu, Tang Baolin, Sun Zimin, Zheng Changcheng. Mechanism of separation of graft-versus-host disease and graft versus leukemia in unrelated cord blood transplantation for hematological malignancies[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(13): 1993-1999.

Figures/Tables 5

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