Abstract

Graft versus host disease (GvHD) is one of the main complications after hematological stem cell transplantation (HSCT). CAMPATH-1H is used in the pre-transplant conditioning regimen to effectively reduce GvHD by targeting CD52 antigens on T cells resulting in their depletion. Information regarding CD52 expression and the effects of CAMPATH-1H on immune cells is scant and limited to peripheral blood (PB) T and B cells. To date, the effects of CAMPATH-1H on cord blood (CB) cells has not been studied. Here we aimed to analyze CD52 expression and the effects of CAMPATH-1H on fresh or frozen, resting or activated, PB mononuclear cells (PBMC) and CB mononuclear cells (CBMC). In resting state, CD52 expression was higher in CB than PB T cell subsets (653.66±26.68 vs 453.32±19.2) and B cells (622.2±20.65 vs 612.0±9.101) except for natural killer (NK) cells where CD52 levels were higher in PB (421.0±9.857) than CB (334.3±9.559). In contrast, CD52 levels were comparable across all cell types after activation. CAMPATH-1H depleted resting cells more effectively than activated cells with approximately 80–95% of apoptosis observed with low levels of necrosis. There was no direct correlation between cell surface CD52 density and depleting effects of CAMPATH-1H. In addition, no difference in cell viability was noted when different concentrations of CAMPATH-1H were used. CD52 was not expressed on HSC but began to be expressed as the cells differentiate, implying that CAMPATH-1H could potentially affect HSC differentiation and proliferation. Our study provides insightful information, which contributes to the better understanding in the use of CAMPATH-1H as part of the conditioning regime in HSCT.

Highlights

  • Hematopoietic stem cell transplantation (HSCT) is currently used to treat hematological and non-hematological malignancies

  • In freshly isolated PB mononuclear cells (PBMC), CD52 expression was higher in B cells and natural killer T (NKT) cells (612.069.101 and 588.5618.61 respectively) than T cell subsets and natural killer (NK) cells (484.2612.99 and 421.069.857 respectively, p,0.0005) (Figure 1A)

  • NKT cells were only studied in PBMC due to the scarcity of this cell type in cord blood (CB)

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Summary

Introduction

Hematopoietic stem cell transplantation (HSCT) is currently used to treat hematological and non-hematological malignancies. Clinical data has shown that CAMPATH-1H is an efficient means to achieve rapid T cell depletion in patients undergoing allogeneic HSCT [10,11]. The incorporation of CAMPATH-1H into the conditioning regimen as GvHD prophylaxis lowers the incidence of GvHD in patients after HSCT [12,13,14,15]. The use of CAMPATH-1H is common when bone marrow (BM) or mobilized peripheral blood (PB) are used as a source of hematopoietic stem cells (HSC) but is currently not routinely used in cord blood transplantation (CBT)

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