Abstract

Hematopoietic stem cell transplantation from anti-cytomegalovirus immunoglobulin G (anti-CMV-IgG) positive donors facilitated immunological recovery post-transplant, which may indicate that chronic CMV infection has an effect on the immune system. This can be seen in the recipients after reconstitution with donor lymphocytes. We evaluated the composition of lymphocytes at hematologic recovery in 99 patients with hematologic malignancies post hematopoietic stem cell transplantation (HSCT). Anti-CMV-IgG seropositivity of the donor was associated with higher proportions of CD4+ (227.963 ± 304.858 × 106 vs. 102.050 ± 17.247 × 106 cells/L, p = 0.009) and CD4+CD25high (3.456 ± 0.436 × 106 vs. 1.589 ± 0.218 × 106 cells/L, p = 0.003) lymphocytes in the blood at hematologic recovery. The latter parameter exerted a diverse influence on the risk of acute graft-versus-host disease (GvHD) if low (1.483 ± 0.360 × 106 vs. 3.778 ± 0.484 × 106 cells/L, p < 0.001) and de novo chronic GvHD (cGvHD) if high (3.778 ± 0.780 × 106 vs. 2.042 ± 0.261 × 106 cells/L, p = 0.041). Higher values of CD4+ lymphocytes in patients who received transplants from anti-CMV-IgG-positive donors translated into a reduced demand for IgG support (23/63 vs. 19/33, p = 0.048), and these patients also exhibited reduced susceptibility to cytomegalovirus (CMV), Epstein–Barr virus (EBV) and/or human herpes 6 virus (HHV6) infection/reactivation (12/50 vs. 21/47, p = 0.032). Finally, high levels (≥0.4%) of CD4+CD25high lymphocytes were significantly associated with better post-transplant survival (56% vs. 38%, four-year survival, p = 0.040). Donors who experience CMV infection/reactivation provide the recipients with lymphocytes, which readily reinforce the recovery of the transplanted patients’ immune system.

Highlights

  • Alloreactivity and poor immune system recovery leading to life-threatening complications post-hematopoietic stem cell transplantation (HSCT) remains a significant challenge for researchers

  • Donor anti-CMV-IgG negativity resulted in (I) lower numbers of CD4+ lymphocytes in the blood at hematologic recovery (102.050 ± 17.247 vs. 227.963 ± 304.858 × 106 cells/L, p = 0.009); (II) a greater proportion of patients that were on intravenous IgG support during the first 100 days post-HSCT

  • Blood work revealed that the above group of patients receiving a graft from anti-CMV-IgG negative donors had lower proportions and numbers of CD4+CD25high lymphocytes

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Summary

Introduction

Alloreactivity and poor immune system recovery leading to life-threatening complications post-hematopoietic stem cell transplantation (HSCT) remains a significant challenge for researchers. The advanced stage of acute graft-versus-host disease (aGvHD) is associated with a level of HLA disparity, a sizeable proportion of patients may still survive despite relatively poor matching [5,6]. Under these conditions, it is believed that T regulatory cells (Tregs) present in the blood can control the vigorousness of the alloreactive response [7,8,9]. CD4+CD25high by Sakaguchi et al [10] This population meets the criteria for cells that control the immune response using suppressor cell machinery, which functions in cells with interleukin 2 (IL-2)

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