ABSTRACT
Non-malignant host immune cells are the main substrate in classical Hodgkin lymphoma (HL) microenvironment. Reconstitution of lymphocyte populations following the high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (auto-HSCT) can support tumor growth in HL patients. We investigated recovery dynamics of circulating CD3+, CD4+, CD8+, CD16+/CD56+, CD19+, CD4+FOXP3+ lymphocytes following auto-HSCT in 79 HL patients and assessed relationship between these populations and the development of early relapse. Studied populations were not statistically significant between patients with high or standard/intermediate risk of relapse. CD3+ T cells at the time of engraftment were increased in patients with the early relapse of HL compared to non-relapsed patients (PU = 0.0028). Area under the curve was 0.76 (Ñ = .0037). In logistic regression models, CD3+ T cell count was associated with early relapse/progression as a trend. These findings elucidate several interactions between early systemic T cell recovery and tumor progression following HDC with auto-HSCT.
Subject(s)
Hodgkin Disease/blood , Hodgkin Disease/diagnosis , Lymphocyte Count , T-Lymphocyte Subsets , Biomarkers , CD3 Complex/metabolism , Female , Flow Cytometry , Hematopoietic Stem Cell Transplantation , Hodgkin Disease/therapy , Humans , Immune Reconstitution , Immunophenotyping , Male , ROC Curve , Recurrence , T-Lymphocyte Subsets/metabolism , Transplantation, Autologous , Treatment OutcomeABSTRACT
We investigated dynamics of CD4+FOXP3+ T cell recovery following the high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients. Circulating CD4+FOXP3+ T cells of 79 MM patients were evaluated using flow cytometry before HDC with auto-HSCT, at the day of engraftment, and following 6 and 12 months. Percentage of CD4+FOXP3+ T cells restored rapidly following auto-HSCT, became higher than pre-transplant level at the day of engraftment and then subsequently decreased for a year. CD4+FOXP3+ T cells at the time of engraftment were increased in patients with the relapse or progression of MM during 12 months following auto-HSCT (n=10) compared to non-relapsed patients (n=50): 6.7% (5.3-8.9%) vs 4.9% (2.8-6.6%); PU = 0.026. Area under the curve was 0.72 (95% CI: 0.570-0.878; Ñ=0.026). Circulating CD4+FOXP3+ T cell count was not associated with the percentage of myeloma plasma cells in a bone marrow but depended on its amount in autografts. CONCLUSIONS: Relative count of CD4+FOXP3+ T cells restored rapidly following auto-HSCT (at the day of engraftment), became higher than pre-transplant level and then subsequently decreased for a year. Their excess at the time of engraftment is associated with early relapse.
ABSTRACT
High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (AHSCT) causes severe and long-lasting immunodeficiency in patients with lymphoproliferative disorders. The thymus begins to restore the T-cell repertoire approximately from the sixth month post-transplant. We assessed the dynamics of post-transplant recovery of CD4+CD45RA+CD31+ T cells, "recent thymic emigrants" (RTEs), and a poorly described subtype of CD4+CD45RA-CD31+ T cells in 90 patients with lymphoproliferative disorders following high-dose chemotherapy with AHSCT. Relative and absolute counts of CD4+CD31+ naïve and memory T cells were evaluated before AHSCT, at the day of engraftment, and 6- and 12-month post-transplant. The pre-transplant count of CD4+CD45RA+CD31+ T cells was lower than in healthy controls, and did not reach donors' values during the 12-month period. The pre-transplant number of CD4+CD45RA-CD31+ T cells was higher than in healthy controls and was restored rapidly following AHSCT. Post-transplant mediastinal radiotherapy reduced counts of RTEs and elongated recovery period. Non-thymic tissue irradiation did not reduce this subset. The obtained data indicate that homeostatic proliferation may decrease the significance of CD31 expression on CD4+CD45RA+ T cells as a marker of RTEs, and suggest that evaluation of RTEs recovery by flow cytometry requires an accurate gating strategy to exclude CD31+ memory T cells.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Immunologic Memory , Lymphoproliferative Disorders/immunology , Lymphoproliferative Disorders/metabolism , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Thymus Gland/immunology , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Case-Control Studies , Cell Membrane/metabolism , Combined Modality Therapy , Female , Gene Expression , Graft Survival , Hematopoietic Stem Cell Transplantation , Humans , Immunophenotyping , Lymphocyte Count , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/therapy , Male , Middle Aged , Phenotype , Platelet Endothelial Cell Adhesion Molecule-1/genetics , Thymectomy , Thymus Gland/surgery , Transplantation, Autologous , Treatment Outcome , Young AdultABSTRACT
Mesenchymal stromal cells (MSCs) possess a multi-lineage potential and immunoregulatory activities and provide a great potential in cell-based technologies. However, MSC suppressive activity raises concerns regarding the possible adverse effect of MSCs on the immune recovery. The influence of autologous MSC co-transplantation on recovery of T cell subsets in patients receiving autologous hematopoietic stem cell transplantation (AHSCT) for malignant lymphomas and multiple myeloma were characterized. Co-transplantation of MSCs improved lymphocyte recovery most effectively in patients with low input of hematopoietic stem cells or low absolute lymphocyte count in apheresis product. MSC co-transplantation improved early recovery of both memory and naive T cells with more prominent effect on naive CD4(+) T cells. Patients with MSC co-transplantation showed more effective reconstitution of recent thymic emigrants. These data indicate the positive impact of MSCs on immune reconstitution and note MSC co-transplantation is feasible to optimize the outcomes of AHSCT in malignant lymphoma patients.
