Increased circulating CD4+FOXP3+ T cells associate with early relapse following autologous hematopoietic stem cell transplantation in multiple myeloma patients

Abstract

// Egor V. Batorov 1 , Marina A. Tikhonova 1 , Natalia V. Pronkina 2 , Irina V. Kryuchkova 3 , Vera V. Sergeevicheva 3 , Svetlana A. Sizikova 3 , Galina Y. Ushakova 3 , Tatiana A. Aristova 3 , Dariya S. Batorova 3 , Elena V. Menyaeva 4 , Andrey V. Gilevich 5 , Ekaterina Y. Shevela 1 , Alexander A. Ostanin 1 and Elena R. Chernykh 1 1 Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia 2 Laboratory of Clinical Immunology, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia 3 Department of Hematology and Bone Marrow Transplantation, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia 4 Clinical Diagnostic Laboratory, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia 5 Intensive Care Unit, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia Correspondence to: Egor V. Batorov, email: Ebatorov@gmail.com Keywords: CD4 + FOXP3 + ; autologous hematopoietic stem cell transplantation; immune recovery; multiple myeloma; relapse Received: April 19, 2018      Accepted: May 19, 2018      Published: June 05, 2018 ABSTRACT 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%); P U = 0.026. Area under the curve was 0.72 (95% CI: 0.570—0.878; p=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.