Abstract

Steroid-resistant GvHD is one of the most significant causes of mortality following allogeneic Hematopoietic Stem Cell Transplantation (HSCT). Treatment with mesenchymal stromal cells (MSC) seems to be a promising solution, however the results from clinical studies are still equivocal. Better selection of candidate patients and improving monitoring of patients following MSC administration can increase treatment effectiveness. In order to determine which characteristics can be used to predict a good response and better monitoring of patients, blood samples were taken prior to therapy, one week and one month after therapy, from 26 allogeneic HSCT patients whom contracted GvHD and were treated with MSCs. Samples were examined for differential blood counts, bilirubin levels and cell surface markers. Serum cytokine levels were also measured. We found that the level of lymphocytes, in particular T and NK cells, may predict a good response to therapy. A better response was observed among patients who expressed low levels of IL-6 and IL-22, Th17 related cytokines, prior to therapy. Patients with high levels of bilirubin prior to therapy showed a poorer response. The results of this study may facilitate early prediction of success or failure of the treatment, and subsequently, will improve selection of patients for MSC therapy.

Highlights

  • Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) enable treatment of a number of hereditary and hematological diseases, the most common implementation of HSCT is for the treatment of hematological malignancies

  • The objective of our study is to identify the immune, hematological, and biochemical parameters that characterize the population of graft versus host disease (GvHD) patients responding to mesenchymal stromal cells (MSC) therapy, relative to non-responding patients

  • No significant difference among groups was found with respect to the origin of the graft, the patient’s gender, indications for transplantation, conditioning protocol, donor, type and severity of GvHD, time from transplant until MSC therapy and the proportion of patients with involvement of the liver

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Summary

Introduction

Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) enable treatment of a number of hereditary and hematological diseases, the most common implementation of HSCT is for the treatment of hematological malignancies. The anti-tumor effect of allogeneic transplants relies on chemical conditioning, and on the action of the graft against the tumor, known as the graft versus leukemia effect (GvL). The immune effect of the graft is not limited to the tumor alone, and in many cases an immune response towards the patient’s body develops, known as graft versus host disease (GvHD). GvHD may appear as an acute or chronic disease.

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