ABSTRACT
BACKGROUND: Relapse of the original disease remains the most common cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-SCT). Patients who relapse post-allo-SCT can achieve prolonged remission after donor lymphocyte infusion. Donor lymphocyte infusion as well as other immunotherapeutic strategies are usually complicated by severe graft versus host disease. AIM: In the present study, we examined the effect of irradiation on the cytotoxic activity of mononuclear cells (MNCs). MATERIALS & METHODS: Cytotoxic activity of fresh and irradiated MNCs from healthy donors was tested against the leukemic cell line K562 and against fresh leukemic cells from patients with acute myeloid leukemia. Cytotoxicity was assessed by using a flow-cytometry assay. RESULTS & DISCUSSION: Interestingly, we observed that 25 Gy irradiated MNCs retain significant cytotoxic activity against K562. Based on these in vitro data, the safety and efficacy of irradiated haploidentical, IL-2-activated lymphocytes were tested in six patients after allo-SCT. Acute skin graft versus host disease developed in two patients and was resolved after a short course of steroids. One patient with mixed chimera converted to full donor chimera after infusion of irradiated donor cells. CONCLUSION: The efficacy of irradiated haploidentical lymphocytes should be further tested in a larger number of patients.
Subject(s)
Gamma Rays , Hematopoietic Stem Cell Transplantation , Killer Cells, Lymphokine-Activated/transplantation , Leukemia, Myeloid, Acute/therapy , Lymphocyte Transfusion , Secondary Prevention/methods , Unrelated Donors , Adult , Allografts , Female , Humans , Immunity, Cellular/immunology , Immunity, Cellular/radiation effects , K562 Cells , Killer Cells, Lymphokine-Activated/immunology , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/pathology , Male , RecurrenceABSTRACT
Extracorporeal photopheresis (ECP) has been established as an effective treatment modality for patients with chronic extensive graft-versus host disease (GVHD). In the present study, we evaluated the influence of ECP on the numbers of CD4+, CD8+, CD20+, CD56+ cells, and on T-regulatory (Tregs), as well as on the numbers of naïve, central memory (CM), and effector memory (EM) T-cells in patients treated for refractory chronic GVHD. Flow cytometric analysis of peripheral blood lymphocytes was performed for the calculation of the different T-cell subsets. Patients with GVHD had a higher percentage of EM-CD4+ cells in comparison with healthy donors (p=0.046). The percentages of naïve-CD8+, naïve-CD4+, CM-CD8+, CM-CD4+, EM-CD8+, and Tregs were not different between patients with GVHD and healthy donors. Similarly there was no statistical difference in the percentages of naïve, CM, and EM CD4+ and CD8+ cells before and after 3 months of treatment with ECP. However, in the subset of Tregs a statistically significant increase was observed after 3 months of treatment with ECP (p=0.015). Responders to ECP had statistically significantly higher absolute numbers of CD4+, and CD8+ cells, in comparison with non-responders. These data further support the concept that ECP does not cause immune-suppression, but should be better considered as an immune-modulating treatment.
