title: Irradiated mononuclear cells express significant in vitro cytotoxic activity: promise for in vivo clinical efficacy of irradiated mismatched donor lymphocytes infusion.
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.
  
  
  OBJECTIVE
  In the present study, we examined the effect of irradiation on the cytotoxic activity of mononuclear cells (MNCs).
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  The efficacy of irradiated haploidentical lymphocytes should be further tested in a larger number of patients.
authors.affiliation: Second Department of Internal Medicine, Medical School, National & Kapodistrian University of Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsirigotis
authors.forename: Igor B
authors.initials: IB
authors.lastname: Resnick
authors.forename: Violetta
authors.initials: V
authors.lastname: Kapsimalli
authors.forename: Liliane
authors.initials: L
authors.lastname: Dray
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Psarra
authors.forename: Simha
authors.initials: S
authors.lastname: Samuel
authors.forename: Alexander
authors.initials: A
authors.lastname: Spyridonidis
authors.forename: Evi
authors.initials: E
authors.lastname: Konsta
authors.forename: Myrofora
authors.initials: M
authors.lastname: Vikentiou
authors.forename: Reuven
authors.initials: R
authors.lastname: Or
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Shapira
mesh_terms: D000328:Adult; D064591:Allografts; D005260:Female; D005720:Gamma Rays; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology / Q000528:radiation effects; D020014:K562 Cells; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology / Q000637:transplantation*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D017710:Lymphocyte Transfusion; D008297:Male; D012008:Recurrence; D055502:Secondary Prevention / Q000379:methods*; D061349:Unrelated Donors