title: Lowering the alemtuzumab dose in reduced intensity conditioning allogeneic hematopoietic cell transplantation is associated with a favorable early intense natural killer cell recovery.
abstract: OBJECTIVE
  The anti-CD52 monoclonal antibody alemtuzumab is employed in allogeneic hematopoietic cell transplantation (alloHCT) for the prevention of graft-versus-host disease (GVHD). However, its optimal dosing in this setting has not been determined yet. We compared three different alemtuzumab dose levels in reduced intensity conditioning (RIC) alloHCT with respect to lymphocyte recovery and outcome.
  
  
  METHODS
  In 127 consecutive patients with predominantly advanced stage hematologic malignancies, a first alloHCT after RIC was performed, applying a fludarabine-based protocol (in 93% FBM: fludarabine, bis-chloroethyl-nitrosourea [BCNU], and melphalan). For GVHD prophylaxis, cyclosporine and alemtuzumab at three different dose levels (40 mg, 20 mg, 10 mg) were administered. Recovery of the peripheral blood (PB) lymphocyte sub-populations and clinical outcome were determined with regard to the alemtuzumab dose.
  
  
  RESULTS
  Natural killer (NK) cell concentrations in PB around day +30 correlated inversely with the alemtuzumab dose, whereas other PB lymphocyte subtypes remained essentially unaffected by dosing of alemtuzumab. Lower alemtuzumab doses were associated with a tendency toward improved overall survival mainly during the early post-transplantation months. With regard to the PB NK cell concentration around day +30, "early intense NK cell reconstituters" tended to show an overall survival benefit.
  
  
  CONCLUSIONS
  An alemtuzumab dose reduction to only 10-20 mg provides sufficient GVHD prophylaxis and supports improved NK cell regeneration early after alloHCT in PB ("NK cell saving effect"), which may have a positive effect on overall survival.
authors.affiliation: Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Gärtner
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hieke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Finke
authors.forename: Hartmut
authors.initials: H
authors.lastname: Bertz
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000074301:CD52 Antigen; D002470:Cell Survival; D002985:Clinical Protocols; D054796:Drug Dosage Calculations; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology* / Q000637:transplantation; D016131:Lymphocyte Subsets / Q000473:pathology* / Q000637:transplantation; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011183:Postoperative Complications / Q000276:immunology / Q000517:prevention & control*; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab
keywords: NK cell saving effect; alemtuzumab; hematopoietic cell transplantation; natural killer cells; reduced intensity conditioning