title: Loss of mismatched HLA in leukemia after stem-cell transplantation.
abstract: BACKGROUND
  Transplantation of hematopoietic stem cells from partially matched family donors is a promising therapy for patients who have a hematologic cancer and are at high risk for relapse. The donor T-cell infusions associated with such transplantation can promote post-transplantation immune reconstitution and control residual disease.
  
  
  METHODS
  We identified 43 patients who underwent haploidentical transplantation and infusion of donor T cells for acute myeloid leukemia or myelodysplastic syndrome and conducted post-transplantation studies that included morphologic examination of bone marrow, assessment of hematopoietic chimerism with the use of short-tandem-repeat amplification, and HLA typing. The genomic rearrangements in mutant variants of leukemia were studied with the use of genomic HLA typing, microsatellite mapping, and single-nucleotide-polymorphism arrays. The post-transplantation immune responses against the original cells and the mutated leukemic cells were analyzed with the use of mixed lymphocyte cultures.
  
  
  RESULTS
  In 5 of 17 patients with leukemia relapse after haploidentical transplantation and infusion of donor T cells, we identified mutant variants of the original leukemic cells. In the mutant leukemic cells, the HLA haplotype that differed from the donor's haplotype had been lost because of acquired uniparental disomy of chromosome 6p. T cells from the donor and the patient after transplantation did not recognize the mutant leukemic cells, whereas the original leukemic cells taken at the time of diagnosis were efficiently recognized and killed.
  
  
  CONCLUSIONS
  After transplantation of haploidentical hematopoietic stem cells and infusion of donor T cells, leukemic cells can escape from the donor's antileukemic T cells through the loss of the mismatched HLA haplotype. This event leads to relapse.
authors.affiliation: Hospital San Raffaele-Telethon Institute for Gene Therapy, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.forename: Serena Kimi
authors.initials: SK
authors.lastname: Perna
authors.forename: Monica
authors.initials: M
authors.lastname: Zanussi
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzi
authors.forename: Cristina
authors.initials: C
authors.lastname: Barlassina
authors.forename: Maria Teresa Lupo
authors.initials: MT
authors.lastname: Stanghellini
authors.forename: Nicola Flavio
authors.initials: NF
authors.lastname: Perrelli
authors.forename: Cristian
authors.initials: C
authors.lastname: Cosentino
authors.forename: Federica
authors.initials: F
authors.lastname: Torri
authors.forename: Andrea
authors.initials: A
authors.lastname: Angius
authors.forename: Barbara
authors.initials: B
authors.lastname: Forno
authors.forename: Monica
authors.initials: M
authors.lastname: Casucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Bernardi
authors.forename: Jacopo
authors.initials: J
authors.lastname: Peccatori
authors.forename: Consuelo
authors.initials: C
authors.lastname: Corti
authors.forename: Attilio
authors.initials: A
authors.lastname: Bondanza
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ferrari
authors.forename: Silvano
authors.initials: S
authors.lastname: Rossini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Roncarolo
authors.forename: Claudio
authors.initials: C
authors.lastname: Bordignon
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonini
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Katharina
authors.initials: K
authors.lastname: Fleischhauer
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002896:Chromosomes, Human, Pair 6; D020544:Graft vs Leukemia Effect / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008285:Major Histocompatibility Complex; D009154:Mutation; D009190:Myelodysplastic Syndromes; D012008:Recurrence; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera
chemical_list: D006680:HLA Antigens