Loss of Mismatched HLA in Leukemia after Stem-Cell Transplantation

Five patients with acute myelogenous leukemia received hematopoietic stem-cell transplants from a haploidentical donor. They also received T cells from the donor. All five patients had a relapse, and at the time of relapse, genomic HLA typing of leukemic blasts could not detect the recipient's...

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Bibliographic Details
Published in:The New England journal of medicine Vol. 361; no. 5; pp. 478 - 488
Main Authors: Vago, Luca, Perna, Serena Kimi, Zanussi, Monica, Mazzi, Benedetta, Barlassina, Cristina, Stanghellini, Maria Teresa Lupo, Perrelli, Nicola Flavio, Cosentino, Cristian, Torri, Federica, Angius, Andrea, Forno, Barbara, Casucci, Monica, Bernardi, Massimo, Peccatori, Jacopo, Corti, Consuelo, Bondanza, Attilio, Ferrari, Maurizio, Rossini, Silvano, Roncarolo, Maria Grazia, Bordignon, Claudio, Bonini, Chiara, Ciceri, Fabio, Fleischhauer, Katharina
Format: Journal Article
Language:English
Published: Waltham, MA Massachusetts Medical Society 30.07.2009
Subjects:
Adult
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Biological and medical sciences
Bone marrow
Bone marrow, stem cells transplantation. Graft versus host reaction
Cells, Cultured
Chromosomes, Human, Pair 6
General aspects
Graft vs Leukemia Effect - genetics
Graft vs Leukemia Effect - immunology
Haplotypes
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
HLA Antigens - genetics
Humans
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - immunology
Leukemia, Myeloid, Acute - therapy
Lymphocytes
Major Histocompatibility Complex
Medical sciences
Mutation
Myelodysplastic Syndromes
Recurrence
Retrospective Studies
Stem cells
T-Lymphocytes - immunology
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Transplantation Chimera
Transplants & implants
Incompatibility
Medicine
HLA-System
Stem cell
Major histocompatibility system
Loss
Hematopoietic cell
Stem cell transplantation
Class I histocompatibility antigen
Tumor cell
ISSN:0028-4793, 1533-4406, 1533-4406
Online Access:Get full text
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Summary:Five patients with acute myelogenous leukemia received hematopoietic stem-cell transplants from a haploidentical donor. They also received T cells from the donor. All five patients had a relapse, and at the time of relapse, genomic HLA typing of leukemic blasts could not detect the recipient's HLA haplotype that differed from the donor's. The loss of the haplotype was due to uniparental disomy. In vitro, the donor's T cells reacted against leukemic blasts obtained at the time of diagnosis, not against blasts obtained at relapse. The results indicate the presence of a mutation that allowed the leukemic cells to escape the immunosurveillance of the donor's T cells. Five patients with acute myelogenous leukemia received hematopoietic stem-cell transplants from a haploidentical donor. They also received T cells from the donor. All five patients had a relapse, and at the time of relapse, genomic HLA typing of leukemic blasts could not detect the recipient's HLA haplotype that differed from the donor's. Transplantation of hematopoietic stem cells from a haploidentical family donor who shares only one HLA haplotype with the recipient is a potentially curative option for patients with high-risk hematologic cancers who lack an HLA-matched donor. 1 – 3 The major limitation of this strategy is the risk of severe graft-versus-host disease (GVHD), which can result from alloreactions mediated by donor T cells against the recipient's unshared HLA haplotype. Since the publication of studies on extensively T-cell–depleted grafts, 1 , 2 a variety of strategies have been developed to prevent or control GVHD after transfer of haploidentical T cells. 4 , 5 The feasibility and efficacy of . . .
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ISSN:0028-4793
1533-4406
1533-4406
DOI:10.1056/NEJMoa0811036