Leukemia Relapse After Stem-Cell Transplant Traced to Loss of Mismatched HLA

Last Updated: 2009-07-29 17:00:26 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Following transplantation of haploidentical hematopoietic stem cells for the treatment of leukemia, genomic loss of the recipient"s mismatched HLA haplotype is one mechanism whereby relapse takes place, Italian researchers report in the July 30 issue of The New England Journal of Medicine.

"Genomic instability is a hallmark of myeloid cancers, and it has been associated with loss of heterozygosity without loss of genetic material (resulting in uniparental disomy), even in leukemic cells with a normal karyotype," the authors explain. "Our data indicate that this loss of heterozygosity can confer a selective advantage on leukemic cells, which become able to escape immunologic pressure from alloreactive donor T cells."

Dr. Fabio Ciceri, at San Raffaele Hospital in Milan, and colleagues identified 43 adults with high-risk hematologic myeloid cancers who had undergone haploidentical hematopoietic stem-cell transplantation at his institution between 2002 and 2007. Transplantation was followed by infusion of donor T cells to achieve immune reconstitution.

Seventeen patients had a leukemia relapse of host origin. Five of these had "mutant leukemic cells, in which the HLA haplotype that differed from the donor"s haplotype had been lost because of acquired uniparental disomy of chromosome 6p."

As a result, the patients carried only the HLA haplotype shared by the donor and the recipient. Therefore the T cells from the donor and those from the patient did not recognize the mutant leukemic cells, rendering this form of immunotherapy ineffective.

"The frequency of this event suggests the value of assessing the HLA genotype of the leukemic cells in cases of relapse after transplantation to identify alternative donors whose T cells could eliminate escape mutants."

Source:

N Engl J Med 2009;361:478-488.


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