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Relapse after bone marrow transplantation: evidence for distinct immunological mechanisms between adult and paediatric populations
Author(s) -
Guimond Martin,
Busque Lambert,
Baron Chantal,
Bonny Yvette,
Bélanger Robert,
Mattioli Johanne,
Perreault Claude,
Roy Denis Claude
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.01961.x
Subject(s) - medicine , immunology , transplantation , donor lymphocyte infusion , hematopoietic stem cell transplantation , bone marrow , haematopoiesis , lymphocyte , natural killer cell , immune system , progenitor cell , stem cell , gastroenterology , cytotoxic t cell , biology , biochemistry , in vitro , genetics
Donor lymphocyte infusions are particularly effective for remission induction in malignant cells in patients who relapse after allogeneic progenitor cell transplantation (PCT) and who remain sensitive to the administration of unprimed donor T and/or natural killer (NK) cells present in donor lymphocyte infusions. To determine whether relapse after unmanipulated PCT could be ascribed to donor T and/or NK cell loss or tolerization, we evaluated the chimeric status of 81 patients with haematological malignancies who were receiving allogeneic unmanipulated PCT. The incidence of mixed chimaerism (MC) in unfractionated mononuclear leucocyte samples decreased rapidly after transplant, and was not detectable 4 months after PCT, even in patients who subsequently relapsed. The chimeric status of immune effector cell subsets was then evaluated in 15 patients at the time of relapse. All adults demonstrated complete donor haematopoiesis (CDH) for all cell lineages, whereas T‐ and NK‐cell MC was only found in patients younger than age 13 years ( P = 0·004). MC was not found in T nor NK cells of a control group consisting of age‐matched paediatric patients in remission after allogeneic PCT. Thus, in adults, T and NK cell MC disappears early after unmanipulated allogeneic PCT and is absent at the time of relapse. However, the identification of donor T and NK cell loss in the paediatric relapsed but not remission patients suggests a distinct mechanism of relapse.