The hematopoietic stem cell in elderly patients with leukemia.
Stem cell reserve and the proliferative capacity of pluripotent hematopoietic progenitors as influenced by age are of intrinsic biologic interest and potential therapeutic importance. The latter is especially true in older persons receiving intensive but not marrow-ablative chemotherapy. Studies of stem cell aging using murine models yield conflicting data. Unfortunately, few studies address the effect of aging on human hematopoietic stem cells, largely because there is no true pluripotent stem cell assay. Some work indicates that the proliferative capacity of human hematopoietic stem cells appears to decrease with age but is unclear whether this is of clinical significance. Our preliminary analysis of more than 500 autotransplant candidates by univariate analysis indicates that higher patient age correlates with reduced committed hematopoietic progenitor cell levels but not with delayed engraftment. In the future, the use of combinations of assays that include phenotypic (CD34+thy1+CD38lo) and functional (long-term culture-initiating cell) characteristics may better identify the effects of aging on candidate stem cells. The development of assays that predict delayed hematopoietic recovery after chemotherapy in older adults may help to tailor therapy for specific patients with the hope of reducing morbidity while retaining efficacy.
Keating
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Leukemia and Transplant Service, Toronto Hospital, Ontario, Canada.
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000367:Age Factors; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000276:immunology / Q000473:pathology*; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000032:analysis; D018800:Thy-1 Antigens / Q000032:analysis
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D018800:Thy-1 Antigens; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1