PERIPHERAL-BLOOD HARVEST OF UNAFFECTED CD34(-) HEMATOPOIETIC PRECURSORS IN PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA() CD38()

Paroxysmal nocturnal hemoglobinuria (PNH) arises from somatic mutation of a bone marrow progenitor that disrupts glycosylinositol phospholip id (GPI) anchoring of cell surface proteins, We recently characterized the expression of GPI-anchored decay accelerating factor (DAF) and CD 59 during hematopoietic development in PNH marrow. We found that, alth ough a subset of early hematopoietic precursors identified by the CD34 (+)CD38(-) phenotype exhibits normal DAF and CD59 expression, DAF and CD59 are absent on the majority of CD34(+)CD38(-) cells. Pluripotent C D34(+)CD38(-) hematopoietic stem cells normally circulate in the perip heral blood and can be collected by apheresis, cryopreserved, and late r used for reconstitution of hematopoiesis. In this study, we examined the phenotypes of CD34(+) cells that are released into the blood of P NH patients. Analyses of apheresis samples from three affected individ uals showed discrete populations of circulating DAF(+)CD59(+)CD34(+) a nd DAF(-)CD59(-)CD34(+) cells. Variable proportions of CD34(+)CD38(-) cells were present within the peripheral blood CD34(+) cells of each p atient, but in all three cases the DAF(+)GD59(+)CD34(+)CD38(-) cell su bset was enriched relative to the DAF(-)CD59(-)CD34(+)CD38(-) cell sub set. Because CD34(+) cells lacking CD38 antigen are highly enriched fo r self-renewing hematopoietic stem cells, these findings indicate that apheresis samples can serve as a source of unaffected stem cells for autologous marrow transplantation of PNH patients. (C) 1995 by The Ame rican Society of Hematology.