CIRCULATING PRIMITIVE STEM-CELLS IN PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA (PNH) ARE PREDOMINANTLY NORMAL IN PHENOTYPE BUT GRANULOCYTE-COLONY-STIMULATING FACTOR TREATMENT MOBILIZES MAINLY PNH STEM-CELLS

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic ane mia resulting from a somatic mutation in a hemopoietic stem cell. In m ost cases of hemolytic PNH, the majority of the marrow cells are deriv ed from the PNH clone. Recent evidence has indicated, however, that th e majority of the most primitive peripheral blood stem cells (PBSCs) i n PNH appear to be of normal phenotype. This has led to tentative sugg estions that normal PBSCs could be collected and used for autologous t ransplantation. We have investigated this possibility in four PNH pati ents by treating them with granulocyte colony-stimulating factor (G-CS F) in an attempt to mobilize normal progenitors. The expression of gly cosylphosphatidylinositol (GPI)-linked proteins was analyzed by flow c ytometry on mature neutrophils, late stem cells (CD34(+)/CD38(+)), and primitive stem cells (CD34(+)/CD38(-)). The phenotyping and stem cell quantitation was performed in steady-state blood and post-G CSF admin istration. The most primitive PBSCs (CD34(+)/CD38(-)) were almost all normal before G-CSF treatment, even when the patients' neutrophils wer e mainly PNH. However, after G-CSF, the cells that were mobilized into the peripheral blood were of a similar phenotype to the mature neutro phils, ie, mainly PNH. it is possible that PNH-stem cells are preferen tially destroyed by complement in the peripheral blood leaving only no rmal cells in the circulation. After G-CSF, the PNH cells in the marro w are released into the blood. Our findings suggest that it would be d ifficult to collect sufficient numbers of normal stem cells for autolo gous transplantation. (C) 1998 by The American Society of Hematology.