Peripheral Blood Harvest of Unaffected CD34+ CD38- Hematopoietic Precursors in Paroxysmal Nocturnal Hemoglobinuria

• Published in: Blood 1995-11, Vol.86 (9), p.3381-3386
• Main Authors: Prince, Gregory M., Nguyen, Mai, Lazarus, Hillard M., Brodsky, Robert A., Terstappen, Leon W.M.M., Medof, M.Edward
• Format: Article
• Language: English
• Subjects: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens, CD; Antigens, CD34 - analysis; Antigens, Differentiation - analysis; Biological and medical sciences; Biomarkers; Blood Component Removal - methods; Blood Preservation; Bone marrow, stem cells transplantation. Graft versus host reaction; CD55 Antigens - analysis; CD59 Antigens - analysis; Cryopreservation; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cells - chemistry; Hemoglobinuria, Paroxysmal - blood; Hemoglobinuria, Paroxysmal - therapy; Humans; Immunophenotyping; Medical sciences; Membrane Glycoproteins; N-Glycosyl Hydrolases - analysis; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V86.9.3381.bloodjournal8693381

Paroxysmal nocturnal hemoglobinuria (PNH) arises from somatic mutation of a bone marrow progenitor that disrupts glycosylinositol phospholipid (GPI) anchoring of cell surface proteins. We recently characterized the expression of GPI-anchored decay accelerating factor (DAF) and CD59 during hematopoietic development in PNH marrow. We found that, although 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 CD34CD38- cells. Pluripotent CD34+CD38- hematopoietic stem cells normally circulate in the peripheral blood and can be collected by apheresis, cryopreserved, and later used for reconstrtution of hematopoiesis. In this study, we examined the phenotypes of CD34+ cells that are released into the blood of PNH patients. Analyses of apheresis samples from three affected individuals showed discrete populations of circulating DAF+CD59+CD34+ and DAF-CD59-CD34+ cells. Variable proportions of CD34+CD38- cells were present within the peripheral blood CD34+ cells of each patient, but in all three cases the DAF+CD59+CD34CD38 cell subset was enriched relative to the DAF-CD59-CD34+CD38- cell subset. Because CD34+ cells lacking CD38 antigen are highly enriched for 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.