Allogeneic CD34-enriched peripheral blood stem cell transplantation in a patient with paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of haematopoietic stem cells associated with a somatic mutation in the phosphatidylinositol glycan complementation class A (PIG-A) gene. The only curative option is an allogeneic stem cell transplant (SCT), although treatment is hazardous. A 46-year-old male patient with PNH and obvious signs of severe, progressive haemolysis was transplanted in July 2002 with highly purified CD34 T-cell depleted peripheral blood stem cells from his HLA-identical brother. Prior to transplantation, the PNH was resistant to immunosuppressive therapy. The patient received 6.1 × 106/kg bodyweight CD34-positive cells with a proportion of CD3-positive cells of 0.81 × 104/kg bodyweight. After engraftment, 12 days post transplant (neutrophils>1.0/nl) the patient's physical condition steadily improved and parameters of haemolysis decreased. No glycophosphatidylinositol-deficient cells in peripheral blood could be detected by flow cytometry 40 and 100 days after transplant. We conclude that PNH may be cured by allogeneic CD34-enriched SCT from a sibling donor attempting to avoid acute GVHD and to reduce cumulative organ toxicity by using this transplantation modality.