Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes.
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem-cell disorder in which the affected cells are deficient in glycosylphosphatidylinositol (GPI)-anchored proteins. Paroxysmal nocturnal hemoglobinuria is frequently associated with aplastic anemia, although the basis of this relation is unknown.


OBJECTIVE
To assess the PNH status of patients with diverse marrow failure syndromes.


METHODS
Correlation of cytofluorometric data with clinical features.


METHODS
Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland.


METHODS
115 patients with aplastic anemia, 39 patients with myelodysplasia, 28 patients who had recently undergone bone marrow transplantation, 18 patients with cancer that was treated with chemotherapy, 13 patients with large granular lymphocytosis, 20 controls who had received renal allografts, and 21 healthy participants.


METHODS
Patients with aplastic anemia, myelodysplasia, or renal allografts received antithymocyte globulin.


METHODS
Flow cytometry was used to assess expression of GPI-anchored proteins on granulocytes.


RESULTS
Evidence of PNH was found in 25 of 115 (22%) patients with aplastic anemia. No patient with normal GPI-anchored protein expression at presentation developed PNH after therapy (n = 16). Nine of 39 (23%) patients with myelodysplasia had GPI-anchored protein-deficient cells. Abnormal cells were not detected in patients with constitutional or other forms of bone marrow failure or in renal allograft recipients who had received antithymocyte globulin. Aplastic anemia is known to respond to immunosuppressive therapy; in myelodysplasia, the presence of a PNH population was strongly correlated with hematologic improvement after administration of antithymocyte globulin (P = 0.0015).


CONCLUSIONS
Flow cytometric analysis is superior to the Ham test and permits concomitant diagnosis of PNH in about 20% of patients with myelodysplasia (a rate similar to that seen in patients with aplastic anemia). The presence of GPI-anchored protein-deficient cells in myelodysplasia predicts responsiveness to immunosuppressive therapy. Early emergence of GPI-anchored protein-deficient hematopoiesis in a patient with marrow failure may point to an underlying immune pathogenesis.
Dunn
D E
DE
National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892-1652, USA.
Tanawattanacharoen
P
P
Boccuni
P
P
Nagakura
S
S
Green
S W
SW
Kirby
M R
MR
Kumar
M S
MS
Rosenfeld
S
S
Young
N S
NS
D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use; D001855:Bone Marrow Diseases / Q000097:blood / Q000150:complications* / Q000276:immunology; D016009:Chi-Square Distribution; D002940:Circadian Rhythm; D005434:Flow Cytometry; D017261:Glycosylphosphatidylinositols / Q000172:deficiency; D006098:Granulocytes / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D010641:Phenotype
D000961:Antilymphocyte Serum; D017261:Glycosylphosphatidylinositols; D007166:Immunosuppressive Agents