A prospective multicenter study of paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure.
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal hematopoietic stem cell disorder, is characterized by chronic, uncontrolled complement activation leading to intravascular hemolysis and an inflammatory prothrombotic state. The EXPLORE study aimed to determine the prevalence of undiagnosed PNH in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), and/or other bone marrow failure (BMF) syndromes and the effect of PNH clone size on hemolysis.


METHODS
Patients, selected from medical office chart reviews, had blood samples collected for hematologic panel testing and for flow cytometry detection of PNH clones.


RESULTS
Granulocyte PNH clones ≥ 1% were detected in 199 of all 5,398 patients (3.7%), 93 of 503 AA patients (18.5%), 50 of 4,401 MDS patients (1.1%), and 3 of 130 other BMF patients (2.3%). Higher-sensitivity analyses detected PNH clones ≥ 0.01% in 167 of 1,746 patients from all groups (9.6%) and in 22 of 1,225 MDS patients (1.8%), 116 of 294 AA patients (39.5%), and four of 54 other BMF patients (7.8%). Among patients with PNH clones ≥ 1%, median clone size was smaller in patients with AA (5.1%) than in those with MDS (17.6%) or other BMF (24.4%), and the percentage of patients with lactate dehydrogenase levels (a marker for intravascular hemolysis) ≥ 1.5 × upper limit of normal was smaller in patients with AA (18.3%) than in those with MDS (42.0%).


CONCLUSIONS
These results confirm the presence of PNH clones in high-risk patient groups and suggest that screening of such patients may facilitate patient management and care.
Department of Medicine, Columbia University, New York, New York.
Azra
A
Raza
Farhad
F
Ravandi
Anjay
A
Rastogi
Jeffrey
J
Bubis
Seah H
SH
Lim
Ilene
I
Weitz
Hugo
H
Castro-Malaspina
Naomi
N
Galili
Rony Abou
RA
Jawde
Andrea
A
Illingworth
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000378:metabolism / Q000473:pathology*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002999:Clone Cells; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000473:pathology*; D006457:Hemoglobinuria, Paroxysmal / Q000378:metabolism / Q000473:pathology*; D006461:Hemolysis; D006801:Humans; D016130:Immunophenotyping; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D011446:Prospective Studies
D007770:L-Lactate Dehydrogenase
bone marrow dysfunction; clinical trial; flow cytometry; hematology; paroxysmal nocturnal hemoglobinuria