Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan.
: To determine and directly compare the clinical course of white and Asian patients with paroxysmal nocturnal hemoglobinuria (PNH), data were collected for epidemiologic analysis on 176 patients from Duke University and 209 patients from Japan. White patients were younger with significantly more classical symptoms of PNH including thrombosis, hemoglobinuria, and infection, while Asian patients were older with more marrow aplasia. The mean fraction of CD59-negative polymorphonuclear cells (PMN) at initial analysis was higher among Duke patients than Japanese patients. In both cohorts, however, a larger PNH clone was associated with classical PNH symptoms, while a smaller PNH clone was associated with marrow aplasia. Thrombosis was significantly more prevalent in white patients than Asian patients, and was associated with a significantly higher proportion of CD59-negative PMN. For individual patients, CD59-negative populations varied considerably over time, but a decreasing PNH clone portended hematopoietic failure. Survival analysis revealed a similar death rate in each group, although causes of death were different and significantly more Duke patients died from thrombosis. Japanese patients had a longer mean survival time (32.1 yr vs. 19.4 yr), although Kaplan-Meier survival curves were not significantly different. Poor survival in both groups was associated with age over 50 years, severe leukopenia/neutropenia at diagnosis, and severe infection as a complication; additionally, thrombosis at diagnosis or follow-up for Duke patients and renal failure for Japanese patients were poor prognostic factors. These data identify important differences between white and Asian patients with PNH. Identification of prognostic factors will help the design of prospective clinical trials for PNH.
Nishimura
Jun-Ichi
JI
From the PNH Research Committee (JN, REW, CMD, SH, KMS, WFR), Duke University Medical Center, Durham, North Carolina, United States; the Research Committee for the Idiopathic Hematopoietic Disorders, Ministry of Health, Labour and Welfare, Government of Japan (JN, YK, AK, HM, MO, TK); the Department of Hematology, Tokyo Women's Medical College (HM), Tokyo; the Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University (JN, TK); the Department of Hematology and Oncology, Osaka University Graduate School of Medicine (JN, YK); the Third Department of Internal Medicine, Kinki University Medical School (AK), Osaka; the Division of Hematology, Department of Medicine, Showa University Fujigaoka Hospital (MO), Kanagawa; the First Department of Internal Medicine, Fukushima Medical University (TS), Fukushima; the Department of Hematology/Oncology, Wakayama Medical University (HNakakuma), Wakayama; the Division of Hematology, College of Medical Technology, University of Tsukuba (HNinomiya), Ibaraki, Japan.
Kanakura
Yuzuru
Y
Ware
Russell E
RE
Shichishima
Tsutomu
T
Nakakuma
Hideki
H
Ninomiya
Haruhiko
H
Decastro
Carlos M
CM
Hall
Sharon
S
Kanamaru
Akihisa
A
Sullivan
Keith M
KM
Mizoguchi
Hideaki
H
Omine
Mitsuhiro
M
Kinoshita
Taroh
T
Rosse
Wendell F
WF
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D018958:CD55 Antigens / Q000097:blood; D018957:CD59 Antigens / Q000097:blood; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006403:Hematologic Tests; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
D018958:CD55 Antigens; D018957:CD59 Antigens