Long-term outcome of fludarabine-based reduced-intensity allogeneic hematopoietic cell transplantation for debilitating paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, venous thrombosis, and bone marrow failure. Seventeen patients with debilitating PNH, including 8 who were HLA-alloimmunized, underwent a reduced-intensity allogeneic hematopoietic cell transplantation (HCT). All received cyclophosphamide/fludarabine +/- antithymocyte globulin followed by a granulocyte colony-stimulating factor-mobilized HCT from an HLA-matched relative. Glycosylphosphatidylinositol-negative neutrophils were detectable after engraftment but disappeared completely at a median 100 days after transplantation. With a median follow-up of nearly 6 years, 15 patients (87.8%) survived, all without any evidence of PNH, transfusion independent, and off anticoagulation. Allogeneic reduced-intensity HCT remains a curative therapeutic option for PNH patients who are not candidates for eculizumab treatment.
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; Division of Hematology and Oncology, Department of Medicine, Georgia Regents University, Augusta, Georgia.
Jeremy
J
Pantin
Office of Biostatistics Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Xin
X
Tian
Office of Biostatistics Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Nancy
N
Geller
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Catalina
C
Ramos
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Lisa
L
Cook
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Elena
E
Cho
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; Hospital São José - Hospital Beneficência Portuguesa de São Paulo, São Paulo, Brazil.
Phillip
P
Scheinberg
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; Division of Hematology, Department of Medicine, Wexner Medical Center, Ohio State University, Columbus, Ohio.
Sumithira
S
Vasu
Department of Transfusion Medicine, Clinical Research Center, National Institutes of Health, Bethesda, Maryland.
Hahn
H
Khuu
Department of Transfusion Medicine, Clinical Research Center, National Institutes of Health, Bethesda, Maryland.
David
D
Stroncek
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
John
J
Barrett
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Neal S
NS
Young
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Theresa
T
Donohue
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: childsr@nih.gov.
Richard W
RW
Childs
D000328:Adult; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006457:Hemoglobinuria, Paroxysmal / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
D014740:Vidarabine; C024352:fludarabine
Fludarabine; Hematopoietic cell transplantation; Paroxysmal nocturnal hemoglobinuria; Reduced-intensity; Survival