title: Late complications following treatment for severe aplastic anemia (SAA) with high-dose cyclophosphamide (Cy): follow-up of a randomized trial.
abstract: High-dose cyclophosphamide (Cy) has been promoted as curative therapy for severe aplastic anemia (SAA). However, our randomized trial comparing antithymocyte globulin (ATG) and Cy was terminated early because of excess morbidity/early mortality in the Cy arm. We now report analysis of secondary endpoints at a median of 38 months. Relapse occurred in 6 (46%) of 13 responders in the ATG arm versus 2 (25%) of 8 in the Cy arm (P =.38). Five (31%) of 16 patients in the ATG arm and 4 (27%) of 15 patients in the Cy arm had evidence of paroxysmal nocturnal hemoglobinuria (PNH) at diagnosis, with no substantial change in the overall percentage of glycophosphatidyl inositol (GPI)-anchored protein-deficient neutrophils over extended follow-up in individual patients in either arm. Bone marrow cytogenetic abnormalities have been observed among surviving patients in both arms (2 of 14 ATG versus 1 of 12 Cy, P =.70). High-dose Cy does not prevent relapse or clonal evolution in SAA.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. johntis@intra.niddk.nih.gov
authors.forename: John F
authors.initials: JF
authors.lastname: Tisdale
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
authors.forename: Olga
authors.initials: O
authors.lastname: Nuñez
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rosenfeld
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000401:mortality; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000648:ultrastructure; D002869:Chromosome Aberrations; D002999:Clone Cells / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D017261:Glycosylphosphatidylinositols / Q000097:blood; D006457:Hemoglobinuria, Paroxysmal / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D009190:Myelodysplastic Syndromes / Q000517:prevention & control; D009504:Neutrophils / Q000737:chemistry; D012008:Recurrence; D013601:T-Lymphocytes; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D017261:Glycosylphosphatidylinositols; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide