Late complications following treatment for severe aplastic anemia (SAA) with high-dose cyclophosphamide (Cy): follow-up of a randomized trial

• Published in: Blood Vol. 100; no. 13; pp. 4668 - 4670
• Main Authors: Tisdale, John F., Maciejewski, Jaroslaw P., Nuñez, Olga, Rosenfeld, Stephen J., Young, Neal S.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-12-2002; The Americain Society of Hematology
• Subjects: Anemia, Aplastic - drug therapy; Anemia, Aplastic - mortality; Antilymphocyte Serum - therapeutic use; Antineoplastic agents; Biological and medical sciences; Bone Marrow Cells - ultrastructure; Chemotherapy; Chromosome Aberrations; Clone Cells - pathology; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Disease Progression; Disease-Free Survival; Follow-Up Studies; Glycosylphosphatidylinositols - blood; Hematologic and hematopoietic diseases; Hemoglobinuria, Paroxysmal - epidemiology; Hemoglobinuria, Paroxysmal - etiology; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Myelodysplastic Syndromes - prevention & control; Neutrophils - chemistry; Pharmacology. Drug treatments; Recurrence; T-Lymphocytes; Treatment Outcome; Antineoplastic agent; Late; Indication; Treatment efficiency; Aplastic anemia; Hemopathy; Long term; Alkylating agent; Chemotherapy; Cyclophosphamide; Oxazaphosphinane derivatives; Treatment; Bone marrow failure; Nitrogen mustard; Complication; Clinical trial; Severe; High dose
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-02-0494

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.