Submitted February 15, 2002
Accepted May 24, 2002
Late Complications Following Treatment for Severe Aplastic Anemia (SAA) with High-Dose Cyclophosphamide (Cy): Follow up of a Randomized Trial
John F Tisdale*, Jaroslaw P Maciejewski, Olga Nunez, Stephen J Rosenfeld, and Neal S Young
Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Bethesda, MD, USA
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Clinical Center, National Institutes of Health, Bethesda, MD, USA
* Corresponding author; email: Johntis{at}intra.niddk.nih.gov.
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 due to 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 of 13 (46%) responders in the ATG arm vs. 2 of 8 (25%) in the Cy arm (p=0.38). Five of 16 (31%) patients in the ATG arm and 4 of 15 (27%) patients in the Cy arm had evidence of PNH at diagnosis, with no significant change in the overall percentage of 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 (2/14 ATG vs. 1/12 Cy, p=0.70). High dose Cy does not prevent relapse or clonal evolution in SAA.
