       Document 0514
 DOCN  M9650514
 TI    Complete remission in severe aplastic anemia after high-dose
       cyclophosphamide without bone marrow transplantation.
 DT    9605
 AU    Brodsky RA; Sensenbrenner LL; Jones RJ; Johns Hopkins Oncology Center,
       Johns Hopkins Medical; Institutions, Baltimore, MD 21287-8967, USA.
 SO    Blood. 1996 Jan 15;87(2):491-4. Unique Identifier : AIDSLINE
       MED/96141068
 AB    Severe aplastic anemia (SAA) can be successfully treated with allogeneic
       bone marrow transplantation (BMT) or immunosuppressive therapy. However,
       the majority of patients with SAA are not eligible for BMT because they
       lack an HLA-identical sibling. Conventional immunosuppressive therapy
       also has major limitations; many of its remissions are incomplete and
       relapse or secondary clonal disease is common. Cyclophosphamide is a
       potent immunosuppressive agent that is used in all BMT conditioning
       regimens for patients with SAA. Preliminary evidence suggested that
       high-dose cyclophosphamide, even without BMT, may be beneficial to
       patients with SAA. Therefore, 10 patients with SAA and lacking an
       HLA-identical sibling were treated with high-dose cyclophosphamide (45
       mg/kg/d) for 4 consecutive days with or without cyclosporine. A complete
       response (hemoglobin level, > 13 g/dL; absolute neutrophil count, > 1.5
       x 10(9)/L, and platelet count > 125 x 10(9)/L) was achieved in 7 of the
       10 patients. One of the complete responders died from the acquired
       immunodeficiency syndrome 44 months after treatment with high-dose
       cyclophosphamide. The 6 remaining patients are alive and in continuous
       complete remission, with a median follow-up of 10.8 years (range, 7.3 to
       17.8 years). The median time to last platelet transfusion and time to
       0.5 x 10(9) neutrophils/L were 85 and 95 days, respectively. None of the
       complete responders has relapsed or developed a clonal disease. These
       results suggest that high-dose cyclophosphamide, even without BMT, may
       be more effective than conventional immunosuppressive therapy in
       restoring normal hematopoiesis and preventing relapse or secondary
       clonal disorders. Hence, further studies confirming the efficacy of this
       approach in SAA are indicated.
 DE    Acquired Immunodeficiency Syndrome/COMPLICATIONS  Adolescence  Adult
       Anemia, Aplastic/COMPLICATIONS/*DRUG THERAPY  Bone Marrow/DRUG
       EFFECTS/PHYSIOLOGY  Child  Comparative Study
       Cyclophosphamide/ADMINISTRATION & DOSAGE/PHARMACOLOGY/  *THERAPEUTIC USE
       Cyclosporine/ADMINISTRATION & DOSAGE/THERAPEUTIC USE  Female  Follow-Up
       Studies  Human  Immunosuppressive Agents/ADMINISTRATION &
       DOSAGE/PHARMACOLOGY/  *THERAPEUTIC USE  Male  Regeneration  Remission
       Induction  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Treatment Outcome  CLINICAL TRIAL  JOURNAL ARTICLE  MULTICENTER STUDY
       RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

