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1996-03-09
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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).