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Durable Treatment-Free Remission after
High-Dose Cyclophosphamide Therapy for Previously Untreated Severe Aplastic

Robert A. Brodsky, MD;
Lyle L. Sensenbrenner, MD; B. Douglas Smith, MD;
Donna Dorr, RN; Phillip J. Seaman, PA-C; Shing M. Lee, ScM;
Judith E. Karp, MD; Isadore Brodsky, MD; and
Richard J. Jones, MD

Pages 477-483


Full TextPublic Access:Abstract


Background:  Severe
aplastic anemia is a life-threatening bone marrow failure disorder. High-dose
cyclophosphamide therapy followed by allogeneic bone marrow transplantation
cures the disease. However, it requires a suitable donor and carries the risk
for graft-versus-host disease. A small pilot study demonstrated that high-dose
cyclophosphamide therapy without bone marrow transplantation leads to durable,
treatment-free complete remission.

Objective:  To confirm the
safety and efficacy of high-dose cyclophosphamide therapy alone in patients with
severe aplastic anemia.

Design:  Uncontrolled
clinical trial.

Setting:  Three tertiary
care hospitals.

Patients:  19 patients with
untreated severe aplastic anemia.

Intervention:  Cyclophosphamide,
50 mg/kg of body weight per day for 4 consecutive days.

Measurements:  Probability
of response and overall survival were measured. Complete remission was defined
as normal blood count for age and sex. Partial remission was defined as
independence from transfusion and an absolute neutrophil count greater than 0.5
× 109 cells/L without growth factor support. Nonresponders were
patients who remained transfusion dependent or died. Relapse was defined as no
longer meeting criteria for partial or complete remission.

Results:  The median time
to an absolute neutrophil count of 0.5 × 109 cells/L was 49 days.
The probability of survival was 84% (95% CI, 59% to 95%) at 24 months. The
probability of achieving treatment-free remission was 73% (CI, 51% to 91%) at 24
months, and the probability of achieving complete remission was 65% (CI, 39% to
89%) at 50 months. No responding patients have had relapse or have developed
secondary clonal disorders.

Conclusions:  High-dose
cyclophosphamide therapy without bone marrow transplantation produces durable
treatment-free remission in severe aplastic anemia. This approach deserves
further study in patients with severe aplastic anemia who are not suitable
candidates for allogeneic bone marrow transplantation.

Ann Intern Med. 2001;135:477-483.




Author and Article

From the Johns Hopkins Oncology Center and the Greenbaum Cancer Center,
University of Maryland, Baltimore, Maryland; and MCP Hahnemann University,
Philadelphia, Pennsylvania.

Acknowledgment: The authors thank the physicians, nurses, and support
staff of the Johns Hopkins University Bone Marrow Transplant Team, MCP Hahnemann
University, and the Greenbaum Cancer Center for their excellent patient care.

Grant Support: In part by grant CA70970 from the National Institutes
of Health. Dr. R. Brodsky is a Leukemia and Lymphoma Society Clinical Research
Scholar and The Thomas E. Sandefur Jr. Fellow in Stem Cell Research.

Request for Single Reprints: Robert A. Brodsky, MD, Johns Hopkins
Oncology Center, Bunting-Blaustein Cancer Research Building, Room 242, 1650
Orleans Street, Baltimore, MD 21231; e-mail,

Current Author Addresses: Dr. R. Brodsky, Dr. Smith, Ms. Dorr, Mr.
Seaman, and Dr. Jones: Johns Hopkins Oncology Center, Bunting-Blaustein Cancer
Research Building, Room 242, 1650 Orleans Street, Baltimore MD 21231.

Dr. Sensenbrenner: 1613 Camden Avenue, Salisbury, MD 21801-7010.

Ms. Lee: Johns Hopkins Oncology Center, Oncology Biostatistics, 550 North
Broadway, Suite 1103, Baltimore, MD 21205.

Dr. I. Brodsky: MCP Hahnemann University, Broad and Vine Streets, Mailstop
412, Philadelphia, PA 19102.

Dr. Karp: Greenbaum Cancer Center, University of Maryland School of Medicine,
22 South Greene Street, Room S9D15, Baltimore, MD 21201-1544.

Author Contributions: Conception and design: R.A. Brodsky, L.L.
Sensenbrenner, R.J. Jones.

Analysis and interpretation of the data: R.A. Brodsky, B.D. Smith, J.E. Karp,
I. Brodsky, R.J. Jones.

Drafting of the article: R.A. Brodsky.

Critical revision of the article for important intellectual content: L.L.
Sensenbrenner, B.D. Smith, R.J. Jones.

Final approval of the article: R.A. Brodsky, R.J. Jones.

Provision of study materials or patients: R.A. Brodsky, J.E. Karp, I. Brodsky.

Statistical expertise: S.M. Lee.

Obtaining of funding: R.A. Brodsky, R.J. Jones.

Administrative, technical, or logistic support: B.D. Smith, D. Dorr, P.J.

Collection and assembly of data: R.A. Brodsky, B.D. Smith, D. Dorr, P.J.

Keywords: Anemia, aplastic; Cyclophosphamide; Dose-response
relationship, drug; Bone marrow transplantation; Graft vs host disease


©2001 American College of Physicians – American Society of Internal Medicine




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