Aplastic Anemia Medication

  • Author: Sameer Bakhshi, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Nov 1, 2011
 

Medication Summary

The goals of pharmacotherapy in cases of aplastic anemia are to reduce morbidity, prevent complications, and eradicate malignancy.

As previously stated, options in immunosuppressive treatment include combination therapy, including ATG, CSA, and methylprednisolone, with or without cytokine support. ATG and CSA alone may also produce a response in aplastic anemia, but the combination improves the likelihood of a response.

Cytokine support with G-CSF and GM-CSF may be considered in refractory infections, although this therapy should be weighed against cost and efficacy.[2, 29, 30, 31]

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Immunosuppressive Agents

Class Summary

The merits of additional immunosuppression versus the increased risk and cost should be considered. Data from a randomized, prospective study indicated that an increased proportion of patients responded to the addition of CSA to ATG but that this did not translate into a long-term survival advantage.

For patients who cannot tolerate equine-based products, use of the commercially available, rabbit-based ATG product (Thymoglobulin) may be considered. This product is currently approved in the United States and has been used for the treatment of aplastic anemia in Europe (although note the different dose schedule).

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Cyclosporine (Sandimmune, Neoral)

 

This is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, graft versus host disease) for a variety of organs.

For children and adults, base the dosing on the ideal body weight. Frequent monitoring of drug levels is needed. To convert to the oral dose, use an intravenous (IV)-to-oral correction factor of 1:4. The dosage and duration of therapy may vary with different protocols.

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Methylprednisolone (Medrol, Solu-Medrol)

 

Steroids ameliorate the delayed effects of anaphylactoid reactions and may limit biphasic anaphylaxis. In severe serum sickness (mediated by immune complexes), parenteral steroids may reduce the inflammatory effects. Hence, methylprednisolone is used with ATG to decrease the adverse effects (eg, allergic reactions, serum sickness). Also an additional immunosuppressive. High doses or long duration may be needed if serum sickness occurs with ATG. The doses and duration may vary with different protocols.

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Lymphocyte immune globulin, equine (Atgam)

 

This agent inhibits the cell-mediated immune response by altering T-cell function or by eliminating antigen-reactive cells.

There is little prospective, randomized data to suggest a single schedule that is superior, but experience suggests that a short infusion is best tolerated.

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Cyclophosphamide (Cytoxan)

 

Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of deoxyribonucleic acid (DNA), which may interfere with the growth of normal and neoplastic cells. Monitor carefully; used only on an investigational basis.

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Antithymocyte globulin, rabbit (Thymoglobulin)

 

This agent may modify T-cell function and possibly eliminate antigen-reactive T lymphocytes in peripheral blood. The dose and duration of therapy vary with the investigational protocols.

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Cytokines

Class Summary

Several preliminary studies have demonstrated that the addition of cytokines (eg, G-CSF, GM-CSF) may hasten the neutrophil recovery and that these agents may improve response rate and survival, although long-term use may increase the risk of clonal evolution.

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Sargramostim (Leukine)

 

A recombinant human GM-CSF, sargramostim can activate mature granulocytes and macrophages. The dose and frequency of administration vary with the investigational protocol.

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Filgrastim (Neupogen)

 

This is a G-CSF that activates and stimulates the production, maturation, migration, and cytotoxicity of neutrophils.

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Antineoplastic Agent, Antimetabolite (purine)

Class Summary

Antimetabolites are antineoplastic agent that inhibit cell growth and proliferation.

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Fludarabine (Fludara)

 

This agent contains fludarabine phosphate, a fluorinated nucleotide analogue of the antiviral agent vidarabine, 9-b-D-arabinofuranosyladenine (ara-A) that enters the cell and is phosphorylated to form the active metabolite 2-fluoro-ara-ATP, which inhibits DNA synthesis. Fludarabine inhibits DNA polymerase, DNA primase, DNA ligase, and ribonucleotide reductase. This inhibits ribonucleic acid (RNA) function, RNA processing, and mRNA translation. Fludarabine also activates apoptosis.

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Contributor Information and Disclosures
Author

Sameer Bakhshi, MD  Additional Professor of Pediatric Oncology, Department of Medical Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, India

Disclosure: Nothing to disclose.

Specialty Editor Board

David Aboulafia, MD  Medical Director, Bailey-Boushay House, Clinical Professor, Department of Medicine, Division of Hematology, Attending Physician, Section of Hematology/Oncology, Virginia Mason Clinic; Investigator, Virginia Mason Community Clinic Oncology Program/SWOG

David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Directors Association, American Society of Hematology, Infectious Diseases Society of America, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors RoyBaynes, MB, BCh, PhD, FACP, andEsteban Abella, MD,to the development and writing of the source article.

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