Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome.

Abstract

CONTEXT:

In most patients, aplastic anemia results from T-cell-mediated immune destruction of bone marrow. Aplastic anemia can be effectively treated by stem cell transplantation or immunosuppression.

OBJECTIVE:

To assess long-term outcomes after immunosuppressive therapy.

DESIGN, SETTING, AND PATIENTS:

Cohort of 122 patients (31 were < or =18 years and 91 were >18 years) with severe aplastic anemia, as determined by bone marrow cellularity and blood cell count criteria, were enrolled in a single-arm interventional research protocol from 1991 to 1998 at a federal government research hospital.

INTERVENTIONS:

A dose of 40 mg/kg per day of antithymocyte globulin administered for 4 days, 10 to 12 mg/kg per day of cyclosporine for 6 months (adjusted for blood levels), and a short course of corticosteroids (1 mg/d of methylprednisolone for about 2 weeks).

MAIN OUTCOME MEASURES:

Survival, improvement of pancytopenia and transfusion-independence, relapse, and evolution to other hematologic diseases.

RESULTS:

Response rates were 60% at 3 months after initiation of treatment, 61% at 6 months, and 58% at 1 year. The blood cell counts of patients who responded no longer satisfied severity criteria and they were transfusion-independent. Overall actuarial survival at 7 years was 55%. Survival was associated with early satisfaction of response criteria (86% vs 40% at 5 years; P<.001) and by blood counts at 3 months (reticulocyte count or platelet count of >50 x 10(3)/ microL predicted survival at 5 years of 90% [64/71] vs 42% [12/34] for patients with less robust recovery [P<.001 by log-rank test]). There were no deaths among responders more than 3 years after treatment. Relapse was common, but severe pancytopenia usually did not recur. Relapse did not influence survival. Thirteen patients showed evolution to other hematologic diseases, including monosomy 7.

CONCLUSIONS:

Approximately half of patients with severe aplastic anemia treated with antithymocyte globulin and cyclosporine have durable recovery and excellent long-term survival. These outcomes were related to the quality of hematologic recovery.

• Authors: Stephen Rosenfeld, Dean Follmann, Olga Nunez, Neal S Young
• Journal: JAMA (JAMA) Vol. 289 Issue 9 Pg. 1130-5 (Mar 05 2003) ISSN: 0098-7484 [Print] United States
• PMID: 12622583 (Publication Type: Clinical Trial, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antilymphocyte Serum
• Glucocorticoids
• Immunosuppressive Agents
• Cyclosporine
• Methylprednisolone

Topics

• Adolescent
• Adult
• Anemia, Aplastic (blood, drug therapy)
• Antilymphocyte Serum (administration & dosage, therapeutic use)
• Blood Cell Count
• Child
• Child, Preschool
• Cyclosporine (administration & dosage, therapeutic use)
• Drug Therapy, Combination
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Immunosuppressive Agents (administration & dosage, therapeutic use)
• Male
• Methylprednisolone (therapeutic use)
• Recurrence
• Survival Analysis
• T-Lymphocytes (immunology)
• Treatment Outcome