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

JAMA. 2003 Mar 5;289(9):1130-5. doi: 10.1001/jama.289.9.1130.

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.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

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