title: Treatment of adults with severe aplastic anemia: primary therapy with antithymocyte globulin (ATG) and rescue of ATG failures with bone marrow transplantation.
abstract: OBJECTIVE
  To evaluate a policy of immunosuppression with antithymocyte globulin (ATG) as primary therapy for adults with severe aplastic anemia (SAA) regardless of the availability of an HLA-identical bone marrow donor.
  
  
  METHODS
  Thirty-one consecutive adults with SAA who satisfied the age criteria for allogeneic bone marrow transplantation (BMT) (age less than 51 years) were treated with ATG 20 mg/kg/day for 10 days along with high-dose corticosteroids. Patients with an HLA-identical donor received a transplant if they did not respond to ATG or if they developed life-threatening complications during or soon after ATG administration. Eight patients with no response to ATG were also treated with oral cyclosporine 12.5 mg/kg/day.
  
  
  RESULTS
  Eleven patients had a complete and five a partial response to ATG; two patients improved with cyclosporine treatment, resulting in an overall response rate of 58% to immunosuppression. Nine of 14 patients with donors received a BMT: seven because they did not respond to ATG and two because of serious infections. Seven grafts were obtained from related and two from unrelated donors. There was no significant difference in survival between those with and without a related HLA-identical donor (log-rank p value = 0.969). At a median follow-up of 58 months, 26 of 31 are alive with an actuarial survival of 80% at 5 years. Two patients died of infection, two died from complications of BMT, and one remains transfusion-dependent. One patient died of refractory leukemia at 30 months; one patient relapsed with hypoplasia 95 months after initial therapy with ATG. He showed a complete response to treatment with cyclosporine. No other late hematologic events have occurred.
  
  
  CONCLUSIONS
  This treatment approach resulted in the restoration of hematopoiesis and independence from transfusion in 80% of patients with SAA entered into the study. The efficacy of allogeneic BMT in salvaging cases in which ATG failed does not appear to be compromised. Follow-up for the development of clonal hematologic disorders remains an important part of this treatment policy.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Crump
authors.forename: L M
authors.initials: LM
authors.lastname: Larratt
authors.forename: E
authors.initials: E
authors.lastname: Maki
authors.forename: J E
authors.initials: JE
authors.lastname: Curtis
authors.forename: M D
authors.initials: MD
authors.lastname: Minden
authors.forename: J M
authors.initials: JM
authors.lastname: Meharchand
authors.forename: J H
authors.initials: JH
authors.lastname: Lipton
authors.forename: H A
authors.initials: HA
authors.lastname: Messner
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D000741:Anemia, Aplastic / Q000097:blood / Q000401:mortality / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000502:physiology / Q000627:therapeutic use*; D001803:Blood Transfusion / Q000592:standards; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000592:standards; D002173:Cancer Care Facilities; D002985:Clinical Protocols / Q000592:standards; D003131:Combined Modality Therapy; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006410:Hematopoiesis / Q000187:drug effects; D006454:Hemoglobins / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods / Q000592:standards*; D007958:Leukocyte Count; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D011379:Prognosis; D016879:Salvage Therapy / Q000009:adverse effects / Q000592:standards; D012720:Severity of Illness Index; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000961:Antilymphocyte Serum; D006454:Hemoglobins; D016572:Cyclosporine