title: Long-term outcome in acquired aplastic anemia treated with an intensified dose schedule of horse antilymphocyte globulin in combination with androgens.
abstract: Aplastic anemia (AA) is a rare hematopoietic stem cell disease, which can be treated with horse antilymphocyte globulin (ALG) for patients not eligible for bone marrow transplantation. ALG gives about 60% overall survival rate (OS) after 5 years, a 30% of persistent complete remission and a 20% early death rate related to failure. ALG has been incriminated in the emergence of 10 to 20% therapy-related AML/MDS (t-AML/MDS) with the usual doses. Questions remain whether higher doses of ALG could improve the response and OS rates and whether the combination with androgens is able to protect patients from t-AML/MDS. We have carried out a single institutional retrospective study of 87 AA treated with higher doses of ALG, twice the usual posology (140 mg/kg instead of 75 mg/kg), combined to androgens. The overall response rate was 77% and the OS rate at 5 years was 78%. Androgens in combination with ALG improved response and OS rates. At diagnosis, 6% of AA had an abnormal karyotype using conventional cytogenetic not related to any time-to-event. Two patients displayed a cytogenetic conversion related to the occurrence of secondary malignancies. The incidence of t-AML/MDS was 2.3% with an estimated 10-year cumulative incidence of 3.1. Our results show that higher doses of ALG combined to androgens are feasible and give results close to those recently describe with the immunosuppressive treatments including ALG associated to cyclosporine, with a low SMD/AML incidence rate.
authors.affiliation: Service des Maladies du Sang, Hôpital Huriez, CHU Lille, France. xavier_leleu@dfci.harvard.edu
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Louis
authors.initials: L
authors.lastname: Terriou
authors.forename: Alain
authors.initials: A
authors.lastname: Duhamel
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Moreau
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.forename: Sophie
authors.initials: S
authors.lastname: Dupire
authors.forename: Valérie
authors.initials: V
authors.lastname: Coiteux
authors.forename: Céline
authors.initials: C
authors.lastname: Berthon
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Micol
authors.forename: Romain
authors.initials: R
authors.lastname: Guieze
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Francis
authors.initials: F
authors.lastname: Bauters
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000728:Androgens / Q000008:administration & dosage* / Q000009:adverse effects; D000741:Anemia, Aplastic / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage* / Q000009:adverse effects; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006736:Horses; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000728:Androgens; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents