title: Reduced incidence of acute and chronic graft-versus-host disease with the addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen.
abstract: To reduce the incidence of graft-versus-host disease (GVHD), we added Thymoglobulin (THY) to dose-adjusted oral busulfan plus cyclophosphamide (targeted BUCY). The starting dose of THY was 4.5 mg/kg given over days -3, -2, and -1, escalated in steps of 1.5 mg/kg in cohorts of 15 evaluable patients. Escalation was dependent on acute GVHD incidence and Epstein-Barr virus reactivation. Fifty-six patients with myelodysplastic syndrome and other myeloid disorders underwent transplantation with peripheral blood progenitor cells from related (n=30) or unrelated (n=26) donors. All but 2 patients achieved engraftment, and 56% survived in remission beyond 1 year. The incidence of acute GVHD was 50%, and that of chronic GVHD was 34%. The highest THY dose was 6.0 mg/kg, a dose at which 1 patient experienced Epstein-Barr virus reactivation. Nine patients did not receive the prescribed THY dose. Results were comparable for related and unrelated transplants and for patients given 4.5 or 6.0 mg/kg THY. Among 27 myelodysplastic syndrome patients (14 with related and 13 with unrelated donors) who underwent transplantation concurrently with targeted BUCY without THY, the incidence of acute and chronic GVHD was 82%. Thus, THY 4.5 to 6.0 mg/kg seemed beneficial for GVHD prevention in BUCY-conditioned patients who underwent transplantation with peripheral blood progenitor cells, although relapse-free survival did not differ significantly from that in comparable historical controls not given THY.
authors.affiliation: Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle, Washington 98109-1024, USA. jdeeg@fhcrc.org
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Jeannine S
authors.initials: JS
authors.lastname: McCune
authors.forename: David
authors.initials: D
authors.lastname: Myerson
authors.forename: Shelly
authors.initials: S
authors.lastname: Heimfeld
authors.forename: Mary E
authors.initials: ME
authors.lastname: Flowers
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Kristine C
authors.initials: KC
authors.lastname: Doney
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Donnell
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Bart L
authors.initials: BL
authors.lastname: Scott
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.forename: E Houston
authors.initials: EH
authors.lastname: Warren
authors.forename: Robert P
authors.initials: RP
authors.lastname: Witherspoon
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000627:therapeutic use*; D002423:Cause of Death; D002648:Child; D002908:Chronic Disease; D015331:Cohort Studies; D015897:Comorbidity; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000517:prevention & control*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D015994:Incidence; D007951:Leukemia, Myeloid / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000601:surgery; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous / Q000009:adverse effects; D016896:Treatment Outcome; D014775:Virus Activation
chemical_list: D000961:Antilymphocyte Serum; D003520:Cyclophosphamide; D002066:Busulfan