title: Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anemia.
abstract: We evaluated a novel alemtuzumab-based conditioning regimen in HSCT for acquired severe aplastic anemia (SAA). In a multicenter retrospective study, 50 patients received transplants from matched sibling donors (MSD; n = 21) and unrelated donors (UD; n = 29), using fludarabine 30 mg/m² for 4 days, cyclophosphamide 300 mg/m² for 4 days, and alemtuzumab median total dose of 60 mg (range:40-100 mg). Median age was 35 years (range 8-62). Overall survival at 2 years was 95% ± 5% for MSD and 83% for UD HSCT (p 0.34). Cumulative incidence of graft failure was 9.5% for MSD and 14.5% for UD HSCT. Full-donor chimerism (FDC) in unfractionated peripheral blood was 42%; no patient achieved CD3 FDC. Acute GVHD was observed in only 13.5% patients (all grade I-II) and only 2 patients (4%) developed chronic GVHD. A low incidence of viral infections was seen. Factors influencing overall survival were HSCT comorbidity 2-year index (92% with score 0-1 vs 42% with score ≥ 2, P < .001) and age (92% for age < 50 years vs 71% ≥ 50 years, P < .001). Our data suggest that the use of an alemtuzumab-based HSCT regimen for SAA results in durable engraftment with a low incidence of chronic GVHD.
authors.affiliation: Department of Hematological Medicine, King's College Hospital/King's College London, London, UK. judith.marsh@nhs.net
authors.forename: Judith C
authors.initials: JC
authors.lastname: Marsh
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Lim
authors.forename: Aloysius Y
authors.initials: AY
authors.lastname: Ho
authors.forename: Robin M
authors.initials: RM
authors.lastname: Ireland
authors.forename: Janet
authors.initials: J
authors.lastname: Hayden
authors.forename: Victoria
authors.initials: V
authors.lastname: Potter
authors.forename: Mickey B
authors.initials: MB
authors.lastname: Koh
authors.forename: M Serajul
authors.initials: MS
authors.lastname: Islam
authors.forename: Nigel
authors.initials: N
authors.lastname: Russell
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagliuca
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D002648:Child; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine