title: Alemtuzumab markedly reduces chronic GVHD without affecting overall survival in reduced-intensity conditioning sibling allo-SCT for adults with AML.
abstract: By retrospective analysis of 88 patients from the British Society of Blood and Marrow Transplantation registry, we investigated the effect of in vivo T-cell depletion in HLA-identical sibling reduced-intensity conditioning (RIC) allografts for adult AML by comparing patients who received alemtuzumab with those without alemtuzumab conditioning. Both groups were equivalent for age, sex, karyotype and disease status at transplant. With a median follow-up of 27 months (3-72 months) and 48 months (7-72 months), the 2- and 5-year overall survival, with or without alemtuzumab, is 60 and 60% (P=0.80) and 61 and 53%, respectively (P=0.85). The 2-year non-relapse mortality is 12% with alemtuzumab, and 17% without alemtuzumab (P=0.49). The 2-year relapse rate is 35% with alemtuzumab compared with 19% without alemtuzumab (P=0.28). Grades II-IV acute GVHD occurred in 22% (8/37) without alemtuzumab compared with 14% (7/51) given alemtuzumab (P=0.25). Extensive chronic GVHD occurred in 47% (14/30) not given alemtuzumab compared with 4% (2/45) who were given alemtuzumab (P=0.001). Among evaluable patients, the risk of infections was higher in those treated with alemtuzumab compared with those not treated with alemtuzumab (79 vs 57%, respectively, P=0.02). In conclusion, alemtuzumab has a beneficial effect by reducing chronic GVHD without affecting overall survival. Further studies are warranted before alemtuzumab can be recommended as standard in RIC allografts for AML.
authors.affiliation: Department of Haematology, John Radcliffe Hospital, Oxford, UK. ram.malladi@ndcls.ox.ac.uk
authors.forename: R K
authors.initials: RK
authors.lastname: Malladi
authors.forename: A J
authors.initials: AJ
authors.lastname: Peniket
authors.forename: T J
authors.initials: TJ
authors.lastname: Littlewood
authors.forename: K E
authors.initials: KE
authors.lastname: Towlson
authors.forename: R
authors.initials: R
authors.lastname: Pearce
authors.forename: J
authors.initials: J
authors.lastname: Yin
authors.forename: J D
authors.initials: JD
authors.lastname: Cavenagh
authors.forename: C
authors.initials: C
authors.lastname: Craddock
authors.forename: K H
authors.initials: KH
authors.lastname: Orchard
authors.forename: E
authors.initials: E
authors.lastname: Olavarria
authors.forename: G
authors.initials: G
authors.lastname: McQuaker
authors.forename: M
authors.initials: M
authors.lastname: Collin
authors.forename: D I
authors.initials: DI
authors.lastname: Marks
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002908:Chronic Disease; D004341:Drug Evaluation; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008212:Lymphocyte Depletion / Q000379:methods; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D035781:Siblings; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab