title: Delayed attainment of full donor chimaerism following alemtuzumab-based reduced-intensity conditioning haematopoeitic stem cell transplantation for acute myeloid leukaemia and myelodysplastic syndromes is associated with improved outcomes.
abstract: This prospective study evaluated the kinetics of lymphoid (CD3) engraftment in 110 patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) after allogeneic transplantation and conditioning with fludarabine, busulphan and alemtuzumab, using ciclosporin for post-transplant immunosuppression. Declining donor CD3 chimaerism beyond day+100 was treated with pre-emptive donor lymphocyte infusion (pDLI). The median age of patients was 53.0 years (range: 19-72 years), and the median follow-up was 690 d (range:168-1470 d). Patients achieving full CD3 donor chimaerism (FDC, n = 46) by day+100 had a significantly inferior disease-free survival (DFS) and overall survival (OS) compared to patients with mixed donor chimaerism (MDC, n = 59). Twenty patients had stable MDC and did not require pDLI. Patients attaining early FDC had a higher transplant-related mortality compared to those who maintained stable levels of MDC (P = 0.02), with no difference between the FDC and pDLI groups (P = 0.07). There was no difference in relapse between all three groups (P = 0.21). On multivariate analysis, only CD3 chimaerism status at day+100 and disease status at transplantation had a significant effect on DFS and OS. In patients with AML/MDS undergoing alemetuzumab based-RIC HSCT, prolonged MDC beyond day+100 is associated with an improved OS. Future studies need to be directed towards establishing the underlying factors that dictate T-cell engraftment, expansion and homing post-transplantation.
authors.affiliation: Department of Haematological Medicine, Kings College London and Kings College Hospital, Denmark Hill, London, UK.
authors.forename: Zi Yi
authors.initials: ZY
authors.lastname: Lim
authors.forename: Laurence
authors.initials: L
authors.lastname: Pearce
authors.forename: Aloysius Y
authors.initials: AY
authors.lastname: Ho
authors.forename: Linda
authors.initials: L
authors.lastname: Barber
authors.forename: Wendy
authors.initials: W
authors.lastname: Ingram
authors.forename: Monica
authors.initials: M
authors.lastname: Usai
authors.forename: Khalid
authors.initials: K
authors.lastname: Tobal
authors.forename: Stephen
authors.initials: S
authors.lastname: Devereux
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagliuca
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
mesh_terms: 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*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D011446:Prospective Studies; D013997:Time Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab