title: BEAM-alemtuzumab reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases: GVHD, toxicity, and survival in 65 patients.
abstract: We report the outcomes of reduced-intensity allogeneic stem cell transplantation using BEAM-alemtuzumab conditioning (carmustine, etoposide, cytosine arabinoside, melphalan, and alemtuzumab 10 mg/d on days -5 to -1) in 6 United Kingdom transplant centers. Sixty-five patients with lymphoproliferative diseases underwent sibling (n = 57) or matched unrelated donor (n = 8) transplantation. Sustained donor engraftment occurred in 60 (97%) of 62 patients. Of the 56 patients undergoing chimerism studies, 35 (63%) had full donor chimerism. Overall, 73% were in complete remission (CR) after transplantation. At a median follow-up of 1.4 years (range, 0.1-5.6 years), 37 remain alive and in CR. Acute graft-versus-host disease (GVHD) occurred in 11 (17%) of 64, grades I-II only. Estimated 1-year transplantation-related mortality (TRM) was 8% for patients undergoing first transplantation but was significantly worse for those who had previously undergone autologous transplantation. Six patients relapsed (estimated 2-year relapse risk, 20%). Histologic diagnosis (mantle cell lymphoma and high-grade non-Hodgkin lymphoma) and age at transplantation (> 46 years) were significantly associated with higher relapse risk and worse event-free survival. Relapse did not occur in any patient who developed acute or chronic GVHD. This study demonstrates that reduced-intensity allogeneic stem cell transplantation for lymphoproliferative diseases using a BEAM-alemtuzumab preparative regimen is associated with sustained donor engraftment, a high response rate, minimal toxicity, and a low incidence of GVHD.
authors.affiliation: Academic Haematology, Clinical Sciences Bldg, City Hospital, Nottingham, NG5 1PB United Kingdom. rowena.bainton@nottingham.ac.uk
authors.forename: Rowena D
authors.initials: RD
authors.lastname: Faulkner
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Byrne
authors.forename: Prem
authors.initials: P
authors.lastname: Mahendra
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Haynes
authors.forename: Hugh G
authors.initials: HG
authors.lastname: Prentice
authors.forename: Michael
authors.initials: M
authors.lastname: Potter
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagliuca
authors.forename: Aloysius
authors.initials: A
authors.lastname: Ho
authors.forename: Stephen
authors.initials: S
authors.lastname: Devereux
authors.forename: Grant
authors.initials: G
authors.lastname: McQuaker
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mufti
authors.forename: John Liu
authors.initials: JL
authors.lastname: Yin
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Russell
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007938:Leukemia / Q000401:mortality / Q000628:therapy; D017710:Lymphocyte Transfusion; D008223:Lymphoma / Q000401:mortality / Q000628:therapy; D008232:Lymphoproliferative Disorders / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000453:epidemiology; D011336:Probability; D012008:Recurrence; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D016019:Survival Analysis; D013997:Time Factors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab