title: Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen.
abstract: A nonmyeloablative conditioning regimen was investigated in 47 patients with hematological malignancy receiving allogeneic progenitor cells from matched, unrelated donors. The median patient age was 44 years. The majority of patients had high-risk features, including having failed a prior transplantation (29 individuals). Twenty of the transplants were mismatched for HLA class I and/or class II alleles. Recipient conditioning consisted of 20 mg CAMPATH-1H on days -8 to -4, 30 mg/m(2) fludarabine on days -7 to -3, and 140 mg/m(2) melphalan on day -2. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine A alone. Primary graft failure occurred in only 2 of 44 evaluable patients (4.5%). Chimerism studies in 34 patients indicated that the majority (85.3%) attained initial full donor chimerism. Only 3 patients developed grade III to IV acute GVHD, and no patients have yet developed chronic extensive GVHD. The estimated probability of nonrelapse mortality at day 100 was 14.9% (95% confidence interval [CI], 4.7%-25.1%). With a median follow-up of 344 days (range, 79-830), overall and progression-free survivals at 1 year were 75.5% (95% CI, 62.8%-88.2%) and 61.5% (95% CI, 46.1%-76.8%), respectively. In summary, a nonmyeloablative regimen incorporating in vivo CAMPATH-1H is effective in promoting durable engraftment in most patients and in reducing the risk of severe GVHD following matched unrelated donor transplantation.
authors.affiliation: Department of Haematology, University College Hospital, 98 Chenies Mews, London WC1E 6HX, United Kingdom.
authors.forename: Ronjon
authors.initials: R
authors.lastname: Chakraverty
authors.forename: Karl
authors.initials: K
authors.lastname: Peggs
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chopra
authors.forename: Donald W
authors.initials: DW
authors.lastname: Milligan
authors.forename: Panagiotis D
authors.initials: PD
authors.lastname: Kottaridis
authors.forename: Stephanie
authors.initials: S
authors.lastname: Verfuerth
authors.forename: Johanne
authors.initials: J
authors.lastname: Geary
authors.forename: Dharsha
authors.initials: D
authors.lastname: Thuraisundaram
authors.forename: Kate
authors.initials: K
authors.lastname: Branson
authors.forename: Suparno
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Premini
authors.initials: P
authors.lastname: Mahendra
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.forename: Anne
authors.initials: A
authors.lastname: Parker
authors.forename: Ann
authors.initials: A
authors.lastname: Hunter
authors.forename: Geoff
authors.initials: G
authors.lastname: Hale
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Williams
authors.forename: Kwee
authors.initials: K
authors.lastname: Yong
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: Stephen
authors.initials: S
authors.lastname: Mackinnon
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality*; D006801:Humans; D007239:Infections / Q000209:etiology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D016019:Survival Analysis; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan