title: Current status of unrelated-donor bone marrow transplantation. The International Marrow Unrelated Search and Transplant (IMUST) Study.
abstract: 1. The International Marrow Unrelated Search and Transplant (IMUST) Study 1 provides novel prognostic data on outcome of unrelated-donor (UD) searches for patients with well-defined clinical characteristics. Case-types analyzed by multifactorial methods reveal the importance of HLA phenotype, ethnic mismatching, and stage of disease at search request, in predicting search outcome. White patients, with common HLA types and early disease, were least likely to suffer search failure. In contrast, searches for non-White patients with unusual HLA phenotypes and advanced disease were most likely to fail. Of importance, 70% of patients had HLA phenotypes defined as uncommon. 2. Overall donor yield at the 2 UK registries between 1989 and 1991 was 7%, significantly below expectations. Reasons for this shortfall are that theoretical predictions did not consider ethnic mismatch and logistical delays incurred by outdated UD search routines and most importantly HLA-typing inaccuracies. 3. IMUST Study 2 is a prospective multicenter-controlled cohort study comparing HLA-identical sibling donor (ID) and UD-bone marrow transplantation (BMT) for factors affecting BMT outcome. Generous support was provided by 83 BMT centers worldwide. An interim analysis of 165 UD- and 368 ID-BMT, with at least 6 months follow-up after BMT, is described. Unifactorial analysis showed a probability of engraftment at day 100 of 89% after UD- compared with 98% after ID-BMT (p < 0.001). Probability of Grades II-IV acute graft-versus-host disease (AGvHD) at 100 days was 52% after UD- compared with 42% after ID-BMT (p < 0.01). Probability of overall survival at day 400 was 42% after UD- compared with 63% after ID-BMT (p < 0.001). Survival on day 400 of those patients receiving UD-BMT for early disease was encouraging at 52%. 4. Multifactorial analysis was performed on combined data from UD- and ID-BMT cohorts to identify various factors predicting engraftment, AGvHD, and overall survival. Survival after UD-BMT was increased by center experience of UD-BMT and the use of additional pretransplant immunosuppression. Survival was decreased in UD- compared with ID-BMT, by female donor to male recipient and poor-risk disease. Engraftment was improved in ID- compared with UD-BMT, and after UD-BMT at centers experienced in UD-BMT. Engraftment worsened with the use of ex-vivo T-cell depletion for GvHD prophylaxis, in chronic myeloid leukemia, and in male recipients of female marrow.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: University of Bristol, Department of Transplantation Sciences, Medical School Unit, Southmead Centre for Medical Education, UK.
authors.forename: B A
authors.initials: BA
authors.lastname: Bradley
authors.forename: J M
authors.initials: JM
authors.lastname: Hows
authors.forename: S M
authors.initials: SM
authors.lastname: Gore
authors.forename: J L
authors.initials: JL
authors.lastname: Bidwell
authors.forename: T
authors.initials: T
authors.lastname: Clay
authors.forename: T R
authors.initials: TR
authors.lastname: Downie
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
authors.forename: M R
authors.initials: MR
authors.lastname: Howard
authors.forename: G J
authors.initials: GJ
authors.lastname: Laundy
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000401:mortality / Q000706:statistics & numerical data*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D006680:HLA Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007390:International Agencies; D008297:Male; D008875:Middle Aged; D012042:Registries; D015996:Survival Rate; D014019:Tissue Donors; D009927:Tissue and Organ Procurement / Q000706:statistics & numerical data*
chemical_list: D006680:HLA Antigens