title: Unrelated donor bone marrow transplantation for thalassemia: the effect of extended haplotypes.
abstract: Allogeneic bone marrow transplantation (BMT) from a genotypically identical family donor is an accepted therapeutic option for homozygous beta-thalassemia. However, only a minority of patients have access to this curative procedure. The aim of this study is to explore the feasibility of matched unrelated transplants in thalassemia and the possibility of reducing the risk of immunologic complications through careful selection of donor/recipient pairs. Since November 1992, 32 patients (age range, 2-28 years) have been enrolled. There were 4 patients assigned to risk-class I, 11 to risk-class II, and 17 to risk-class III of the Pesaro classification. Extended haplotype analysis and family segregation studies were employed for identification of suitable donors. Of the 32 donor/recipient pairs, 24 were identical for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5, DQA1, and DQB1 loci; 7 pairs were identical for 2 extended haplotypes, and 15 pairs shared one extended haplotype. Grade II-IV acute graft-versus-host disease (GVHD) developed in 11 cases (41%) and chronic GVHD in 6 (25%) out of 24 patients at risk. There are 22 patients (69%) who are alive and transfusion-independent after a median follow-up of 30 months (range, 7-109 months). There were 6 patients (19%) who engrafted and subsequently died from transplant-related complications. In 4 cases (12.5%) graft rejection was observed within 30 days and it was followed by autologous reconstitution. Out of 22 patients with a donor identical for at least one extended haplotype, there are 19 who survived, 17 of them being transfusion-independent. Among the 10 recipients who did not share any extended haplotype with the donor, only 5 are alive without thalassemia and 3 patients died. Of the 6 patients who died, 5 belonged to risk-class III and only 1 to risk-class II. BMT from well-selected unrelated donors may offer results comparable to those obtained in transplantations using HLA-identical family donors, especially for patients with lesser iron overload.
authors.affiliation: Centro Trapianti Midollo Osseo, Ospedale Binaghi-Cattedra di Genetica Medica, and the Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Italy. lanasa@tiscalinet.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Nasa
authors.forename: Claudio
authors.initials: C
authors.lastname: Giardini
authors.forename: Francesca
authors.initials: F
authors.lastname: Argiolu
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Marcella
authors.initials: M
authors.lastname: Arras
authors.forename: Piero
authors.initials: P
authors.lastname: De Stefano
authors.forename: Antonio
authors.initials: A
authors.lastname: Ledda
authors.forename: Antonella
authors.initials: A
authors.lastname: Pizzati
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sanna
authors.forename: Adriana
authors.initials: A
authors.lastname: Vacca
authors.forename: Guido
authors.initials: G
authors.lastname: Lucarelli
authors.forename: Licinio
authors.initials: L
authors.lastname: Contu
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; D006239:Haplotypes / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016019:Survival Analysis; D013789:Thalassemia / Q000401:mortality / Q000628:therapy*; D014019:Tissue Donors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous / Q000276:immunology / Q000401:mortality / Q000706:statistics & numerical data; D016896:Treatment Outcome