title: Unrelated donor bone marrow transplantation in Fanconi anaemia: the Leiden experience.
abstract: Fanconi anaemia (FA) is an accepted indication for treatment with allogeneic HLA-identical BMT. Most patients, however, lack a suitable HLA-identical donor. In our centre, six FA patients were transplanted with a matched unrelated donor. Due to hypersensitivity to DNA cross-linking agents, a low-dose cyclophosphamide (CY) and thoraco-abdominal irradiation (TAI) regimen is recommended for conditioning in FA. We added Ara-C upfront and anti-T cell antibodies to enhance engraftment and to prevent GVHD, in combination with T cell depletion in four out of six of the first transplants. One patient did not engraft. In three patients rejection was observed. In three of these four patients a second BMT, using full bone marrow grafts, resulted in successful engraftment. The other patient died before a second BMT could be performed. The incidence and severity of acute GVHD was low: only one patient with grade III acute GVHD was seen. Two out of four surviving patients suffered from chronic GVHD. Four patients survived (median survival time 43 months after BMT), three with good and one with acceptable quality of life. Two patients died, one patient due to adenoviral reactivation with multi-organ failure, and one due to sepsis complicated by ARDS. In conclusion, MUD BMT is feasible in FA patients with bone marrow failure in whom no HLA-identical sibling donor is available. In our study group, the major problem was graft rejection, despite the administration of a combination of graft enhancing anti-T cell antibodies. Multicentre studies are needed to determine a more intensive, but still tolerable, conditioning regimen.
authors.affiliation: Department of Paediatrics, Subdivision of Bone Marrow Transplantation, Leiden University Hospital, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Zwaan
authors.forename: M H
authors.initials: MH
authors.lastname: Van Weel-Sipman
authors.forename: W E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: M
authors.initials: M
authors.lastname: Oudshoorn
authors.forename: J M
authors.initials: JM
authors.lastname: Vossen
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D005199:Fanconi Anemia / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D017619:Hemibody Irradiation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning
chemical_list: D007166:Immunosuppressive Agents; D003561:Cytarabine; D003520:Cyclophosphamide