title: Allogeneic marrow grafts from donors with congenital chromosomal abnormalities in marrow cells.
abstract: To determine whether siblings with chromosomal abnormalities in marrow cells which are associated with cellular defects (e.g. Down syndrome or heterozygosity for Fanconi syndrome) are suitable donors for allogeneic bone marrow transplants, we have reviewed the patient files at the Fred Hutchinson Cancer Research Center (FHCRC) and carried out a survey among member centres of the International Bone Marrow Transplant Registry (IBMTR). The 57 of 253 (23%) member centres which responded to the survey reported seven transplants from donors with the following conditions: Down syndrome (n = 2), suspected heterozygotes for Fanconi syndrome (n = 3), and 47,XXX syndrome (n = 2), among a total of 5,561 allogeneic transplants from HLA-identical siblings. Adding the three cases seen at the Fed Hutchinson Cancer Research Center among 2,927 HLA-identical sibling transplants during 1992 resulted in 10 transplants among 8,488 cases transplanted overall: four with Down syndrome, four suspected of being heterozygous for Fanconi syndrome, and two trisomy X. Three out of four grafts from siblings with Down syndrome had complications, including poor graft function (n = 2) and graft failure (n = 1). Two of four recipients of marrow from presumed Fanconi syndrome heterozygotes presented with poor graft function and a third recipient developed graft failure after initial evidence of engraftment. The two patients given marrow from siblings with 47,XXX syndrome engrafted uneventfully. The experience reported here shows a low frequency of encountering an HLA-identical sibling donor who has chromosomal abnormalities in marrow cells consistent with Down syndrome or heterozygosity for Fanconi syndrome, about one case among 1,000 transplants. The much higher than expected incidence of graft problems with marrow from such a donor would make it reasonable to look either for an alternative marrow donor or consider an autologous transplant, in case a sibling marrow donor with Down syndrome or heterozygosity for Fanconi syndrome is encountered, although a donor with trisomy X seems acceptable.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: J
authors.initials: J
authors.lastname: Barquinero
authors.forename: R
authors.initials: R
authors.lastname: Witherspoon
authors.forename: J
authors.initials: J
authors.lastname: Sanders
authors.forename: M M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: A
authors.initials: A
authors.lastname: Montuoro
authors.forename: D F
authors.initials: DF
authors.lastname: Patton
authors.forename: A
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: M M
authors.initials: MM
authors.lastname: Abecasis
authors.forename: T
authors.initials: T
authors.lastname: Miale
authors.forename: C
authors.initials: C
authors.lastname: Rozman
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002869:Chromosome Aberrations; D000075202:Contraindications; D004314:Down Syndrome / Q000235:genetics; D005198:Fanconi Syndrome / Q000235:genetics; D005260:Female; D006084:Graft Rejection; D006801:Humans; D008297:Male; D009679:Nuclear Family; D014019:Tissue Donors; D014314:Trisomy