ALLOGENEIC MARROW GRAFTS FROM DONORS WITH CONGENITAL CHROMOSOMAL-ABNORMALITIES IN MARROW-CELLS

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 alloge neic bone marrow transplants, we have reviewed the patient files at th e Fred Hutchinson Cancer Research Center (FHCRC) and carried out a sur vey among member centres of the International Bone Marrow Transplant R egistry (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 s yndrome (n=3), and 47,XXX syndrome (n=2), among a total of 5561 alloge neic transplants from HLA-identical siblings. Adding the three cases s een at the Fed Hutchinson Cancer Research Center among 2927 HLA-identi cal sibling transplants during 1992 resulted in 10 transplants among 8 488 cases transplanted overall: four with Down syndrome, four suspecte d 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 gr aft failure after initial evidence of engraftment. The two patients gi ven 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 marro w cells consistent with Down syndrome or heterozygosity for Fanconi sy ndrome, about one case among 1000 transplants. The much higher than ex pected 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.