ENGRAFTMENT FOLLOWING IN-UTERO BONE-MARROW TRANSPLANTATION FOR GLOBOID-CELL LEUKODYSTROPHY

To date, in utero bone marrow transplantation (BMT) has had limited su ccess, largely because of poor donor engraftment, The poor engraftment is probably the result of performing the procedure late in gestation after significant fetal immunocompetence has developed and/or transpla nting insufficient numbers of donor hematopoietic stem cells for compe ting successfully with ongoing fetal hematopoiesis. To overcome these problems, we performed in utero BMT on a fetus with globoid cell leuko dystrophy during the first trimester of gestation using selected pater nal bone marrow stem (CD34(+)) cells, CD34 selection allowed a substan tially greater number of stem cells to be transplanted, Although the f etus died 7 weeks after the procedure (during the 20th week of gestati on), full donor engraftment was established, Moreover, the cause of de ath appeared to be overwhelming donor engraftment and leukostasis with paternal myeloid cells infiltrating most tissues, The ability of in u tero BMT to produce this degree of engraftment provides great promise for the use of this approach in the treatment of a variety of inherite d disorders that can be diagnosed prenatally.