LONG-TERM PERSISTENCE OF HEMATOPOIETIC CHIMERISM FOLLOWING SEX-MISMATCHED BONE-MARROW TRANSPLANTATION

Fifty-eight samples of bone marrow (31), whole peripheral blood (8) an d separated fractions of circulating mononuclear (11) and polymorphonu clear (8) cells from 18 male patients, transplanted for hematological diseases from related (14) or unrelated (4) female donors were analyze d for chimerism at subsequent intervals (range, 1-72 months) following bone marrow transplantation, by means of PCR amplification of the Y-c hromosome-specific DYS14 sequence, revealed by a radiolabelled hybridi zation probe (dot blot technique, 0.01% sensitivity). Detection of mal e cells was positive in all but two of 52 samples collected within the third year after transplantation and negative in six samples collecte d from three patients after the third year. In the first year after tr ansplantation, mixed chimerism was found in all patients, apparently w ith no correlation with graft-versus-host disease. Comparable results were found in fractions of mononuclear and polymorphonuclear cells, wh en analyzed separately. The persistence of very low levels of recipien t cells in patients in continuous complete remission until the third g ear after transplantation, suggests the persistence of normal host hem opoiesis for a long period of time after the so-called myeloablative r egimen. The progressive negativization, occurring in our patients betw een the second and the fourth year after transplantation, could signif y the disappearance of residual host hemopoiesis or its decrease to be low the detection level of this highly sensitive method.