Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210BCR-ABL and p190BCR-ABL after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190BCR-ABL detection precede cytogenetic relapse

摘要: We studied lineage-specific chimerism and minimal residual disease (MRD) in sequential posttransplant samples from 55 patients who underwent unmanipulated (n = 44) or partially T-cell-depleted 11) allogeneic bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Chimerism was assessed by polymerase chain reaction (VNTR [variable number of tandem repeats]-PCR) analysis highly purified CD19+, CD3+, CD15+, CD56+ cell fractions, whereas MRD investigated whole blood reverse transcriptase-PCR (RT-PCR) both p210(BCR-ABL) p190(BCR-ABL) hybrid transcripts. Of patients, 14 (including 6 patients) had cytogenetic relapse at 5-80 months progressed to hematologic relapse, while 41 remained prolonged remission 12-107 post-BMT. Before recurrence, the group showed a consistent evolution pattern sequentially featured persistent positivity, increasing mixed (MC) cells, and, finally, relapse. Myeloid MC preceded 2-12 months, p190(BCR/ABL) detected 1-6 prior 11 concomitant with 3 patients. In group, all invariably tested negative p190(BCR-ABL); 10 positive variable time-points but full donor (DC), 31 displayed DC transient due persistence recipient T cells. Two were successfully reinduced into molecular lymphocyte infusion. Sequential after such treatment inverse that observed ie, progressive disappearance transcripts, conversion type, negativity. conclude messenger RNA (mRNA) analyses contribute better characterization CML BMT enable early identification highest risk (Blood. 2000;95:2659-2665)