To explore the association between chimerism, minimal residual disease (MRD) and relapse after sex-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemia.
Fifty-seven patients with leukemia received allogeneic hematopoietic stem cell grafts from HLA-matched or partially matched, but sex-mismatched donors. Chimeric status and MRD were detected by dual-color interphase fluorescence in situ hybridization (I-FISH) using X/Y sex chromosome centromere DNA probe and bcr/abl dual fusion DNA probe, respectively, at different time points after transplantation. SPSS software was used to analyse the correlation between chimeric status, MRD and relapse.
In comparison with karyotype analysis, I-FISH was of higher sensitivity in detecting sex chromosome and bcr/abl fusion gene. Chimeric status was negatively correlated with MRD (r=-0.9690, P<0.01). In the early times of transplantation (within 3 months), mixed chimerism had higher relapse rate than did complete chimerism. Chimeric status and MRD were correlated with leukemic relapse (r=-8240, P<0.01; r=-0.9040, P<0.01). The decrease in chimeric status occurred before leukemic relapse in hematology.
I-FISH is a more specific and sensitive test for monitoring MRD after transplantation. The clinical value of sex chromosome is identical to that of the special tumor gene for monitoring MRD after transplantation. Chimeric status is negatively correlated with MRD. Chimeric status and MRD are associated with leukemic relapse. The decrease in chimeric status is considered a mark of leukemic relapse after transplantation.
[Show abstract][Hide abstract] ABSTRACT: Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for follow-up of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units.
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