Early detection of relapse and evaluation of treatment for mixed chimerismusing fluorescence in situ hybridization following allogeneic hematopoietic cell transplant for hematological malignancies

In order to detect chimerism, fluorescence in situ hybridization (FISH) and cytogenetic analyses were performed on bone marrow cells from 47 patients with hematological malignancies following allogeneic hematopoietic cell tra nsplant (HCT). The dual-color XY, major Bcr-Abl (M-Bcr-Abl), and specific x -satellite probes were used for sex-mismatched HCT, chronic myeloid leukemi a (CML), and myelodysplastic syndrome (MDS) cases with karyotypic abnormali ties before HCT, respectively. Donor cells were found using FISH analysis i n all 32 cases examined within 2 months following HCT, confirming engraftme nt. In six cases, however, cytogenetic analysis failed to detect donor cell s due to lack of metaphases. Relapse occurred in four of the six cases in w hich mixed chimerism was detected using FISH analysis after 6 months of HCT . In contrast, after 12 months of HCT no relapse was found in 24 patients w ithout host cells. For two patients with mixed chimerism, gradual reduction of immunosuppressants or donor lymphocyte infusion resulted in the disappe arance of host cells as analyzed using FISH analysis. In three extramedulla ry relapse cases, however, cytogenetic relapse preceded morphological and F ISH relapse. These findings suggest that FISH analysis is mon useful for de tecting residual host cells after HCT, and the combination of FISH and cyto genetic analyses provide a more detailed evaluation for HCT patients. The r esults also indicate that monitoring of mixed chimerism using FISH analysis after 6 months of HCT is important far allowing the early detection of hem atological relapse.