Comparison of Conventional Versus Lineage-Specific Chimerism Analysis for Detection of Minimal Residual Disease or Relapse in Myeloid Malignancies after Myeloablative Allogeneic Hematopoietic Cell Transplantation with Respect to Clinical Follow-Up.

In order to detect minimal residual disease (MRD) or relapse after allogeneic hematopoietic cell transplantation (aHCT) the immunophenotype of the original leukemic clone can be used for separation of distinct cell populations, expected to harbor malignant cells.

Since conventional (CCA) and lineage-specific (LCA) chimerism analysis as diagnostic means have potential pitfalls, the present study assesses the results of both methods, to determine how predictive the evaluations prior to a hematological relapse were with respect to the risk that the patient would develop a relapse during the course of his disease.

118 individuals with acute myeloid leukemia (n=98) and myelodysplastic syndrome (n=20), investigated with CCA and LCA, were evaluated with a median follow-up of 26.6 months (range: 8–47).

Subset chimerism samples were cell-separated by using immunomagnetic beads with respect to the patient’s leukemia phenotype, expressed at diagnosis. Mean purity of the positive-selected CD34 fractions were 97% (93–99%). PCR products were analyzed and quantified by capillary electrophoresis. 33 patients experienced a clinical relapse after aHCT. CCA and LCA detected a mixed chimerism (MC) in 27/118 and 25/118 patients, respectively. MC was detected at a median of 27 (12–54) and 34 (10–71) days before clinical relapse by CCA and LCA, respectively. LCA reached a significantly higher sensitivitiy than CCA with 91% (CI:54–98%) as compared to 83% (CI: 69–91%) and was also more sensitive as compared to bone marrow morphology examination (BME) (61%; CI:44–75%). Specificity was also higher with LCA (98%, CI: 89–100%) as compared to CCA (92%; CI: 75–99%) and BME (91%; CI: 82–96%).

Our data suggest a higher sensitivity and specificity of LCA as compared to CCA and BME with respect to the clinical follow-up. We conclude from these data that due to the high predictive value subset chimerism monitoring may be employed for clinical decision making concerning adoptive immunotherapy after myeloablative aHCT for patients with AML and MDS, especially when lacking other molecular markers for detection of MRD.

Differential accuracy of Lineage-specific versus Conventional Chimerism analysis