Monitoring of post-transplant remission of childhood malignancies: is there a standard?

Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia

“…The latter may be particularly warranted in the setting of persistent or newly developed MRD after transplantation, because numerous studies have established that post-HCT MRD detected by PCR, flow cytometry, or (as a surrogate) levels of mixed chimerism accurately identifies a subset of patients at high risk for relapse and poor outcome. 16,17,[33][34][35]40,63,[66][67][68][69][70][71][72][73] As there are no data available from controlled trials addressing these questions, inferences need to be made from observational studies that compare subgroups …”

Detection of Low Level Mixed Chimerism Using High Throughput SNP Genotyping

“…Minimal residual disease (MRD [1,2]) monitoring involves detection and quantification of the malignancyspecific markers, while measuring the extent of mixed chimerism [3] requires measuring the fraction of recipient cells in peripheral blood samples. MRD approaches require monitoring the malignant clone via molecular (PCR-based) or immunophenotypic methods [4]. For example, the gene-specific markers for acute lymphoblastic leukemia (ALL) include TCR and Ig-gene rearrangements and BCR/ABL gene fusion products [4], while mutations in the NPM1 gene can be used as the markers in CML [5].…”

“…MRD approaches require monitoring the malignant clone via molecular (PCR-based) or immunophenotypic methods [4]. For example, the gene-specific markers for acute lymphoblastic leukemia (ALL) include TCR and Ig-gene rearrangements and BCR/ABL gene fusion products [4], while mutations in the NPM1 gene can be used as the markers in CML [5].…”

“…Recent SNP-based methods coupled with qPCR [16,22] report quantification of the target template as low as 0.1%. For reviews of MRD and MC detection methods see [4,5,23].…”

“…This is attributed to the hematopoiesis of the recipient's native CD34+ derived cells despite the cytoreductive treatment prior to the allograft transplant. Several studies have shown strong positive correlation between the extent of mixed chimerism and the likelihood of patient hematologic relapse [4,[6][7][8][9]. The magnitude of mixed chimerism is frequently measured using PCR-based methods [10,11] as a ratio of the recipient genotype signal to that of the donor.…”