Detection and quantification of residual disease in chronic myelogenous leukemia

Abstract

The degree of tumor load reduction after therapy is an important prognostic factor for patients with CML. Conventional metaphase analysis has been considered to be the 'gold standard' for evaluating patient response to treatment but this technique normally requires bone marrow aspiration and is therefore invasive. The frequency of cytogenetic analyses can be considerably reduced if patients are also monitored by molecular methods, which can be performed on peripheral blood specimens.

Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: recommendations by the International Neuroblastoma Risk Group Task Force

“…These studies have resulted in the introduction of new interventions to target this disease with the expectation of improved patient outcome (Faderl et al, 1999;Foroni et al, 1999;Hochhaus et al, 2000;Roman et al, 2000;Campana et al, 2001). Amplification of known tumour-specific gene rearrangements has also provided a powerful tool to detect potential significant MD in solid cancers including those of the Ewing's sarcoma family of tumours (de Alava et al, 1998;Zoubek et al, 1998;Schleiermacher et al, 2003;Avigad et al, 2004), alveolar rhabdomyosarcoma (Thomson et al, 1999;Athale et al, 2001;Gallego et al, 2006) and desmoplastic small round cell tumours (Athale et al, 2001).…”

Assessing minimal residual disease (MRD) in leukemia: a changing definition and concept?

“…In APL, evidence suggests that outcome may be improved if patients are treated at the time of solely molecular evidence of disease. 37 Is it, however, justified to speak about molecular relapse if extremely low levels of BCR/ABL are found in every single CML patient after allogeneic transplant 54,55 and to suggest basing treatment decisions on molecular criteria, particularly in studies performed over long periods of times during which quantitative parameters for molecular monitoring were modified within the study group? 56 Consideration of molecular relapse may require the reappearance of disease following a period of molecular negativity, the reversal of a negative slope of test results or a rise in the level of disease above that determined to be compatible with remission in a particular disease, if applicable.…”

An “Age” Structured Model of Hematopoietic Stem Cell Organization with Application to Chronic Myeloid Leukemia

“…Therefore, in contrast to the ABM, which requires a down-scaling of stem cell numbers to about 1/10 of the realistic value in patients to guarantee feasible simulation times, the PDE model allows us to explicitly simulate those systems. This is particularly important because PCR techniques that are applied to monitor the tumor load in terms of the BCR-ABL1 transcript levels, have an extremely high sensitivity (Hochhaus et al, 2000). They are able to detect about one leukemic cell within 10 5 cells.…”

“…To obtain these values, transcripts of the BCR-ABL1 oncogene are quantified using quantitative polymerase chain reaction (PCR) techniques. In order to compensate for variations in the amplification efficiency, the number of BCR-ABL1 transcripts is normalized using the number of transcripts of a control gene, e.g., ABL1 (Hochhaus et al, 2000). As a strong correlation of the proportion of BCR-ABL1 positive cells and quantitative PCR measurements of BCR-ABL1 transcript levels has been reported (Branford et al, 1999), we can use the proportion of leukemic cells in order to estimate BCR-ABL1 transcript levels in the model simulations.…”