[4] Molecular tests that uncover minimal residual disease are helpful for directing treatment and monitoring or preventing relapse.
[5][6] Subsequently MRD research has broadened out to other hematological malignancies such as Multiple Myeloma,[7] as well as to solid tumors.
Symptoms do not occur until the disease is advanced, and there are 1 kg or one trillion leukemic cells in the body.
However, pre-leukemic clones may survive treatment, and persist at frequencies of less than 0.1% in the bone marrow for months or years.
[8] This minimal residual disease can be identified by sensitive molecular tests such as DNA sequencing, but not by other methods such as viewing cells under a microscope.
The detection method may be "tumor-informed", using mutation information from sequencing an individual's tumor tissue biopsy samples before subsequent MRD monitoring.
The tumor-agnostic approach is chosen when mutation information from an individual's primary tumor tissue is not available.
Typically tens or hundreds of mutations are chosen for MRD monitoring, and these tests can have a limit of detection of 0.001%, or one cell in 100,000.
For example, the t(9;22) BCR-ABL translocation may occur over a large length of the chromosome which makes DNA-based testing difficult and inefficient.
From this sequence, PCR primers are designed that will only amplify the specific leukemic clone from the patient.
Both the DNA- and RNA-based tests require that a pathologist examine the bone marrow to determine which leukaemic specific sequence to target.
The limit of detection of immunological tests is generally about one in 10,000 cells and cannot be used on leukaemias that don't have an identifiable and stable leukaemic phenotype.
Targets: t(9;22) BCR-ABL, t(12;21) ETV6-RUNX1 (TEL-AML1), Patient specific assays for immunoglobulin and T cell receptor genes Uses: Chromosomal translocation MRD detection is widely used as a standard clinical practice.
[2] New research uses Whole genome sequencing and Artificial Intelligence to find MRD across multiple solid tumors.
[13] Cancer could potentially be monitored similarly in non-human animals, however, no known evidence of such veterinary applications exists to date.
The molecular tests can show tumour levels starting to rise, very early, possibly months before symptoms recur.
For instance, the initial five-week induction treatment might rapidly clear disease for some patients.
In other words, it identifies patients' individual risks of relapse, and can theoretically allow them to receive just enough treatment to prevent it.
Identification of risk factors, to help individualise treatment, is a big field in medicine.
Generally the approach is to bring a cancer into remission first (absence of symptoms) and then try to eradicate the remaining cells (MRD).
Treatments which specifically target MRD can include: It is important that doctors interpreting tests, base what they say on scientific evidence.
In plain English, this means the doctors are likely to be very cautious, and rely more on other tests which they know and trust, than these, at least at present, while evidence is accumulating.
But there is some evidence from animal studies, that leukaemic cells can lie dormant for years in the body and do not regrow.
There is thus an argument that as the test is not necessary: it might involve an additional procedure for the patient; it will contribute no useful information on treatment, it is not necessary.