Minimal residual disease (MRD) is the name given to small numbers of leukaemic cells (cancer cells from the bone marrow) that remain in the patient during treatment, or after treatment when the patient is in remission (no symptoms or signs of disease). It is the major cause of relapse in cancer and leukemia. Up until a decade ago, none of the tests used to assess or detect cancer were sensitive enough to detect MRD. Now, however, very sensitive molecular biology tests are available, based on DNA, RNA or proteins. These can measure minute levels of cancer cells in tissue samples, sometimes as low as one cancer cell in a million normal cells.
In cancer treatment, particularly leukaemia, MRD testing has several important roles: determining whether treatment has eradicated the cancer or whether traces remain, comparing the efficacy of different treatments, monitoring patient remission status as well as detecting recurrence of the leukaemia or cancer, and choosing the treatment that will best meet those needs .
The tests are not simple, are often part of research or trials, and some have been accepted for routine clinical use.
Most research on MRD has been done on leukaemia, particularly two types: adult chronic myeloid leukemia, and childhood acute lymphoblastic leukemia (the most common childhood cancer).
Leukemia is a cancer of cells in the blood, and primarily affects the bone marrow where they are made. For most human leukemias, the cause is not known. Risk factors can include chemicals and X-rays.
Leukemia involves a genetic abnormality that can begin in a single cell and then multiply rapidly, leading to a disruption in the proportion of cell types in the blood. When a bone marrow sample is drawn, leukemic cells can be viewed under a microscope. Leukemic cells look like normal immature blood cells, and healthy marrow is often 1–2% immature (blasts) cells. However, in leukaemia, there are abnormally high numbers of immature cells, making up 40–90% of marrow. Additional examination of the bone marrow by tests including flow cytometry and FISH are necessary to diagnose the specific malignancy.
Symptoms do not occur until the disease is advanced, and there are 1 kg or 1,000,000,000,000 leukemic cells in the body.
The initial five weeks of treatment kill most leukaemic cells, and the marrow begins to recover. Immature white blood cells may be present in the patient, although they are not necessarily malignant cells. In most cases, a few leukemic cells (approximately 0.001%) survive this treatment, and persist in the marrow for months or years. Cancerous cells can be identified by DNA-based or immunological tests, but they can not be identified as cancerous when viewed under a microscope.