Minimal Residual Disease and Implications In ALL (Acute Lymphoblastic Leukemia)

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Minimal residual disease (MRD) predicts risk of relapse in leukemia.

Minimal residual disease or MRD detections are used for classifying leukemia patients as well as predict outcomes of treatments.

So, what is MRD?

MRD is defined as, the name given to small numbers of leukemic cells that remain in the patient during treatment or after treatment when the patient is in remission (no symptoms or signs of disease). (Courtesy Wikipedia)

MRD is usually mentioned with reference to two cancers, adult chronic myeloid leukemia, and childhood acute lymphoblastic leukemia. To explain the occurrence of MRD let me begin at the very beginning,

Acute lymphoblastic leukemia is a condition where in there is excess immature leukemic cells (blast cells) in the bone marrow. The number of leukemia cells is in the range of 40-90% in the marrow by the time leukemia is diagnosed. The extent of spread or malignancy is detected using FISH and flow cytometry. Naturally, treatment follows (chemotherapy, radiation therapy) and this initial treatment manages to destroy majority of leukemia cells. However, there are few blast cells, which persist.

These cells live in bone marrow, sometimes for years. These cells can cause a relapse or remission once treatment for leukemia is discontinued. These cells or the remaining disease causing cells/cancerous cells are termed as minimal residual disease.

Immature cancerous blast cells are difficult to detect using standard tests and it is with the development of molecular techniques and immunology test that these cells can now be identified.

Even one single cancer cell can bring about a relapse eventually and hence detection of minimal residual disease is helpful in planning treatment regimen as well as preventing relapse.

What is the significance of MRD with reference to ALL?

MRD can be used to determine prognosis of a leukemia patient at any time during treatment or afterwards. It can be used as a measure of cancer that is remaining and needs to be treated. Currently, bone marrow sample is taken and tested for MRD after 5 weeks during treatment for childhood leukemia.

Patients with higher risk of relapse were defined as those with more than 1 leukemia cell in 1000, while those with levels less than 1 in 100,000 were defined as having low risk of relapse. Thus, MRD testing could be used for predicting outcome. Several studies on adult and childhood acute lymphoblastic leukemia (ALL) have shown that, through monitoring of PCR molecular targets, detection of minimal residual disease (MRD) after initial chemotherapy could predict outcome.

Regular monitoring or surveillance of MRD in patients following treatment or stem cell transplant can alert physicians on early signs of recurring leukemia. MRD information can also be used to individualize treatment.