VERIFIED CONTENTAuthor: Sara Janowska, MA in pharmacy

Residual disease describes the situation in the body when a trace number of neoplastic cells remain after oncological treatment. They are undetectable by standard diagnostic methods. The presence of a residual disease does not cause symptoms in the patient, but is important for the risk of recurrence of the neoplastic disease. The diagnosis of residual disease is of the greatest importance in the treatment of patients in remission after oncological treatment of leukemia.

Residual diseaseis often abbreviated asMRD , which comes from the English term Minimal Residual Disease. It occurs in patients suffering from cancer, especially leukemia, who have received or are undergoing treatment. Patients with MRD have small amounts of disease cells in their body.

The presence of a residual disease is indicated by the percentage of neoplastic cells greater than 10-3. Due to the fact that they are not detectable by standard methods, conventional assessment usually shows complete remission of the neoplastic disease. Detecting and properly diagnosing MRD is important as it is the leading cause of leukemia recurrence.

Residual disease - diagnosis

Residual disease is not detectable in tests such as blood count and bone marrow tests. During the examination, the patient also does not observe any symptoms indicative of a disease state. MRD can only be detected using highly sensitive diagnostic methods. These include modern tests using the achievements of molecular biology, based on the detection of DNA, RNA or specific tumor proteins. These methods are either flow cytometry or genetic testing techniques. An example of one of them is the PCR analysis of fusion gene transcripts.

Detection of residual disease requires the use of a sensitive diagnostic method, capable of registering 1 cancer cell per 10,000 cells. For example, the sensitivity of a standard technique, which is microscopic evaluation, is 1 tumor cell per 20 he althy cells.

Most of the research on MRD focuses on leukemia and lymphomas. Scientists hope that the discoveries made can stayalso used in the treatment of other cancers.

Residual disease - the role of diagnostics in leukemia therapy

The diagnosis of residual disease is of the greatest importance in the treatment of patients in remission after oncological treatment of leukemia. We can list specific types of this disease in which the detection of MRD is of particular importance:

  • adult chronic myeloid leukemia
  • acute lymphoblastic leukemia in children, which is the most common childhood cancer

In the treatment of cancer, especially leukemia, the diagnosis of MRD is important for several reasons:

  • Determine if treatment has eliminated all cancer cells. If there are traces of them left, there is a risk of the disease recurring.
  • Early detection of cancer recurrence.
  • Support in choosing the most effective treatment method.
  • The test results allow you to compare the effectiveness of different treatment methods.
  • Performing regular examinations allows you to monitor the patient's remission status.

Leukemias are cancers of the blood. These diseases primarily affect the bone marrow, where its cells are produced.

In standard diagnostic methods, bone marrow samples are observed using a microscope. Leukemia cells look like normal immature blood cells, except that there are many more than normal.

He althy marrow usually contains 1-2% of immature cells. In leukemia, they account for 40-90% of it. In this case, the microscopic evaluation of the disease is quite simple. In MRD, the number of diseased cells is negligible. At the same time, under the microscope, they do not differ in appearance from he althy, immature cells. Therefore, standard diagnostic methods are ineffective in detecting residual disease.

Cancer therapy kills most leukemia cells. In most cases, trace amounts of leukemia cells (about 0.001%) survive treatment. A small number of them may persist in the marrow for months or years. Cancer cells can be identified using DNA tests or immunoassays. However, they cannot be distinguished from he althy ones when viewed under a microscope.

Tests that reveal minimal residual disease can help target treatment and prevent leukemia from coming back. Even a single tumor cell left after treatment can lead to a fatal relapse.

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Residual disease - the importance of MRD diagnostics

The MRD level is primarily an indicator in assessing the risk of cancer recurrence.

Diagnosing residual disease is also important in monitoring patients for the early symptoms of recurrent leukemia. This requires regular blood or bone marrow sampling.

Thanks to molecular tests, it is possible to detect an increase in the level of cancer cells in the patient's body at a very early stage, before the symptoms of the disease recur. This is very beneficial for a number of reasons:

  • A patient who is diagnosed with relapse at an early stage will be in better he alth during oncological treatment. Thanks to this, the therapy will be less strenuous.
  • In the early stages of tumor recurrence, there are fewer leukemic cells in the patient's body that need to be eliminated during treatment
  • Cells are usually more susceptible to treatment in the period before symptoms return. They may become more resistant to medications during the course of treatment.

Assessment of residual disease and individualization of oncological treatment

The development of diagnostics of residual disease gives hope for the individualization of cancer treatment. Today, most patients with a given type of disease receive the same treatment. Leukemia is a disease that shows great variability. Accordingly, different patients require a different route of therapy to overcome the cancer. This approach is called the individualization of treatment.

Measuring MRD levels helps clinicians decide what treatment is most beneficial for a given patient. Assessment of residual disease helps to determine the individual risk of recurrence in patients. As a result, a specialist can better select the appropriate strength of treatment to prevent relapses, while putting as little strain on the patient's body as possible.

Without information on MRD, doctors can only provide the same treatment for all cancer patients. Such therapy will be too gentle for some patients and too burdensome for others. Therefore, individual identification of risk factors is extremely important for the development of oncology.

Residual disease - tests used in MRD assessment

  • DNA tests

One of the diagnostic methods is tests that detect leukemia-specific DNA sequences in samples taken from the patient's blood or bone marrow. For this purpose, polymerase chain reactions are used. It is a highly sensitive technique.It is one of the basic methods used in molecular biology.

  • RNA tests

For the evaluation of residual disease, tests based on the detection of the RNA sequence specific for leukemia are also used. For this purpose, the method of reverse RNA transcription followed by the polymerase chain reaction is used. RNA-based tests are typically used when a DNA test is ineffective for a given type of tumor mutation. However, this method is more time-consuming and complicated.

  • Immunoassays

Immunoassays used in the assessment of residual disease use specific proteins found on the surface of cells. Leukemia cells often show quite unusual and unique combinations of these. These proteins can be stained with antibodies labeled with a fluorescent dye. They are then detected using flow cytometry.

The limit of detection of immunoassay is usually about 1 in 10,000 cells. The method is not effective for leukemias that do not have an identified and stable phenotype, i.e. the external features of the cells.

Residual disease - treatment

Treatment of residual disease is important as it is a major source of relapse. In order to eliminate MRD, further treatment is used during remission of disease symptoms. It involves therapy with the use of high doses of cytostatics. Important for the course of treatment and full recovery is the selection of the appropriate dose of the drug and the protection of the patient against complications.

The optimal route of therapy is to eliminate or at least reduce the level of MRD. Treatment of residual disease may include methods such as:

  • Conventional cancer treatment (chemotherapy) with high doses of drugs.
  • Stem cell transplant, e.g. bone marrow transplant. Such a procedure increases the body's resistance to intensive chemotherapy. A transplanted bone marrow can also help eliminate trace amounts of cancer cells in the patient's body.
  • Immunotherapy.
  • Monitoring the patient for early symptoms of recurrence of the neoplastic disease.
  • Therapy with monoclonal antibodies directed against neoplastic cells.
  • Cancer vaccines.

Importance of residual disease diagnostics for modern cancer therapy

MRD assessment tests are not yet routine tests. Access to them is very limited, they can only be made in certain laboratories.

Currently, most of them are carried outResidual disease evaluation tests are carried out during scientific clinical trials. These tests are not performed in most diagnostic laboratories because they are complex, expensive and time consuming.

Another problem with MRD assessment tests is the small number of specialist physicians able to analyze their results. Most clinical trials have been performed millions of times in the history of medicine.

Such tests include, for example, blood counts. As a result, medical personnel is able to interpret the results with confidence, based on this extensive knowledge gathered by generations of specialists.

MRD tests are a new diagnostic method. Scientists and doctors are still building an extensive knowledge base needed to accurately assess the results of these studies.

About the authorSara Janowska, MA in pharmacyPhD student of interdisciplinary doctoral studies in the field of pharmaceutical and biomedical sciences at the Medical University of Lublin and the Institute of Biotechnology in Białystok. A graduate of pharmaceutical studies at the Medical University of Lublin with a specialization in Plant Medicine. She obtained a master's degree defending a thesis in the field of pharmaceutical botany on the antioxidant properties of extracts obtained from twenty species of mosses. Currently, in his research work, he deals with the synthesis of new anti-cancer substances and the study of their properties on cancer cell lines. For two years she worked as a master of pharmacy in an open pharmacy.

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Oncology