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After treatment and remission

MRD monitoring

Measurable residual disease (MRD) means very small numbers of leukaemia cells that cannot be seen with an ordinary microscope. Measuring MRD regularly during remission can help spot relapse early. This topic explains how MRD monitoring works.

Last updated: ~3 min read
Among thousands of healthy translucent cells, one is picked out by a soft ring of light.
Figure 1.MRD — one leukaemia cell among millions of healthy cells.

01Short answer

MRD monitoring is the regular search for leukaemia cells during remission using very sensitive methods. The main methods are flow cytometry (based on “tags” on the cell surface) and molecular tests (for example looking for a gene change by PCR). They can find one leukaemia cell among 10,000 to 1,000,000 normal cells. Monitoring is only possible when the leukaemia has a suitable marker, and its schedule depends on the type of disease. A rising MRD level may let the doctor act before relapse. Results are always interpreted with your doctor.

02Simple explanation

MRD means a few leukaemia cells that a microscope cannot see.

Measuring it needs very sensitive tests.

The leukaemia must have a specific marker.

MRD can be measured in blood or bone marrow.

What matters is the trend: stable and low, or rising.

03Scientific explanation

Sensitivity: according to the ELN MRD consensus, multiparameter flow cytometry reaches about 10⁻³–10⁻⁴ and quantitative PCR 10⁻⁴–10⁻⁶.

AML: ELN 2021 recommends molecular MRD monitoring after treatment in NPM1-mutated and CBF AML (RUNX1::RUNX1T1, CBFB::MYH11), for example about every 3 months for 2 years.

Molecular relapse: the ELN describes a previously negative MRD rising above a set threshold as “molecular relapse”; it can appear before clinical relapse.

ALL: according to the NCI, MRD in ALL is one of the strongest prognostic factors in decisions about treatment intensity.

04What happens in the body?

What is MRD?

In remission the marrow has fewer than 5% blasts under the microscope, but that does not mean all leukaemia cells are gone. The very few remaining cells are called measurable residual disease. Only special sensitive tests can find them.

How is it measured?

Flow cytometry passes cells one by one in front of a laser beam and recognises leukaemia cells by the proteins on their surface. Molecular tests (PCR, NGS) look for a gene change typical of the leukaemia.

Cells passing through a thin teal laser beam in a glowing flow chamber.
Figure 2.Flow cytometry checks cells one at a time with a laser beam.

The monitoring schedule

In some types of leukaemia, MRD is checked at set intervals after remission — for example every few months — in blood or marrow. Your doctor sets the schedule according to the disease genetics and the protocol.

A ribbon of light descending and levelling off over a dark horizon.
Figure 3.Your doctor looks at how the MRD level changes over time.

What does a result mean?

“Negative” — no leukaemia cells were found within the test’s sensitivity. “Positive” — a small number of cells were found. In some cases low-level MRD stays stable for a long time. Your doctor looks at the direction of change rather than one result.

If a rise is seen

A repeat test is usually done to confirm it. If needed, your doctor may discuss a marrow test, a change in treatment or a transplant. These decisions are always individual.

05The path of MRD monitoring

From marker to decision.

Marker — Found at diagnosis.1MarkerFound at diagnosis.
Sample — Blood or marrow.2SampleBlood or marrow.
Sensitive search — Even a few cells show.3Sensitive searchEven a few cells show.
Decision — Follow-up or treatment.4DecisionFollow-up or treatment.
Early warningA signal before relapse.
Precise measurementEven a few cells show up.
An individual decisionA plan that fits the result.

06Key points at a glance

TopicIn brief
What is MRD?In remission the marrow has fewer than 5% blasts under the microscope, but that does not mean all leukaemia cells are gone. The very few remaining cells are called measurable residual disease. Only special sensitive tests can find them.
How is it measured?Flow cytometry passes cells one by one in front of a laser beam and recognises leukaemia cells by the proteins on their surface. Molecular tests (PCR, NGS) look for a gene change typical of the leukaemia.
The monitoring scheduleIn some types of leukaemia, MRD is checked at set intervals after remission — for example every few months — in blood or marrow. Your doctor sets the schedule according to the disease genetics and the protocol.
What does a result mean?“Negative” — no leukaemia cells were found within the test’s sensitivity. “Positive” — a small number of cells were found. In some cases low-level MRD stays stable for a long time. Your doctor looks at the direction of change rather than one result.
If a rise is seenA repeat test is usually done to confirm it. If needed, your doctor may discuss a marrow test, a change in treatment or a transplant. These decisions are always individual.

07Key terms

MRD
Measurable (minimal) residual disease.
Flow cytometry
A method that recognises cells by their surface proteins.
PCR
A test that finds a stretch of DNA or RNA by copying it many times.
NGS
Next-generation sequencing — reading many genes at once.
Sensitivity
The smallest share of cells a test can find.
Molecular relapse
A rising marker before clinical signs.

08Key points

  • MRD is disease the microscope cannot see.
  • Measuring it needs a marker.
  • Flow cytometry and PCR are the main methods.
  • The schedule depends on the disease type.
  • The trend matters more than one result.
  • All decisions are individual.

09Frequently asked questions

Is an MRD test painful?

If it is done on blood, it is like an ordinary blood test. If on marrow, a marrow aspiration is needed.

Does negative MRD mean cure?

It is a very good sign but not a full guarantee; follow-up continues.

How long does the result take?

From a few days to a few weeks, depending on the laboratory.

Why am I not having MRD tests?

Some leukaemias have no suitable marker or method. Ask your doctor.

My result is positive — have I relapsed?

Not necessarily. Your doctor will consider the level, the trend and a repeat test.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Is an MRD test painful?

  2. Does negative MRD mean cure?

  3. How long does the result take?

  4. Why am I not having MRD tests?

  5. My result is positive — have I relapsed?

My questions

12Sources

  1. Blood, 2021. Heuser M et al. 2021 update on MRD in AML: a consensus document from the ELN MRD Working Party
  2. Blood, 2022. Döhner H et al. Diagnosis and management of AML in adults: 2022 ELN recommendations
  3. National Cancer Institute (NCI). Definition: minimal residual disease
  4. Leukemia & Lymphoma Society (LLS). Minimal/Measurable Residual Disease
  5. Leukemia & Lymphoma Society (LLS). Minimal Residual Disease (MRD) — overview
  6. American Cancer Society. Living as an Acute Lymphocytic Leukemia Survivor
  7. National Cancer Institute (NCI). Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version
  8. Centers for Disease Control and Prevention (CDC). Medical Tourism: Getting Medical Care in Another Country
  9. New England Journal of Medicine, 2020. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission
  10. Blood, 2021. 2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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