Leukemia

Leukemia, a type of cancer that causes large numbers of abnormal blood cells to be produced and enter the bloodstream, is categorized as “acute” (fast-growing) or “chronic” (slow growing), and as “lymphoid” (arising from B or T cells) or “myeloid” (arising from white blood cells other than B and T cells, red blood cells, or platelet-making cells).

Standard post-treatment assessment and monitoring

Your doctor will use blood tests (CBC), and microscopic evaluation of your blood and bone marrow to assess your response to treatment for acute lymphoblastic leukemia (ALL) after the initial course of therapy (induction), before consolidation and maintenance therapy. If you fail to achieve a complete response (CR) at this point (see below) it is an indication of refractory disease that may need more aggressive treatment.27

For several years after the completion of all chemotherapy (e.g., after maintenance therapy is completed), your doctor will see you every few months to conduct a physical exam and blood tests (CBC with differential) to check for relapse. In the first year, if needed, your doctor may also examine your bone marrow and/or cerebrospinal fluid.27

Categories of treatment response:
  • No immature B/T cells in the bloodstream or organs/tissues outside of the bone marrow
  • Normal levels of all blood cell types in the bone marrow, with less than 5% being immature B/T cells
  • Absolute neutrophil count more than 1000/microliter
  • Platelets greater than 100,000/microliter
  • No recurrence for 4 weeks
  • Failure to achieve CR at the end of induction treatment
  • Increase of at least 25% in the absolute number of immature B/T cells in the blood or bone marrow

OR

  • New finding of immature B/T cells in other organs/tissues

Role of mrd testing

Minimal residual disease (MRD) refers to small numbers of cancer cells that may remain in your body after treatment and eventually cause your disease to come back. These residual cells are present at such low levels that they cannot be detected with the laboratory techniques used for standard post-treatment response assessment and monitoring. Instead, more sensitive tests must be used.

National guidelines recommend MRD testing with a sensitivity of at least 1 in 10,000 cells upon achievement of CR after induction therapy for both children and adults treated for ALL.27 MRD testing may also be done at other times during and after treatment (e.g., before/after transplant, during maintenance, during surveillance after treatment ends). ASO-PCR, flow cytometry and next-generation sequencing MRD tests can all be used in ALL.27

Children with ALL who become MRD-negative after treatment live longer without their disease coming back (disease-free survival, DFS) and live longer overall (overall survival, OS).28-46 Ongoing studies are investigating whether MRD-status as measured in the middle of treatment can be used to adjust therapy in children with ALL (less treatment for MRD-negative, more treatment for MRD-positive).39, 47-53

Although not as well studied as in children, MRD status at various time points during and after treatment initiation has been shown to predict outcome in adults with ALL.29, 54-63 Studies have also shown that detection of MRD after allogeneic (donor) transplant is associated with an increased risk of relapse in adults with ALL.57, 64, 65

next steps

Find resources that can help you prepare to talk with your doctor about disease level testing and how it might play a part in your treatment plan.