Korean J Hematol.  2012 Dec;47(4):245-254. 10.5045/kjh.2012.47.4.245.

Measurements of treatment response in childhood acute leukemia

• Campana D
• Coustan-Smith E

• KMID: 1832102
• DOI: http://doi.org/10.5045/kjh.2012.47.4.245

Abstract

Measuring response to chemotherapy is a backbone of the clinical management of patients with acute leukemia. This task has historically relied on the ability to identify leukemic cells among normal bone marrow cells by their morphology. However, more accurate ways to identify leukemic cells have been developed, which allow their detection even when they are present in small numbers that would be impossible to be recognized by microscopic inspection. The levels of such minimal residual disease (MRD) are now widely used as parameters for risk assignment in acute lymphoblastic leukemia (ALL) and increasingly so in acute myeloid leukemia (AML). However, different MRD monitoring methods may produce discrepant results. Moreover, results of morphologic examination may be in stark contradiction to MRD measurements, thus creating confusion and complicating treatment decisions. This review focusses on the relation between results of different approaches to measure response to treatment and define relapse in childhood acute leukemia.

Keyword

Acute lymphoblastic leukemia; Acute myeloid leukemia; Flow cytometry; Polymerase chain reaction; Minimal residual disease; Remission

MeSH Terms

Bone Marrow Cells
Flow Cytometry
Humans
Leukemia
Leukemia, Myeloid, Acute
Neoplasm, Residual
Polymerase Chain Reaction
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence

Figure

• 

  Fig. 1 Relation between morphologic and flow cytometric detection of residual disease during and after treatment in childhood AML. (A) Percentage of bone marrow mononucleated cells expressing leukemia-associated immunophenotypes as measured by flow cytometry within groups defined by the percentage of myeloblasts counted by morphology. Gray area corresponds to measurements below the 0.1% threshold used to define MRD positivity. (B) Flow cytometric MRD data within groups defined by the hemopathologists' judgement regarding the presence of leukemic myeloblasts. From Inaba et al. [73] with permission.

• 

  Fig. 2 Relation between event-free survival (EFS) for patients with childhood AML according to flow cytometry and morphology after Induction I. (A) EFS of patients who were MRD-negative (<0.1%) by flow cytometry according to percentage of blasts by morphology. (B) EFS of patients who were MRD-positive (≥0.1%) by flow cytometry according to percentage of blasts by morphology. (C) EFS of patients with <5% blasts by morphology according to MRD levels by flow cytometry. (D) EFS of patients with ≥5% blasts by morphology according to MRD levels by flow cytometry. From Inaba et al. [73] with permission.

• 

  Fig. 3 Possible scenarios that may explain concordant or discordant MRD results by flow cytometry and PCR after chemotherapy. This can either be ineffective (top), result in leukemia cell death (middle), or induce leukemic cell differentiation (bottom). In the latter case, MRD by flow cytometry might be negative, owing to the loss of aberrant immunophenotypes but MRD by PCR would be positive as the cells retain leukemia fusion transcripts. However, these cells may also lack clonogenic potential.

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