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Published on: March 5, 2018
The definition of remission in acute leukemia with immunologic techniques
D Campana1, E Coustan-Smith, F G Behm
1Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38101.
Insights
Detecting minimal residual disease in acute leukemia requires sensitive methods beyond morphology. Immunologic markers and molecular techniques improve precision, aiding in early detection of relapse and guiding treatment strategies.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Morphology is the standard for monitoring acute leukemia residual disease.
- Morphology has limitations in precision for detecting minimal residual disease.
Purpose of the Study:
- To explore advanced methods for precise detection of minimal residual disease in acute leukemia.
- To evaluate immunologic and molecular techniques for monitoring treatment response.
Main Methods:
- Conventional cytogenetics, flow karyotyping, in situ hybridization, and PCR for chromosomal abnormalities.
- Southern blotting and PCR for immunoglobulin and T cell receptor gene analysis.
- Immunophenotyping using flow cytometry and fluorescence microscopy to identify leukemia-associated phenotypes.
Main Results:
- Immunologic methods are reliable for about half of acute leukemia patients.
- Specific marker combinations on leukemic blasts aid in residual disease detection.
- Detection of leukemia-associated phenotypes in bone marrow predicts relapse.
Conclusions:
- Sensitive techniques like immunophenotyping and molecular assays enhance residual disease monitoring in acute leukemia.
- A combination of methods is likely necessary for comprehensive patient management.
- Further pre-clinical investigations are needed to compare techniques and inform therapeutic strategies.
Abstract:
In acute leukemia residual disease is usually monitored by morphology. The precision of this approach can be improved by several methods including the investigation of chromosomal abnormalities by conventional cytogenetics, flow karyotyping, in situ hybridization and polymerase chain reaction (PCR), and the analysis of immunoglobulin and T cell receptor genes by Southern blotting and PCR. Immunologic methods represent a reliable option for studying residual disease in approximately half of the patients with acute leukemia. This strategy is based on the observation that some marker combinations are expressed on leukemic blasts but are absent or rarely present in normal peripheral blood (PB), bone marrow (BM) or cerebrospinal fluid cells. In patients with T cell-acute lymphoblastic leukemia, even one cell simultaneously expressing terminal deoxynucleotidyl transferase and CD3, CD5 or CD1 amongst 10(5) PB or BM cells indicates residual disease. Some cases of B lineage and myeloid acute leukemias also exhibit phenotypes potentially useful for monitoring response to treatment. Such phenotypes are identified by double or triple color staining techniques using fluorescence microscopy or flow cytometry. Independent studies have demonstrated that detection of cells with leukemia-associated phenotypes in BM samples of patients in clinic and morphologic remission heralds the recurrence of leukemia. It is likely that a combination of techniques will be needed to monitor the majority of patients with acute leukemia. Advantages and disadvantages of individual methods should be determined in comparative preclinic investigations. These studies should yield sufficient information to initiate the testing of therapeutic strategies planned according to the data provided by use of modern sensitive techniques.
