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Clinical use of minimal residual disease detection in acute lymphoblastic leukemia

Authors
Wendy Stock, MD
Zeev Estrov, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD

INTRODUCTION

The large majority of patients with newly diagnosed acute lymphoblastic leukemia (ALL) attain a morphologic and cytogenetic complete remission after induction chemotherapy. While most children and up to one-half of adults experience prolonged disease-free survival, many adults and some children will relapse and die of leukemia. Relapse is thought to result from residual leukemic cells that remain following the achievement of "complete" remission, but are below the limits of detection using conventional morphologic assessment. These subclinical levels of residual leukemia are termed "minimal residual disease" (MRD) or "measureable residual disease" and can be evaluated using more sensitive assays. (See "Detection of minimal residual disease in acute lymphoblastic leukemia".)

MRD status is one of the most powerful predictors of disease-free and overall survival for children and adults with ALL. However, not all patients with MRD positivity will relapse clinically, and some patients relapse despite negative MRD studies. The immunophenotypic or genetic markers identified at diagnosis on the bulk of malignant cells may not be identical to those expressed by other leukemia clones. Thus, recurrent disease may arise from occult malignant progenitor cells that lack the markers assayed on their more populous progeny. Alternatively, some ALL cells with abnormal markers may persist for some time after treatment but lack the ability to recapitulate the disease either because of an inherited defect or the immune system.

While the timing and type of tests applied varies, MRD assays are routinely used in the clinical care of children and adults with ALL. This topic review will focus on the clinical relevance of MRD monitoring in ALL. The methods for MRD monitoring in ALL and the use of MRD testing in acute myeloid leukemia and chronic myeloid leukemia are covered separately. (See "Detection of minimal residual disease in acute lymphoblastic leukemia" and "Remission criteria in acute myeloid leukemia and monitoring for residual disease" and "Overview of the treatment of chronic myeloid leukemia", section on 'Monitoring response'.)

GENERAL CONSIDERATIONS

Testing for MRD has become a common part of the management of children and adults with ALL. MRD status at various time points during and after treatment has prognostic value, and initial studies suggest that altering therapy based on the results of MRD testing will improve morbidity and mortality.

Ongoing clinical trials are examining the use of MRD both as a prognostic factor and as a factor in decision making to determine whether therapy intensity should be escalated or reduced in a given patient. Specific questions regarding MRD testing that remain include:

                  

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Literature review current through: Nov 2016. | This topic last updated: Wed Aug 17 00:00:00 GMT+00:00 2016.
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