Minimal Residual Disease in Acute Lymphoblastic Leukemia: How to Recognize and Treat It

Abstract

In recent years, the identification of minimal residual disease (MRD) that persists after chemotherapy has emerged as the most powerful tool in determining the prognosis of patients with ALL, often superseding historically relevant prognostic factors. Multiple methods to detect MRD exist, each with their own advantages and disadvantages. Multiparameter flow cytometry and quantitative polymerase chain reaction are the most commonly used methods of MRD detection in clinical practice, although there is promise in the use of more sensitive assays utilizing next-generation sequencing that may be able to further refine MRD-based risk stratification. By accurately identifying patients with persistent MRD who are at highest risk for relapse, we may be able to better design rational post-remission therapies using novel agents, such as inotuzumab ozogamicin, blinatumomab, and CD19-directed chimeric antigen receptor T cells, all of which have been shown to be effective in achieving MRD negativity, even in patients with relapsed or refractory disease. Future studies will be required to determine whether these post-remission strategies can obviate the need for allogeneic stem cell transplantation for patients with ALL in whom MRD can be eradicated.

A Next-Generation Sequencing Primer—How Does It Work and What Can It Do?

“…Test results can be helpful for the initial diagnosis, tumor classification, determining the origin of the cancer, and prognosis. 76 Table 2 77 – 130 provides a partial list of cancers where NGS information has provided value for managing patients. Thyroid nodules are a specific example where fine needle aspiration and cytologic examination may not yield a definitive diagnosis, while NGS has been shown to have high specificity and sensitivity for cancer detection.…”

Improved prognosis with additional medium‐dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults

“…From the registry database, we extracted data on pretransplant characteristics and post‐transplant clinical courses and prognoses. With respect to disease risk, patients were considered to have advanced risk if they had positive minimal residual disease (MRD; mostly determined by multiparameter flow cytometry), presence of poor‐risk cytogenetics (such as hypodiploidy, rearrangement of the mixed lineage leukemia [MLL] gene, Philadelphia chromosome, or complex karyotype), or an initial elevated leukocyte count (for B lineage ≥ 30 × 10 9 /L, and for T lineage ≥ 100 × 10 9 /L) according to the National Comprehensive Cancer Network Guidelines. Disparities in human leukocyte antigen (HLA)‐A, ‐B, and ‐DR antigens were determined at the serologic level in Rel‐BMT and Rel‐PBSCT.…”

Minimal Residual Disease Detection in Acute Lymphoblastic Leukemia

“…The prognostic limit of 0.01% is based on the immunohistochemical detection limits of 3-4-color flow cytometers. The clinical significance of the 0.01% MRD cutoff level is that when a patient has cellular MRD levels ≥0.01% in a bone marrow sample at important measurement time points during therapy, the patient will have a significantly higher risk for leukemia relapse than if MRD levels are less than 0.01% [3][4][5]. Data also suggest that the higher the MRD value (e.g., MRD > 1%) at the end of the induction phase of chemotherapy, the higher the risk of relapse and the lower the survival rate [6].…”