Recommendations for the assessment and management of measurable residual disease in adults with acute lymphoblastic leukemia: A consensus of North American experts

Abstract

Measurable residual disease (MRD) that persists after initial therapy is a powerful predictor of relapse and survival in acute lymphoblastic leukemia (ALL). However, the optimal use of this information to influence therapeutic decisions is controversial. Herein, we comprehensively review the role of MRD assessment in adults with ALL, including methods to quantify residual leukemia cells during remission, prognostic impact of MRD across ALL subtypes, and available therapeutic approaches to eradicate MRD. This review presents consensus statements and provides an evidence-based framework for practicing hematologists and oncologists to use MRD information to make rational treatment decisions in adult patients with ALL.

Figure 1.. Patterns of response and relapse in ALL according to quantitative clearance of leukemic burden.

Arrows represent sensitivity of assay. CR, complete remission; MFC, multiparameter flow cytometry; NGS, next-generation sequencing; PCR, polymerase chain reaction. Republished with permission of the American Society of Hematology, from “Has MRD monitoring superseded other prognostic factors in adult ALL?” Brüggemann M, Raff T, Kneba M, 120(23), 2012; permission conveyed through Copyright Clearance Center, Inc.

Figure 2.. Consensus algorithm for MRD-based management of adults with ALL.

(A) Newly diagnosed Ph-negative B-cell ALL or T-cell ALL. (B) Newly diagnosed Ph-positive ALL. *MRD should be assessed on a bone marrow specimen using an assay with a sensitivity of at least 10^-4. MRD negativity should be achieved within 3 months from the start of therapy. ^†Allogeneic HSCT may also be considered in patients with low hypodiploidy or complex karyotype. ^‡In patients who do not undergo HSCT, MRD should be assessed approximately every 3 months for at least 3 years. MRD should be assessed immediately prior to HSCT in all patients undergoing transplant. ^§MRD should be assessed with PCR for BCR-ABL on a bone marrow specimen. MRD negativity should be achieved within 3 months from the start of therapy. ^||In patients who do not undergo HSCT, MRD should be assessed approximately every 3 months for at least 5 years. MRD should also be assessed immediately prior to HSCT in all patients undergoing transplant. CRi, CR with incomplete blood count recovery; CRp, CR with incomplete platelet recovery; MLL, mixed lineage leukemia.

Figure 2.. Consensus algorithm for MRD-based management of adults with ALL.

(A) Newly diagnosed Ph-negative B-cell ALL or T-cell ALL. (B) Newly diagnosed Ph-positive ALL. *MRD should be assessed on a bone marrow specimen using an assay with a sensitivity of at least 10^-4. MRD negativity should be achieved within 3 months from the start of therapy. ^†Allogeneic HSCT may also be considered in patients with low hypodiploidy or complex karyotype. ^‡In patients who do not undergo HSCT, MRD should be assessed approximately every 3 months for at least 3 years. MRD should be assessed immediately prior to HSCT in all patients undergoing transplant. ^§MRD should be assessed with PCR for BCR-ABL on a bone marrow specimen. MRD negativity should be achieved within 3 months from the start of therapy. ^||In patients who do not undergo HSCT, MRD should be assessed approximately every 3 months for at least 5 years. MRD should also be assessed immediately prior to HSCT in all patients undergoing transplant. CRi, CR with incomplete blood count recovery; CRp, CR with incomplete platelet recovery; MLL, mixed lineage leukemia.