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New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation.

ABSTRACT: Minimal residual disease (MRD) is a complex topic that has been studied extensively in hematologic malignancies given its clinical implications related to prognosis. However, methods to monitor and treat MRD, especially after stem cell transplantation, are not well defined and vary in different disease processes. Alternative transplant strategies, such as reduced-intensity conditioning, have altered the way we assess and address MRD after transplantation. Development of new diagnostic tools have allowed for higher sensitivity and specificity of testing. Both targeted chemotherapeutic agents and immunotherapies have been developed to treat MRD in hopes of improving patient outcomes. This article aims to address ways to define and manipulate MRD specifically after stem cell transplantation.

SUBMITTER: Rein LA

PROVIDER: S-EPMC3841006 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation.

Rein Lindsay Am LA Sung Anthony D AD Rizzieri David A DA

International journal of hematologic oncology 20130201 1

Minimal residual disease (MRD) is a complex topic that has been studied extensively in hematologic malignancies given its clinical implications related to prognosis. However, methods to monitor and treat MRD, especially after stem cell transplantation, are not well defined and vary in different disease processes. Alternative transplant strategies, such as reduced-intensity conditioning, have altered the way we assess and address MRD after transplantation. Development of new diagnostic tools have ...[more]

PMID: 24303095

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Project description:In patients with t(8;21) acute myeloid leukemia (AML), recurrent minimal residual disease (MRD) measured by RUNX1-RUNX1T1 transcript levels can predict relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to compare the efficacy of preemptive interferon (IFN)-α therapy and donor lymphocyte infusion (DLI) in patients with t(8;21) AML following allo-HSCT. We also evaluated the appropriate method for patients with different levels of RUNX1-RUNX1T1 transcripts. In this retrospective study, consecutive patients who had high-risk t(8;21) AML and received allo-HSCT were enrolled. The inclusion criteria were as follows: (1) age ≤65 years; (2) regained MRD positive following allo-HSCT. MRD positive was defined as the loss of a ≥4.5-log reduction and/or <4.5-log reduction in the RUNX1-RUNX1T1 transcripts, and high-level, intermediate-level, and low-level MRDs were, respectively, defined as <2.5-log, 2.5-3.5-log, and 3.5-4.5-log reductions in the transcripts compared with the pretreatment baseline level. Patients with positive RUNX1-RUNX1T1 could receive preemptive IFN-α therapy or DLI, which was primarily based on donor availability and the intentions of physicians and patients. The patients received recombinant human IFN-α-2b therapy by subcutaneous injection twice a week every 4 weeks. IFN-α therapy was scheduled for six cycles or until the RUNX1-RUNX1T1 transcripts were negative for at least two consecutive tests. The rates of MRD turning negative for patients with low-level, intermediate-level, and high-level RUNX1-RUNX1T1 receiving IFN-α were 87.5%, 58.1%, and 22.2%, respectively; meanwhile, for patients with intermediate-level and high-level RUNX1-RUNX1T1 receiving DLI, the rates were 50.0% and 14.3%, respectively. For patients with low-level and intermediate-level RUNX1-RUNX1T1, the probability of overall survival at 2 years was higher in the IFN-α group than in the DLI group (87.6% vs. 55.6%; p = 0.003). For patients with high levels of RUNX1-RUNX1T1, the probability of overall survival was comparable between the IFN-α and DLI groups (53.3% vs. 83.3%; p = 0.780). Therefore, patients with low-level and intermediate-level RUNX1-RUNX1T1 could benefit more from preemptive IFN-α therapy compared with DLI. Clinical outcomes were comparable between preemptive IFN-α therapy and DLI in patients with high-level RUNX1-RUNX1T1; however, they should be further improved.

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New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation.

Publications

New approaches to manipulate minimal residual disease after allogeneic stem cell transplantation.

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