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Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

ABSTRACT: Relapse remains the main cause of treatment failure in acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Emerging evidence has demonstrated that AML patients might benefit from maintenance therapy post-transplantation, especially for high-risk AML patients. In this mini-review, we will summarize targeted drugs, such as hypomethylating agents, FLT3 inhibitors and isocitrate dehydrogenase inhibitors, as maintenance therapy post-transplantation in AML patients undergoing allo-HSCT.

SUBMITTER: Xuan L

PROVIDER: S-EPMC7786934 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

Xuan Li L Liu Qifa Q

Journal of hematology & oncology 20210106 1

Relapse remains the main cause of treatment failure in acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Emerging evidence has demonstrated that AML patients might benefit from maintenance therapy post-transplantation, especially for high-risk AML patients. In this mini-review, we will summarize targeted drugs, such as hypomethylating agents, FLT3 inhibitors and isocitrate dehydrogenase inhibitors, as maintenance therapy post-transplantation ...[more]

PMID: 33407700

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Project description:Objective: This study aimed to evaluate the maintenance therapy following an anti-CD19-CAR T-cell therapy for a B-cell acute lymphoblastic leukemia (ALL) patient who relapsed after allogeneic hematopoietic cell transplantation (allo-HSCT) and investigate the effect of donor stem cells and donor T lymphocyte infusion on the amplification of CD19 CAR-T cells. Methods: One refractory B-ALL patient relapsed after murine CD19 CAR-T cell therapy followed by a sibling allo-HSCT. He underwent a humanized CD19 CAR-T cell therapy followed by donor stem cell and donor T lymphocytes infusions as maintenance therapy in our hospital. The level of cytokines, the proportion of CD19 CAR-T cell, the level of CAR19 DNA expression in the peripheral blood, and the proportion of leukemia cells and donor chimerism in the bone marrow were detected. Correspondingly, T lymphocytes from the C57 spleen were separated to modify the CD19 CAR lentivirus and refused into C57 mice, and after 14 days, the B lymphocytes from C57 mice were separated and refused into the same C57 mice. The CD19 CAR T cells, B cells, and CD19 CAR gene counts in the peripheral blood were evaluated at different time points. Results: ?The patient achieved a complete response (CR) 14 days after a humanized CD19 CAR-T therapy with grade 1 cytokine release syndrome (CRS) and restored a donor chimerism to 99.76%. ? Following the remission from humanized CD19 CAR-T therapy, the patient received a maintenance therapy of donor stem cell infusion. Mild graft-versus-host disease (GVHD) manifested 24 days after infusion with an increased proportion of CD19 CAR-T cells and an increased level of CAR19 DNA expression in the peripheral blood. It fell with the remission of GVHD. The patient maintained CR and 99.69% donor chimerism during this period. ? Throughout the subsequent donor T lymphocytes maintenance therapy, mild GVHD surfaced12 days after infusion without an increased proportion of CD19 CAR-T cells and an increased level of CAR19 DNA expression in the peripheral blood. The patient maintained CR and 99.87% donor chimerism during this period. ? In vivo experiments on C57 mice confirmed that the proportion of CD19 CAR-T cells and the level of CAR19 DNA expression were upregulated in mice following CAR-T cell infusion, accompanied by depletion of CD19(+) B lymphocyte. After infusion of CD19(+) B lymphocyte cells, an increased proportion of CD19 CAR-T cells and an increased level of CAR19 DNA expression in the peripheral blood were observed again. Conclusions: The infusion of donor stem cells and donor T lymphocytes could be used as a maintenance treatment after CD19 CAR-T cell therapy for B-ALL patients who relapsed after allo-HSCT. Infusion of donor stem cells induced an increased proportion of CD19 CAR-T cells and an increased level of CAR19 DNA expression with the occurrence of GVHD. It might lead to further elimination of minimal residual disease.

Project description:PurposeThis study assessed and compared preferences for treatment attributes of maintenance therapies post-hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) and in physicians who treat these patients.Patients and methodsPatients with AML post HSCT and physicians from the United States, United Kingdom, Canada, and Australia (physicians only) completed a web-based discrete choice experiment (DCE). The DCE used inputs identified via a targeted literature review and qualitative interviews to ascertain relevant treatment attributes and associated levels. Six treatment attributes were selected (chance of 2-year relapse-free survival, quality of life [QoL], risk of serious infections, risk of nausea, chance of achieving transfusion independence, and duration of hospitalization annually), each with three or four levels. The experimental design included 36 choice tasks that presented a pair of hypothetical treatment profiles with varying attribute levels; participants chose a preferred treatment for each choice task. Choice tasks were divided into three blocks of 12 tasks each in the patient survey and 4 blocks of 9 tasks each in the physician survey; survey participants were randomly assigned to one of the blocks. Random parameter logit regression models were used to assess the impact of stated attributes on preferences for maintenance treatment post HSCT.ResultsSurveys from 84 patients and 149 physicians were assessed. For patients, QoL was the most important attribute, followed by duration of hospitalization and chance of 2-year relapse-free survival. For physicians, chance of 2-year relapse-free survival was the most important attribute, followed by QoL and risk of serious infections.ConclusionDifferences in how patients and physicians valued post-HSCT maintenance treatment attributes were identified. These differences suggest that patient-centered decision-making may help physicians choose maintenance treatments for patients with AML post HSCT that better meet their treatment needs and improve their treatment satisfaction.

Dataset Information

Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

Publications

Maintenance therapy in acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

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