Reprint of: Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

Vyas, Paresh; Appelbaum, Frederick R.; Craddock, Charles

doi:10.1016/j.bbmt.2014.12.032

Cited by 5 publications

(2 citation statements)

References 89 publications

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“…[1][2][3][4][5] Many studies indicate that allogeneic HCT reduces patient risk of experiencing relapse and improves relapse-free and overall survival (OS) in adverse-risk and intermediate-risk AML in first morphologic complete remission (CR). 3 Current treatment algorithms and research protocol assignments as well as analyses of post-HCT outcomes typically separate patients in morphologic remission (ie, , 5% bone marrow blasts) from those with active disease ($ 5% blasts in bone marrow) after either experiencing relapse or failure to enter initial remission with chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease–Based Definition of Complete Remission?

Araki

Wood

Othus

et al. 2016

JCO

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343

217

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Patients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, $ 5% marrow blasts by morphology) in treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre-HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution. Patients and MethodsWe retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive. ResultsThree-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups. ConclusionThe similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD-rather than morphology-based disease assessments.

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Section: Introductionmentioning

confidence: 99%

Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease–Based Definition of Complete Remission?

Araki

Wood

Othus

et al. 2016

JCO

Self Cite

343

217

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“…More importantly, haematopoietic stem cell transplantation, immunotherapy, radiotherapy, MRD evaluation and access to clinical trials were strictly reserved for patients who were seen by a trained haematologist. Given the positive impact of transplantation on the survival of AML patients, 27 and the innovative therapies proposed in clinical trials, 28 , 29 working to improve patient access to specialised haematology unit will be essential to improve AML patient survival in the general population.…”

Section: Discussionmentioning

confidence: 99%

Factors influencing access to specialised haematology units during acute myeloblastic leukaemia patient care: A population‐based study in France

et al. 2023

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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Allogeneic Human Double Negative T Cells as a Novel Immunotherapy for Acute Myeloid Leukemia and Its Underlying Mechanisms

Lee

Minden

Chen

et al. 2018

Clinical Cancer Research

118

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To explore the potential of expanded healthy donor-derived allogeneic CD4 and CD8 double-negative cells (DNT) as a novel cellular immunotherapy for leukemia patients. Clinical-grade DNTs from peripheral blood of healthy donors were expanded and their antileukemic activity and safety were examined using flow cytometry-based killing assays and xenograft models against AML patient blasts and healthy donor-derived hematopoietic cells. Mechanism of action was investigated using antibody-mediated blocking assays and recombinant protein treatment assays. Expanded DNTs from healthy donors target a majority (36/46) of primary AML cells, including 9 chemotherapy-resistant patient samples , and significantly reduce the leukemia load in patient-derived xenograft models in a DNT donor-unrestricted manner. Importantly, allogeneic DNTs do not attack normal hematopoietic cells or affect hematopoietic stem/progenitor cell engraftment and differentiation, or cause xenogeneic GVHD in recipients. Mechanistically, DNTs express high levels of NKG2D and DNAM-1 that bind to cognate ligands preferentially expressed on AML cells. Upon recognition of AML cells, DNTs rapidly release IFNγ, which further increases NKG2D and DNAM-1 ligands' expression on AML cells. IFNγ pretreatment enhances the susceptibility of AML cells to DNT-mediated cytotoxicity, including primary AML samples that are otherwise resistant to DNTs, and the effect of IFNγ treatment is abrogated by NKG2D and DNAM-1-blocking antibodies. This study supports healthy donor-derived allogeneic DNTs as a therapy to treat patients with chemotherapy-resistant AML and also reveals interrelated roles of NKG2D, DNAM-1, and IFNγ in selective targeting of AML by DNTs. .

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Reprint of: Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

Cited by 5 publications

References 89 publications

Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease–Based Definition of Complete Remission?

Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease–Based Definition of Complete Remission?

Factors influencing access to specialised haematology units during acute myeloblastic leukaemia patient care: A population‐based study in France

Allogeneic Human Double Negative T Cells as a Novel Immunotherapy for Acute Myeloid Leukemia and Its Underlying Mechanisms

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