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Open Access Green as soon as Postprint is submitted to ZB.
In vitro generated dendritic cells of leukemic origin predict response to allogeneic stem cell transplantation in patients with AML and MDS.
J. Immunother. 45, 104-118 (2021)
Allogeneic stem cell transplantation (alloSCT) is the treatment of choice for many patients with acute myeloid leukemia (AML) and myelodysplastic syndrome. The presentation of leukemic or allospecific antigens by malignant blasts is regarded as a crucial trigger for an effective allogeneic immune response. Conversely, insufficient stimulatory capacity by the leukemic blasts is thought to be a relevant escape mechanism from cellular immunotherapy (alloSCT). Our purpose was to test, whether the ability of malignant blasts to differentiate in vitro toward dendritic cells of leukemic origin (DCleu) is associated with clinical outcome. We isolated leukemic blasts from peripheral blood or bone marrow of AML and myelodysplastic syndrome patients before alloSCT (n=47) or at relapse after alloSCT (n=22). A panel of 6 different assays was used to generate DCleu in vitro. Results were correlated with clinical outcome. DCleu could be generated from all 69 samples. Significantly higher mean frequencies of DCleu were found in clinical long-term responders versus nonresponders to SCT (76.8% vs. 58.8%, P=0.006). Vice versa, the chance for response to SCT was significantly higher, if a DCleu+/dendritic cells (DC) ratio of >50% could be reached in vitro (P=0.004). Those patients were characterized by a longer time to relapse (P=0.04) and by a higher probability for leukemia-free survival (P=0.005). In vitro generation of DC and DCleu from leukemic blasts correlated with the clinical outcome. This observation may support a role of leukemic antigen presentation by "leukemia-derived DC" for the stimulation of an allogeneic immune response in AML.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Acute Myeloid Leukemia ; Dendritic Cells ; Immunotherapy ; Myelodysplastic Syndromes ; Serum Free Culture ; Stem Cell Transplantation; Acute Myeloid-leukemia; Antigen-presenting Cells; Serum-free Generation; Reduced-intensity; Risk-factors; Ex-vivo; Gm-csf; Blasts; Maturation; Adults
ISSN (print) / ISBN
1524-9557
e-ISSN
1537-4513
Journal
Journal of Immunotherapy
Quellenangaben
Volume: 45,
Issue: 2,
Pages: 104-118
Publisher
Lippincott Williams & Wilkins
Publishing Place
Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CCG Immunotherapy (KKG-KIT)