Delayed Haematological recovery after autologous stem cell transplantation is associated with favourable outcome in acute myeloid leukaemia

Wetzel, Dana L.; Mueller, Beatrice U.; Taleghani, Behrouz Mansouri; Baerlocher, Gabriela M.; Seipel, Katja; Leibundgut, Kurt; Pabst, Thomas

doi:10.1111/bjh.13118

Cited by 17 publications

(23 citation statements)

References 23 publications

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“…Recently it was shown that engagement of the inhibitory receptors on macrophages and dendritic cells delivers a suppressive signal from the T cell to the myeloid cell [55–57]. Thus, the interaction between PD-1 and PD-L1/2 is likely to have a bi-directional effect.…”

Section: Discussionmentioning

confidence: 99%

Splenic CD4+ T Cells in Progressive Visceral Leishmaniasis Show a Mixed Effector-Regulatory Phenotype and Impair Macrophage Effector Function through Inhibitory Receptor Expression

et al. 2017

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Visceral leishmaniasis (VL), caused by infection with the intracellular protozoan Leishmania donovani, is a chronic progressive disease with a relentlessly increasing parasite burden in the spleen, liver and bone marrow. The disease is characterized by fever, splenomegaly, cachexia, and pancytopenia, and progresses to death if not treated. Control of Leishmania infection is mediated by Th1 (IFNγ-producing) CD4+ T cells, which activate macrophages to produce nitric oxide and kill intracellular parasites. However, despite expansion of CD4+ T cells and increased IFNγ expression in the spleen, humans with active VL do not control the infection. We used an experimental model of chronic progressive VL in hamsters, which mimics clinical and pathological features seen in humans, to better understand the mechanisms that lead to progressive disease. Transcriptional profiling of the spleen during chronic infection revealed expression of markers of both T cell activation and inhibition. CD4+ T cells isolated from the spleen during chronic progressive VL showed mixed expression of Th1 and Th2 cytokines and chemokines, and were marginally effective in controlling infection in an ex vivo T cell-macrophage co-culture system. Splenic CD4+ T cells and macrophages from hamsters with VL showed increased expression of inhibitory receptors and their ligands, respectively. Blockade of the inhibitory receptor PD-L2 led to a significant decrease in parasite burden, revealing a pathogenic role for the PD-1 pathway in chronic VL. PD-L2 blockade was associated with a dramatic reduction in expression of host arginase 1, but no change in IFNγ and inducible nitric oxide synthase. Thus, the expression of counter-regulatory molecules on splenic CD4+ T cells and macrophages promotes a more permissive macrophage phenotype and attenuates intracellular parasite control in chronic progressive VL. Host-directed adjunctive therapy targeting the PD-1 regulatory pathway may be efficacious for VL.

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Section: Discussionmentioning

confidence: 99%

Splenic CD4+ T Cells in Progressive Visceral Leishmaniasis Show a Mixed Effector-Regulatory Phenotype and Impair Macrophage Effector Function through Inhibitory Receptor Expression

et al. 2017

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“…In such patients, it offers distinct anti-leukemic effectiveness and prolongs survival similar to allogeneic transplantation while avoiding morbidity and mortality of graft versus host disease associated with allogeneic transplantation [2,17]. However, prospective studies in elderly AML patients comparing chemotherapy consolidation with autologous stem cell transplantation (ASCT) or allogeneic transplantation are lacking.…”

Section: Introductionmentioning

confidence: 99%

Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years

et al. 2017

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“…In previous studies including various AML subtypes, we have observed a wide variation in mobilized circulating CD34+ cells at the day of peripheral stem cell collection after two induction cycles [11][12]. We identified a poor stem cell mobilization potential (CD34+ low ) to predict favorable long-term outcome after autologous SCT, whereas high levels of mobilized CD34+ cells (CD34+ high ) were associated with adverse outcome.…”

Section: Lettermentioning

confidence: 76%

Molecular minimal residual disease negativity and decreased stem cell mobilization potential predict excellent outcome after autologous transplant in NPM1 mutant acute myeloid leukemia

et al. 2019

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Delayed Haematological recovery after autologous stem cell transplantation is associated with favourable outcome in acute myeloid leukaemia

Cited by 17 publications

References 23 publications

Splenic CD4+ T Cells in Progressive Visceral Leishmaniasis Show a Mixed Effector-Regulatory Phenotype and Impair Macrophage Effector Function through Inhibitory Receptor Expression

Splenic CD4+ T Cells in Progressive Visceral Leishmaniasis Show a Mixed Effector-Regulatory Phenotype and Impair Macrophage Effector Function through Inhibitory Receptor Expression

Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years

Molecular minimal residual disease negativity and decreased stem cell mobilization potential predict excellent outcome after autologous transplant in NPM1 mutant acute myeloid leukemia

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