Outcomes of acute leukemia patients transplanted with naive T cell–depleted stem cell grafts

4,657

5,387

The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease

Section: Org Frommentioning

confidence: 99%

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

Döhner

Estey

Grimwade

et al. 2017

4,657

5,387

“…21,22 Because allogeneic mHAgs are not expressed by thymic antigen-presenting cells (APCs) of self-origin, alloreactive T cells specific for mHAgs occur almost exclusively in the naive T-cell repertoire. 16 Recent clinical protocols of selective depletion of naive T cells from the graft 23,24 therefore have the potential to profoundly ablate T-cell alloreactivity after HLA-matched sibling HCT. This approach is promising for nonmalignant disorders where GVL is not an issue, but must be carefully weighed against the disease risk for individual patients transplanted for malignant disease.…”

Section: Introductionmentioning

confidence: 99%

HLA-DP in unrelated hematopoietic cell transplantation revisited: challenges and opportunities

Fleischhauer

Shaw

2017

When considering HLA-matched hematopoietic cell transplantation (HCT), sibling and unrelated donors (UDs) are biologically different because UD-HCT is typically performed across HLA-DP disparities absent in sibling HCT. Mismatched HLA-DP is targeted by direct alloreactive T cell responses with important implications for graft-versus-host disease and graft-versus-leukemia. This concise review details special features of HLA-DP as model antigens for clinically permissive mismatches mediating limited T-cell alloreactivity with minimal toxicity, and describes future avenues for their exploitation in cellular immunotherapy of malignant blood disorders.

“…However, it must be noted that although the CMV-specific memory T cells within this polyclonal T-cell population effectively controlled CMV, the contaminating naive T cells were also capable of inducing GVHD. Thus, logical clinical approaches to treat CMV infection in patients with GVHD should focus on comparing the transfer of pathogen-specific memory T cells expanded by in vitro culture with appropriate antigen, vs the transfer of naive T-cell-depleted memory T cells, as recently described by Bleakley et al 42 The longevity of these adoptively transferred T cells is an important clinical consideration and future studies should address this issue. Most current clinical protocols focus on managing CMV disease with preemptive antiviral therapy administered at first evidence of active infection.…”

mentioning

confidence: 99%

Acute GVHD results in a severe DC defect that prevents T-cell priming and leads to fulminant cytomegalovirus disease in mice

Wikström

Fleming

Kuns

et al. 2015