In vitro generated dendritic cells of leukemic origin predict response to allogeneic stem cell transplantation in patients with AML and MDS

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

Changing the system by changing the workforce: employing consumers to increase access, cultural diversity, and engagement

Services to families have traditionally been delivered in a medical model. This presents challenges including workforce shortages, lack of cultural diversity, lack of training in strength-based work, and difficulty in successfully engaging and retaining families in the therapy process. The system of care (SOC) effort has worked to establish formal roles for caregivers in SOC to improve services. This paper provides an example of one community\u27s efforts to change the SOC by expanding the roles available to caregivers in creating systems change. It describes the model developed by Communities of Care (CoC), a SOC in Central Massachusetts, and its evolution over a 10 year period. First person accounts by system partners, caregivers hired into professional roles as well as a family receiving services, demonstrate how hiring caregivers at all levels can change systems and change lives, not only for those being served but for the caregiver/professionals doing the work. It also demonstrates, however, that change at the system level is incremental, takes time, and can be fleeting unless an ongoing effort is made to support and sustain those changes

In vitro-induced response patterns of antileukemic T cells: characterization by spectratyping and immunophenotyping

Reuther S, Schmetzer H, Schuster FR, et al. In vitro-induced response patterns of antileukemic T cells: characterization by spectratyping and immunophenotyping. Clinical and Experimental Medicine. 2013;13(1):29-48.Myeloid leukemic cells can be induced to differentiate into leukemia-derived dendritic cells (DC(leu)) regaining the stimulatory capacity of professional DCs while presenting the leukemic antigen repertoire. But so far, the induced antileukemic T-cell responses are variable both in specificity and in efficacy. In an attempt to elucidate the underlying causes of different T-cell response patterns, T-cell receptor (TR) Vβ chain rearrangements were correlated with the T cells corresponding immunophenotypic profile, as well as their proliferative response and cytolytic capacities. In three different settings, donor T cells, either human leukocyte antigen matched or mismatched (haploidentical), or autologous T cells were repeatedly stimulated with myeloid blasts or leukemia-derived DC/DC(leus) from the corresponding patients diseased from acute myeloid leukemia (AML). Although no significant differences in T-cell proliferation were observed, the T-cell-mediated cytolytic response pattern varied considerably and even caused blast proliferation in two cases. Spectratyping revealed a remarkable restriction (>75 % of normal level) of the CD4(+) or CD8(+)-TR repertoire of blast- or DC/DC(leu)-stimulated T cells. Although in absolute terms, DC/DC(leu) stimulation induced the highest grade of restriction in the CD8(+) T-cell subset, the CD4(+) T-cell compartment seemed to be relatively more affected. But most importantly, in vitro stimulation with DC/DC(leu) resulted into an identical TR restriction pattern (β chain) that could be identified in vivo in a patient sample 3 months after allo-SCT. Thus, in vitro tests combining functional flow cytometry with spectratyping might provide predictive information about T cellular response patterns in vivo