STAT3 mutations indicate the presence of subclinical T-cell clones in a subset of aplastic anemia and myelodysplastic syndrome patients.

Large granular lymphocyte leukemia (LGL) is often associated with immune cytopenias and can cooccur in the context of aplastic anemia (AA) and myelodysplastic syndromes (MDS). We took advantage of the recent description of signal transducer and activator of transcription 3 (STAT3) mutations in LGL clonal expansions to test, using sensitive methods, for the presence of these mutations in a large cohort of 367 MDS and 140 AA cases. STAT3 clones can be found not only in known LGL concomitant cases, but in a small proportion of unsuspected ones (7% AA and 2.5% MDS). In STAT3-mutated AA patients, an interesting trend toward better responses of immunosuppressive therapy and an association with the presence of human leukocyte antigen-DR15 were found. MDSs harboring a STAT3 mutant clone showed a lower degree of bone marrow cellularity and a higher frequency of developing chromosome 7 abnormalities. STAT3-mutant LGL clones may facilitate a persistently dysregulated autoimmune activation, responsible for the primary induction of bone marrow failure in a subset of AA and MDS patients.

A Scoping Literature Review: The State of Knowledge on Home Care Equipment and Supplies.

We explored the state of knowledge on home care supplies and equipment because not much is known about this topic. We used a scoping review for the literature review because it was the most appropriate approach considering the state of the literature. We searched for articles published in both the gray and peer-reviewed literature. We established five overarching themes based on the findings. These were supply management, durable medical equipment, wound care, best practices, and costs. This review demonstrates that although knowledge about home care supplies and equipment is growing, it is still an understudied area.

Leukemic cluster growth in culture is an independent risk factor for acute myeloid leukemia and short survival in patients with myelodysplastic syndrome.

In patients with myelodysplastic syndrome (MDS) precursor cell cultures (colony-forming unit cells, CFU-C) can provide an insight into the growth potential of malignant myeloid cells. In a retrospective single-center study of 73 untreated MDS patients we assessed whether CFU-C growth patterns were of prognostic value in addition to established criteria. Abnormalities were classified as qualitative (i.e. leukemic cluster growth) or quantitative (i.e. strongly reduced/absent growth). Thirty-nine patients (53%) showed leukemic growth, 26 patients (36%) had strongly reduced/absent colony growth, and 12 patients showed both. In a univariate analysis the presence of leukemic growth was associated with strongly reduced survival (at 10 years 4 vs. 34%, p = 0.004), and a high incidence of transformation to AML (76 vs. 32%, p = 0.01). Multivariate analysis identified leukemic growth as a strong and independent predictor of early death (relative risk 2.12, p = 0.03) and transformation to AML (relative risk 2.63, p = 0.04). Quantitative abnormalities had no significant impact on the disease course. CFU-C assays have a significant predictive value in addition to established prognostic factors in MDS. Leukemic growth identifies a subpopulation of MDS patients with poor prognosis.

Seeing the good and bad in aplastic anemia: is autoimmunity in AA dysregulated or antineoplastic?

Aplastic anemia (AA) is considered to be an autoimmune disease directed against hematopoietic stem cells (HSC), though knowledge on the inciting autoantigen(s) is scant. According to the traditional concept of autoimmunity the target tissue in autoimmune disease is essentially normal, and misdirected self-attack is caused by disturbed self-recognition. Recently, this theory has been challenged by the hypothesis that autoimmunity against solid tissues is directed against intrinsically abnormal, transforming cells, i.e. autoimmune reactions are essentially antineoplastic, attempting to eliminate cells signalling 'danger'. This theory might apply to AA as well. Observations such as the dysplastic traits typical of non-severe AA, the high prevalence of one or several abnormal hematopoietic clones and their resistance to apoptosis in newly diagnosed AA patients suggest that these cell populations do not develop secondarily, but expand primarily und could be the primary target of AA, normal hematopoietic stem cells being destroyed as innocent bystanders. If bone marrow hypoplasia/aplasia indeed reflects an immune reaction incited by outgrowth of transformed cells, immunosuppressive treatment of AA would have to be reconsidered, since a two-edged sword. As a consequence, AA patients with a hyperreactive immune system may require more intense immunosuppressive therapy (IS), whereas patients with an anergic immune system may fare better with IS of lower intensity than the currently recommended standard.

Uncovering the Meaning of Home Care Using an Arts-Based and Qualitative Approach.

The need for home care is increasing in Canada, yet little is known about the home care experience of clients and their families. Uncovering the meaning of the home care experience is an important step towards developing understanding and public awareness. We explored the experiences of home care using arts-based methods and individual interviews with 11 participants (one client and 10 family caregivers). Participants discussed the numerous ways formal home care and family caregiving affected their lives, how they coped with these effects, their experiences in hospitals or assisted living facilities, and aspects of the home care experience they liked or disliked. Participants agreed that home care facilitated a better quality of life for families and clients, although they acknowledged some challenges with it. The artistic outputs produced by participants facilitated interview dialogue and fostered understanding of key themes within the research team.

Acquired immune mediated aplastic anemia: is it antineoplastic?

There is increasing evidence that autoimmunity can inhibit growth of solid tumors. We propose that anti-tumor activity also operates in autoimmunity against hematopoietic stem cells in acquired aplastic anemia (AA). Reduction/dysfunction of regulatory T cells (T(REG)) in AA - rather than being the primary event - could be a response to insufficient or failing anti-tumor reactivity in predisposed individuals, causing elimination of tumor cells and collateral damage to adjacent normal hematopoietic tissue. This pathophysiological mechanism could also apply to otherwise unexplained pancytopenic syndromes which frequently occur in patients with leukemia and lymphoma and non-hematological malignancies. Observations supporting an anti-tumor effect of marrow hypoplasia/aplasia are presented and illustrated with case reports. The conclusion would be that pancytopenia occurring in AA or in AA-like syndromes reflects an ongoing immune reaction against underlying malignancy or infection.

Quality-adjusted survival analysis shows differences in outcome after immunosuppression or bone marrow transplantation in aplastic anemia.

Bone marrow transplantation (BMT) and immunosuppression (IS) have improved the prognosis of aplastic anemia; both treatments have specific advantages and drawbacks but similar survival rates. Analysis of additional endpoints may help in treatment decisions. In a single-center study, patients with aplastic anemia treated with IS (n=155) or BMT (n=52) were compared for survival, event-free survival, and quality-adjusted time without symptoms and toxicity (Q-TWiST). Probability of overall and event-free survival at 15 years was similar among both groups (BMT 51+/-15% and 25+/-14%, IS 53+/-10% and 27+/-8%), with more early deaths in the transplant group and more late deaths in the IS group. There were differences in terms of mean duration of seven analyzed health states: time with symptoms from treatment-related toxicity (IS 0.36 years, BMT 0.27), transfusion dependency (IS 0.66 years, BMT 0.1 years), partial remission (IS 3.27 years, BMT 1.42), and secondary clonal disorder (IS 0.68 years, BMT 0.04) was significantly longer for IS compared to BMT (p< or =0.001). Patients treated with BMT spent more time with extensive chronic graft-versus-host disease (GvHD) (IS 0 years, BMT 0.96, p<0.023) and in CR without drugs (IS 1.22 years, BMT 2.43, p=0.056). In conclusion, survival, event-free survival, and Q-TWiST are similar. BMT-treated patients had longer periods free from symptoms, while IS-treated patients needed closer medical care, transfusion support, and medications.

Reconstitution of dendritic and natural killer-cell subsets after allogeneic stem cell transplantation: effects of endogenous flt3 ligand.

Recovery of dendritic cells (DCs) and natural killer (NK) cells after allogeneic stem cell transplantation (SCT) is important for allograft responses and antitumor immunity and thus for treatment outcome. Regulation of this regenerative process is not well understood. We investigated the influence of endogenous cytokines on the recovery and diversification of DC and NK cell subsets up to 6 months after SCT. Reconstitution of circulating DCs and NK cells was rapid but accompanied by prolonged skewing of cell subsets. The speed of recovery of CD11c(+)CD123(low) DC1 exceeded that of CD11c(-) CD123(+) DC2, and correlated with plasma levels of flt3 ligand (FL), but not with granulocyte or granulocyte-macrophage colony-stimulating factors and stem cell factor. There was a 5-fold increase in interferon-gamma-producing CD56(high)CD16(-)/low NK cells and a corresponding reduction in the CD56(low)CD16(high) subset, accompanied by strongly reduced NK cell cytotoxicity. In vitro data implicate an inhibitory effect of cyclosporin A on NK cell differentiation and cytotoxicity. NK cell numbers did not correlate with plasma levels of FL or interleukin 15. Our results demonstrate that endogenous FL has distinct effects on the kinetics of reconstitution of DCs and NK cells and have potential implications for the modulation of immune responses after allogeneic SCT.