Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation

Because information on management and outcome of AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of EBMT. Among 2815 RIC transplants performed for AML in complete remission (CR) between 1999 and 2008, cumulative incidence of relapse was 32% ± 1%. Relapsed patients (263) were included into a detailed analysis of risk factors for overall survival (OS) and building of a prognostic score. CR was reinduced in 32%; remission duration after transplantation was the only prognostic factor for response (P = .003). Estimated 2-year OS from relapse was 14%, thereby resembling results of AML relapse after standard conditioning. Among variables available at the time of relapse, remission after HSCT > 5 months (hazard ratio [HR] = 0.50, 95% confidence interval [CI], 0.37-0.67, P < .001), bone marrow blasts less than 27% (HR = 0.53, 95% CI, 0.40-0.72, P < .001), and absence of acute GVHD after HSCT (HR = 0.67, 95% CI, 0.49-0.93, P = .017) were associated with better OS. Based on these factors, 3 prognostic groups could be discriminated, showing OS of 32% ± 7%, 19% ± 4%, and 4% ± 2% at 2 years (P < .0001). Long-term survival was achieved almost exclusively after successful induction of CR by cytoreductive therapy, followed either by donor lymphocyte infusion or second HSCT for consolidation.     

Younger donor's age and upfront tandem are two independent prognostic factors for survival in multiple myeloma patients treated by tandem autologous-allogeneic stem cell transplantation: a retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Background

How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Design and Methods

This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure.

Results

Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2–132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39–57 %) and 27% (95% CI 19–36), respectively. Eighteen patients (12%) experienced grade III–IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant-related mortality rate at 1 year was 15% (95% CI 10–22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor’s age ≤50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor’s age ≤50 years and full chimerism were independent prognostic factors for better outcome.

Conclusions

We confirmed the feasibility of tandem autologour-allogeneic transplantation in heavily treated patients with multiple myeloma. We identified younger donor’s age and upfront tandem transplantation as two independent prognostic factors for survival which could be further explored in prospective studies.     

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy

TRACK‐HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3‐Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross‐sectional data from this large well‐characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene‐positive subjects (120 PreHD and 119 early HD) from the TRACK‐HD study were included. Using voxel‐based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti‐saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

The evolving role of the personal support worker in home care in Ontario,Canada

To meet increasing demand for home care, the role of personal support workers (PSWs) is shifting from providing primarily personal and supportive care to include care activities previously provided by regulated health professionals (RHPs). Much of the research examining this shift focuses on specialty programmes, with few studies investigating the daily care being provided by PSWs, frequency of care activities being provided by PSWs, and characteristics of the population receiving more complex tasks. Between January and April 2015, a review of 517 home‐care service user charts was undertaken in Ontario, Canada, to: (1) describe the range of tasks being performed by PSWs in home care, (2) identify tasks transferred by RHPs to PSWs, and (3) examine characteristics of service users receiving transferred care. Findings indicate that normally, PSWs provide personal and supportive care commensurate with their training. However, in approximately one quarter of care plans reviewed, PSWs also completed more complex care activities transferred to them by RHPs. Service users receiving transferred care were older and had higher levels of cognitive and functional impairment. Although there is potential for the expansion of home‐care services through increased utilisation of PSWs, healthcare leadership must ensure that the right provider is being utilised at the right time and in the right place to ensure safe and effective quality care. Thus, several actions are recommended: PSW core competencies be clearly articulated, processes used to transfer care activities from RHPs to PSWs be standardised and a team‐based approach to the delivery of home‐care services be considered. Utilisation of a team‐based model can help establish positive relationships among home‐care providers, provide increased support for PSWs, allow for easier scheduling of initial training and ensure regular reassessments of PSW competence among PSWs providing added skills.     

Integrative Pharmacology: Advancing Development of Effective Immunotherapies

With the recent advances in cancer immunotherapy, it is now evident that the antigen-specific activation of the patients’ immune responses can be utilized for achieving significant therapeutic benefits. Novel molecules have been developed and promising advances have been achieved in cancer therapy. The recent success of cancer immunotherapy clearly reflects the novelty of the approach and importance of this class of therapeutics. Due to the nature of immunotherapy, i.e., harnessing the patient’s immune system, it becomes critical to evaluate the important variables that can guide preclinical development, translational strategies, patient selection, and effective clinical dosing paradigms following single and combination therapies. To further boost the durability and efficacy profiles of IO (immuno-oncology) drugs following single agent therapy, novel combination therapies are being sought. Combination strategies have become critical for enhancing the anti-tumor immunity in broader cancer indications. Comprehensive methods are being developed to quantify the synergistic combination effect profiles at various development phases. Further evaluation of the signaling and pathway components can potentially establish a unique “signature” characteristic for specific combination therapies following modulation of various immunomodulatory pathways. In this article, critical topics related to preclinical, translational, and clinical development of IO agents are discussed.     

Characteristics of ''best'' and ''worst'' clinical teachers as perceived by university nursing faculty and students

This study identified and compared characteristics of 'best' and 'worst' clinical teachers as perceived by university nursing faculty and students. The Nursing Clinical Teacher Effectiveness Inventory (NCTEI) was distributed to 201 volunteer subjects. This survey instrument, developed by the authors, contains 48 clinical teacher characteristics grouped into five categories. Each participant was asked to rate, using the NCTEI, the 'best' and them the 'worst' clinical teacher from past observations. Results showed both groups perceived that being a good role model was the highest rated characteristic for 'best' teachers and the 'lowest' rated characteristic for 'worst' teachers. Faculty and students' perceptions were fairly similar as to highest rated characteristics of 'best' clinical teachers. Less agreement was noted about the characteristics of 'worst' clinical teachers. When categories of clinical teacher characteristics were compared, there were significant differences between the ratings of faculty and students for 'best' clinical teachers, but none for 'worst' clinical teachers.