Impact of timing of stem cell return following high dose melphalan in multiple myeloma patients with renal impairment: a single center experience

High dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) remains the standard consolidation in transplant eligible multiple myeloma (MM) patients. The timing between HDM administration and hematopoietic stem cell return (HSCR) varies among institutions, with a 'rest period' of 48 hours (h) employed by some for patients with renal impairment (RI). We investigated the differences in hematopoietic recovery and HDM toxicity between MM patients with RI who had HSCR after 24 vs 48 h from HDM. Fifty MM patients with RI (48 h group; n = 31 and 24 h group; n = 19) were included. No statistically significant differences were noted in surrogates for hematopoietic recovery and HDM toxicity between both groups. Only one death occurred in the 24 h group. No patients required renal replacement therapy. Therefore, a 24 h period between HDM and AHSC infusion appears safe for MM patients with RI

Predictors of recovery following allogeneic CD34+-selected cell infusion without conditioning to correct poor graft function

Poor graft function is a serious complication following allogeneic hematopoietic stem cell transplantation. Infusion of CD34+-selected stem cells without pre-conditioning has been used to correct poor graft function, but predictors of recovery are unclear. We report the outcome of 62 consecutive patients who had primary or secondary poor graft function who underwent a CD34+-selected stem cell infusion from the same donor without further conditioning. Forty-seven of 62 patients showed hematological improvement and became permanently transfusion and growth factor-independent. In multivariate analysis, parameters significantly associated with recovery were shared CMV seronegative status for recipient/donor, the absence of active infection and matched recipient/donor sex. Recovery was similar in patients with mixed and full donor chimerism. Five -year overall survival was 74.4% (95% CI 59-89) in patients demonstrating complete recovery, 16.7% (95% CI 3-46) in patients with partial recovery and 22.2% (CI 95% 5-47) in patients with no response. In patients with count recovery, those with poor graft function in 1-2 lineages had superior 5-year overall survival (93.8%, 95% CI 82-99) than those with tri-lineage failure (53%, 95% CI 34-88). New strategies including cytokine or agonist support, or second transplant need to be investigated in patients who do not recover

A novel predictive algorithm to personalize autologous T-cell harvest for chimeric antigen receptor T-cell manufacture.

BACKGROUND AIMS The most widely accepted starting materials for chimeric antigen receptor T-cell manufacture are autologous CD3+ T cells obtained via the process of leukapheresis, also known as T-cell harvest. As this treatment modality gains momentum and apheresis units struggle to meet demand for harvest slots, strategies to streamline this critical step are warranted. METHODS This retrospective review of 262 T-cell harvests, with a control cohort of healthy donors, analyzed the parameters impacting CD3+ T-cell yield in adults with B-cell malignancies. The overall aim was to design a novel predictive algorithm to guide the required processed blood volume (PBV) (L) on the apheresis machine to achieve a specific CD3+ target yield. RESULTS Factors associated with CD3+ T-cell yield on multivariate analysis included peripheral blood CD3+ count (natural log, ×109/L), hematocrit (HCT) and PBV with coefficients of 0.86 (95% confidence interval [CI], 0.80-0.92, P < 0.001), 1.30 (95% CI, 0.51-2.08, P = 0.001) and 0.09 (95% CI, 0.07-0.11, P < 0.001), respectively. The authors' model, incorporating CD3+ cell count, HCT and PBV (L), with an adjusted R2 of 0.87 and root-mean-square error of 0.26 in the training dataset, was highly predictive of CD3+ cell yield in the testing dataset. An online application to estimate PBV using this algorithm can be accessed at https://cd3yield.shinyapps.io/cd3yield/. CONCLUSIONS The authors propose a transferrable model that incorporates clinical and laboratory variables accessible pre-harvest for use across the field of T-cell therapy. Pending further validation, such a model may be used to generate an individual leukapheresis plan and streamline the process of cell harvest, a well-recognized bottleneck in the industry

Insect pollinators: linking research and policy. Workshop report.

EXECUTIVE SUMMARY Pollinators interact with plants to underpin wider biodiversity, ecosystem function, ecosystem services to agricultural crops and ultimately human nutrition. The conservation of pollinators is thus an important goal. Pollinators and pollination represent a tractable example of how biodiversity can be linked to an ecosystem service. This represents a case study for exploring the impacts of various policy instruments aiming to halt/reverse the loss of ecosystem services. There is a need to understand how multiple pressures (e.g. habitat loss, fragmentation and degradation, climate change, pests and diseases, invasive species and environmental chemicals) can combine or interact to affect diversity, abundance and health of different pollinator groups. Decision makers need to balance consideration of the effects of single pressures on pollinators against the suite of other pressures on pollinators. For instance, the threat from pesticide use (with its high public and media profile) also needs to be considered in the context of the other threats facing pollinators and balanced against the need for food security. An independent review of the balance of risks across pollinator groups from pesticide use would help synthesise current knowledge into an accessible form for decision makers. To manage or lessen these threats to pollinators (wild and managed) and pollination requires improved knowledge about their basic ecology. We still need to know where and in what numbers different pollinator species occur, how they use different environments, how they interact with each other through shared plants and diseases and how wild pollinator abundance is changing. Decision makers need clear factual evidence for i) the relative contribution of different managed and wild pollinator groups to wildflower and crop pollination and ii) how this varies across different land-uses, ecosystems and regions. Addressing these basic and applied questions will improve our ability to forecast impacts on pollination service delivery to agricultural crops arising from current and future environmental changes, pesticide use and emerging diseases. The development of a long-term, multi-scale monitoring scheme to monitor trends in pollinator (wild and managed) population size and delivery of pollination services (ideally tied to data collection on land-use, pesticide applications and disease incidence at relevant spatial scales) would provide the evidence base for developing the effectiveness of policy and management interventions over time. Such a monitoring scheme would benefit from including research council organisations (e.g. CEH), governmental departments (e.g. Fera), universities, museums and NGOs (e.g. BBKA,SBA, Bumblebee Conservation Trust etc) Insect Pollinators: linking research and policy Workshop Report | 5 In the context of agricultural intensification and conservation we need to establish what type, quality and quantity of interventions (e.g. agri-environment schemes, protected areas) are needed, where to place them and how they can sustain different pollinator populations and effective pollination services. Current monitoring of the risks from diseases and pesticides requires broadening to consider other insects aside from honey bees, unless we can demonstrate that honey bees are good surrogates for all other pollinators. There is a need to increase confidence in regulatory risk assessments pertaining to pathogens and pesticides by incorporating other pollinator species, investigating chronic exposure to multiple chemicals and using field relevant dosages (specific to regions, not using other data sources as surrogates). At present the effects of spatial, social and temporal scales on the benefits stakeholders receive from pollination services are only beginning to be understood. Economic valuation of pollination services can help optimise the cost-effectiveness of service management measures and offer new opportunities to incentivise action or raise awareness among stakeholders. Novel tools and instruments (e.g. education and training) are needed to translate broad international (e.g. CBD, EU Biodiversity Strategy) and national (e.g. England‟s Biodiversity Strategy) policies into local actor (e.g. beekeeper, farmer, citizen scientist) contributions to meet biodiversity commitments Refocusing some public funding to link basic science to development of practical solutions (e.g. better crop protection products, improved disease resistance or treatment) could help science deliver better-targeted evidence for pollinator protection. Scientists need to make more use of opportunities (e.g. POSTnotes1; practitioner guides) to transfer knowledge to a broad audience in order to better influence decision maker and practitioner behaviours. Improved knowledge exchange between scientists and decision makers is important to combating threats to pollination. Central to this is improved understanding of the respective positions of policy makers and scientists. For instance, policy-makers usually need to be presented with a range of options to balance against other areas of policy. Science does not always arrive at a consensus due to uncertainties in data or models. Policy-makers need to understand that scientists are communicating the “best available knowledge at present” and that consequently it is not always possible to give a definitive answer