CPX-351 Pharmacokinetics and Safety in Adults with Hematologic Malignancies and Renal Function Impairment: Phase 1 Trial.

This open-label phase 1 study (clinicaltrials.gov, NCT03555955) assessed CPX-351 pharmacokinetics (PK) and safety in patients with hematologic malignancies with normal or impaired renal function. Patients were enrolled into three cohorts based on their creatinine clearance (CrCl): ≥90 mL/min (Cohort 1, normal renal function, n = 7), 30 to <59 mL/min (Cohort 2, moderate renal impairment, n = 8), or <30 mL/min (Cohort 3, severe renal impairment, n = 6). Patients received intravenous CPX-351 for initial induction; blood and urine samples were collected for PK analysis. The primary objective was to assess the PK parameters for cytarabine, daunorubicin, and their respective metabolites, arabinosyluracil (Ara-U) and daunorubicinol. Renal impairment did not significantly impact the cytarabine, daunorubicin, or daunorubicinol exposure, but it caused a slight increase in the Ara-U exposure. The CPX-351 side effect profile was similar in patients with impaired renal function compared to those with normal renal function. All the patients reported ≥1 treatment-emergent adverse event (TEAE), most commonly febrile neutropenia and nausea (57% each) and hyperglycemia (43%); no patients discontinued treatment due to TEAEs. These data suggest that CPX-351 dose adjustment is not required for patients with hematologic malignancies with moderate or severe renal impairment.

The influence of body painting on L4 spinous process palpation accuracy in novice palpators.

OBJECTIVES: Current literature remains inconclusive regarding the best methodology to accurately palpate lumbar spinous processes (SP). Body painting (BP) uses markers to draw anatomical structures on the skin's surface. While BP can be a useful tool for engaging learners, it is unknown whether it improves palpation accuracy. The purpose of this study was to investigate whether the addition of body painting to palpation education improves lumbar spinous process palpation accuracy in first-year Doctor of Physical Therapy (DPT) students. METHODS: Thirty-eight DPT students were randomized into a traditional palpation group and a body painting (BP) group. Each group received identical instruction on palpating the lumbar spine, with the BP group additionally drawing lumbar SPs on their laboratory partner with a marker. Students were then assessed on their ability to accurately palpate the L4 SP on randomly assigned subjects. Two Certified Registered Nurse Anesthetists (CRNAs) used ultrasound imaging to confirm the location of each student's palpation. Palpation time was also recorded. The BP group also completed a survey on the learning experience. RESULTS: Forty-five percent of students were able to accurately palpate the L4 SP. There was no significant difference (p = 0.78) in palpation accuracy between the traditional and BP group, although students in the BP group were randomly assigned subjects with a significantly (p = 0.005) higher BMI. Ninety-five percent of students were able to palpate within one spinal level of the L4 SP. Students in the BP group reported that the BP activity facilitated learning and active participation. There was no significant difference in palpation time (p = 0.98) between groups. There was a fair correlation (r=-0.41) between palpation accuracy and subject BMI. DISCUSSION/CONCLUSION: While body painting was an enjoyable activity to incorporate into palpation laboratory, it is unclear whether it enhanced lumbar SP palpation accuracy in first-year DPT students.

Bearded or smooth? Awns improve yield when wheat experiences heat stress during grain fill in the southeastern United States.

The presence or absence of awns-whether wheat heads are 'bearded' or 'smooth' - is the most visible phenotype distinguishing wheat cultivars. Previous studies suggest that awns may improve yields in heat or water-stressed environments, but the exact contribution of awns to yield differences remains unclear. Here we leverage historical phenotypic, genotypic, and climate data for wheat (Triticum aestivum) to estimate the yield effects of awns under different environmental conditions over a 12-year period in the southeastern USA. Lines were classified as awned or awnless based on sequence data, and observed heading dates were used to associate grain fill periods of each line in each environment with climatic data and grain yield. In most environments, awn suppression was associated with higher yields, but awns were associated with better performance in heat-stressed environments more common at southern locations. Wheat breeders in environments where awns are only beneficial in some years may consider selection for awned lines to reduce year-to-year yield variability, and with an eye towards future climates.

Genetic Variation and Heritability of Sensory and Artisan Bread Traits in a Set of SRW Wheat Breeding Lines.

Focus on local food production and supply chains has heightened in recent years, as evidenced and amplified by the COVID-19 pandemic. This study aimed to assess the suitability of soft red winter (SRW) wheat breeding lines for local artisan bakers interested in locally sourced, strong gluten wheat for bread. Seventy-six genotyped SRW wheat breeding lines were milled into whole wheat flour and baked into small loaves. Bread aroma, flavor, and texture were evaluated by a sensory panel, and bread quality traits, including sedimentation volume, dough extensibility, and loaf volume, were measured to estimate heritability. SE-HPLC was performed on white flour, and breeding lines were characterized for different protein fraction ratios. Heritability of loaf volume was moderately high (h2 = 0.68), while heritability of sedimentation volume, a much easier trait to measure, was slightly lower (h2 = 0.55). Certain protein fraction ratios strongly related to loaf volume had high heritability (h2 = 0.7). Even though only a moderate heritability estimate of dough extensibility was found in our study, high positive correlations were found between this parameter and sedimentation volume (r = 0.6) and loaf volume (r = 0.53). This low-input and highly repeatable parameter could be useful to estimate dough functionality characteristics. Flavor and texture heritability estimates ranged from 0.16 to 0.37, and the heritability estimate of aroma was not significantly different from zero. However, the sensorial characteristics were significantly correlated with each other, suggesting that we might be able to select indirectly for aroma by selecting for flavor or texture characteristics. From a genome-wide association study (GWAS), we identified six SNPs (single nucleotide polymorphisms) associated with loaf volume that could be useful in breeding for this trait. Producing high-quality strong gluten flour in our high rainfall environment is a challenge, but it provides local growers and end users with a value-added opportunity.

Sustaining productivity gains in the face of climate change: A research agenda for US wheat.

Wheat is a globally important crop and one of the "big three" US field crops. But unlike the other two (maize and soybean), in the United States its development is commercially unattractive, and so its breeding takes place primarily in public universities. Troublingly, the incentive structures within these universities may be hindering genetic improvement just as climate change is complicating breeding efforts. "Business as usual" in the US public wheat-breeding infrastructure may not sustain productivity increases. To address this concern, we held a multidisciplinary conference in which researchers from 12 US (public) universities and one European university shared the current state of knowledge in their disciplines, aired concerns, and proposed initiatives that could facilitate maintaining genetic improvement of wheat in the face of climate change. We discovered that climate-change-oriented breeding efforts are currently considered too risky and/or costly for most university wheat breeders to undertake, leading to a relative lack of breeding efforts that focus on abiotic stressors such as drought and heat. We hypothesize that this risk/cost burden can be reduced through the development of appropriate germplasm, relevant screening mechanisms, consistent germplasm characterization, and innovative models predicting the performance of germplasm under projected future climate conditions. However, doing so will require coordinated, longer-term, inter-regional efforts to generate phenotype data, and the modification of incentive structures to consistently reward such efforts.

Real-World Treatment Patterns and Clinical Outcomes in Canadian Patients with AML Unfit for First-Line Intensive Chemotherapy.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.

Management of Acute Myeloid Leukemia: A Review for General Practitioners in Oncology.

Acute myeloid leukemia (AML) is a hematologic malignancy that most frequently develops in older adults. Overall, AML is associated with a high mortality although advancements in genetic risk stratification and new treatments are leading to improvements in outcomes for some subgroups. In this review, we discuss an individualized approach to intensive therapy with a focus on the role of recently approved novel therapies as well as the selection of post-remission therapies for patients in first remission. We discuss the management of patients with relapsed and refractory AML, including the role of targeted treatment and allogeneic stem cell transplant. Next, we review non-intensive treatment for older and unfit AML patients including the use of azacitidine and venetoclax. Finally, we discuss the integration of palliative care in the management of patients with AML.

Healthcare resource utilization trends in patients with acute myeloid leukemia ineligible for intensive chemotherapy receiving first-line systemic treatment or best supportive care: A multicenter international study.

OBJECTIVES: This retrospective chart review examined real-world healthcare resource utilization (HRU) in patients with AML ineligible for intensive therapy who received first-line systemic therapy or best supportive care (BSC). METHODS: Data were collected anonymously on patients with AML who initiated first-line hypomethylating agents (HMA), low-dose cytarabine (LDAC), other systemic therapy, or BSC. HRU endpoints included hospitalizations, outpatient consultations, transfusions, and supportive care. RESULTS: Of 1762 patients included, 46% received HMA, 11% received LDAC, 17% received other systemic therapy, 26% received BSC; median treatment durations were 118, 35, 33, and 57 days, respectively. Most patients were hospitalized, most commonly for treatment administration, transfusion, or infection (HMA 82%, LDAC 93%, other systemic therapy 83%, BSC 83%). A median number of hospitalizations were 2-6 across systemic groups and two for BSC, with median durations of 8-18 days. Transfusion rates and outpatient consultations were highest for HMA (80% and 79%) versus LDAC (57% and 53%), other systemic therapy (57% and 63%), and BSC (71% and 66%). Antivirals/antibiotics and antifungals were used more frequently than growth factors (72-92%, 34-63%, and 7-27%, respectively). CONCLUSION: Patients with AML ineligible for intensive therapy have high HRU; novel therapies are needed to alleviate this burden.

Real-world treatment patterns and clinical outcomes in patients with AML unfit for first-line intensive chemotherapy.

Acute myeloid leukemia (AML) predominantly affects the elderly, and prognosis declines with age. Induction chemotherapy plus consolidation therapy is standard of care for fit patients; options for unfit patients include hypomethylating agents (HMA), low-dose cytarabine (LDAC), targeted therapies, and best supportive care (BSC). This retrospective chart review evaluated clinical outcomes in unfit patients with AML who initiated first-line treatment or BSC 01/01/2015-12/31/2018. Overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), and response rates were assessed. Of 1762 patients, 1310 received systemic therapies: 809 HMA, 199 LDAC, and 302 other therapies; 452 received BSC. Median OS was 9.9, 7.9, 5.4, and 2.5 months for HMA, LDAC, other, and BSC, respectively. Median PFS was 7.5, 5.3, 4.1, and 2.1 months for HMA, LDAC, other, and BSC, respectively; median TTF was 4.9, 2.1, 2.2, and 2.1 months, respectively. Our findings highlight the unmet need for novel therapies for unfit patients.

Incidence and socioeconomic factors in older adults with acute myeloid leukaemia: Real-world outcomes from a population-based cohort.

OBJECTIVES: Acute myeloid leukaemia (AML) is a disease of older adults, who are vulnerable to socio-economic factors. We determined AML incidence in older adults and the impact of socio-economic factors on outcomes. METHODS: We included 3024 AML patients (1996-2016) identified from a population-based registry. RESULTS: AML incidence in patients ≥60 years increased from 11.01 (2001-2005) to 12.76 (2011-2016) per 100 000 population. Among 879 patients ≥60 years in recent eras (2010-2016), rural residents (<100 000 population) were less likely to be assessed by a leukaemia specialist (39% rural, 47% urban, p = .032); no difference was seen for lower (43%, quintile 1-3) vs. higher (47%, quintile 4-5) incomes (p = .235). Similar numbers received induction chemotherapy between residence (16% rural, 18% urban, p = .578) and incomes (17% lower, 17% high, p = 1.0). Differences between incomes were seen for hypomethylating agent treatment (14% low, 20% high, p = .041); this was not seen for residence (13% rural, 18% urban, p = .092). Among non-adverse karyotype patients ≥70 years, 2-year overall survival was worse for rural (5% rural, 12% urban, p = .006) and lower income (6% low, 15% high, p = .017) patients. CONCLUSIONS: AML incidence in older adults is increasing, and outcomes are worse for older rural and low-income residents; these patients face treatment barriers.

Genetic Trends in Fusarium Head Blight Resistance from 20 Years of Winter Wheat Breeding and Cooperative Testing in the Northern U.S.A.

Fusarium head blight (FHB) is a devastating disease of wheat and barley. In the U.S.A., a significant long-term investment in breeding FHB-resistant cultivars began after the 1990s. However, to this date, no study has been performed to understand and monitor the rate of genetic progress in FHB resistance as a result of this investment. Using 20 years of data (1998 to 2018) from the Northern Uniform and Preliminarily Northern Uniform winter wheat scab nurseries that consisted of 1,068 genotypes originating from nine different institutions, we studied the genetic trends in FHB resistance within the northern soft red winter wheat growing region using mixed model analyses. For the FHB resistance traits incidence, severity, Fusarium-damaged kernels, and deoxynivalenol content, the rate of genetic gain in disease resistance was estimated to be 0.30 ± 0.1, 0.60 ± 0.09, and 0.37 ± 0.11 points per year, and 0.11 ± 0.05 parts per million per year, respectively. Among the five FHB-resistance quantitative trait loci assayed for test entries from 2012 to 2018, the frequencies of favorable alleles from Fhb 2DL Wuhan1 W14, Fhb Ernie 3Bc, and Fhb 5A Ning7840 were close to zero across the years. The frequency of the favorable at Fhb1 and Fhb 5A Ernie ranged from 0.08 to 0.33 and 0.06 to 0.20, respectively, across years, and there was no trend in changes in allele frequencies over years. Overall, this study showed that substantial genetic progress has been made toward improving resistance to FHB. It is apparent that today's investment in public wheat breeding for FHB resistance is achieving results and will continue to play a vital role in reducing FHB levels in growers' fields.

Mitochondrial metabolism: powering new directions in acute myeloid leukemia.

There has been an explosion of knowledge about the role of metabolism and the mitochondria in acute myeloid leukemia (AML). We have also recently seen several waves of novel therapies change the treatment landscape for AML, such as the selective B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. In this new context, we review the rapidly advancing literature on the role of metabolism and the mitochondria in AML pathogenesis, and how these are interwoven with the mechanisms of action for novel therapeutics in AML. We also review the role of oxidative phosphorylation (OxPhos) in maintaining leukemia stem cells (LSCs), how recurrent genomic alterations in AML alter downstream metabolism, and focus on how the BCL-2 pathway and the mitochondria are inextricably linked in AML. Thus, we provide an overview of the mitochondria and metabolism in the context of our new therapeutic world for AML and outline how targeting these vulnerabilities may produce novel therapeutic strategies.

Mortality from Multiple Myeloma Within One Year Following Autologous Stem Cell Transplantation: Defining an Ultra-high Risk Population.

Despite improvements in therapy, approximately 5% of patients who undergo autologous stem cell transplantation (ASCT) experience early mortality (EM), death within 1 year of transplant (EM post-ASCT). Such patients tend to have few comorbidities suggesting their EM is owing to aggressive underlying disease. We sought to characterize this ultra-high risk population through a retrospective review of patients with newly diagnosed multiple myeloma (MM) treated with first-line ASCT. Patients who died within 1 year of ASCT were matched for age, sex, and year of transplant in a 1:2 fashion with a control group. Of 962 transplants performed between January 1, 2007, and May 1, 2019, 41 patients (4.3%) died within 1 year of ASCT from MM-related causes. In a multivariate analysis, anemia, hypercalcemia, high-risk cytogenetics, and elevated lactate dehydrogenase were associated with EM post-ASCT. Forty patients (97.6%) received at least 1 novel agent. Most patients with EM post-ASCT received second-line chemotherapy (80.5%), although survival from initiation of second-line chemotherapy was only 2.1 months. The primary reason for not receiving second-line therapy was rapid relapse. Clinical parameters reflecting disease burden, as well as high-risk cytogenetics, are associated with EM post-ASCT. These patients have a dismal overall survival despite significant advances in treatment of patients with relapsed or refractory myeloma. Further study of these ultra-high risk patients is required to improve disease management and may give further insights into the biology of relapse and resistance in myeloma.

Optical Sorter-Based Selection Effectively Identifies Soft Red Winter Wheat Breeding Lines With Fhb1 and Enhances FHB Resistance in Lines With and Without Fhb1.

Previous results from our lab have shown that using an optical sorter to identify Fusarium head blight (FHB) resistant breeding lines was effective at reducing the toxin deoxynivalenol (DON) and FHB-associated kernel damage. In this paper we quantified the proportion of desirable genotypes at FHB resistance QTL in lines from three selection cycles of optical sorting. Breeding lines were genotyped at loci on chromosomes 3BS, 2DL, and 5A using the following DNA markers: TaHRC, CFD233, and GWM304. TaHRC is a KASP marker for Fhb1, a major FHB resistance QTL on chromosome 3BS. CFD233 is an SSR marker for Qfhs.nau-2DL on chromosome 2DL. GWM304 is an SSR marker for Qfhs.ifa-5A on chromosome 5A. Sorter selection was effective at identifying lines that had the resistant genotype at TaHRC; in other words, the sorter was able to identify lines with resistance alleles at Fhb1. The sorter was less effective at selecting for the resistant genotype at CFD233 and GWM304. However, the proportion of lines with resistant genotypes at GWM304 did increase with additional sorter selection, just not to the degree that was observed for the Fhb1-associated marker. The proportion of lines with resistant alleles at CFD233 did not show a consistent trend. In addition to increasing the proportion of lines with Fhb1 and Qfhs.ifa-5A each selection cycle, optical sorter-based mass selection enhanced FHB resistance in different marker genotype combinations evaluated in this study. For example, there were net reductions in DON and kernel damage after two cycles of sorter selection in 15X110601S07002, a line with Fhb1, with Qfhs.nau-2DL, and with Qfhs.ifa-5A; final C3 DON levels were 63% of the resistant check (KY02C-3005-25). Kernel damage was also reduced in 15X110601A08221 a line without Fhb1, without Qfhs.nau-2DL, and without Qfhs.ifa-5A. Our findings suggest the increased resistance observed in different marker genotype combinations was conferred by QTL other than Fhb1, QFhs.nau-2DL, and Qfhs.ifa-5, and validate our previous results that the optical sorter is effective at selecting FHB-resistant breeding material.

Integrating Management Practices to Decrease Deoxynivalenol Contamination in Soft Red Winter Wheat.

Fusarium graminearum, the major causal agent of Fusarium head blight (FHB) of wheat (Triticum aestivum) in the U.S., can produce mycotoxins, such as deoxynivalenol (DON), during infection. Contamination of wheat grain with DON is a major concern for wheat producers and millers, and the U.S. Food and Drug Administration (FDA) has set advisory levels for DON in finished wheat products for human and animal consumption. Practices utilized to manage FHB and DON contamination include planting wheat cultivars with moderate resistance to FHB and applying efficacious fungicides at the beginning of anthesis. Under severe epidemics, DON contamination can exceed FDA advisory levels despite implementation of these measures. Additionally, fungicide efficacy can be limited when anthesis is not uniform among plants in the field, which can occur when planting is delayed or if there is non-uniform seedling establishment. The objectives of this study were to evaluate the effect of (1) in-furrow phosphorus application at planting and seeding rate on heading and anthesis uniformity, FHB symptomology, DON contamination, grain yield, yield components, and test weight; and (2) harvesting at different grain moisture concentrations on FHB symptomology, DON contamination, grain yield and test weight. Field trials were established in Princeton, Kentucky, from 2017 to 2019, to evaluate in-furrow phosphorus application at planting (0 kg P2O5 ha-1 and 47 kg P2O5 ha-1); seeding rate (377 live seeds m-2 and 603 live seeds m-2); and grain moisture at harvest (20 to 22% and 13 to 15%). In-furrow phosphorus increased grain yield and spikes m-2, but had no effect on heading and anthesis uniformity or DON contamination. The 603 live seeds m-2 seeding rate decreased the number of days to Zadoks 60 for the November planted wheat, and decreased FHB incidence, but did not decrease DON contamination. Harvesting at 20 to 22% grain moisture decreased Fusarium damaged kernel ratings and percent kernel infection but increased DON contamination in the harvested grain. Although in-furrow phosphorus, seeding rate, and harvesting 20 to 22% grain moisture did not decrease DON contamination, there is potential for these treatments to alleviate negative effects of late planted wheat grown in stressful environments.

Training Population Design With the Use of Regional Fusarium Head Blight Nurseries to Predict Independent Breeding Lines for FHB Traits.

Fusarium head blight (FHB) is a devastating disease in cereals around the world. Because it is quantitatively inherited and technically difficult to reproduce, breeding to increase resistance in wheat germplasm is difficult and slow. Genomic selection (GS) is a form of marker-assisted selection (MAS) that simultaneously estimates all locus, haplotype, or marker effects across the entire genome to calculate genomic estimated breeding values (GEBVs). Since its inception, there have been many studies that demonstrate the utility of GS approaches to breeding for disease resistance in crops. In this study, the Uniform Northern (NUS) and Uniform Southern (SUS) soft red winter wheat scab nurseries (a total 452 lines) were evaluated as possible training populations (TP) to predict FHB traits in breeding lines of the UK (University of Kentucky) wheat breeding program. DON was best predicted by the SUS; Fusarium damaged kernels (FDK), FHB rating, and two indices, DSK index and DK index were best predicted by NUS. The highest prediction accuracies were obtained when the NUS and SUS were combined, reaching up to 0.5 for almost all traits except FHB rating. Highest prediction accuracies were obtained with bigger TP sizes (300-400) and there were not significant effects of TP optimization method for all traits, although at small TP size, the PEVmean algorithm worked better than other methods. To select for lines with tolerance to DON accumulation, a primary breeding target for many breeders, we compared selection based on DON BLUES with selection based on DON GEBVs, DSK GEBVs, and DK GEBVs. At selection intensities (SI) of 30-40%, DSK index showed the best performance with a 4-6% increase over direct selection for DON. Our results confirm the usefulness of regional nurseries as a source of lines to predict GEBVs for local breeding programs, and shows that an index that includes DON, together with FDK and FHB rating could be an excellent choice to identify lines with low DON content and an overall improved FHB resistance.

Day 14 Bone Marrow Evaluation During Acute Myeloid Leukemia Induction in a Real-world Canadian Cohort.

INTRODUCTION: The 2017 National Comprehensive Cancer Network guidelines for acute myeloid leukemia have recommended performing bone marrow (BM) aspiration and BM trephine biopsy (BMTB) 14 to 21 days after starting induction therapy (commonly referred to as "day 14 [D14] marrow"). Those who do not achieve a hypoplastic marrow, with cellularity < 20% and blasts < 5%, are recommended to undergo 2-cycle induction (2CI). We performed a retrospective analysis to determine the impact of D14 BM characteristics in predicting for remission, association with overall survival (OS), and the effect of 2CI according to the D14 BM results. PATIENTS AND METHODS: Patients aged 18 to 70 years undergoing induction therapy with standard "7 + 3" regimens were included. D14 cellularity was determined from BMTB samples and the blast percentage was assessed by morphology on BM aspiration and BMTB samples. The outcomes evaluated included the rates of complete remission (CR) and OS. RESULTS: A total of 486 patients with results from D14 BM evaluation were included in the present study. On multivariate analysis, cytogenetic risk and D14 blasts < 5% were predictive of CR/CR with incomplete count recovery (P < .001). Cytogenetic risk (P < .001), age < 60 years (P = .001), and D14 blasts < 5% (P = .045) predicted for OS. 2CI was performed in 131 patients (27%). Patients with hypocellular D14 BM but residual blasts (n = 106) underwent 2CI in 46% of cases, with improved remission rates (43.9% vs. 72.0%; P = .004) but no difference in OS. CONCLUSIONS: The results from D14 BM evaluations are predictive of subsequent remission and OS. Our findings did not show a survival benefit with D14 BM-driven 2CI.

Outpatient Autologous Stem Cell Transplants for Multiple Myeloma: Analysis of Safety and Outcomes in a Tertiary Care Center.

BACKGROUND: Autologous stem cell transplant (ASCT) is the preferred consolidation strategy to treat eligible patients with multiple myeloma (MM) and related plasma cell dyscrasias. Given the increasing volume of patients and longer wait time, outpatient ASCT for MM is the standard of care at the Vancouver General Hospital. PATIENTS AND METHODS: Patients with MM, POEMS syndrome, and amyloidosis undergoing ASCT were included in this analysis. We analyzed patient characteristics, the number of patients requiring admission, duration of admission, 30-day and 100-day mortality, and overall survival. RESULTS: Between January 2007 and June 2016, 724 patients underwent 752 ASCTs. Of these, 702 were first ASCTs, 44 were second, and 6 were third. The median age was 60 years (interquartile range [IQR], 54-65 years). Reasons for ASCTs were MM (96.9%) amyloidosis (2.4%), and POEMS syndrome (0.7%). There were 431 (59.5%) males in this group. The median time from diagnosis to transplant was 5 months. Conditioning was melphalan 200 mg/m2 for 89.6% of the patients. Admission to the inpatient ward was required by 245 (32.6%) patients within the first 30 days. The median time to admission was 9 days post-transplant (IQR, 5-13 days). The median duration of admission was 6 days (IQR, 3-9 days). The day 100 all-cause mortality rate was 0.9%, and transplant-related mortality was 0.4%. CONCLUSION: Outpatient ASCT is a safe and feasible treatment strategy with low transplant-related mortality. Overall resource utilization is significantly lower than inpatient ASCT: however, this requires a multidisciplinary approach with close follow-up.

Management of cardiovascular health in acute leukemia: a national survey.

Cardiovascular (CV) disease is a common comorbidity in acute leukemia (AL) patients and can be worsened by the use of anthracyclines. Interruptions and underutilization of CV medications during AL treatments may negatively impact the CV health of these patients. A 30-question electronic survey was distributed to Canadian hematologists who treat adults with AL to determine the frequency, timing and rationale for interruptions in statins, antiplatelets and angiotensin antagonists in patients undergoing intensive chemotherapy. Strategies for mitigating anthracycline cardiotoxicity, methods of establishing baseline CV risk and utilization of clinical pharmacists were also assessed. Results indicate that it is common for AL patients undergoing intensive chemotherapy to require CV medication interruptions. This highlights the need for collaboration between hematology and cardiology healthcare teams and utilization of multidisciplinary healthcare professionals to improve CV care during AL.

Genome-wide association studies for yield-related traits in soft red winter wheat grown in Virginia.

Grain yield is a trait of paramount importance in the breeding of all cereals. In wheat (Triticum aestivum L.), yield has steadily increased since the Green Revolution, though the current rate of increase is not forecasted to keep pace with demand due to growing world population and increasing affluence. While several genome-wide association studies (GWAS) on yield and related component traits have been performed in wheat, the previous lack of a reference genome has made comparisons between studies difficult. In this study, a GWAS for yield and yield-related traits was carried out on a population of 322 soft red winter wheat lines across a total of four rain-fed environments in the state of Virginia using single-nucleotide polymorphism (SNP) marker data generated by a genotyping-by-sequencing (GBS) protocol. Two separate mixed linear models were used to identify significant marker-trait associations (MTAs). The first was a single-locus model utilizing a leave-one-chromosome-out approach to estimating kinship. The second was a sub-setting kinship estimation multi-locus method (FarmCPU). The single-locus model identified nine significant MTAs for various yield-related traits, while the FarmCPU model identified 74 significant MTAs. The availability of the wheat reference genome allowed for the description of MTAs in terms of both genetic and physical positions, and enabled more extensive post-GWAS characterization of significant MTAs. The results indicate a number of promising candidate genes contributing to grain yield, including an ortholog of the rice aberrant panicle organization (APO1) protein and a gibberellin oxidase protein (GA2ox-A1) affecting the trait grains per square meter, an ortholog of the Arabidopsis thaliana mother of flowering time and terminal flowering 1 (MFT) gene affecting the trait seeds per square meter, and a B2 heat stress response protein affecting the trait seeds per head.