Knowledge of Palliative Care and Barriers to Access Among Outpatients with Cancer.

CONTEXT: Palliative Care (PC) is poorly understood by laypersons. However, little is known about what ambulatory patients with cancer understand about PC or what barriers to access exist. METHODS: Outpatients undergoing cancer treatment completed a survey evaluating their familiarity and knowledge of PC, Palliative Care Knowledge Scale (PaCKS), feelings towards PC (before and after reading a definition of PC), barriers to PC, and prognostic understanding. We summarized responses descriptively and used logistic regression models to examine variables associated with familiarity and interest. RESULTS: The survey response rate was 32%. Of 151 participants, 58.9% reported familiarity with PC. The average PaCKs score was 11.9 out of 13 (standard deviation, 1.4), with 46.4% receiving a perfect score, indicating high knowledge of PC. Patients diagnosed more than one year ago had significantly increased odds of being familiar with PC (OR 2.93; 95% CI 1.37-6.25). More participants reported future interest in PC compared to current interest (74.2% vs 44.4%, respectively). Patients with stage III or IV cancer had significantly increased odds of having a current interest in receiving PC compared to patients with stage I or II disease (OR 2.66; 95% CI: 1.05, 6.76). Participants reported feeling significantly less anxious and more reassured after reading a standardized definition of PC (P < 0.05). CONCLUSION: Outpatients with cancer who are being treated at a large academic cancer center exhibit high awareness and knowledge of PC, but anxiety toward PC persists. Factors beyond knowledge may perpetuate the delayed or lack of involvement with PC. KEY MESSAGE: In this cross-sectional study of outpatients with cancer, findings suggest that high knowledge of PC may co-exist with a lingering uneasiness towards the service. Additionally, factors beyond knowledge, such as logistic barriers, anxiety, and oncologists' preference may be perpetuating the delay or lack of involvement in PC.

Impact of Public Reporting of Center-Specific Survival Analysis Scores on Patient Volumes at Hematopoietic Cell Transplant Centers.

The Center for International Blood and Marrow Transplant Research reports the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) at United States transplantation centers (TC) annually through its Center-Specific Survival Analysis (CSA). The CSA compares the actual 1-year overall survival (OS) and predicted 1-year OS rate after alloHCT at each TC, which is then reported as 0 (OS as expected), -1 (OS worse than expected), or 1 (OS better than expected). We evaluated the impact of public reporting of TC performance on their alloHCT patient volumes. Ninety-one TCs that serve adult or combined adult and pediatric populations and had CSA scores reported for 2012-2018 were included. We analyzed prior-calendar-year TC volume, prior-calendar-year CSA score, whether the CSA score had changed in the prior year from two years earlier, calendar year, TC type (adult only vs. combined adult and pediatric), and years of alloHCT experience for their impact on patient volumes. A CSA score of -1, as compared with 0 or 1, was associated with an 8% to 9% reduction in the mean TC volume (P < 0.001) in the subsequent year, adjusting for the prior year center volume. Additionally, being a TC neighboring an index TC with a -1 CSA score, was associated with a 3.5% increase in mean TC volume (P = 0.04). Our data show that public reporting of CSA scores is associated with changes in alloHCT volumes at TCs. Additional investigation into the causes of this shift in patient volume and the impact on outcomes is ongoing.

Feasibility Study of Cord Tissue Derived Mesenchymal Stromal Cells in COVID-19-Related Acute Respiratory Distress Syndrome.

BACKGROUND: Treatment options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) are desperately needed. Allogeneic human umbilical cord derived mesenchymal stromal cells (hCT-MSCs) have potential therapeutic benefits in these critically ill patients, but feasibility and safety data are lacking. MATERIALS AND METHODS: In this phase I multisite study, 10 patients with COVID-19-related ARDS were treated with 3 daily intravenous infusions of hCT-MSCs (1 million cells/kg, maximum dose 100 million cells). The primary endpoint assessed safety. RESULTS: Ten patients (7 females, 3 males; median age 62 years (range 39-79)) were enrolled at 2 sites and received a total of 30 doses of study product. The average cell dose was 0.93 cells/kg (range 0.56-1.45 cells/kg and total dose range 55-117 million cells) with 5/30 (17%) of doses lower than intended dose. Average cell viability was 85% (range 63%-99%) with all but one meeting the >70% release criteria. There were no infusion-related reactions or study-related adverse events, 28 non-serious adverse events in 3 unique patients, and 2 serious adverse events in 2 unique patients, which were expected and unrelated to the study product. Five patients died: 3 by day 28 and 5 by day 90 of the study (median 27 days, range 7-76 days). All deaths were determined to be unrelated to the hCT-MSCs. CONCLUSION: We were able to collect relevant safety outcomes for the use of hCT-MSCs in patients with COVID-19-related ARDS. Future studies to explore their safety and efficacy are warranted.

Unrelated Donor Cord Blood Transplantation in Children: Lessons Learned Over 3 Decades.

Four decades ago, Broxmeyer et al. demonstrated that umbilical cord blood (CB) contained hematopoietic stem cells (HSC) and hypothesized that CB could be used as a source of donor HSC for rescue of myeloablated bone marrow. In 1988, Gluckman et al. reported the first successful matched sibling cord blood transplant (CBT) in a child with Fanconi Anemia. In 1991, Rubinstein et al. established an unrelated donor CB bank, and in 1993, the first unrelated CBT used a unit from this bank. Since that time, >40 000 CBTs have been performed worldwide. Early outcomes of CBT were mixed and demonstrated the importance of cell dose from the CB donor. We hypothesized that improvements in CB banking and transplantation favorably impacted outcomes of CBT today and performed a retrospective study combining data from Eurocord and Duke University in 4834 children transplanted with a single unrelated CB unit (CBU) from 1993 to 2019. Changes in standard transplant outcomes (overall survival [OS], disease free survival [DFS], acute and chronic graft-versus-host disease [GvHD], treatment related mortality [TRM], and relapse) over 3 time periods (1: <2005; 2: 2005 to <2010; and 3: >2010 to 2019) were studied. Increased cell dose and degree of HLA matching were observed over time. OS, times to engraftment, and DFS improved over time. The incidence of TRM and GvHD decreased while the incidence of relapse remained unchanged. Relative contributions of cell dose and HLA matching to transplant outcomes were also assessed and showed that HLA matching was more important than cell dose in this pediatric cohort.

Patient-Reported Distress and Clinical Outcomes with Immuno-Oncology Agents in Metastatic Non-Small Cell Lung Cancer (mNSCLC): A Real-World Retrospective Cohort Study.

OBJECTIVES: There are limited real-world data about patient-reported outcomes with immunotherapies (IO) in metastatic non-small cell lung cancer (mNSCLC). We describe patient-reported distress and clinical outcomes with IO-based treatments or cytotoxic chemotherapies (Chemo). METHODS: We conducted a single-institution retrospective chart review of adults with mNSCLC treated at Duke from 03/2015 to 06/2020. At each visit, patients self-reported their distress level and sources of distress using the NCCN Distress Thermometer (DT) and its 39-item Problem List. We abstracted demographic, clinical, distress, and investigator assessed-clinical response data, then analyzed these using descriptive statistics and generalized estimating equations. RESULTS: Data from 152 patients were analyzed in four groups: Chemo alone, IO + Chemo, single agent IO, dual agent IO. Distress was worse before treatment start in all groups, and the odds of actionable distress (DT score > 4) decreased by 10 % per month. The most frequent sources of distress were physical symptoms (e.g., fatigue, pain), which remained high longitudinally. Patients receiving IO had higher clinical response rates and a lower rate of unplanned healthcare encounters compared to patients treated with Chemo alone. Only one-third of all patients were seen by palliative care. CONCLUSIONS: This single-center, real-world evidence study demonstrates that patients with mNSCLC experience significant distress prior to starting first-line treatment. IO treatment was associated with higher clinical benefit rates and lower healthcare utilization compared to chemotherapy. Symptom distress persists over time, highlighting potential unmet palliative and supportive care needs in mNSCLC care in the IO treatment era.

Tumor marker response to SARS-CoV-2 infection among patients with cancer.

BACKGROUND: Inflammatory responses from benign conditions can cause non-cancer-related elevations in tumor markers. The severe acute respiratory coronavirus 2 (SARS-CoV-2) induces a distinct viral inflammatory response, resulting in coronavirus disease 2019 (COVID-19). Clinical data suggest carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and cancer antigen 125 (CA 125) levels might rise in patients with COVID-19. However, available data excludes cancer patients, so little is known about the effect of COVID-19 on tumor markers among cancer patients. METHODS: We conducted a case series and identified patients with a positive SARS-CoV-2 PCR test, diagnosis of a solid tumor malignancy, and a CEA, CA 19-9, CA 125, or CA 27-29 laboratory test. Cancer patients with documented COVID-19 infection and at least one pre- and two post-infection tumor marker measurements were included. We abstracted the electronic health record for demographics, cancer diagnosis, treatment, evidence of cancer progression, date and severity of COVID-19 infection, and tumor marker values. RESULTS: Seven patients were identified with a temporary elevation of tumor marker values during the post-COVID-19 period. Elevation in tumor marker occurred within 56 days of COVID-19 infection for all patients. Tumor markers subsequently decreased at the second time point in the post-infectious period among all patients. CONCLUSION: We report temporary elevations of cancer tumor markers in the period surrounding COVID-19 infection. To our knowledge this is the first report of this phenomenon in cancer patients and has implications for clinical management and future research.

Patient-reported distress as an early warning sign of unmet palliative care needs and increased healthcare utilization in patients with advanced cancer.

INTRODUCTION: Cancer patients' sources of distress are often unaddressed, and patient-reported distress data could be utilized to identify those with unmet and impending care needs. We explored the association between moderate/severe distress and healthcare utilization in a large sample of non-small cell lung cancer (NSCLC) and non-colorectal gastrointestinal cancer patients. METHODS AND MATERIALS: Adult patients treated between July 2013 and March 2019. Data from the NCCN Distress Thermometer (DT) and the accompanying "Problem List" were extracted from the EHR. A DT score of ≥ 4 indicates "actionable distress." Statistical analysis was performed using descriptive analysis for patient characteristics, clinical outcomes, and sources of distress. Generalized linear mixed models were fit to determine the relationship between distress and healthcare utilization (hospitalization, emergency department (ED) visit, or both). RESULTS: The ten most frequently reported problems were from the Physical and Emotional domains of the Problem List. Distress was mostly related to physical symptoms (pain, fatigue) and emotional issues (worry, fears, sadness, nervousness). Patients with actionable distress generally reported more problems across all their visits. Actionable distress was associated with higher odds of the composite outcome measure of hospitalization or visiting the ED, within both the next 3 months (OR = 1.37; 95% CI = 1.19, 1.58; p < 0.001) and 6 months (OR = 1.19; 95% CI = 1.03, 1.37; p = 0.019). CONCLUSION: Patients with significant distress had marked utilization of ED and inpatient services. DT scores are a source of untapped data in the EHR that can highlight patients in need of intervention, including palliative care and cancer support services.

The relationship between emotional well-being and understanding of prognosis in patients with acute myeloid leukemia (AML).

PURPOSE: Adults with acute myeloid leukemia (AML) face considerable distress and often have a poor prognosis. However, little is known about these patients' perceptions of prognosis and how this relates to emotional well-being (EWB). METHODS: We conducted a prospective, observational study of 50 adult patients with AML initiating chemotherapy, and surveyed them longitudinally for 6 months about their prognosis, treatment goals, quality of life, and EWB (by FACT-G). We derived a prognostic estimate for each patient based on data from published trials summarized in National Comprehensive Care Network Guidelines. We used descriptive statistics and longitudinal modeling to test the hypothesis that more accurate prognostic awareness is associated with worse EWB. RESULTS: Most patients (n = 43; 86%) had an objectively poor prognosis attributable to relapsed disease, complex karyotype, or FLT3 mutation. Yet, 74% of patients reported expecting a 50% or greater chance of cure. Patients with a poor prognosis more often had discordant prognostic estimates, compared to those with favorable risk AML (OR = 7.25, 95% CI 1.21, 43.37). Patient-reported prognostic estimates did not vary significantly over time. At baseline, patients who better understood their prognosis had worse EWB and overall quality-of-life scores (EWB 12 vs. 19.5; p = 0.01; FACT-G 65 vs. 75.5; p = 0.01). CONCLUSION: Patients with AML overestimate their prognosis, and awareness of a poor prognosis is associated with worse emotional well-being. Efforts are needed to improve patients' understanding of their prognosis, and to provide more psychosocial support and attention to well-being as part of high-quality leukemia care.

Parental limited English proficiency in pediatric stem cell transplantation: Clinical impact and health care utilization.

BACKGROUND: Limited English proficiency (LEP) is associated with adverse clinical outcomes. The clinical impact of LEP in hematopoietic stem cell transplant (HSCT) has not been studied. The objectives of this study were to compare HSCT outcomes and health care utilization of Hispanic pediatric patients with and without parental LEP. METHODS: We conducted a retrospective review of Hispanic/Latino pediatric patients receiving HSCT at a single institution. Families were identified as LEP or English proficient (EP) based on clinicians' notes, social work documentation, or the signature of a Spanish interpreter on treatment consents. RESULTS: A total of 83 Hispanic/Latino patients were identified with 53 (65.1%) having parental LEP. More patients in the LEP group had a documented financial burden at pretransplant psychosocial evaluation (72.2% vs. 41.4%, p = .009). LEP patients were more likely to have health insurance coverage through government-sponsored Medicaid (76.9% vs. 27.6%, p < .001). LEP patients were hospitalized on average 13 days longer than EP patients, and LEP patients were more likely to have pretransplant cytomegalovirus (CMV) reactivity (67.3%) than EP patients (p = .001). Overall survival was lower in LEP than EP, but was not statistically significant (p = .193). Multivariable Cox modeling suggested a potentially higher risk of death in LEP versus EP (hazard ratio = 1.56, 95% CI: 0.38, 6.23). CONCLUSIONS: Parental LEP in HSCT is associated with prolonged hospitalization and pretransplant CMV reactivity. These factors are associated with posttransplant complications and death. Our results suggest parental LEP is a risk factor for poor HSCT outcomes. Further study is warranted in a larger cohort.

Mobile Application to Identify Cancer Treatment-Related Financial Assistance: Results of a Randomized Controlled Trial.

PURPOSE: Insured patients with cancer face high treatment-related, out-of-pocket (OOP) costs and often cannot access financial assistance. We conducted a randomized, controlled trial of Bridge, a patient-facing app designed to identify eligible financial resources for patients. We hypothesized that patients using Bridge would experience greater OOP cost reduction than controls. METHODS: We enrolled patients with cancer who had OOP expenses from January 2018 to March 2019. We randomly assigned patients 1:1 to intervention (Bridge) versus control (financial assistance educational websites). Primary and secondary outcomes were self-reported OOP costs and subjective financial distress 3 months postenrollment. In post hoc analyses, we analyzed application for and receipt of financial assistance at 3 months postenrollment. We used chi-square, Mann-Whitney tests, and logistic regression to compare study arms. RESULTS: We enrolled 200 patients. The median age was 57 years (IQR, 47.0-63.0). Most patients had private insurance (71%), and the median household income was $62,000 in US dollars (USD) (IQR, $36,000-$100,000 [USD]). Substantial missing data precluded assessment of primary and secondary outcomes. In post hoc analyses, patients in the Bridge arm were more likely than controls to both apply for and receive financial assistance. CONCLUSION: We were unable to test our primary outcome because of excessive missing follow-up survey data. In exploratory post hoc analyses, patients who received a financial assistance app were more likely to apply for and receive financial assistance. Ultimately, our study highlights challenges faced in identifying measurable outcomes and retaining participants in a randomized, controlled trial of a mobile app to alleviate financial toxicity.

The patient experience of ABVD treatment in Hodgkin lymphoma: a retrospective cohort study of patient-reported distress.

PURPOSE: Psychological distress is prevalent in Hodgkin lymphoma (HL). Many patients, regardless of prognosis, receive ABVD chemotherapy as first-line treatment, but few studies have specifically examined the nature of distress during this shared treatment experience. METHODS: We conducted a retrospective study of patient-reported distress in HL patients receiving ABVD treatment at a single tertiary care facility. Distress was measured using the National Comprehensive Cancer Network Distress Thermometer and Problem List (PL). We used descriptive statistics and generalized estimating equations to assess the prevalence of distress and specific problem items during treatment and associations with patient- and disease-related factors. RESULTS: We collected data from 50 patients comprising 467 unique encounters, with 369/467 (79.0%) reporting a distress thermometer score. Median distress score was 2 (IQR: 0-5), but actionable distress (distress thermometer ≥4) was noted for 118/369 (32.0%) encounters. Actionable distress was only related to having a prior cancer, which conferred lower odds of actionable distress (OR 0.23, 95% CI 0.07-0.74, p=0.01) Physical and emotional problems were reported for 287/369 (77.8%) and 125/369 (33.9%) visits, respectively. Female patients had greater odds of both physical (OR 3.17, 95% CI 1.32-7.66, p=0.01) and emotional (OR 3.31, 95% CI 1.25-8.73, p=0.02) problems. CONCLUSION: ABVD treatment is associated with a high frequency of actionable distress, with physical and emotional problems acting as primary drivers. Female patients may be particularly vulnerable, while cancer survivors may be uniquely resilient. These findings demonstrate the need to thoroughly screen for and appropriately tailor distress management strategies for HL patients during treatment with ABVD.

A novel decision aid for acute myeloid leukemia: a feasibility and preliminary efficacy trial.

PURPOSE: Acute myeloid leukemia (AML) is a hematologic malignancy characterized by a poor prognosis but also a paradoxical possibility of cure. This renders decision-making complex and imminent. Unfortunately, many patients with AML misestimate their prognosis and treatment risk. While decision aids can improve illness understanding and reduce decisional conflict, there are no validated decision aids for AML. We developed and tested a novel AML decision aid (NCT03442452). METHODS: Patients (n = 20) were recruited at Duke University from May 2018 to February 2019. Participants completed assessments of AML knowledge and decisional conflict, before and after using the electronic decision aid. The primary endpoint was feasibility (endpoint met if > 80% of study participants completed all study components). Secondary analyses of efficacy were conducted using paired t tests for dependent pre-/post-samples. RESULTS: The primary endpoint of feasibility was met (100% of participants completed all study components). Secondary analyses showed improved knowledge and reduced decisional conflict after using the decision aid. Knowledge scores improved from a mean of 11.8 (out of 18) correct items at baseline to 15.1 correct items after using the decision aid (mean difference 3.35; p < 0.0001). Decisional conflict scores reduced significantly from baseline to post-test as well (mean difference - 6.5; p = 0.02). CONCLUSION: These findings suggest that our AML decision aid is a useful tool to improve the patient experience and promote shared decision-making in AML. A randomized efficacy trial is planned.

An analysis of missing items in real-world electronic patient reported outcomes data: implications for clinical care.

PURPOSE: Utilization of electronic patient-reported outcomes (ePROs) in the clinic can improve quality of life and prolong survival in cancer care. However, there remain unanswered questions regarding trends in missing data and the potential effect on real-time patient care. METHODS: This study utilized a prospectively collected dataset of ePROs from oncology clinics that administered the Patient Care Monitor 2.0 (PCM), a validated symptoms survey assessing 78 items for men, and 86 for women. We tabulated the frequency of missing items, by item and domain (emotional, functional and physical symptom-related), and examined these by age, gender, education, race and marital status. RESULTS: Within 20,986 encounters, there were responses to at least 1 PCM item from 6933 unique patients. The highest frequency of missing answers occurred for: "attend a paid job" (10.7%), "reduced sexual enjoyment" (3.8%), and "run" (3.7%). By domain, 12.3% of functional, 8.4% of physical symptom-related, and 1.6% of emotional constructs contained at least one missing item. For functional and physical symptom-related items, missingness was most common in patients >60 years old. CONCLUSION: The frequency of missingness was highest for functional items, like attending a paid job, suggesting that some respondents (e.g., retirees without a paid job) skipped questions that were less applicable to them. More universal issues for cancer patients, such as emotional well-being, had much lower frequencies of missingness. This suggests differential item completion that warrants further study to understand the inherent drivers. Identifying causes of missingness could improve the clinical utility of ePROs and highlight opportunities to personalize care.

The National MDS Natural History Study: design of an integrated data and sample biorepository to promote research studies in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS), a spectrum of heterogeneous hematopoietic stem cell diseases, vary in clinical severity, response to therapy, and propensity toward progression to acute myeloid leukemia. These are acquired clonal disorders resulting from somatic mutations within the hematopoietic stem or progenitor cell population. Understanding the natural history and the risk of developing leukemia and other adverse outcomes is dependent on access to well-annotated biospecimens linked to robust clinical and molecular data. To facilitate the acquisition and distribution of MDS biospecimens to the wider scientific community and support scientific discovery in this disease, the National MDS Natural History study was initiated by the National Heart, Lung, and Blood Institute (NHLBI) and is being conducted in collaboration with community hospitals and academic medical centers supported by the National Cancer Institute (NCI). The study will recruit up to 2000 MDS patients or overlapping myeloproliferative neoplasms (MDS/MPN) and up to 500 cases of idiopathic cytopenia of undetermined significance (ICUS). The National MDS Natural History Study (NCT02775383) will offer the world's largest disease-focused tissue biobank linked to longitudinal clinical and molecular data in MDS. Here, we report on the study design features and describe the vanguard phase of 200 cases. The study assembles a comprehensive clinical database, quality of life results, laboratory data, histopathology slides and images, genetic information, hematopoietic and germline tissues representing high-quality biospecimens and data from diverse centers across the United States. These resources will be available to the scientific community for investigator-initiated research.

Patient-reported distress in Hodgkin lymphoma across the survivorship continuum.

PURPOSE: Hodgkin lymphoma (HL) survivors face long-term, elevated risk of treatment-related sequelae, including psychosocial distress associated with poor health outcomes. The magnitude and sources of distress are not well described in the routine care of HL outside of clinical trials. METHODS: We conducted a retrospective cohort study of patients visiting a tertiary-care center for treatment or long-term follow-up of HL. Patient-reported distress was documented using the National Comprehensive Cancer Network Distress Thermometer (DT) and Problem List. Three survivor groups were compared using descriptive methods: on treatment, surviving < 5 years, and surviving ≥ 5 years since diagnosis. RESULTS: A total of 1524 DT were abstracted for 304 patients (106 on treatment, 77 surviving < 5 years, and 121 surviving ≥ 5 years). Distress was low overall (median DT = 1, inter-quartile range 0-4) and was similar across survivor groups. However, actionable distress (score ≥ 4) was reported at 29.5% of clinical encounters. Patients on treatment more frequently reported actionable distress (32.5% of visits) compared with patients surviving < 5 years (20.4%) and ≥ 5 years (28.7%) (P = 0.065). Distress was associated primarily with physical and emotional problems, especially fatigue, worry, and sleep. We did not observe any associations between distress and clinical prognostic factors. CONCLUSIONS: Distress burden is low in HL, but survivorship is marked by periods of actionable distress, largely related to physical symptoms and emotional issues. This burden may be higher when on treatment and is unrelated to disease-related prognostic factors. Survivorship research typically focuses on the post-therapy period, but our results support testing the efficacy of interventions to address distress in HL during active treatment as well.

Automated thawing increases recovery of colony-forming units from banked cord blood unit grafts.

BACKGROUND: The cell dose infused for cord blood transplantation strongly correlates with outcomes following transplantation. Post thaw recoveries can be improved by washing cord blood units (CBUs) in dextran/albumin. Early methods used a labor-intensive manual process. We have recently developed and validated an automated washing method. We now report our results of a study comparing cellular recoveries achieved after manual and automated wash, as well as the impact on engraftment following allogeneic transplantation. STUDY DESIGN AND METHODS: CBUs distributed by the Carolinas Cord Blood Bank for clinical use at Duke University after manual or automated wash were included in this report. Precryopreservation total nucleated cell count, total CD34+, colony-forming units, recoveries, and sterility were analyzed by wash method. Patient age, cell dose/weight, diagnosis, conditioning regimen, immunosuppression, and time to neutrophil engraftment were also analyzed. RESULTS: Manual and automated washed CBUs yielded similar total nucleated cell count and total CD34+ recoveries. Significantly higher colony-forming units recoveries were achieved after automated washing. Patients who received CBUs washed via an automated method experienced earlier neutrophil engraftment. CONCLUSION: While manual and automated washing achieved similar post thaw cellular recoveries, automated washed CBUs demonstrated higher colony-forming unit recovery, which is an important predictor of potency and engraftment. Furthermore, we demonstrated that automated washing was associated with earlier neutrophil engraftment. Our findings favor the use of an automated wash method over a manual approach.

Associations between expression levels of nucleotide excision repair proteins in lymphoblastoid cells and risk of squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of head and neck (SCCHN) is one of the most common malignancies worldwide, and nucleotide excision repair (NER) is involved in SCCHN susceptibility. In this analysis of 349 newly diagnosed SCCHN patients and 295 cancer-free controls, we investigated whether expression levels of eight core NER proteins were associated with risk of SCCHN. We quantified NER protein expression levels in cultured peripheral lymphocytes using a reverse-phase protein microarray. Compared with the controls, SCCHN patients had statistically significantly lower expression levels of ERCC3 and XPA (P = 0.001 and 0.001, respectively). After dividing the subjects by controls' median values of expression levels, we found a dose-dependent association between an increased risk of SCCHN and low expression levels of ERCC3 (adjusted OR, 1.75, and 95% CI: 1.26-2.42; Ptrend = 0.008) and XPA (adjusted OR, 1.88; 95% CI, 1.35-2.60; Ptrend = 0.001). We also identified a significant multiplicative interaction between smoking status and ERCC3 expression levels (P = 0.014). Finally, after integrating demographic and clinical variables, we found that the addition of ERCC3 and XPA expression levels to the model significantly improved the sensitivity of the expanded model on SCCHN risk. In conclusion, reduced protein expression levels of ERCC3 and XPA were associated with an increased risk of SCCHN. However, these results need to be confirmed in additional large studies.

Patient-Reported Distress in Myelodysplastic Syndromes and Its Association With Clinical Outcomes: A Retrospective Cohort Study.

Background: NCCN defines distress as a multifactorial, unpleasant emotional experience of a psychological nature that may interfere with patients' ability to cope with cancer symptoms and treatment. Patients with myelodysplastic syndromes (MDS) are at risk for distress due to the largely incurable nature of this hematopoietic malignancy and its symptom burden, yet associations with clinical outcomes are unknown. Methods: We retrospectively reviewed patient-reported distress data from adult ambulatory patients with MDS visiting a single, tertiary care medical center from July 2013 to September 2015. Demographic, diagnostic, treatment, and comorbidity information were abstracted from records along with NCCN Distress Thermometer (DT) and Problem List (PL) scores. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Results: We abstracted 376 DT scores (median, 1; range, 0-10) from 606 visits and 110 patients (median, 2 DT scores/patient; range, 1-16). NCCN Guidelines suggest that patients with DT scores ≥4 should be evaluated for referral to specialty services to address unmet needs. A total of 54 patients (49%) had at least 1 DT score ≥4 and 20 (18%) had 2 or more DT scores ≥4; 98 patients (89.1%) reported 1,379 problems during 23,613 person-days of follow-up (median, 4 problems/patient/visit; range, 1-23). The 5 most frequently reported problems were fatigue (181 times; 78 patients), pain (95 times; 46 patients), worry (80 times; 45 patients), sleep (78 times; 41 patients), and tingling hands/feet (68 times; 33 patients). After adjustment for risk stratification at diagnosis, a single point increase on the DT was associated with an increased risk of death (hazard ratio, 1.18; 95% CI, 1.01-1.36). Conclusions: Patients with MDS experience a high burden of distress, and patient-reported distress is associated with clinical outcomes. Distress should be further studied as a prognostic variable and a marker of unmet needs in MDS.

Durable Chimerism and Long-Term Survival after Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis: A Single-Center Experience.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success. Unrelated umbilical cord blood transplantation (UCBT) provides a readily available alternative donor source for patients lacking matched related donors. Accordingly, we report the results of UCBT in 14 children treated between 1998 and 2016. All children received standard HLH chemotherapy before UCBT. The median age at diagnosis was 2.7 months (range, .8 to 10.4) and at transplantation was 7.5 months (range, 3.8 to 17). Ten patients received MAC with busulfan/cyclophosphamide/etoposide /antithymocyte globulin (ATG) (n = 5), busulfan/cyclophosphamide /ATG (n = 4), or busulfan /melphalan/ATG (n = 1). Four patients received reduced-toxicity conditioning (RTC) with alemtuzumab/fludarabine/melphalan/hydroxyurea ± thiotepa. Cord blood units were mismatched at either 1 (n = 9) or 2 (n = 5) loci and delivered a median total nucleated cell dose of 11.9 × 107/kg (range, 4.6 to 27.9) and CD34+ dose of 3.1 × 105/kg (range, 1.1 to 6.8). The cumulative incidence of neutrophil engraftment by day 42 was 78.6% (95% confidence interval [CI], 42.9% to 93.4%) with a median of 19 days (range, 13 to 27), and that for platelet (50,000) engraftment by day 100 was 64.3% (95% CI, 28.2% to 85.7%) with a median of 51 days (range, 31 to 94). Six patients developed either grade II (n = 5) or grade IV (n = 1) acute graft-versus-host disease (GVHD); no extensive chronic GVHD was seen. Ten patients (71.4%) are alive and well at a median of 11.2 years after transplantation (range, .85 to 18.25), 9 of whom maintain sustained full donor chimerism after a single UCBT, whereas 1 patient with autologous recovery after first UCBT with RTC has achieved full donor chimerism after a second UCBT with MAC. This series demonstrates that, in combination with standard HLH therapy, UCBT after MAC or RTC conditioning can provide long-term survival with durable complete donor chimerism comparable to that of conventional donors. UCBT should be considered for patients with HLH lacking a fully matched related or unrelated adult donor.