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Older patients with hematologic malignancies are increasingly considered for allogeneic hematopoietic cell transplant (allo-HCT). However, older patients often have increased comorbidities and thus may require an increased level of post-transplant care. These factors can contribute to increased caregiver distress, which has been associated with worsened health outcomes for caregivers and patients. To examine predictors of caregiver distress and support group participation in caregivers of older allo-HCT patients, we retrospectively reviewed charts of 208 patients aged 60 and older who underwent their first allo-HCT at our institution from 2014 through 2016. We systematically characterized and identified the incidence of caregiver distress and attendance in a caregiver support group from the start of conditioning through 1 year post allo-HCT. Evidence of caregiver distress and support group participation was recorded by reviewing clinical and/or social work documentation. We found that 20 caregivers (10%) endorsed stress and 44 caregivers (21%) attended our support group at least once. A patient’s prior history of psychiatric diagnosis (p = .046) or the use of potentially inappropriate medications for older adults (p = .046) was found to be associated with caregiver stress. Caregivers who were spouses or partners of patients (p = .048) or caregivers of married patients were more likely to attend the support group (p = .007). While limited by retrospective design and likely underreporting, this study reveals factors associated with caregiver distress in the older allo-HCT caregiver population. This information can help providers identify caregivers at risk for distress and improve caregiver resources, which may improve both caregiver and patient outcomes.

Endothelial activation and stress index (EASIX) predicts nonrelapse mortality (NRM) when assessed before hematopoietic cell transplantation (HCT). We sought to determine whether changes in EASIX after HCT may be an informative marker of NRM. We evaluated 509 adults who underwent reduced intensity, unmodified (N = 149, 29%), or myeloablative ex vivo CD34+-selected allogeneic HCT (allo-HCT) (N = 306, 71%) between 2008 and 2016. Patients who underwent unmodified allo-HCT received tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, whereas CD34+-selected patients received no planned immunosuppression. EASIX (lactate dehydrogenase × creatinine/platelet count) was calculated continuously until 1-year after HCT. Log transformation using base 2 (log2) was applied to all EASIX variables to reduce skew. In total, 360 patients (71%) received CD34+-selected and 149 (29%) unmodified allo-HCT. Among all patients, EASIX scores increased rapidly, peaked at day +8, then declined rapidly until day +33. Thereafter, scores declined gradually but remained above the pre-HCT baseline. In unmodified HCT, scores appeared higher over time than in CD34+-selected patients. EASIX discrimination of NRM was highest around day +180 (concordance index = 0.85) in both platforms, but the prognostic impact of EASIX across time points differed between the 2 platforms. Mean EASIX scores were higher in men (mean log2 +0.52) and in patients who developed grade 2 to 4 GVHD (+0.81) and lower in patients who received matched vs mismatched donors (−0.81, all P < .01). EASIX scores are dynamic and variably concordant with NRM when analyzed longitudinally, and patterns differ between HCT platforms. Compared to pre-HCT evaluation, post-HCT EASIX scores may better predict risk of NRM as patients acquire additional endothelial injury and toxicities.

Cytomegalovirus infection is associated with the expansion of a mature NKG2C+FcεR1γ- NK population, which is distinct and thought to derive from the less differentiated NKG2A+ NK population. The exact mechanism underlying the emergence of NKG2C+ NK cells, however, remains unknown. Allogeneic hematopoietic cell transplantation (HCT) provides an opportunity to longitudinally study lymphocyte recovery in the setting of CMV reactivation, particularly in patients receiving T cell-depleted (TCD) allografts, in whom lymphocyte populations recover with variable rapidity. We analyzed peripheral blood lymphocytes at serial timepoints from 119 patients following infusion of their TCD allograft and compared immune recovery to samples obtained from recipients of T cell-replete (T-replete) (n=96) or double umbilical cord blood (DUCB) (n=52) allografts. NKG2C+ NK cells were detected in 92% of TCD-HCT patients who experienced CMV reactivation (n=45/49). While NKG2A+ cells were routinely identifiable early post-HCT, NKG2C+ NK cells were identified only after T cells could be detected. T cell reconstitution occurred at variable times post-HCT among patients and was comprised predominantly of CD8+ T cells. In patients with CMV reactivation, TCD-HCT patients expressed significantly higher frequencies of NKG2C+ and CD56neg NK cells compared to T-replete-HCT or DUCB transplant patients. NKG2C+ NK cells following TCD-HCT were CD57+FcεR1γ+ and degranulated significantly more in response to target cells compared to the adaptive NKG2C+CD57+FcεR1γ- NK cell population. We conclude that the presence of circulating T cells is associated with the expansion of the CMV-induced NKG2C+ NK cell population, a potentially novel example of developmental cooperation between lymphocyte populations in response to viral infection.

Background: Modifiable lifestyle-related factors heighten the risk and severity of coronavirus disease 2019 (COVID-19) in patients with cancer. Whether exercise lowers susceptibility or severity is not known. Methods: We identified 944 cancer patients from Memorial Sloan Kettering Cancer Center (mean age: 64; 85% female; 78% White) completing an exercise survey before receiving a confirmed positive or negative SARS-CoV-2 test. Exercise was defined as reporting moderate-intensity ≥5 days per week, ≥30 minutes/session or strenuous-intensity ≥3 days per week, ≥20 minutes/session. Multivariable logistic regression was used to determine the relationship between exercise and COVID-19 susceptibility and severity (i.e., composite of hospital admission or death events) with adjustment for clinical–epidemiologic covariates. Results: Twenty-four percent (230/944) of the overall cohort were diagnosed with COVID-19 and 35% (333/944) were exercisers. During a median follow-up of 10 months, 26% (156/611) of nonexercising patients were diagnosed with COVID-19 compared with 22% (74/333) of exercising patients. The adjusted OR for risk of COVID-19 was 0.65 [95% confidence interval (CI), 0.44–0.96, P = 0.03] for exercisers compared with nonexercisers. A total of 20% (47/230) of COVID-19 positive patients were hospitalized or died. No difference in the risk of severe COVID-19 as a function of exercise status was observed (P > 0.9). Conclusions: Exercise may reduce the risk of COVID-19 infection in patients with a history of cancer, but not its severity. Impact: This study provides the first data showing that exercise might lower the risk of COVID-19 in cancer patients, but further research is required.

Dysgeusia is a common but understudied complication in patients undergoing autologous hematopoietic cell transplantation (auto-HCT). We assessed the feasibility of using chemical gustometry (CG) to measure dysgeusia and explored its associations with symptom burden, nutrition, chemotherapy pharmacokinetics (PK), and the oral microbiome.We conducted a single-center, prospective feasibility study (NCT03276481) of patients with multiple myeloma undergoing auto-HCT. CG was performed longitudinally testing five flavors (sweet, sour, salty, bitter, umami) to calculate a total taste score (maximum score, 30). We measured caloric intake and patient-reported symptoms, assessing their correlation with oral microbiota composition and salivary and blood melphalan PK exposure.Among all 45 patients, 39 (87%) completed at least four (60%) and 22 (49%) completed all six CG assessments. Median total CG scores remained stable over time but were lowest at day +7 (27, range 24-30) with recovery by day +100. Symptom burden was highest by day +10 (area under the curve, 2.9; range, 1.0-4.6) corresponding with the lowest median overall caloric intake (1624 kcal; range, 1345-2267). Higher serum/salivary melphalan levels correlated with higher patient-reported dysgeusia and lower caloric intake. Oral microbiota α-diversity was stable early and increased slightly by day +100.Assessment of dysgeusia by CG is feasible after auto-HCT. Most dysgeusia, symptom burden, and lowest caloric intake occurred during the blood count nadir. Higher melphalan concentrations correlated with more dysgeusia and poorer caloric intake. Future studies will aim to modulate melphalan exposure by PK-targeted dosing and characterize patient taste preferences to personalize diets for improved nutritional intake.Taste changes after cancer treatments are very common. We used chemical gustometry (taste testing) to study taste changes and to better understand why patients with multiple myeloma experience this symptom after autologous hematopoietic cell transplantation. We found that taste testing was feasible, taste changes peaked when blood counts were lowest, and most patients recovered their taste by 100 days after transplantation. Taste changes correlated with lower food intake and with higher levels of chemotherapy in the body. Future work will focus on using personalized chemotherapy doses to reduce taste changes and to match patients' individual taste preferences with their diets.

528 Background: ‘Synthetic’ control arms (SCAs), created using electronic health records (EHRs), have immense potential to augment clinical trial findings and provide a rich context of real-world evidence (RWE) while reducing patient (pt) and sponsor burden (Gottlieb 2019). PICI0002 (PRINCE) is a ph1b/2 study evaluating APX005M with gemcitabine (gem) and nab-paclitaxel (NP) ± nivolumab for the treatment of metastatic pancreatic adenocarcinoma (mPDAC; NCT03214250). PRINCE pts were enrolled from select US academic cancer centers and a global, ph3 study was utilized for an historical reference control (Von Hoff 2013). To address the perceived limitations of this design, we explored the feasibility and utility of developing a contemporary SCA using real-world data (RWD). Methods: The SCA was derived using retrospective pt data from the two highest enrolling participating centers on PRINCE. Pts meeting key PRINCE eligibility criteria, who received gem/NP in the two years preceding the trial start date, were identified using an electronic phenotyping algorithm applied to cancer registry and EHR data, followed by manual review. Baseline characteristics, treatment exposure, efficacy and survival data were extracted electronically and via manual chart abstraction. Data were stored in a REDCap database built and housed by the Parker Institute for Cancer Immunotherapy. SCA pt characteristics were compared with PRINCE and overall survival (OS; time from initiation of gem/NP to death) was compared to historical reference controls (Table). Results: N=68 pts treated with gem/NP meeting PRINCE eligibility criteria were identified. All pts were deceased at the time of analysis. SCA pts had comparable baseline characteristics to PRINCE pts; key differences included inferior performance status and a higher proportion of pts presenting with a de novo mPDAC diagnosis. Median time on gem/NP was 4.8 months (mos; range 0-39). Median OS was 11.5 mos (95% CI 9.0-13.6) and 1-year OS was 43% (95% CI 31-55), in line with historical controls (Table). Conclusions: This study confirms the feasibility and utility of generating a control arm via a semi-automated approach. Current limitations entail manual oversight requirements as well as the known constraints of RWD, including associated biases and lack of available RECIST data. These limitations stand to evolve alongside EHR technologies. SCAs using RWD may help inform the value of prospective data by providing a contemporary reference of RWE. In some circumstances, SCAs may also serve as an alternative to traditional control arms, particularly for well-characterized standard therapies.[Table: see text]

How cord blood (CB) CD34+ cell content and dose, and 8-allele human leukocyte antigen (HLA)-match, vary by patient ancestry is unknown. We analyzed cell content, dose and high-resolution HLA-match of units selected for CB transplantation (CBT) by recipient ancestry. Of 544 units (286 infused, 258 next best back-ups) chosen for 144 racially diverse adult patients (median weight 81 kilograms), the median total nucleated cell (TNC) (x 10(7)) and CD34+ (x 10(5)) content was higher for Europeans than for non-Europeans: 216 versus 197 (p = 0.002) and 160 versus 132 (p = 0.007), respectively. There were marked cell content disparities between ancestry groups with units selected for Africans having the lowest TNC (189 × 10(7)) and CD34+ cell (122 × 10(5)) contents. Units for non-Europeans were also more HLA-mismatched (p = 0.017). When only the 286 transplanted units were analyzed, the adverse effect of reduced cell content was exacerbated by higher weight in some groups. For example, northwestern Europeans (high patient weight, high unit cell content) had the best dosed units whereas Africans (high weight, low unit cell content) had the lowest. In Asians, low cell content was partially compensated by lower weight. Marked differences in 8-allele HLA-match distribution were also observed by ancestry group (e.g. 23% of units for northwestern Europeans were 3–4/8 HLA-matched versus 40% for southern Europeans, 46% for White Hispanics and 51% for Africans). During the study period, 20 additional patients (17 non-European, median weight 98 kilograms) did not receive a CBT due to lack of a suitable graft. CB extends transplant access to most patients but racial disparities exist in cell content, dose and HLA-match.

Antithymocyte globulin (ATG) use mitigates the risk of graft rejection and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), but ATG overexposure in the setting of lymphopenia negatively affects immune recovery. We hypothesized that standard empiric weight-based dosing of ATG, used to prevent graft rejection in ex vivo CD34-selected allo-HCT, may lead to serious adverse consequences on outcomes in certain patients. We evaluated 304 patients undergoing myeloablative-conditioned ex vivo CD34-selected allo-HCT with HLA-matched donors for the treatment of hematologic malignancies. Patients received rabbit ATG at a dose of 2.5 mg/kg/day i.v. on days -3 and/or -2. An ATG dosing cutoff of 450 mg was used for statistical analyses to assess the relationship between ATG and overall survival (OS). Among all patients, median total ATG dose was 360 mg (range, 130 to 510 mg); 279 (92%) received a total dose of ATG ≤450 mg, and 25 (8%) received a total dose450 mg. On the first day of ATG administration (day -3), the median absolute lymphocyte count was .0 K/µL. For patients who received a total dose of ATG450 mg or ≤450 mg, the incidences of acute and late-acute GVHD grade II-IV were statistically similar. At 3 years post-HCT, for patients who received a total dose of ATG450 mg or ≤450 mg, nonrelapse mortality (NRM) rates were 35% and 18%, respectively (P = .029), disease-free survival (DFS) rates were 37% and 61%, respectively (P = .003), and OS rates were 40% and 67%, respectively (P = .001). Among all patient and HCT characteristics in multivariable analyses, receipt of a total dose of ATG450 mg was associated with an increased risk of NRM (hazard ratio [HR], 2.9; P = .01), shorter DFS (HR, 2.0; P = .03), and inferior OS (HR, 2.1; P = .01). In summary, the use of weight-based ATG at a time of relative lymphopenia before ex vivo CD34-selected allo-HCT results in overdosing in heavier patients, leading to higher NRM and lower DFS and OS. Further pharmacokinetic investigation in this setting is critical to determining the optimal dosing strategy for ATG.

To evaluate the association between the hematopoietic cell transplantation-comorbidity index (HCT-CI) and the recently developed age-adjusted HCT-CI (HCT-CI/age) and transplant outcomes in the setting of CD34-selected allogeneic HCT, we analyzed a homogeneous population of patients undergoing allogeneic HCT with CD34-selected grafts for acute myeloid leukemia and myelodysplastic syndrome (n = 346). Median HCT-CI and HCT-CI/age scores were 2 (percentile 25 to 75, 1 to 4) and 3 (percentile 25 to 75, 1 to 5), respectively. Higher HCT-CI and HCT-CI/age scores were associated with higher nonrelapse mortality (NRM) and lower overall survival (OS). The HCT-CI distinguished 2 risk groups (0 to 2 versus ≥3), whereas, with the HCT-CI/age, there was a progressive increase in NRM and decrease in OS with increasing scores in all 4 groups (0 versus 1 to 2 versus 3 to 4 versus ≥5). Higher scores in both models were associated with lower chronic graft-versus-host disease relapse-free survival but not with higher relapse. Both models showed a promising predictive accuracy for NRM (c- = .616 for HCT-CI and c- = .647 for HCT-CI/age). In conclusion, the HCT-CI and HCT-CI/age predict transplant outcomes in CD34-selected allo-HCT, including NRM, OS, and chronic graft-versus-host disease relapse-free survival and may be used to select appropriate patients for this approach.