Abnormal metaphase cytogenetics predicts venous thromboembolism in myeloma: derivation and validation of the PRISM score.

Although venous thromboembolism (VTE) is an important treatment and disease-related complication in myeloma, a validated risk prediction model including disease-specific variables such as cytogenetics or tumor burden is lacking. The aim of this study was to develop a new risk prediction model for VTE in the context of modern antimyeloma therapy. All consecutive patients diagnosed at the Cleveland Clinic between 2008 and 2018 and with available data on baseline candidate risk factors constituted the derivation cohort. The primary outcome was VTE (deep venous thrombosis/pulmonary embolism) within 1 year of treatment initiation. A multivariable model was used, and weights were derived from subdistribution hazard ratios to construct a risk score. The model was validated both by internal bootstrap validation and in an external validation cohort. The derivation cohort consisted of 783 patients. A 5-component risk prediction tool, named the PRISM score, was developed, including the following variables: prior VTE, prior surgery, immunomodulatory drug use, abnormal metaphase cytogenetics, and Black race. The c-statistic of the model was 0.622 (95% confidence interval [CI], 0.567-0.674). The model stratified patients into low, intermediate, and high risk, with 12-month cumulative VTE incidence of 2.7%, 10.8%, and 36.5%, respectively. Risk of VTE increased significantly with increasing score in both the derivation and the external validation data sets, with a subdistribution hazard ratio per 1-point increase of 1.28 (95% CI, 1.19-1.39; P < .001) and 1.23 (95% CI, 1.07-1.41; P = .004) respectively. Although the PRISM score can guide clinicians in identifying patients at a high risk of VTE, additional external validation is necessary for incorporation into routine clinical practice.

Toxicity analysis of busulfan pharmacokinetic therapeutic dose monitoring.

Busulfan-based conditioning regimens are associated with serious toxicities and literature reports increased risk of toxicities when daily area under the curve concentrations exceed 6000 µM-minute. We implemented real time pharmacokinetic-guided therapeutic drug monitoring of busulfan for myeloablative conditioning regimens. The objective was to compare toxicity of intravenous busulfan before and after therapeutic drug monitoring implementation. The primary endpoint was incidence of hepatotoxicity. Medical records were retrospectively reviewed with weight-based dose Busulfan/Cyclophosphamide (BuCy) conditioning from August 2017 through March 2018 (N = 14) and therapeutic drug monitoring from April 2018 through December 2018 (N = 22). Recipients of busulfan therapeutic drug monitoring were younger than those receiving weight-based dose (median: 45 vs. 58 years, p = 0.008). No other baseline differences were observed. There was no difference in hepatotoxicity between therapeutic drug monitoring and weight-based dose (median 1 vs. 0 days, p = 0.40). In the therapeutic drug monitoring group, 45% of patients had increases and 41% had decreases in busulfan dose after Bu1. Repeat pharmacokinetic after Bu2 were required in 32% of patients. A pharmacokinetic dose monitoring program for myeloablative conditioning intravenous busulfan regimens may be considered a safe practice in stem cell transplant recipients. The majority of patients receiving pharmacokinetic-guided therapeutic drug monitoring required dose changes and therapeutic drug monitoring patients had no significant difference in toxicity compared to those receiving weight-based dose.

Development and validation of a comprehensive clinical risk-scoring model for prediction of overall survival in patients with endometrioid endometrial carcinoma.

OBJECTIVE: To develop and validate a comprehensive overall survival (OS) risk-scoring model in women with endometrioid endometrial cancer (EC). METHODS: Patients with EC diagnosed from 2004 to 2013 were identified through the National Cancer Database (NCDB). Patients with known lymphovascular space invasion (LVSI) status who were treated surgically (with or without adjuvant therapy) were included. Cox proportional hazards analysis was used to identify prognostic factors for OS. This model was used to assign points based on hazard ratios for risk factors and a risk score was obtained. Recursive partitioning analysis (RPA) was used to categorize patients into risk groups. Results were internally validated in a cohort of patients from our institution (CCF cohort). Risk scores were calculated and assessed in a Cox regression model, and Harrell's c-index was calculated to assess model fit. RESULTS: Among 349,404 women with EEC during the study period, 42,107 fulfilled inclusion criteria. Factors associated with worse OS were age ≥ 60, African American race, Charlson-Deyo score 1 or 2+, higher grade, LVSI, tumor size ≥2 cm, and no lymphadenectomy performed. Six risk groups were identified (scores 0-30) and OS estimated for each risk group. Risk score per 1-point increase in HR were comparable between NCDB and CCF cohorts (HR 1.21 (1.20-1.22 p < 0.001 vs 1.18 (1.12-1.25), p < 0.001), and c-index 0.80 (0.79-0.81) vs. 0.77 (0.68-0.86). Similar analysis was done in stage IA and IB. Adjuvant therapy had a beneficial effect on survival in the majority of stage IB patients, but only one of the six risk groups in stage IA EC. CONCLUSIONS: We report a comprehensive validated OS risk-scoring model for patients with.

Secular trends of Blood stream infections in allogeneic hematopoietic cell transplant recipients 72 hours prior to death.

INTRODUCTION: Blood stream infections (BSI) frequently cause morbidity and mortality in allogeneic (allo) hematopoietic cell transplant (HCT) recipients. Characteristics of causative organisms shortly before death have not been previously described. Early treatment with antimicrobial agents targeting the recent surge in multidrug-resistant (MDR) pathogens may lead to better outcomes. METHODS: This is retrospective study including 529 allo HCT recipients who died between 2000 and 2013. All patients who had BSI that happened 72 hours before death were included. BSI and criteria for antimicrobial resistance were defined according to the Centers for Disease Control and Prevention and the National Healthcare Safety Network surveillance criteria. RESULTS: Overall, 104 BSI were identified from 91 patients. Bacterial infections accounted for 87% of the infections which were comprised by 37% gram-negative organisms and 50% gram-positive bacteria. The most common species were Enterococcus (30%), Staphylococcus (16%), and Pseudomonas (16%). Most enterococci were vancomycin resistant (87%), 100% of staphylococci were resistant to methicillin, and 64% of Pseudomonas were MDR. Over time there was a significant increase in vancomycin-resistant enterococcal (P = .01) and gram-negative BSI (P = .01). Blood stream infections were either the primary or secondary cause of death in 53% of patients. CONCLUSIONS: In allo HCT recipients, vancomycin-resistant enterococcal infections caused the majority of BSI 72 hours prior to death. Our findings provide information that may guide empiric antibiotic coverage in critically ill HCT recipients.

Pain or fatigue: which correlates more with suffering in hospitalized cancer patients?

BACKGROUND: The association of pain and suffering seems intuitive, but evidence substantiating this association is lacking. In studies of cancer patients, fatigue, rather than pain, is the most prevalent and debilitating symptom. This study aimed to compare the correlation of pain and fatigue to suffering, and identify other potential sources of suffering in cancer patients treated in a palliative care unit. METHODS: One hundred fifty cancer patients were surveyed. Fifteen variables were measured on a 0- to 10-point scale: suffering, pain, level of acceptable pain, effect of pain on quality of life, fatigue, level of acceptable fatigue, effect of fatigue on quality of life, and specific types of suffering. Univariable associations with suffering were made with Pearson correlation (continuous variables) or t test (binary predictors). Multivariable associations with suffering were assessed with linear regression analysis and bootstrapping. RESULTS: In multivariable analysis, highest pain (parameter estimate 0.38) had a greater impact on suffering than highest fatigue (parameter estimate 0.21). When other variables were assessed, 38% of the variability in suffering was accounted for by pain "now", fatigue in the past 24 hours, and age. CONCLUSION: The most important predictors of greater suffering in hospitalized cancer patients are pain, younger age, and fatigue. Despite their significant effect on suffering, other underlying contributors to suffering have yet to be identified. Designing interventions to reduce fatigue, in addition to pain management, may help in alleviating overall suffering.

Therapeutic Dose Monitoring of Busulfan Is Associated with Reduced Risk of Relapse in Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.

Optimal administration of busulfan (Bu) is hampered by variable and unpredictable drug metabolism in individual patients. At our institution, Bu was previously administered with fixed weight-based dosing (WBD) in combination with cyclophosphamide (Cy) and etoposide (E) for patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). In 2014, we adopted real-time pharmacokinetic (PK)-guided therapeutic drug monitoring (TDM) of Bu for all NHL patients undergoing Bu-containing ASCT. Here we compare outcomes of NHL patients who underwent ASCT with Bu/Cy/E using WBD and those who did so using TDM of Bu. We studied 336 consecutive adult NHL patients who underwent ASCT with Bu/Cy/E using WBD from January 2007 to December 2013 (n = 258) or TDM from May 2014 to December 2017 (n = 78), excluding patients with mantle cell lymphoma. Clinical outcomes, including relapse, nonrelapse mortality (NRM), progression-free survival (PFS), and overall survival (OS), hepatotoxicity and pulmonary toxicity were compared in the 2 groups. To adjust for differences in baseline characteristics between the groups, propensity-matched cohorts of WBD and TDM patients were also studied. After the first dose of Bu, the dose was increased in 36% of the patients and decreased in 41%. Changes in pulmonary and liver function from baseline to transplantation were not different between the 2 groups, although these changes showed significantly less variability with TDM than with WBD. Relapse was significantly lower and PFS was improved with TDM; 2-year estimates were 19% for TDM and 38% for WBD for relapse (P = .004) and 69% and 55%, respectively, for PFS (P = .038). No significant between-group differences in NRM or OS were seen. In multivariable analysis, TDM remained prognostic for lower risk of relapse (hazard ratio [HR], .52; 95% confidence interval [CI], .30 to .89; P = .018), but did not remain prognostic for PFS (HR, .74; 95% CI, .48 to 1.16; P = .19). Propensity-matched cohorts displayed similar patterns of outcomes. In subset analysis based on disease status at ASCT, TDM was associated with less relapse and better PFS than WBD for patients who underwent transplantation in less than complete remission (CR) compared with those who underwent transplantation in CR. Compared with WBD, PK-directed TDM of Bu reduces the incidence of relapse when used in combination with Cy and E for patients with NHL undergoing ASCT, particularly for patients in less than CR. These data support the continued use of personalized PK-guided dosing for all NHL patients undergoing ASCT with Bu-containing preparative regimens.

Quality-of-Life Trajectories in Adolescent and Young Adult versus Older Adult Allogeneic Hematopoietic Cell Transplantation Recipients.

Hematopoietic cell transplantation (HCT) is physically and psychologically challenging, potentially exposing patients to quality-of-life (QoL) impairments. Adolescent and young adults (AYAs, aged 15 to 39 years) are a vulnerable cohort facing multiple hurdles due to dynamic changes in several aspects of their lives. The AYA population may be particularly prone to QoL issues during HCT. We hypothesized that due to the unique psychosocial challenges faced by AYAs, they would have an inferior quality of life. We studied QoL differences between AYA (aged 15 to 39 years) and older adult (aged 40 to 60 years) allogeneic HCT recipients before and after HCT. Additionally, we determined if pre-HCT QoL for AYA transplant recipients changed over time. QoL data were collected prospectively before and after transplant on 431 recipients aged 15 to 60 years from June 2003 through December 2017 using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) questionnaire. Repeated-measures analysis of variance was used to assess differences among age groups. Pearson correlation (r) was used to determine if baseline QoL had improved after HCT from June 2003 through December 2017 in the AYA cohort. QoL did not differ among younger AYAs, older AYAs, or older adults at any time in the first year after allogeneic HCT. At 1 year post-HCT, total FACT-BMT score and all FACT-BMT domains except physical well-being improved from pre-HCT in all age groups. From 2003 to 2017, AYA allogeneic recipients experienced modest improvement in additional concerns (r = 0.26, P = .003), trial outcome index (r = 0.23, P = .008), and total FACT-BMT score (r = 0.19, P = .031), although no improvements were seen in physical, social, emotional, or functional well-being. Contrary to our hypothesis, we found that QoL in the AYA population is similar to that of older adults before and after HCT. Improvements in QoL of AYA allogeneic patients since 2003 were driven by the additional concerns domain, which addresses multiple psychosocial aspects such as vocation, hobbies, and acceptance of illness. Continued efforts to tailor treatment and support for AYA HCT recipients is critical to improving QoL outcomes.

Real-world data on safety and efficacy of venetoclax-based regimens in relapsed/refractory t(11;14) multiple myeloma.

The treatment for relapsed/refractory multiple myeloma (RRMM) continues to be challenging despite recent therapeutic advancements. Venetoclax, an inhibitor of the anti-apoptotic protein BCL-2, is a promising agent, especially in patients harbouring t(11;14). Our objective was to review our experience with venetoclax-based regimens at our institution. All ten RRMM patients treated with venetoclax were included and had a median of six prior lines of therapy. The overall response rate was 78% and one patient with cardiac amyloidosis and MM achieved a cardiac organ response. Haematologic toxicities requiring red blood cell and platelet transfusion and non-haematologic toxicities, most commonly gastrointestinal upset, were observed.

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma.

Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma (MM) is lacking in the current literature. We evaluated 258 patients with relapsed MM, diagnosed from 2008 to 2015, to investigate the prognostic impact of deep immunoparesis on post-relapse survival. On qualitative immunoparesis assessment, no, partial and full immunoparesis was present in 9%, 30% and 61% of patients, respectively. Quantitative immunoparesis was assessed by computing the average relative difference (ARD) between polyclonal immunoglobulin(s) and corresponding lower normal limit(s), with greater negative values indicating deeper immunoparesis. The median ARD was -39%, with an optimal cut-off of -50% for overall survival (OS) by recursive partitioning analysis. Deep immunoparesis (ARD ≤-50%) was associated with a higher tumour burden at first relapse compared to none/shallow [ARD >-50%] immunoparesis. The OS (P = 0·007) and progression-free survival (PFS; P < 0·001) differed significantly between the deep and none/shallow immunoparesis groups. Kaplan-Meier estimates for 3-year OS were 36% and 46%, and for 2-year PFS were 17% and 27%, respectively. On multivariable analysis (MVA) for PFS, both qualitative and quantitative immunoparesis retained negative prognostic impact independently. However, only quantitative immunoparesis was independently prognostic for OS on MVA. Depth of immunoparesis in relapsed MM is an important prognostic factor for post-relapse survival in the era of novel agents and continuous therapy.

Severity of acute gastrointestinal graft-vs-host disease is associated with incidence of bloodstream infection after adult allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Infections are the most common cause of non-relapse mortality in adult allogeneic hematopoietic stem cell transplant (allo HSCT) recipients. Acute gastrointestinal graft-vs-host disease (GI GVHD) often leads to friable mucosa as well as treatment interventions which can increase risk of infection. Our primary objective was to describe the relationship between increasing grades of acute GI GVHD and incidence of bloodstream infections (BSI). METHODS: We reviewed 441 adults who underwent allo HSCT from 2011 to 2017 and were clinically diagnosed with GI GVHD, non-GI GVHD, or no GVHD based on the modified Glucksberg scale within the first 100 days of transplantation. The maximum grades of acute GI GVHD and non-GI GVHD were used in the analysis. BSI was defined based on the presence of a blood culture positive for bacteria or fungi and treatment with antibiotics. The incidence of BSI within the first 180 days of transplantation was estimated with the cumulative incidence method. Fine and Gray regression was used to assess association between clinical grade of acute GI GVHD and BSI risk, adjusting for grade of non-GI GVHD and for other significant baseline patient risk factors for BSI identified by multivariable analysis. Results are shown as hazard ratio (HR) and 95% confidence interval (CI). A similar analysis was conducted in 130 patients with histologic grade of acute GI GVHD. RESULTS: Overall BSI incidence by day 180 was 32%; gram-negative bacilli were the predominant organisms, followed by gram-positive cocci and fungi. Patients with grade 4 acute GI GVHD had higher risk of BSI as compared to patients with no GI GVHD (HR 2.98, CI 1.65-5.37, P < .001), while those with grade 3 acute GI GVHD had similar BSI risk (HR 0.89, CI 0.36-2.21, P = .81). Grade of GI GVHD had no association with risk of non-BSI. Results were similar in patients with histologic grade acute GI GVHD. Patients who developed BSI or non-BSI had significantly higher overall mortality risk compared to those without infectious complications (HR 2.52, CI 1.92-3.31, P < .001 for BSI; HR 1.60, CI 1.20-2.13, P = .001 for non-BSI). CONCLUSIONS: Grade 4 acute GI GVHD is associated with a higher risk of BSI, which is in turn associated with a higher risk of overall mortality in this population. Understanding the relationships between acute GI GVHD, BSI, and overall mortality can guide future treatment strategies for adult allo HSCT recipients.

Impact of vaginal brachytherapy on survival in stage I endometrioid endometrial carcinoma.

OBJECTIVE: To evaluate trends in use of radiation therapy and its impact on overall survival in low- and high-grade stage I endometrioid endometrial carcinoma. METHODS: Patients with stage I endometrial cancer who underwent hysterectomy from 2004 to 2013 were identified through the National Cancer Database and classified as: stage IA G1/2, stage IA G3, stage IB G1/2, and stage IB G3. Trends in use of vaginal brachytherapy and external beam radiation therapy were assessed. Overall survival was measured from surgery and estimated using the Kaplan-Meier method. The effect of radiation therapy on overall survival was assessed within each stage/grade group using Cox proportional hazards analysis in propensity-matched treatment groups. RESULTS: A total of 132 393 patients met inclusion criteria, and 81% of patients had stage IA and 19% had stage IB endometrial cancer. Adjuvant therapy was administered in 18% of patients: 52% received vaginal brachytherapy, 30% external beam radiation therapy, and 18% chemotherapy ±radiation therapy. External beam radiation therapy use decreased from 9% in 2004 to 4% in 2012, while vaginal brachytherapy use increased from 8% to 14%. Stage IA G1/2 patients did not benefit from either external beam radiation therapy or vaginal brachytherapy, while administration of vaginal brachytherapy improved overall survival in stage IB G1/2 compared with no treatment (p<0.0001). In stage IB G1/2 and stage IA G3, vaginal brachytherapy was superior to external beam radiation therapy (p=0.0004 and p=0.004, respectively). Stage IB G3 patients had improved overall survival with either vaginal brachytherapy or external beam radiation therapy versus no treatment but no difference in overall survival was seen between vaginal brachytherapy and external beam radiation therapy (p=0.94). CONCLUSIONS: The delivery of adjuvant radiation therapy in patients with stage IA G1/2 endometrial carcinoma is not associated with improvement in overall survival. Patients with stage IB G1/2 and G3 as well as stage IA G3 are shown to benefit from improved overall survival when adjuvant radiation therapy is administered. These findings demonstrate potential opportunities to reduce both overtreatment and undertreatment in stage I endometrial cancer patients.

Conditional Long-Term Survival after Autologous Hematopoietic Cell Transplantation for Diffuse Large B Cell Lymphoma.

Autologous hematopoietic cell transplantation (AHCT) is standard therapy for patients with chemosensitive, relapsed, diffuse large B cell lymphoma (DLBCL). We performed a retrospective cohort study to delineate subsequent (conditional) and relative survival in 371 adult patients with DLBCL who underwent AHCT between 2000 and 2014 and had survived for 1, 2, 3, or 5 years after transplant. The probability of overall survival at 10 years after AHCT was 62%, 71%, 77%, and 86%, respectively, for the 4 cohorts, whereas that of progression-free survival (PFS) was 55%, 65%, 72%, and 81%, respectively. The respective cumulative incidence of nonrelapse mortality (NRM) at 10 years after transplantation was 13%, 12%, 11%, and 8%, respectively. In multivariable analysis, older age was associated with greater mortality risk among all but 5-year survivors; relapse within the landmark time was associated with greater mortality risk in all groups. Older age and relapse within the landmark time were associated with worse PFS in all groups. Standardized mortality ratio (SMR) was significantly higher than an age-, gender-, and race-matched general population, with the magnitude of SMR decreasing as the landmark time increased (4.0 for 1-year, 3.0 for 2-year, 2.4 for 3-year, and 1.8 for 5-year survivors). Our study provides information on long-term survival and prognosis that will assist in counseling patients with DLBCL who have received AHCT. Survival improves with longer time in remission post-transplant, although patients continue to remain at risk for NRM, underscoring the need for continued vigilance and prevention of late complications.

Time to surgery and its impact on survival in patients with endometrial cancer: A National cancer database study.

OBJECTIVE: To determine patient and facility-specific factors associated with time to surgery (TTS) in patients with endometrial cancer (EC), and define the impact of delay in TTS >6 weeks on overall survival (OS) by tumor histology and stage. METHODS: The National Cancer Database (NCDB) was queried to identify patients with EC who underwent definitive primary surgical treatment between 2004 and 2013. Patients were stratified by EC histology into type I (endometrioid) and type II (non-endometrioid). TTS (number of days from diagnosis to definitive surgery) was calculated and trends in TTS during the study period were analyzed. Poisson regression was used to identify factors associated with TTS for patients with type I and type II EC, respectively. Cox regression was used to assess the impact of delay in TTS > 6 weeks on OS by tumor histology and stage. RESULTS: Out of 284,499 patients included in the study, 83% had type I EC and 17% had type II EC. Median (interquartile range; IQR) TTS for type I and II EC was 27 days (10-41) and 26 days (13-40), respectively. TTS increased over the study period in both groups. In Type I EC, delay in TTS was associated with worse OS in patients with early stage (I-II) EC only. In type II EC, delay in TTS had no significant impact on OS in stage I-III EC, while a paradoxical relationship between TTS > 6 weeks and improved OS was observed for stage IV EC. CONCLUSION: TTS increased over the study period. TTS >6 weeks was negatively associated with OS in early stage type I EC. Interventions to reduce TTS in specific stages and settings for EC are necessary given this impact on mortality.

Progression with clinical features is associated with worse subsequent survival in multiple myeloma.

Response rate and survival in multiple myeloma (MM) has improved in the era of proteasome inhibitors and immunomodulatory drugs. However, most patients eventually relapse with biochemical progression (BP) alone or with clinical features of end-organ damage (CP: clinical progression), without or without extramedullary (EM) disease. We conducted a retrospective cohort study of 252 patients with MM experiencing first relapse (time, T0 ) to evaluate survival following CP with and without EM as a function of BP. Patients were divided into three groups: BP (n = 134; 53%), CP/EM- (n = 87; 35%) and CP/EM+ (n = 31; 12%). The median time from diagnosis to T0 was significantly shorter in CP/EM+ compared to CP/EM- and BP groups (13 vs 25 vs 25 months; P < 0.001). The incidence of abnormal metaphase cytogenetics at diagnosis was significantly higher in CP/EM+ compared to CP/EM- and BP groups (46% vs 18% vs 11% respectively; P < 0.001). At a median follow-up of 26 months from T0 , median overall survival was 50, 19 and 10 months for BP, CP/EM- and CP/EM+ groups, respectively (P < 0.001). On multivariable analysis, pattern of progression was a significant prognostic factor for OS (HR for CP/EM- vs BP: 3.6; CP/EM+ vs BP: 8.7 and CP/EM+ vs CP/EM-: 2.42; P < 0.001 for all comparisons), along with age at T0 . In conclusion, progression pattern is an important prognostic factor in the current era, with subsequent survival being dismal in patients with end-organ damage or EM disease at relapse. Clinical trials in relapsed MM should consider reporting patterns of progression at baseline to ensure balance between study arms.

Early infectious complications after autologous hematopoietic cell transplantation for multiple myeloma.

BACKGROUND: The spectrum of infectious complications in autologous hematopoietic cell transplant recipients (AHCT) with multiple myeloma has not been well described in the recent era of novel agent induction and improved supportive care. METHODS: We conducted a retrospective cohort study of 413 adult myeloma AHCT recipients at our institution from 2007-2016 to describe the cumulative incidence and risk factors for various infections and FN occurring within the first 100 days after AHCT. Additionally, landmark analysis was done among 404 patients who survived at least 100 days after transplant admission to estimate the association of infections with subsequent non-relapse mortality (NRM), overall survival (OS), and relapse-free survival (RFS). RESULTS: Cumulative incidences (95% CI) of infection events by day 100 were: FN 43% (38-48), any infection 21% (17-25), bacterial 17% (14-21), viral 4% (3-7) and fungal 1% (0.5-3), central line-associated blood stream infection 3% (2-6), and Clostridium difficile colitis 6% (4-8). Patients with infection had a longer initial transplant hospitalization (median 17 vs 16 days, P < 0.01), more readmissions (31% vs 8%, P < 0.01), and spent more days in hospital in first 100 days (median 18 vs 16 days, P < 0.01). A 100-day mortality was low and similar between groups (2% vs 1%, P = 0.28). In landmark analysis of 404 100-day survivors, OS was worse among patients with early infections (hazard ratio 1.54 [1.03-2.30], P = 0.03), although there was no difference in NRM and RFS. CONCLUSIONS: Notwithstanding advances in supportive care, early infectious complications remain a relevant source of morbidity and require attention in myeloma AHCT recipients.

Penicillin allergy skin testing as an antibiotic stewardship intervention reduces alternative antibiotic exposures in hematopoietic stem cell transplant recipients.

BACKGROUND: Antibiotic allergy de-labeling using penicillin allergy skin testing (PAST) can reduce the use and cost of alternative, non-ß-lactam antibiotics in general inpatient populations. This strategy's role in hematopoietic stem cell transplant (HSCT) recipients is unclear. METHODS: This study aimed to determine the effect of a pre-transplant PAST protocol on antibiotic use, days of therapy (DOT), and cost in an immunocompromised population at a single center from 7/1/2010-2/1/2019. Patients who received chimeric antigen receptor (CAR) T-cell therapy and those who underwent transplantation in the outpatient setting were excluded. RESULTS: Of 1560 patients who underwent inpatient HSCT during the study period, 208 reported ß-lactam allergy (136/844 [16%] pre- and 72/716 [10%] post-implementation; P < .001). PAST was performed on 7% and 54% of HSCT recipients pre- and post-implementation, respectively. Only two positive PAST were noted. There were no adverse reactions to PAST. There were no significant differences in the disease and transplant characteristics between the two groups. Days of therapy and cost of alternative antibiotics significantly decreased post-implementation (mean 788 vs 627 days, P = .01; mean $24 425 vs $17 518, P = .009). CONCLUSION: Penicillin allergy skin testing adjudicates reported ß-lactam allergy in HSCT recipients, lowering use, DOT, and cost of alternative antibiotics and promoting effective formulary agents to treat immunocompromised HSCT recipients.

Undifferentiated endometrial carcinoma: a National Cancer Database analysis of prognostic factors and treatment outcomes.

BACKGROUND: Undifferentiated endometrioid endometrial carcinoma of the uterus is a rare, highly aggressive, and under-recognized subtype of endometrial cancer. OBJECTIVE: This study evaluates survival, prognostic factors for survival, and treatment outcomes associated with undifferentiated endometrial cancer. METHODS: The National Cancer Database was queried to identify patients with undifferentiated endometrial cancer who underwent definitive primary surgical treatment. Patients with all other histologic subtypes or incomplete treatment data were excluded. Univariable and multivariable Cox proportional hazards analyses were used to determine independent prognostic factors for survival. Points for each prognostic factor were assigned from regression coefficients in the final multivariable model and summed for a total score. Recursive partitioning analysis was used to determine cut-offs in the score to identify unique prognostic groups. RESULTS: Among 349 404 women diagnosed with endometrial cancer from 2004 to 2013, 3994 (1.1%) met the criteria for diagnosis of undifferentiated endometrial cancer and 3486 had survival data. Median age at diagnosis was 65 years (interquartile range (IQR) 57-74) and 58% of patients had early stage disease. Median interval from diagnosis to surgery was 3.7 weeks (IQR 2.0-5.7). Five year overall survival was 57% (standard error (SE) 1%). Stage was the strongest predictor of survival, with a 15-20% decrement in 5 year survival for each advance in stage. Stage, age, race, and presence of comorbidities were independent predictors of survival and were used to categorize patients into five prognostic groups. Adjuvant therapy was associated with improved survival across most disease stages and prognostic groups. Multimodal adjuvant therapy was superior to unimodal treatment particularly in advanced stage unfavorable and very unfavorable groups. CONCLUSION: In women with undifferentiated endometrial cancer, survival is primarily driven by stage. Despite the poor overall prognosis of undifferentiated endometrial cancer, multimodal adjuvant therapy is a key component of treatment.

Body mass index does not impact hematopoietic progenitor cell mobilization for autologous hematopoietic cell transplantation.

BACKGROUND: Obesity has implications for hematopoietic progenitor cell (HPC) mobilization, chemotherapy administration, and medication dosing. We analyzed the impact of obesity on HPC mobilization as well as key outcomes that are associated with cell dose in autologous hematopoietic cell transplantation (AHCT) recipients. METHODS: We conducted a retrospective cohort study on 556 consecutive eligible AHCT recipients at our institution from 1/2004 to 12/2009. Patients were categorized into four groups based on the body mass index (BMI): underweight (BMI < 18.5), normal (18.5-24.9), overweight (25.0-29.9), or obese (≥30.0). Primary endpoints of interest included HPC mobilization, neutrophil and platelet recovery, hospital stay and survival. RESULTS: The diagnoses were mostly non-Hodgkin lymphoma, multiple myeloma, and Hodgkin lymphoma. The majority of the patients had received three or less prior chemotherapy regimens and had not received prior radiation therapy. Most patients had chemosensitive disease at time of transplant. For HPC mobilization regimen, 68% received chemotherapy and G-CSF, 32% received G-CSF alone. Busuflan/etoposide/cyclophosphamide, melphalan, and busulfan/cyclophosphamide were used for conditioning. Obesity did not correlate with HPC mobilization and had no association with neutrophil or platelet recovery, or length of transplant hospitalization. On multivariable analysis, obese patients demonstrated better survival than those who were not obese. CONCLUSION: Obese AHCT recipients had similar rates of HPC mobilization, neutrophil and platelet engraftment and length of transplant hospitalization, and experienced better survival compared with recipients with lower BMI. High BMI by itself should not be considered as a contraindication to AHCT.

Community Risk Score for Evaluating Health Care Disparities in Hematopoietic Cell Transplantation.

There is a critical need for tools to comprehensively describe disparities in hematopoietic cell transplant (HCT) recipients. We conducted a retrospective cohort study to evaluate a Community Risk Score (CRS) tool for this purpose. CRS included 10 community health indicators based on county or state of residence obtained from several secondary data sources and a composite score was assigned to each county (range 0 to 40), that was further categorized into six tiers (I to VI) with higher tiers indicating poor community health. CRS was assessed for 509 allogeneic and 1033 autologous HCT recipients from 2003 to 2013. Our cohort represented allogeneic and autologous HCT recipients from 300 and 431 unique ZIP codes from 99 and 125 counties in 15 and 16 states, although 86% and 90% patients were from Ohio, respectively. A greater proportion of patients had adverse individual community risk indicators in higher-risk tiers (P < .001 for trend for all). In multivariable analysis, clear trends toward association of CRS with outcomes were not observed. For autologous HCTs, Tier III has higher risks of relapse mortality (hazard ratio [HR] 2.2, P = .02) and all-cause mortality (HR 1.8, P = 0.03). In conclusion, CRS was able to categorize patients into groups representing greater levels of health care disparities. We did not see a clear association between CRS and transplant outcomes, although our cohort was limited to a relatively small group of counties. Community-based risk score model may serve as a tool for evaluating disparities in HCT recipients, but its validation in a nationally representative cohort of patients is needed.

Association of Socioeconomic Status with Chronic Graft-versus-Host Disease Outcomes.

Chronic graft-versus host disease (GVHD) is a chronic and disabling complication after hematopoietic cell transplantation (HCT). It is important to understand the association of socioeconomic status (SES) with health outcomes in patients with chronic GVHD because of the impaired physical health and dependence on intensive and prolonged health care utilization needs in these patients. We evaluated the association of SES with survival and quality of life (QOL) in a cohort of 421 patients with chronic GVHD enrolled on the Chronic GVHD Consortium Improving Outcomes Assessment study. Income, education, marital status, and work status were analyzed to determine the associations with patient-reported outcomes at the time of enrollment, nonrelapse mortality (NRM), and overall mortality. Higher income (P = .004), ability to work (P < .001), and having a partner (P = .021) were associated with better mean Lee chronic GVHD symptom scores. Higher income (P = .048), educational level (P = .044), and ability to work (P < .001) also were significantly associated with better QOL and improved activity. In multivariable models, higher income and ability to return to work were both significantly associated with better chronic GVHD Lee symptom scores, but income was not associated with activity level, QOL, or physical/mental functioning. The inability to return to work (hazard ratio, 1.82; P = .019) was associated with worse overall mortality, whereas none of the SES indicators were associated with NRM. Income, race, and education did not have statistically significant associations with survival. In summary, we did not observe an association between SES variables and survival or NRM in patients with chronic GVHD, although we found some association with patient-reported outcomes, such as symptom burden. Higher income status was associated with less severe chronic GVHD symptoms. More research is needed to understand the psychosocial, biological, and environmental factors that mediate this association of SES with major HCT outcomes.