Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention.

Tacrolimus (Tac)/methotrexate (MTX) is standard graft-versus-host disease (GVHD) prophylaxis; however, is associated with several toxicities. Tac, reduced-dose MTX (mini-MTX), and mycophenolate mofetil (MMF) have been used but never compared with standard MTX. We performed a randomized trial comparing Tac/MTX (full-MTX) with Tac/mini-MTX/MMF (mini-MTX/MMF) for GVHD prevention after allogeneic hematopoietic cell transplantation (HCT). Patients (pts) receiving first myeloablative HCT using an 8/8 HLA-matched donor were eligible. Primary end points were incidence of acute GVHD (aGVHD), mucositis, and engraftment. Secondary end points included chronic GVHD (cGVHD), organ toxicity, infection, relapse, nonrelapse mortality (NRM), and overall survival (OS). Ninety-six pts were randomly assigned to full-MTX (N = 49) or mini-MTX (N = 47). The majority (86%) used bone marrow grafts. There was no significant difference in grade 2-4 aGVHD (28% mini-MTX/MMF vs 27% full-MTX; P = .41); however higher incidence of grade 3-4 aGVHD (13% vs 4%; P = .07) with mini-MTX/MMF. Pts receiving mini-MTX/MMF had lower grade 3 or 4 mucositis and faster engraftment. There were no differences in moderate-to-severe cGVHD at 1 year or infections. Pts receiving mini-MTX/MMF experienced less nephrotoxicity and respiratory failure. There was no difference in the 1-year relapse (19% vs 21%; P = .89) and OS (72% vs 71%; P = .08), and mini-MTX/MMF was associated with lower but nonsignificant NRM (11% vs 22%; P = .06). Compared with full-MTX, mini-MTX/MMF was associated with no difference in grade 2-4 aGVHD and a more favorable toxicity profile. The higher severe aGVHD warrants further study to optimize this regimen. The trial was registered at www.clinicaltrials.gov as #NCT01951885.

A Pilot Trial of Patient-Reported Outcomes for Acute Graft-Versus-Host-Disease.

Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Acute GVHD is associated with severe physical and psychosocial symptoms. We sought to evaluate the feasibility of capturing patient-reported outcome (PRO) measures in acute GVHD to better measure symptom burden and quality of life (QOL). We conducted a pilot study of adult patients undergoing first allogeneic HCT. Questions from Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT), Patient-Reported Outcomes Measurement Information System (PROMIS-10), and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) were selected, and the survey was administered electronically before HCT, at days 14, 50, and 100 after HCT. In addition, patients who developed grade 2-4 acute GVHD received it weekly for 4 weeks and then monthly up to 3 months. From 2018 to 2020, 73 patients were consented, of which 66 went on to undergo HCT and were included in the analysis. Median age at transplantation was 63 years, and 92% were Caucasian. Only 47% of expected surveys were completed (range 0%-67% for each time point). Descriptive exploratory analysis demonstrate an expected trajectory of QOL using the FACT-BMT and PROMIS-10 scores throughout transplantation. Patients who developed acute GVHD (N = 15) generally had lower QOL scores compared to those with no or mild GVHD post-HCT. The PRO-CTCAE captured several physical and mental/emotional symptoms in all patients and those with GVHD. Fatigue (100%), decreased appetite (92%), problem tasting (85%), loose stools (77%), pain (77%), skin itching (77%), and depression (feeling sad) (69%) were the most prevalent symptoms among patients with grade 2-4 acute GVHD. Patients with acute GVHD generally reported worse symptoms than those with no/mild GVHD in frequency, severity, and interference in normal activities. Several challenges were identified including poor access/literacy of electronic surveys, acute illness, and need for extensive research/resource support. We demonstrate the challenges yet potential of using PRO measures in acute GVHD. We demonstrate that the PROMIS-10 and PRO-CTCAE measures are able to capture several symptoms and QOL domains of acute GVHD. Further investigation into making PROs feasible in acute GVHD are needed.

Patient-Reported Outcomes in Long-Term Survivors of Autologous Hematopoietic Cell Transplantation in Multiple Myeloma.

The overall survival in patients with transplantation-eligible multiple myeloma has tripled over the past 2 decades, leading to a growing population of myeloma survivors. However, there is a paucity of data on health-related quality of life (HRQoL), distress, and health behaviors in long-term myeloma survivors who are in stable remission after autologous hematopoietic cell transplantation (AHCT). In this cross-sectional study using data from 2 randomized controlled trials of survivorship care plans and internet-based self-management intervention in transplantation survivors, the primary objective was to measure HRQoL (using the Short Form-12, version 2.0 [SF-12 v2]), distress (using the Cancer- and Treatment-Related Distress [CTXD] instrument), and health behaviors of myeloma survivors in stable remission after AHCT. A total of 345 patients at a median of 4 years (range, 1.4 to 11 years) post-AHCT were included. The mean SF-12 v2 Physical Component Summary (PCS) score was 45.5 ± 10.5, and the mean Mental Component Summary (MCS) score was 51.3 ± 10.1, compared with US population norms of 50 ± 10 for both (P < .001 and P = .021 for PCS and MCS comparisons, respectively). Notably, neither reached the threshold for a minimal clinically important difference. Approximately one-third of the patients had clinically significant distress based on the CTXD total score, with distress reported by 53% of the patients in the Health Burden domain, by 46% in the Uncertainty domain, by 33% in the Finances domain, by 31% in the Family Strain domain, by 21% in the Identity domain, and by 15% in the Medical Demands domain. Preventive care guidelines were adhered to by 81% of the myeloma survivors; however, adherence to exercise and diet guidelines were relatively low, at 33% and 13%, respectively. Myeloma AHCT survivors in stable remission have no clinically meaningful worsening in physical functioning compared with the general population. Survivorship programs should address ongoing distress due to health burden, uncertainty, and finances in myeloma survivors, along with evidence-based targeted interventions for modifiable health behaviors, such as nutrition and exercise.

Prophylactic Trimethoprim-Sulfamethoxazole for Allogeneic Hematopoietic Stem Cell Transplant Recipients During the Pre-engraftment Period.

BACKGROUND: Our institution has used trimethoprim-sulfamethoxazole (TMP-SMX) as the antibacterial agent of choice for infection prophylaxis during the pre-engraftment period in the allogeneic transplant (allo-HCT) population. METHODS: This retrospective, single center study was developed to compare the safety of that antibacterial prophylaxis to fluoroquinolones in allo-HCT. The primary endpoint was time to neutrophil engraftment. RESULTS: A total of 366 patients were reviewed (TMP-SMX n = 332, fluoroquinolone n = 34). No difference in days to neutrophil engraftment was found (median 15 versus 16 days, p = 0.62). Hyperkalemia was more common in the TMP-SMX cohort (32.2% versus 14.7%, p = 0.035); this did not contribute to a higher rate of agent discontinuation or arrhythmia. There was no significant difference in the incidence of neutropenic fever; however, those in the TMP-SMX cohort were more likely to have microbiologically confirmed bacteremia (24.1% versus 8.8% respectively, p = 0.043). There was no significant difference in infections. No long-term implication of prophylactic antibacterial agent selection was observed in terms of graft-versus-host-disease, underlying disease relapse, or mortality. CONCLUSION: The use of TMP-SMX was associated with a higher likelihood of bacteremia and hyperkalemia; however, this did not result in increased hospital stay, escalation of care, or mortality. The use of TMP-SMX for prophylaxis during the pre-engraftment period for allo-HCT recipients is safe and effective.

Response Rates to Methylnaltrexone in Hospitalized Cancer Patients.

Context: Methylnaltrexone is a peripherally-acting mu-opioid receptor antagonist studied in both cancer and non-cancer patients with opioid-induced constipation (OIC), but mostly in the outpatient setting. For adult hospitalized cancer patients with OIC, its effectiveness is unknown. Objectives: Describe the efficacy of methylnaltrexone for OIC in the inpatient setting, defined as bowel movement (BM) within 24 hours of methylnaltrexone administration. Methods: We performed a single-center, retrospective chart review of all hospitalized, adult patients with a cancer diagnosis who received methylnaltrexone from the palliative care team between January 1st, 2012 and July 1st, 2019. Results: We identified 194 patients. The mean age was 59, 50.5% were male and 88% were white. 192 patients (98%) received the 8 mg dose subcutaneously. The median oral morphine equivalent (OME) was 135 mg (IQR 70-354 mg). 45% (95% confidence interval, 38-53%) had a BM within 24 hours. Higher OME was correlated with successful BM, with a response in 93% (86/92) of patients receiving ≥150 OME and 2% (2/102) of patients receiving <150 OME (P < .0001). Prior laxative use did not predict response at 24 hours whether these were osmotic laxatives (40.7% vs 47.1%, P = .52), stimulant laxatives (45.7% vs 45.2%, P > .99), or stool softeners (44.7% vs 46.1%, P = .89). Conclusion: Methylnaltrexone has a high response rate when used as treatment for OIC in hospitalized adult cancer patients, especially for patients taking ≥150 OME.

Characteristics of Patients with Cancer Readmitted Within 30 Days to an Acute Palliative Care Unit.

OBJECTIVE(S): For patients with cancer, the emergence of acute palliative care units (APCU) may hold promise in curtailing hospital readmissions. The study aims to describe the characteristics of patients readmitted to an APCU. METHODS: This retrospective study examined patients with cancer readmitted within 30 days to an APCU. Readmissions were further classified as either potentially preventable or non-preventable. RESULTS: Out of 734 discharges from July 1, 2014 to July 1, 2015, 69 (9%) readmissions were identified and analyzed. For index admissions, median length of stay was five days, and one (1%) was discharged home with hospice care. For readmissions, median time from index admission to readmission was nine days, median length of stay was six days, three (4%) patients died, and 20 (30%) went home with hospice. Ten (14.5%) readmissions were deemed potentially preventable (95% CI 7.2-25.0%). Race/ethnicity-White/Black/Hispanic/Others-was 60%, 10%, 20% and 10%, respectively, among potentially preventable readmissions and 76%, 22%, 2% and 0%, respectively, among potentially non-preventable readmissions (P = .012). Potentially preventable readmissions were more likely to have venous thromboembolism (40% vs. 12%, P = .046) and more reasons for readmission (median 2 vs. 1, P = .019). CONCLUSIONS: Among patients with cancer readmitted to an APCU, one out of seven was potentially preventable and a far larger proportion was discharged with hospice care compared to the index admission. Recognition of disease course, meaningful goals of care discussions and timely transition to hospice care may reduce rehospitalization in this population.

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.

Acellular mucin in lymph nodes isolated from treatment-naïve colorectal cancer resections: a clinicopathologic analysis of 16 cases.

Lymph nodes with acellular mucin harvested from treated colorectal cancers (CRC) are staged as pN0. However, there is variability among pathologists while reporting the pN stage when acellular mucin is found within nodes of untreated CRCs. While the UICC guidelines suggest staging them as pN1, the AJCC and CAP do not offer any recommendations. In order to characterize their clinicopathologic features and outcome, we compared 16 untreated CRCs (study group; mean age: 68 years) harboring nodes with acellular mucin with 34 pN0 and 25 pN1 untreated CRC controls. All tumors were unifocal; 12 (75%) were right-sided lesions. Most cases (75%) showed one node with acellular mucin (range: 1-3). MMR-deficient tumors were significantly more common in the study group (83%) compared to pN0 (33%; p = 0.006) and pN1 controls (8%; p < 0.001). The overall survival of study group patients was closer to pN0 compared to pN1 controls; however, this difference was not statistically significant. In conclusion, untreated CRC that harbor acellular mucin within lymph nodes commonly present as right-sided, MMR-deficient tumors in older women that show a non-mucinous phenotype. While the limited number of cases precludes us from making any formal recommendations about staging, we suggest that the finding of acellular mucin in a node should prompt evaluation of deeper levels (with or without cytokeratin immunohistochemistry) and submission of all pericolonic fat for additional lymph node harvest. Whether acellular mucin in nodes of untreated CRCs is related to the indolent biology of the disease, a robust local immune response or MMR deficiency requires further investigation.

Comparison of Quality of Life and Outcomes between Haploidentical and Matched Related/Unrelated Donor Allogeneic Hematopoietic Cell Transplantation.

Haploidentical (haplo) donor grafts are a well-established alternative donor source for allogeneic hematopoietic cell transplantation (HCT); however, data comparing health-realted quality of life (HRQOL) measures between haplo-HCT and HCT using other donor sources are lacking. We hypothesized that post-transplantation HRQOL might not differ between haplo-HCT and HCT with other graft sources. We conducted a single-institution retrospective analysis comparing HRQOL of haplo-HCT with matched-related donor (MRD) HCT and matched unrelated donor (MUD) HCT for hematologic diseases. We included 90 haplo, 102 MRD, and 229 MUD adult first allogeneic HCTs performed between May 2014 and December 2019. HRQOL for haplo-HCT, MRD-HCT, and MUD-HCT were compared separately for myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC). HRQOL was assessed using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale pretransplantation and at days +100 and +180 post-transplantation. MAC haplo-HCT showed no difference in all domains of HRQOL and other transplantation outcomes, including overall survival, compared with MAC MRD/MUD-HCT, except for a higher incidence of non-cytomegalovirus infections (P = .003). RIC haplo-HCT was associated with significantly better emotional well-being (P = .008) and functional well-being (P = .011) compared with MUD-HCT. RIC haplo-HCT was associated with higher rates of non-cytomegalovirus infections (P < .001) and relapse mortality (P = .044) but a lower rate of nonrelapse mortality (P = .008) compared with RIC MUD-HCT. Haplo-HCT had comparable total HRQOL scores and overall survival to MRD/MUD-HCT in both the MAC and RIC cohorts. Interrogation of HRQOL among disease-specific groups may further elucidate the existence of any additional benefits with these different transplantation modalities.

Allogeneic blood or marrow transplantation with haploidentical donor and post-transplantation cyclophosphamide in patients with myelofibrosis: a multicenter study.

We report the results from a multicenter retrospective study of 69 adult patients who underwent haploidentical blood or marrow transplantation (haplo-BMT) with post-transplantation cyclophosphamide (PTCy) for chronic phase myelofibrosis. The median age at BMT was 63 years (range, 41-74). Conditioning regimens were reduced intensity in 54% and nonmyeloablative in 39%. Peripheral blood grafts were used in 86%. The median follow-up was 23.1 months (range, 1.6-75.7). At 3 years, the overall survival, relapse-free survival (RFS), and graft-versus-host-disease (GVHD)-free-RFS were 72% (95% CI 59-81), 44% (95% CI 29-59), and 30% (95% CI 17-43). Cumulative incidences of non-relapse mortality and relapse were 23% (95% CI 14-34) and 31% (95% CI 17-47) at 3 years. Spleen size ≥22 cm or prior splenectomy (HR 6.37, 95% CI 2.02-20.1, P = 0.002), and bone marrow grafts (HR 4.92, 95% CI 1.68-14.4, P = 0.004) were associated with increased incidence of relapse. Cumulative incidence of acute GVHD grade 3-4 was 10% at 3 months and extensive chronic GVHD was 8%. Neutrophil engraftment was reported in 94% patients, at a median of 20 days (range, 14-70). In conclusion, haplo-BMT with PTCy is feasible in patients with myelofibrosis. Splenomegaly ≥22 cm and bone marrow grafts were associated with a higher incidence of relapse in this study.

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.

Influence of Killer Immunoglobulin-Like Receptors and Somatic Mutations on Transplant Outcomes in Acute Myeloid Leukemia.

Natural killer (NK) cells are regulated by killer immunoglobulin-like receptor (KIR) interactions with human leukocyte antigen class I ligands. Various models of NK cell alloreactivity have been associated with outcomes after allogeneic hematopoietic cell transplant (alloHCT), but results have varied widely. We hypothesized that somatic mutations in acute myeloid leukemia (AML) in the context of KIR profiles may further refine their association with transplant outcomes. In this single-center, retrospective, observational study, 81 AML patients who underwent matched-related donor alloHCT were included. Post-HCT outcomes were assessed based on mutational status and KIR profiles with the Kaplan-Meier method and log-rank test. On multivariable analysis those with any somatic mutations and C1/C2 heterozygosity had less acute graft-versus-host disease (GvHD) (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.14-0.75; P = .009), more relapse (HR, 3.02; 95% CI, 1.30-7.01; P = .010), inferior relapse-free survival (RFS; HR, 2.22; 95% CI, 1.17-4.20; P = .014), and overall survival (OS; HR, 2.21; 95% CI, 1.17-4.20; P = .015), whereas those with a missing KIR ligand had superior RFS (HR, 0.53; 95% CI, 0.30-0.94; P = .031). The presence of a somatic mutation and donor haplotype A was also associated with less acute GvHD (HR, 0.38; 95% CI, 0.16-0.92; P = .032), more relapse (HR, 2.72; 95% CI, 1.13-6.52; P = .025), inferior RFS (HR, 2.11; 95% CI, 1.07-4.14; P = .030), and OS (HR, 2.20; 95% CI, 1.11-4.38; P = .024). Enhanced NK cell alloreactivity from more KIR activating signals (donor B haplotype) and fewer inhibitory signals (recipient missing KIR ligand or C1 or C2 homozygosity) may help mitigate the adverse prognosis associated with some AML somatic mutations. These results may have implications for improving patient risk stratification prior to transplant and optimizing donor selection.

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.