Multiple Myeloma in Young Patients: A Scoping Review.

Data on the disease course, presenting features, outcomes, and prognosis of younger patients with multiple myeloma (MM) are lacking. Younger patients with MM have historically been considered to have better outcomes primarily based on better tolerance of treatment and lack of medical comorbidities, but the specific age range of this population has not been uniformly defined. Given the lack of consistent data reporting in patients considered to be young MM patients, we performed a scoping review to highlight the research currently available to start drawing conclusions about these patients and highlight unmet areas of need to focus on further investigation. We searched Embase, Cochrane Central Register of Controlled Trials, CINAHL Plus, Web of Science, and the OVID version of MEDLINE including broad terms that embody the concept of young patients with MM. Our final review included 201 studies which were then categorized according to age group, number of patients, outcomes, and comparators to older patients, along with location and database when available. We have chosen to categorize 3 age groupings: <50: young adults with MM (YA MM), 50 to 65: mid-life adults with multiple myeloma (ML MM) and 65+: older adults with multiple myeloma (OA MM). This review demonstrates the heterogeneity that exists in defining and describing young patients with MM, highlights the lack of studies specifically addressing the unique needs of younger patients, and emphasizes areas of future research unique to this population.

Impact of academic medical center access on outcomes in multiple myeloma.

Treatment at academic cancer centers (ACs) is associated with improved survival across hematologic malignancies, though the benefit in multiple myeloma (MM) has not been examined. This study aims to evaluate survival outcomes at Commission on Cancer accredited ACs compared to non-academic centers (NACs) for patients receiving MM-directed therapy. The National Cancer Database (NCDB) was used to identify demographics and overall survival (OS) of MM patients diagnosed from 2004 to 2017 and to compare outcomes by facility type. Survival analysis was repeated in a propensity score matched cohort, with NACs matched 1:1 to ACs by age, race, comorbidity score, insurance, year of diagnosis, distance traveled, and income. Of 163 375 MM patients, 44.5% were treated at ACs. Patients at ACs were more likely to receive MM-directed therapy compared to NACs (81% vs. 73%, p < .001). For patients receiving treatment, median OS at ACs was 71.3 months versus 41.2 months at NACs (p < .001). When adjusted for baseline demographics, patients treated at ACs had reduced mortality; hazard ratio (HR) 0.79 (95% CI 0.78-0.81, p < .001). The propensity score matched cohort maintained this survival benefit with a median OS of 59.9 months at ACs versus 37.0 months at NACs (p < .001), HR of 0.66 (95% CI 0.64-0.67, p < .001). ACs treated younger patients with fewer comorbidities and were more likely to treat racial minorities and patients with Medicaid or private insurance, and the uninsured. In this analysis, MM patients treated at ACs have significantly improved survival. While potentially related to access to specialized care, socioeconomic factors that drive facility selection may also contribute.

Predicting In-Hospital Mortality After Acute Myeloid Leukemia Therapy: Through Supervised Machine Learning Algorithms.

PURPOSE: Despite careful patient selection, induction chemotherapy for acute myeloid leukemia (AML) is associated with a considerable risk for treatment-related mortality (5%-20%). We evaluated machine learning (ML) algorithms trained using factors available at the time of admission for AML therapy to predict death during the hospitalization. METHODS: We included AML discharges with age > 17 years who received inpatient chemotherapy from State Inpatient Database from Arizona, Florida, New York, Maryland, Washington, and New Jersey for years 2008-2014. The primary objective was to predict inpatient mortality in patients undergoing chemotherapy using covariates present before initiation of chemotherapy. ML algorithms logistic regression (LR), decision tree, and random forest were compared. RESULTS: 29,613 hospitalizations for patients with AML were included in the analysis each with 4,177 features. The median age was 58.9 (18-101) years, 13,689 (53.7%) were male, and 20,203 (69%) were White. The mean time from admission to chemotherapy was 3 days (95% CI, 2.9 to 3.1), and 2,682 (9.1%) died during the hospitalization. Both LR and random forest models achieved an area under the curve (AUC) score of 0.78, whereas decision tree achieved an AUC of 0.70. The baseline LR model with age yielded an AUC of 0.62. To clinically balance and minimize false positives, we selected a decision threshold of 0.7 and at this threshold, 51 of our test set of 5,923 could have potentially averted treatment-related mortality. CONCLUSION: Using readily accessible variables, inpatient mortality of patients on track for chemotherapy to treat AML can be predicted through ML algorithms. The model also predicted inpatient mortality when tested on different data representations and paves the way for future research.

Palliative care utilization, transfusion burden, and end-of-life care for patients with multiple myeloma.

INTRODUCTION: Despite treatment advances, multiple myeloma (MM) remains a significant source of morbidity and mortality. We aimed to examine specialist palliative care (SPC) involvement and end-of-life care for patients with MM. METHODS: We assessed all deceased patients with a diagnosis of MM who received care at a single institution from January 2010 to December 2019 and assessed SPC involvement. RESULTS: We reviewed 456 deceased patients. Overall, 207 patients (45.4%) received SPC visits by clinicians during their disease, and 153 (33.5%) were on MM treatment in the month before death. Median time from SPC consultation to death was 1 month, with 42 (9.2%) of patients receiving SPC visits 6 or more months before death. Amongst the patients for which a place of death was reported (351), 117 (33.3%) died in the acute care setting. Outpatient SPC did not correlate with a reduction of death in the acute care setting. In the group of patients who received outpatient SPC, 22/84 (26.2%) died in an acute care setting, whereas 95/267 (35.5%) patients who did not receive outpatient SPC also died in an acute care setting, (p = .11). CONCLUSION: In our analysis of the entire trajectory of the MM patient experience from diagnosis to death, we found low rates of SPC involvement and a significant proportion of patients receiving aggressive care at end-of-life. While there is no clear correlation that SPC involvement impacted the rate of acute care deaths or decreased utilization of MM treatment in the last month of life, further prospective research on optimal utilization of SPC is required.

Unraveling a rare cause of spinal stenosis: Coexistent AL and ATTR amyloidosis involving the ligamentum flavum.

BACKGROUND: Amyloidosis is a protein misfolding disorder that leads to the deposition of beta-pleated sheets of a fibrillar derivative of various protein precursors. Identification of the type of precursor protein is integral in treatment decision-making. The presence of two different types of amyloid in the same patient is unusually rare, and there are no previous reports of two different types of amyloid deposition in the ligamentum flavum (LF) in the same patient. CASE DESCRIPTION: Here, we describe two patients with spinal stenosis who underwent laminectomies and were found to have AL and ATTR amyloid deposits in the LF. CONCLUSION: As the spine is becoming recognized as a site for ATTRwt amyloid deposition, patients undergoing spinal decompression surgery may potentially benefit from evaluation for amyloidosis in the LF.

Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNFα-antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure.

BACKGROUND: A feedforward pathological signaling loop generated by TNFα and IFN-γ synergy in the inflamed lung, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define the inflammatory biology of lethal COVID-19 respiratory failure. METHODS: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5 mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥50 compared to baseline and sustained for 48 h. Secondary endpoints included 28-day mortality, dynamic cytokine profiles, secondary infections, duration of supplemental oxygen support, and hospitalization. FINDINGS: Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 years, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953 ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days; 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Three deaths were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 to 483 pg/ml at Day 3 and 146 pg/ml at Day 14/discharge. Significant Day 3 declines in IFN-, TNFα, IL-27, CRP, and ferritin occurred. IP-10 and CXCL-9 declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, P-value 0.0006). INTERPRETATION: Infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19.

Association between spinal stenosis and wild-type ATTR amyloidosis.

Age-related cardiac amyloidosis results from deposits of wild-type tranthyretin amyloid (ATTRwt) in cardiac tissue. ATTR may play a role in carpal tunnel syndrome (CTS) and in spinal stenosis (SS), indicating or presaging systemic amyloidosis. We investigated consecutive patients undergoing surgery for SS for ATTR deposition in the resected ligamentum flavum (LF) and concomitant risk of cardiac amyloidosis. Each surgical specimen (LF) was stained with Congo red, and if positive, the amyloid deposits were typed by mass spectrometry. Patients with positive specimens underwent standard of care evaluation with fat pad aspirates, serum and urine protein electrophoresis with immunofixation, free light-chain assay, TTR gene sequencing and technetium 99 m-pyrophosphate-scintigraphy. In 2018-2019, 324 patients underwent surgery for SS and 43 patients (13%) had ATTR in the LF with wild-type TTR gene sequences. Two cases of ATTRwt cardiac amyloidosis were diagnosed and received treatment. In this large series, ATTRwt was identified in 13% of the patients undergoing laminectomy for SS. Patients with amyloid in the ligamentum flavum were older and had a higher prevalence of CTS, suggesting a systemic form of ATTR amyloidosis involving connective tissue. Further prospective study of patients with SS at risk for systemic amyloidosis is warranted.

HIV-associated Burkitt lymphoma: outcomes from a US-UK collaborative analysis.

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.

Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNF-α antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure.

BACKGROUND: A feed-forward pathological signaling loop generated by TNFα and IFN-γ in inflamed lung tissue, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define, sustain and amplify the inflammatory biology of lethal COVID-19 respiratory failure. METHODS: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥ 50 compared to baseline and sustained for 48 hours. Secondary endpoints included 28-day mortality, dynamic cytokine profiles (Human Cytokine 48-Plex Discovery Assay, Eve Technologies), secondary infections, duration of supplemental oxygen support and hospitalization. FINDINGS: Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 yrs, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days, 15/18 (83%) recovered from respiratory failure, and 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Deaths among three patients ≥ 65yrs age with pre-existing lung disease or multiple comorbidities were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 pg/ml to 483 pg/ml at Day 3 and further to 146 pg/ml at Day 14/discharge. Significant declines in IFN- γ , TNFα, IL-27, CRP and ferritin were specifically observed at Day 3 whereas other cytokines were unmodified. IL-6 levels declined sharply among patients with baseline levels >10 pg/ml. Among 13 lymphopenic patients, six (46%) had resolution of lymphopenia by day 3, and 11 by day 14. CXCR3-ligand (IP-10 and CXCL-9) declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, p-value: 0.0006). INTERPRETATION: Consistent with a pathophysiological role of TNFα, the clinical and cytokine data indicate that infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19. Randomized studies are required to formally assess mortality outcomes. Funding: National Center for Advancing Translational Sciences.

Lumbar ligamentum flavum burden: Evaluating the role of ATTRwt amyloid deposition in ligamentum flavum thickness at all lumbar levels.

BACKGROUND: Wild-type transthyretin (ATTRwt) amyloid deposition has been found in the ligamentum flavum (LF) of patients undergoing spinal stenosis surgery. Our group previously reported that ATTRwt amyloid is associated with an increased lumbar ligamentum flavum thickness at symptomatic levels that required surgery. A comprehensive evaluation of LF thickness at asymptomatic levels in addition to symptomatic, treated levels has never been performed in ATTRwt patients. In this study, we compare the total LF thickness of all lumbar levels (lumbar LF burden) in ATTRwt and non-ATTRwt patients. METHODS: We retrospectively identified 177 patients who underwent lumbar spine surgery. Ligamentum flavum thickness of 885 lumbar levels was measured on T2-weighted axial MRI. Amyloid presence was confirmed through Congo red staining of specimens, and subtype of ATTRwt was confirmed using mass-spectrometry and gene sequencing. RESULTS: Of the 177 patients, 30 (16.9%) were found to have ATTRwt in the ligamentum flavum. One hundred and fifty ATTRwt levels and 735 non-ATTRwt levels were measured by four different reviewers, with an intraclass coefficient (ICC) of 0.79. Mean ligamentum flavum thickness was 4.64 (±1.31) mm in the ATTRwt group and 3.99 (±1.45) mm in the non-ATTRwt group (p < 0.001). The lumbar LF burden (sum of ligamentum flavum thickness at all lumbar levels) for ATTRwt patients was 23.22 (±4.48) mm, and for non-ATTRwt patients was 19.96 (±5.49) mm (p = 0.003) CONCLUSION: The lumbar LF burden is greater in patients with ATTRwt amyloid compared to non-ATTRwt patients. This supports prior evidence that ATTRwt amyloid deposition might be associated with increased LF thickness and lumbar stenosis. This potential association requires more research and could be an important finding, as medications have recently become available that can treat patients with ATTRwt amyloid deposition.

Outcomes of Burkitt lymphoma with central nervous system involvement: evidence from a large multicenter cohort study.

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P<0.001), worse 3-year progression-free survival (adjusted hazard ratio [aHR], 1.53, 95% confidence interval [CI], 1.14-2.06, P=0.004) and overall survival (aHR, 1.62, 95%CI, 1.18-2.22, P=0.003). The 3-year cumulative incidence of CNS recurrence was 6% (95%CI, 4-8%). It was significantly lower among patients receiving other regimens (CODOX-M/IVAC, 4%, or hyperCVAD/MA, 3%) compared with DA-EPOCH-R (13%; adjusted sub-HR, 4.38, 95%CI, 2.16-8.87, P<0.001). Baseline CNS involvement in BL is relatively common and portends inferior prognosis independent of first-line regimen selection. In real-world practice, regimens with highly CNS-penetrant intravenous systemic agents were associated with a lower risk of CNS recurrence. This finding may be influenced by observed suboptimal adherence to the strict CNS staging and intrathecal therapy procedures incorporated in DA-EPOCH-R.

Increased thickness of lumbar spine ligamentum flavum in wild-type transthyretin amyloidosis.

BACKGROUND: Wild-type transthyretin (ATTRwt) amyloid deposits have been found in the ligamentum flavum of patients undergoing surgery for spinal stenosis. The relationship between ATTRwt and ligamentum flavum thickness is unclear. We used pre-operative magnetic resonance imaging (MRI) to analyze ligamentum flavum thickness in lumbar spinal stenosis patients with and without ATTRwt amyloid. METHODS: We retrospectively identified 178 patients who underwent lumbar spine surgery. Ligamentum flavum thickness of 253 specimens was measured on T2-weighted axial MRI. Amyloid presence was confirmed through Congo red staining of specimens, and ATTRwt was confirmed using mass-spectrometry and gene sequencing. RESULTS: Twenty four of the 178 patients (13.5%) were found to have ATTRwt in the ligamentum flavum. Forty ATTRwt specimens and 213 non-ATTRwt specimens were measured. Mean ligamentum flavum thickness was 4.92 (±1.27) mm in the ATTRwt group and 4.00 (±1.21) mm in the non-ATTRwt group (p < 0.01). The ligamentum flavum was thickest at L4-L5, with a thickness of 5.15 (±1.27) mm and 4.23 (±1.29) mm in the ATTRwt and non-ATTRwt group, respectively (p = 0.007). There was a significant difference in ligamentum flavum thickness between ATTRwt and non-ATTRwt case for both patients younger than 70 years (p = 0.016) and those older than 70 years (p = 0.004). ATTRwt patients had greater ligamentum flavum thickness by 0.83 mm (95% confidence interval (CI): 0.41-1.25 mm, p < 0.001) when controlled for age and lumbar level. CONCLUSION: Patients with ATTRwt had thicker ligamentum flavum compared to patients without ATTRwt. Further studies are needed to investigate the pathophysiology of ATTRwt in ligamentum flavum thickening.

Burkitt lymphoma in the modern era: real-world outcomes and prognostication across 30 US cancer centers.

We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%. Treatment-related mortality was 10%, with most common causes being sepsis, gastrointestinal bleed/perforation, and respiratory failure. With 45-month median follow-up, 3-year PFS and OS rates were 64% and 70%, respectively, without differences by HIV status. Survival was better for patients who received rituximab vs not (3-year PFS, 67% vs 38%; OS, 72% vs 44%; P < .001) and without difference based on setting of administration (ie, inpatient vs outpatient). Outcomes were also improved at an academic vs community cancer center (3-year PFS, 67% vs 46%, P = .006; OS, 72% vs 53%, P = .01). In multivariate models, age ≥ 40 years (PFS, hazard ratio [HR] = 1.70, P = .001; OS, HR = 2.09, P < .001), ECOG PS 2 to 4 (PFS, HR = 1.60, P < .001; OS, HR = 1.74, P = .003), lactate dehydrogenase > 3× normal (PFS, HR = 1.83, P < .001; OS, HR = 1.63, P = .009), and CNS involvement (PFS, HR = 1.52, P = .017; OS, HR = 1.67, P = .014) predicted inferior survival. Furthermore, survival varied based on number of factors present (0, 1, 2 to 4 factors) yielding 3-year PFS rates of 91%, 73%, and 50%, respectively; and 3-year OS rates of 95%, 77%, and 56%, respectively. Collectively, outcomes for adult BL in this real-world analysis appeared more modest compared with results of clinical trials and smaller series. In addition, clinical prognostic factors at diagnosis identified patients with divergent survival rates.

Myelodysplastic Syndrome in Patients with Gastro-Pancreatic Malignancies: A Case Series and Review of Literature.

Patients who develop one primary neoplasm are at increased risk for second cancers. Chemotherapeutic agents can result in DNA damage leading to clonal hematopoiesis, thereby causing myelodysplastic syndrome (MDS). Alkylating agents and topoisomerase inhibitors are most frequently implicated in therapy-related MDS. We report four patients with gastropancreatic malignancies (two with pancreatic adenocarcinoma and two with gastric adenocarcinoma) who developed MDS during or after the treatment of their primary gastrointestinal (GI) malignancies. Two of these patients were diagnosed with MDS during maintenance therapy with ramucirumab. To our knowledge, development of MDS in association with ramucirumab has not been previously reported in the literature. Our findings also suggest that with continued improvement in survival of patients with GI and pancreatic malignancies, more cases of treatment-related MDS might be identified.

Length of Stay and Hospital Costs for Patients Undergoing Allogeneic Stem-Cell Transplantation.

PURPOSE: Patients who undergo allogeneic hematopoietic stem-cell transplantation (allo-HSCT) usually require a prolonged hospital stay that varies greatly across patients. Limited information exists on the factors associated with hospital length of stay (LOS) after allo-HSCT and the impact on transplant-related costs. The objective of this study was to determine predictors for longer LOS for allo-HSCT and to assess their impact on the cost of transplant stay. METHODS: Using the National Inpatient Sample database, adult patients hospitalized for allo-HSCT were identified using International Classification of Diseases, Ninth Revision, primary and secondary procedure codes. RESULTS: Between 2002 and 2015, 68,296 hospitalizations for allo-HSCT were identified. Peripheral blood was the most common stem-cell source (80%) followed by bone marrow (15%) and cord blood (5%). Median LOS was 25.8 days (interquartile range [IQR], 21-34.0 days), and the overall inpatient mortality rate was 8%. Stem-cell source was a significant predictor for longer LOS, being significantly longer for cord blood (median, 36.9 days; IQR, 26.7-49.9 days) compared with bone marrow (median, 27.2 days; IQR, 21.5-35.2 days) and peripheral blood (median 25.4 days; IQR, 20.8-32.7 days). Other predictors for longer LOS were patient characteristics such as age and race, transplant/post-transplant characteristics, and complications such as total body irradiation use, acute graft-versus-host disease, and infections. Longer LOS was also found to be associated with higher hospital costs. CONCLUSION: In patients who undergo allo-HSCT, LOS can be predicted using patient- and transplant-related characteristics as well as post-transplant complications. LOS is also a driver for increased cost, and further efforts are needed to mitigate transplant complications and resource utilization.