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CALGB (Alliance) 100001 was a phase II study evaluating autologous stem cell transplant (ASCT) followed by nonmyeloablative allogeneic stem cell transplant (alloSCT) in patients with multiple myeloma who had received no more than 18 months of prior therapy and had experienced no more than 1 prior progression event. Conditioning for ASCT was with high-dose melphalan (200 mg/m2). The alloSCT reduced-intensity conditioning (RIC) regimen consisted of fludarabine (30 mg/m2/d i.v. on days -7 through -3) and cyclophosphamide (1 g/m2/d i.v. on days -4 through -3). The primary objective was to determine the 6-month post-alloSCT treatment-related mortality (TRM) rate. Additional objectives included determining the proportion of patients who could complete this tandem ASCT-alloSCT approach in a cooperative group setting, overall response rates, rates of donor chimerism, rates of graft-versus-host disease (GVHD), disease-free survival, and overall survival (OS). Sixty patients were enrolled, of whom 57 (95%) completed ASCT and 49 (82%) completed tandem ASCT-alloSCT. The TRM rate was 2% (1/49; 90% confidence interval, 0.10% to 9.3%). Moderate to severe (grades 2 to 3) acute GVHD was observed in 13 of 49 alloSCT patients (27%). One patient died due to GVHD within 9 months of alloSCT. Twenty-seven of the 49 patients (55%) who underwent alloSCT reported chronic GVHD as either limited (15/49; 31%) or extensive (12/49; 24%) in the first year post-alloSCT and prior to the start of nonprotocol therapy for progressive disease. With a median follow-up for survival of 11 years, the median OS time is 6.6 years and the median time to disease progression is 3.6 years. Similar to other studies, this study confirmed that tandem ASCT/alloSCT is associated with durable disease control in a subset of patients. This study demonstrated the feasibility of performing tandem ASCT/alloSCT in a cooperative group setting and determined that a fludarabine/cyclophosphamide RIC regimen is associated with a very low TRM rate.

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

PURPOSE: If identifiable, potentially avoidable hospitalizations (PAHs) can serve as an important target for cost containment efforts in oncology. METHODS: PAHs among a cohort of Medicare patients with prostate cancer were identified using a two-stage consensus-driven review process. In stage 1, two clinicians independently evaluated admissions records using a case review form, which we modified from a previous study to assess for PAHs. In stage 2, any admissions that the reviewers disagreed on or were unsure of were re-examined in a larger group of clinicians to yield a consensus determination regarding avoidability. Univariable and multivariable regression analyses were performed to identify factors predictive of PAH. RESULTS: There were 160 admissions among this cohort of 210 patients from January 2012 to June 2015, of which 99 were evaluable. Consensus-driven clinical review yielded an overall PAH rate of 28.3%. Factors associated with increased PAH risk were admission for symptoms related to cancer (odds ratio [OR], 7.33; P < .001), presence of a social contributor to admission (OR, 4.40; P = .014), and history of alcohol or drug abuse (OR, 4.93; P = .025). Admission for a noncancer condition was associated with decreased PAH risk (OR, 0.32; P = .011). On multivariable analysis, presence of a social contributor to admission (OR, 9.35; P = .002) and admission as a result of a noncancer condition (OR, 0.16; P = .038) remained predictive of PAH risk. CONCLUSION: A significant proportion of hospitalizations among patients with prostate cancer are potentially avoidable. Understanding factors predictive of risk for PAH can help inform programs aimed at avoiding such admissions to improve overall care quality and value.

PURPOSE: As expenditures for cancer care continue to grow substantially, value-based payment models are being tested to control costs. The Oncology Care Model (OCM) is the largest value-based payment program in oncology. The primary objective of this analysis was to determine the impact of high-cost novel agents on total cost of care for multiple myeloma (MM) episodes of care in the OCM. METHODS: This was a retrospective analysis using Medicare claims data for 258 MM OCM episodes initiated between July 1, 2016, and July 1, 2017. Patients were organized into 3 cohorts: those who received pomalidomide (cohort A), those who received lenalidomide (cohort B), and those who did not receive either drug but had received another chemotherapy agent (cohort C). We compared the actual episode expenditures and the Centers for Medicare and Medicaid target price to create an observed versus expected (O/E) ratio. RESULTS: The average O/E for cohort A (n = 73) was 1.73, compared with 1.31 for cohort B (n = 84) and 1.01 for cohort C (n = 101). The difference the in O/E ratio among the groups was statistically significant ( P < .001). The average episode target price for cohorts A, B, and C was $66,149, $63,483, and $63,937, respectively. Despite the high cost of pomalidomide and lenalidomide, there was no significant difference in the average episode target prices of the cohorts. CONCLUSION: The O/E ratio and target prices of the cohorts demonstrate a lack of adequate adjustment to the OCM target price for episodes in which pomalidomide and lenalidomide were used to treat patients with MM.

Purpose/Objectives We sought to estimate the expected cost savings generated if a set of potentially avoidable hospitalizations (PAHs) among oncology care model (OCM) patients with prostate cancer were shifted to an acute care model in the outpatient setting. Methods We previously identified a set of 28 PAHs among OCM prostate cancer patients. Outpatient management costs for a characteristically similar cohort of cancer patients were obtained from our institution’s ambulatory acute-care Oncology Care Unit (OCU). We excluded OCU visits resulting in hospitalization, involving non-cancer diagnoses, and those missing clinical/financial information. Exact-matching based on the strata of age, categorically-defined presenting complaint, and systemic disease was used to match PAHs to OCU acute care visits. PAH costs obtained from OCM data were compared to costs from matched OCU visits. Results We identified 130 acute care OCU visits, of which 47 met inclusion criteria. Twenty-four PAHs (89%) matched to 26 of these OCU visits. PAHs accounted for 5.8% of OCM expenditures during our study period. The mean inpatient cost among matched PAHs was $15,885 compared to $6227 for matched OCU visits. Boot strapping within each match stratum produced a mean estimated cost savings of $12,151 (95% CI $10,488 to $13,814) per PAH. We estimate this per event savings to yield a 4.4% (95% CI 3.8% to 5.0%) an overall spending decrement for OCM prostate cancer episodes. Conclusions PAHs contribute meaningfully to costs of care in oncology. Investment in specialized ambulatory acute care services for oncology patients could lead to substantial cost savings.

Graft-versus-host disease has been reported to occur rarely in syngeneic hematopoietic stem cell transplant recipients. Clinical and histological changes consistent with graft-versus-host disease have been reported to occur in this patient population. We report a case of a 46-year-old Caucasian male with diffuse large B-cell lymphoma in complete remission who underwent a syngeneic hematopoietic stem cell transplant. He was diagnosed with grade III acute skin and gastrointestinal graft-versus-host disease requiring high-dose corticosteroids and immunosuppressive therapy and resulting in a complete response. Syngeneic graft-versus-host disease is an anomaly that needs to be considered as a differential diagnosis of patients experiencing dermatitis, gastroenteritis, or hepatitis after an identical twin hematopoietic stem cell transplant.

In the CALGB (Alliance) 100104 study, lenalidomide versus placebo after autologous stem-cell transplantation (ASCT) was investigated for patients with newly diagnosed myeloma. That study showed improved time to progression and overall survival and an increase in second primary malignancies for lenalidomide at a median follow-up of 34 months. Here we report an updated intention-to-treat analysis of CALGB (Alliance) 100104 at a median follow-up of 91 months.Patients were eligible for this randomised, double-blind, placebo-controlled, phase 3 trial if they had symptomatic disease requiring treatment; had received, at most, two induction regimens; and had achieved stable disease or better in the first 100 days after ASCT. We randomly assigned patients to either lenalidomide or placebo groups using permuted block randomisation, with a fixed block size of six. Randomisation was stratified by three factors: normal or elevated β2 microglobulin concentration at registration (≤2·5 mg/L vs2·5 mg/L), previous use or non-use of thalidomide during induction therapy, and previous use or non-use of lenalidomide during induction therapy. The starting dose was two capsules (10 mg) per day, escalated to three capsules (15 mg) per day after 3 months. The primary endpoint was time to progression (time of progressive disease or death from any cause), with intention-to-treat analysis. This study is registered with ClinicalTrials.gov, identifier NCT00114101. New patients are no longer being recruited, but some patients remain on treatment and in follow-up.Between April 14, 2005, and July 2, 2009, 460 patients were randomly assigned to receive either lenalidomide (n=231) or placebo (n=229). After three interim analyses, the study was unblinded at a median follow-up of 18 months, at which point 86 (67%) of 128 patients without progressive disease in the placebo group chose to cross over to the lenalidomide group. The median follow-up for the updated survival analysis, as of Oct 19, 2016, was 91 months (IQR 83·6-103·1). The median time to progression was 57·3 months (95% CI 44·2-73·3) for the lenalidomide group and 28·9 months (23·0-36·3) for the placebo group (hazard ratio 0·57, 95% CI 0·46-0·71; p0·0001). The most common grade 3-4 adverse events were neutropenia (116 [50%] patients in the lenalidomide group and 41 [18%] patients in the placebo group) and thrombocytopenia (34 [15%] patients in the lenalidomide group and 12 [5%] patients in the placebo group). 18 (8%) haematological and 14 (6%) solid tumour second primary malignancies were diagnosed after randomisation and before disease progression in the lenalidomide group, compared with three (1%) haematological and nine (4%) solid tumour second primary malignancies in the placebo group. Three haematological and five solid tumour second primary malignancies in the placebo group were in the crossover subgroup.Despite an increase in haematological adverse events and second primary malignancies, lenalidomide maintenance therapy after ASCT significantly improved time to progression and could be considered a standard of care.The National Cancer Institute.

Myelofibrosis (MF) is a chronic progressive hematologic malignancy with a median overall survival (OS) of approximately 6 years. Allogeneic hematopoietic stem cell transplantation (HSCT) is the sole treatment approach that offers curative potential. The use of reduced-intensity conditioning regimens has expanded the application of HSCT to patients with MF up to age 70 years. Recent retrospective and prospective reports have suggested worse HSCT outcomes for patients with MF receiving an unrelated donor graft compared with those receiving a related donor graft. To identify patient- and HSCT-specific variables influencing outcomes, we conducted a retrospective analysis of 42 patients with chronic and advanced-phase MF who underwent HSCT at our institution. For this cohort, at a median follow-up of 43 months, progression-free survival (PFS) was 15 months and OS was 25 months. In multivariable analysis, the sole clinical variable that negatively influenced outcome was the use of an unrelated donor, with a median PFS and OS both of 11 months versus not yet reached in patients receiving a related donor graft. At 2 years, OS was 38% (95% confidence interval [CI], 20%-56%) and nonrelapse mortality (NRM) was 53% (95% CI, 36%-78%) in the unrelated donor graft group, compared with 75% (95% CI, 46%-90%) and 21% (95% CI, 9%-47%) in the related donor graft group. There was no difference in the rates of grade III-IV acute graft-versus-host disease between the unrelated and related donor groups (38% versus 38%). Despite a more aggressive disease state, 2-year PFS and OS were both 42% (95% CI, 15%-67%) in patients with myeloproliferative neoplasm-blast phase undergoing HSCT. Graft failure rate was higher in patients receiving a mismatched donor graft compared with those receiving a matched donor graft (60% versus 13%; P = .0398). Retransplantation of patients with graft failure resulted in long-term survival. Baseline splenomegaly did not affect transplantation outcomes. Given the particularly poor outcomes seen in the unrelated donor cohort here and elsewhere, a formal exploration of alternative hematopoietic stem cell sources is warranted.

Relapse remains the major cause of death in older patients transplanted for acute myeloid leukemia (AML) in first complete remission or for patients with advanced myelodysplastic syndrome (MDS) at any age. Conventional myeloablative conditioning followed by allogeneic blood or marrow transplantation is associated with significantly less relapse compared with reduced-intensity conditioning when performed in younger patients with AML or MDS, but the toxicity of this approach in older patients is prohibitive. We hypothesized that pharmacokinetic targeting to optimize busulfan (BU) exposure, combined with the administration of azacitidine (AZA) post-transplant would mitigate the risk of relapse while reducing nonrelapse mortality and ultimately improve progression-free survival (PFS). On this phase II multicenter study, 63 patients (40 unrelated donors and 23 matched related donors) received a uniform conditioning regimen consisting of fludarabine i.v. (days –7 to –3), BU targeted to a daily area under the curve (AUC) of 4000 μM/min (days –6 to –3) after the administration of a 25-mg/m2 i.v. test dose on 1 day between days –14 to –9, and antithymocyte globulin (days –6, –5, and –4 (2 doses for matched related donors and 3 for matched unrelated donors only). Beginning on days +42 to +90, all patients were planned to receive up to 6 monthly cycles of AZA at 32 mg/m2 subcutaneously for 5 days. The median age was 62 years (range, 44 to 74); 13 had AML and 50 had MDS; 87% of patients were within 20% of the target AUC based on a validation sample. Forty-one patients (65%) started AZA at a median of 61 days (range, 43 to 91) post-transplant, and 17 patients (41%) completed all 6 cycles of AZA. The cumulative incidence of nonrelapse mortality at 2 years was 33.4% (95% confidence interval [CI], 22%-45%). The cumulative incidence of relapse was 25% (95% CI, 15%-37%) at 2 years. With a median follow-up of 58.9 months, the estimated PFS probability at 2 years and 5 years after transplantation was 41.2% (80% CI, 33.9%-49.9%) and 26.9% (80% CI, 20.4%-35.5%), respectively, for the entire group with a median PFS of 15.8 months (95% CI, 6.7 to 28.3). The probability of overall survival at 2 and 5 years was 45.7% (95% CI, 34.9%-59.9%) and 31.2% (95% CI, 21.3% to 45.8%), respectively, for the entire group with a median overall survival of 19.2 months (95% CI, 8.7 to 37.5). In summary, we demonstrated the feasibility of a novel reduced-intensity conditioning regimen with test dose BU targeted to an AUC of 4000 μM/min. The feasibility of AZA in this setting appears to be limited if applied to an unselected population of older hematopoietic stem cell transplantation recipients. (ClinicalTrials.gov Identifier: NCT01168219.)

PURPOSE: The Oncology Care Model (OCM) must be clinically relevant, accurate, and comprehensible to drive value-based care. METHODS: We studied OCM data detailing observed and expected expenses for 6-month-long episodes of care for patients with prostate cancer. We constructed seven disease state–treatment dyads into which we grouped each episode on the bases of diagnoses, procedures, and medications in OCM claims data. We used this clinical-administrative stratification model to facilitate a comparative cost analysis, and we evaluated emergency department and hospital utilization and drug therapy as potential drivers of cost. RESULTS: We examined 377 episodes of care, pertaining to 210 patients, that took place within our health system from January 2012 to June 2015. Ninety-six percent of episodes were assigned to clinically meaningful dyads. Excessive expenses were seen in metastatic, castration-resistant dyads containing second-line hormone therapy (ratio of observed to expected expenses [O/E], 2.66), chemotherapy (O/E, 2.09), and radium-223/sipuleucel-T (O/E, 3.01). An OCM update correcting for castration-resistant prostate cancer led to small differences in observed expenses (0% to +2%) but large changes in expected expenses (−17% to −27% for hormone-sensitive dyads and +136% to +141% for castration-resistant dyads). O/E increased up to 38% for hormone-sensitive dyads and decreased up to 58% for castration-resistant dyads. Emergency department and hospital utilization seems to drive cost for castration-resistant dyads but not for hormone-sensitive dyads. In the revised OCM model, overall O/E for all episodes improved by 22%, from 1.48 to 1.15. CONCLUSION: Our experience with OCM highlights the limitations of administrative claims data within this model and illustrates a method of translating these data into clinically meaningful information to improve value.

Antibiotic stewardship is an integral aspect of hospital care, limiting the potential for resistance while working to minimize waste. A similar system is needed in oncology, given the rapid proliferation of new therapies and the challenges of navigating a complicated reimbursement environment. A "cancer therapy stewardship program" has never been described in the literature. Here, we detail our efforts to design and implement such a program and share lessons learned to inform future projects.For 1 year, a hematologist-oncologist (the "cancer therapy steward") at Mount Sinai Hospital was in charge of addressing all requests for nonformulary or off-label chemotherapeutic and supportive medications and regimens. Requests consisted of the rationale for use and supporting data from medical journal articles. This pilot initiative was focused mainly on inpatient malignant hematology.Sixty-seven requests were made by 23 physicians, and all requests were ultimately approved. Requests tended to fall into 3 categories: 1) use of a single drug in a setting not approved by the FDA, 2) use of multiple drugs in novel combinations not approved by the FDA, and 3) adding novel drugs to existing FDA-approved regimens.Our cancer therapy stewardship program yielded many useful insights into how our physicians face challenging clinical situations. It also helped to improve overall clinical quality and patient care by emphasizing the importance of value-based care and evidence-based medicine. Expanding this program will likely lead to many interesting experiments aimed at improving medical education and research, patient safety outcomes, and clinical quality.

Background aims Stem cell collection can be a major component of overall cost of autologous stem cell transplantation (ASCT). Plerixafor is an effective agent for mobilization; however, it is often reserved for salvage therapy because of its high cost. We present data on the pharmacoeconomic impact of the use of plerixafor as an up-front mobilization in patients with multiple myeloma (MM). Methods Patients with MM who underwent ASCT between January 2008 and April 2011 at the Mount Sinai Medical Center were reviewed retrospectively. In April 2010, practice changes were instituted for patients with MM to delay initiation of granulocyte-colony-stimulating factor (G-CSF) support from day 0 to day +5 and to add plerixafor to G-CSF as an up-front autologous mobilization. Targets of collection were 5–10 × 10 6 CD34 + cells/kg. Results Of 50 adults with MM who underwent ASCT, 25 received plerixafor/filgrastim and 25 received G-CSF alone as an up-front mobilization. Compared with the control, plerixafor mobilization yielded higher CD34 + cell content (16.1 versus 8.4 × 10 6 CD34 + cells/kg; P = 0.0007) and required fewer sessions of apheresis (1.9 versus 3.1; P = 0.0001). In the plerixafor group, the mean number of plerixafor doses required per patient was 1.8. Although the overall cost of medications was higher in the plerixafor group, the cost for blood products and overall cost of hospitalization were similar between the two groups. Conclusions Up-front use of plerixafor is an effective mobilization strategy in patients with MM and does not have a substantial pharmacoeconomic impact in overall cost of hospitalization combined with the apheresis procedure.

Objective Although hematopoietic stem cell transplant (HSCT) patients may experience neurocognitive impairment, experiences of neurobehavioral problems (including apathy and disinhibition) are understudied. These experiences reflect behavioral signs and symptoms of neurological dysfunction that can potentially reduce health-related quality of life (HRQOL). Understanding them is important because they may be confused with other diagnoses, including depression, potentially leading to inappropriate treatments. The objectives of this preliminary cross-sectional study were to describe HSCT patients' neurobehavioral functioning pre-HSCT and post-HSCT and to examine relations with HRQOL. Methods Patients (n = 42) 9 months to 3 years post-HSCT completed measures of neurobehavioral functioning to report apathy and disinhibition pre-HSCT (retrospectively) and post-HSCT (currently). Paired t-tests and McNemar tests were used to explore differences in the incidence of patient-reported neurobehavioral problems within and across time points. Regression analyses were conducted to examine relations between neurobehavioral functioning and physical and mental HRQOL. Results Elevated levels of apathy were reported by many patients post-HSCT (36%) and increased significantly from pre-HSCT to post-HSCT (p = 0.001). Hierarchical regression analysis indicated that higher levels of apathy were associated with reduced mental HRQOL (p

Psycho-Oncology Psycho-Oncology (2014) Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/pon.3553 Clinical Correspondence Systematic light exposure in the treatment of cancer-related fatigue: a preliminary study William H. Redd 1 *, Heiddis Valdimarsdottir 1,2 , Lisa M. Wu 1 , Gary Winkel 1 , Emily E. Byrne 1 , Melba A. Beltre 1 , Elizabeth S. Liebman 1 , Tanya Erazo 1 , Judy A. Hayes 1 , Luis Isola 3 , Eileen Scigliano 3 , Yeraz Meschian 1 , Susan Lutgendorf 4 and Sonia Ancoli-Israel 5 Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA Department of Psychology, Reykjavik University, Iceland Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA Department of Psychology, University of Iowa, Iowa, IA, USA Departments of Psychiatry and Medicine, University of California, San Diego, CA, USA *Correspondence to: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. E-mail: william. redd@mssm.edu Received: 1 October 2013 Revised: 13 March 2014 Accepted: 25 March 2014 Dear Editor, Introduction Cancer-related fatigue (CRF) is the most commonly reported side effect of cancer treatment [1]. It is defined by the National Comprehensive Cancer Network as ‘a distressing, persistent, subjective sense of physical, emotional, and cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity’. Patients feel tired even after resting, have reduced capacity to carry out normal activities, experience slow physical recovery from tasks, and report diminished concentration. Most patients experience CRF during their treatment, and many continue to experience CRF long after all treatment has ended. In our research with survivors of hematopoietic stem cell transplantation (HSCT) 1–3 years off treatment, 40% of those interviewed reported clinically significant CRF. Various pharmacological and nonpharmacological interventions have been studied to treat CRF with generally mild to moderate effect sizes [1]. An alternate intervention may be systematic bright white light (BWL) exposure, which is far less costly and involves less patient burden than other interventions. Reviews and meta-analyses [2] have reported that BWL is effective in reducing sleep and circadian rhythm problems associated with other disorders (e.g., depression and jet lag) but has not been previously tested for the effect on fatigue. Recent research from our group has shown that, when given during chemotherapy, BWL compared with Copyright © 2014 John Wiley & Sons, Ltd. dim red light (DRL) keeps CRF from getting worse [3]. However, to date, the impact of BWL on fatigue among survivors of cancer has not been examined. This preliminary efficacy trial sought to determine the impact of BWL on CRF among survivors of breast and gynecologic cancers who had completed all cancer treat- ment and survivors of hematological malignancy who had completed HSCT. We tested the hypothesis that the BWL condition would result in a significant reduction in CRF compared with the DRL condition. Methods Participants Thirty-six survivors of cancer from the Mount Sinai Hospital in New York, NY, participated in the study (Figure 1) across all four seasons. Inclusion criteria were the following: up to 3.5 years post-HSCT, up to 3 years postcompletion of che- motherapy or chemotherapy and radiation for breast cancer, or any time postcompletion of treatment for gynecologic cancer; 18 years of age or older; and reporting clinically significant fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale. Exclusion criteria were the following: pregnancy, confounding underlying medical illnesses such as signi- ficant preexisting anemia, history of mania (which is a contraindication for light treatment) or current clinical depression, and any other physical or psychological impairment including a sleep disorder that would limit par- ticipation. The study was approved by the Program for the Protection of Human Subjects at Mount Sinai Hospital.

298 Background: A comprehensive chemotherapy informed consent process improves shared decision-making. Additionally, the Oncology Care Model (OCM) emphasizes providing patients with a documented care plan that contains the 13 components in the Institute of Medicine Care Management Plan. Within our health system, we incorporated the care plan into our existing chemotherapy consent process and utilized technology to increase compliance and reduce administrative burden. Methods: Our 2 phase PDSA included: 1) updating our existing paper chemotherapy form with the 13 components of the IOM care plan and then 2) piloting an electronic version of the chemotherapy consent form. We updated our new chemotherapy consent with the addition of Prognosis, Expected Response to Treatment, Potential Effect on Quality of Life, Potential Benefits/Goals of Treatment, and added more options for potential side effects/harm. Given the increased administrative burden, we created and piloted the use of an electronic version of the consent form in our breast oncology program. Results: Baseline, monthly random chart audit of 20-40 patients revealed compliance with completing every question of the paper chemotherapy consent at 30% of all patients receiving IV chemotherapy at our cancer center that month- 7/2018. When the new chemotherapy consent incorporating the IOM elements was rolled out, compliance initially rose to 50% (8/2018), however the following months dropped to 10-20% (9-11/2018) and then back up to 41% briefly (12/2018). The results were low and inconsistent. A pareto chart confirmed that redundancy and too many questions were the reasons for under-completion. By auto-populating fields for certain questions on the paper consent, compliance increased to 75% (2/2019). Finally within our breast cancer pilot group our compliance rose to 100% (3-4/2019), by converting to an electronic form with the maximum options for auto-population and drop-down selections for certain fields. Conclusions: Incorporating regulatory requirements into an existing workflow can reduce administrative burden. The use of innovative technology can further increase clinician and OCM compliance while delivering value to patients.

114 Background: Hospital-based care remains a major contributor to cost in oncology and thus represents an important cost-saving opportunity. We previously developed a rigorous two-stage consensus driven review process to identify potentially avoidable hospitalizations (PAHs) among oncology care model (OCM) patients with prostate cancer and reported a 28% rate of PAHs between 1/2012-6/2015. Our current objective was to estimate the magnitude of any expected cost savings generated if inpatient care from these PAHs were shifted to an acute care model in the outpatient setting. Methods: Costs for ambulatory acute care management among a separate but characteristically similar cohort of cancer patients were obtained from our institution’s recently established Oncology Care Unit (OCU), where acute clinical issues are managed in an enhanced ambulatory setting. We used an exact-matching algorithm to match previously identified PAHs to OCU visits based on strata of age (≤ 70 years vs. > 70 years), categorically defined chief complaint (infusion/transfusion, lab abnormalities, symptom control, and diagnostic work-up), and the presence of “systemic disease” (metastatic disease or hematologic malignancy). PAH costs obtained from OCM data were compared to costs from these matched OCU encounters. Results: We identified 89 acute care OCU visits occurring from 5/2017-12/2018, of which 48 were fully evaluable based on documentation. Twenty-five of our initial 28 PAHs (89%) matched to 29 OCU acute care visits. The mean inpatient cost among matched PAHs was $15,879 compared to $975 for matched OCU visits. Boot strapping within each match produced a mean estimated cost savings of $15,120 (95% CI $13,682 to $16,557) per PAH. We estimate this per event savings to yield an overall spending decrement of 5.7% for OCM prostate cancer episodes. Conclusions: PAHs contribute substantially to costs of care in oncology. Investment in specialized ambulatory acute care services for oncology patients could lead to meaningful cost savings by shifting avoidable inpatient care to the outpatient setting.

International audience; Prediction of subsequent leukemia-free survival (LFS) and chronic graft-versus-host disease (GVHD) in adults with acute leukemia who survived at least 1 year after allogeneic hematopoietic cell transplantation is difficult. We analyzed 3339 patients with acute myeloid leukemia and 1434 patients with acute lymphoblastic leukemia who received myeloablative conditioning and related or unrelated stem cells from 1990 to 2005. Most clinical factors predictive of LFS in 1-year survivors were no longer significant after 2 or more years. For acute myeloid leukemia, only disease status (beyond first complete remission) remained a significant adverse risk factor for LFS 2 or more years after transplantation. For lymphoblastic leukemia, only extensive chronic GVHD remained a significant adverse predictor of LFS in the second and subsequent years. For patients surviving for 1 year without disease relapse or extensive chronic GVHD, the risk of developing extensive chronic GVHD in the next year was 4% if no risk factors were present and higher if noncyclosporine-based GVHD prophylaxis, an HLA-mismatched donor, or peripheral blood stem cells were used. Estimates for subsequent LFS and extensive chronic GVHD can be derived for individual patients or populations using an online calculator (http://www.cibmtr.org/LeukemiaCalculators). This prognostic information is more relevant for survivors than estimates provided before transplantation.

Background The current FDA-approved time interval between plerixafor dosing and apheresis initiation is approximately 11 hours, but this time interval is impractical for most care providers. Few studies have examined mobilization kinetics beyond 11 hours in multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) patients. Therefore, this study's intent was to analyze an interval of 17 to 18 hours between plerixafor dosing and apheresis initiation. Study Design and Methods In 11 patients with MM or NHL, 240 μg/kg plerixafor was administered at 5 p.m. on Day 4 of granulocyte–colony-stimulating factor (G-CSF) mobilization. Peripheral blood (PB) CD34+ and CD34+CD38− concentrations were enumerated every 2 hours until 7 a.m. and immediately before apheresis on Day 5, for a total interval time of 17 to 18 hours after plerixafor. Data were analyzed using mixed-model analysis of repeated measures and paired t testing. Results Ten of the 11 subjects achieved a CD34+ product count of more than 2 × 106/kg with a single leukapheresis procedure. All 10 had a preplerixafor PB CD34+ concentration ([CD34+]) of at least 10/μL. PB [CD34+] was not different between 10 and 18 hours after plerixafor (p = 0.8). In contrast, PB CD34+CD38− concentrations significantly increased from 10 to 18 hours after plerixafor (p = 0.03). Conclusions In MM and NHL patients with adequate preplerixafor [CD34+], leukapheresis initiated 14 to 18 hours after plerixafor and G-CSF mobilization may not impair adequate CD34+ collection and may increase more primitive CD34+CD38− collection. In this subset of patients, late-afternoon dosing of plerixafor at 5 p.m. with initiation of next-day apheresis as late as 11 a.m. appears feasible without loss of efficacy.

Autologous hematopoietic cell transplantation (auto-HCT) is performed to treat relapsed and recurrent malignant disorders and as part of initial therapy for selected malignancies. This study evaluated changes in use, techniques, and survival in a population-based cohort of 68,404 patients who underwent first auto-HCT in a US or Canadian center between 1994 and 2005 and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The mean annual number of auto-HCTs performed was highest during 1996-1999 (6948), and decreased subsequently 2000-2003 (4783), owing mainly to fewer auto-HCTs done to treat breast cancer. However, the mean annual number of auto-HCTs increased from 5278 annually in 1994-1995 to 5459 annually in 2004-2005, reflecting increased use for multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Despite an increase in the median recipient age from 44 to 53 years, there has been a significant improvement in overall survival (OS) from 1994 to 2005 in patients with chemotherapy-sensitive relapsed non-Hodgkin lymphoma (day +100 OS, from 85% to 96%; 1-year OS, from 68% to 80%; P 40 years) and older (>60 years) individuals.

Purpose Acute lymphoblastic leukemia (ALL) has a predilection for CNS involvement. Patients with high-risk ALL are often managed with transplant using a radiation-based conditioning regimen. Historically, a high-dose prophylactic cranial boost (CB) of ≥12 Gy was given to reduce risk of central nervous system (CNS) recurrence. However, the use of CB has fallen out of favor because of toxicity concerns. In high-risk adults undergoing transplant at our institution, we have used a low-dose 6 Gy CB to reduce toxicity while conditioning adults with fully developed brains. The safety, efficacy, and utility of a low-dose CB in adults are poorly studied; herein, we report their outcomes and toxicity. Methods and materials We identified all high-risk ALL patients undergoing total body irradiation as part of their conditioning regimen. Those who received 6 Gy CB or no CB were included (55 total). Their charts were reviewed and statistical analyses were completed with R, version 2.15.2. Results In patients undergoing CB, 3-year CNS disease-free survival and overall survival were 94.7% and 62.7%. In those not undergoing CBs, survivals were 81.8% and 51.5%. Notably, within the CB cohort, patients without prior CNS involvement had no CNS failures. In contrast, in the non-CB cohort, there were 2 CNS failures in patients with no history of CNS involvement. In the CB cohort, the only notable acute toxicity was parotitis (2.8%). Late toxicity in the CB cohort included 1 instance of cataracts (2.8%) without any evidence of cognitive impairment or potential radiation induced secondary malignancy. Conclusions A dose of 6 Gy CB is well-tolerated in the adult ALL population as part of a radiation-based conditioning regimen. Low-dose CB may be considered in adult patients with high-risk ALL without prior CNS involvement to reduce the likelihood of recurrence.

The best conditioning regimen before allogeneic transplantation for high-risk diffuse large B-cell lymphoma (DLBCL) remains to be clarified. We analyzed data from 396 recipients of allotransplants for DLBCL receiving myeloablative (MAC; n = 165), reduced intensity (RIC; n = 143), or nonmyeloablative conditioning (NMAC; n = 88) regimens. Acute and chronic GVHD rates were similar across the groups. Five-year nonrelapse mortality (NRM) was higher in MAC than RIC and NMAC (56% vs 47% vs 36%; P = .007). Five-year relapse/progression was lower in MAC than in RIC/NMAC (26% vs 38% vs 40%; P = .031). Five-year progression-free survival (15%-25%) and overall survival (18%-26%) did not differ significantly between the cohorts. In multivariate analysis, NMAC and more recent transplant year were associated with lower NRM, whereas a lower Karnofsky performance score (< 90), prior relapse resistant to therapy, and use of unrelated donors were associated with higher NRM. NMAC transplants, no prior use of rituximab, and prior relapse resistant to therapy were associated with a greater risk of relapse/progression. In conclusion, allotransplantation with RIC or NMAC induces long-term progression-free survival in selected DLBCL patients with a lower risk of NRM but with higher risk of lymphoma progression or relapse.

Hematopoietic stem cell transplantation (HSCT) is a demanding treatment for hematologic malignancies. The toxic preparative regimen most patients receive (high-dose chemotherapy, sometimes with total body irradiation) suppresses or destroys their immune function, necessitating protective isolation and causing side effects including fatigue, cognitive difficulties, and sexual dysfunction [1–2]. For many survivors these difficulties are resolved within the first year after transplant; however, they can persist, and survivors continue to face increased risk of all-cause mortality [3–5]. HSCT has also been associated with depression, anxiety, fear of cancer recurrence, and symptoms of post-traumatic stress disorder before, during, and after transplant [4, 6–7]. These physical and psychological effects occur in conjunction with practical difficulties that have been conceptualized as chronic stressors in other populations. Here we focus on three that are interrelated and commonly reported after transplant: persistent financial, employment, and insurance stressors. These stressors (which we refer to collectively as economic survivorship stressors) have the potential to exacerbate negative physical and psychological effects of transplant, thereby reducing survivors' health-related quality of life (HRQOL). HRQOL encompasses the extent to which survivors experience a sense of well-being, have the ability to carry out activities of daily living, and experience disease-related symptoms. It represents a critical aspect of the transplant recovery and survivorship experience, and economic survivorship stressors may adversely affect HRQOL through biological, behavioral, and psychological pathways [8–9]. For instance, financial stress (perceived inadequacy of financial resources) is associated with worse physical and psychological health in community populations [10–12], and has been associated with decreased HRQOL and elevated distress among low-income survivors of breast and gynecologic cancers [13]. Cancer-related financial stress and strain have also been associated with adverse psychological well-being among survivors of breast, prostate, and lung cancer [14]. Furthermore, qualitative work conducted with cancer survivors and their caregivers has demonstrated that financial worries and difficulties have a negative impact on family lifestyle, activities, roles, and relationships [15]. In HSCT, the potential for financial stress is high because of the costliness of the treatment [2], and additional expenses due to treatment-related complications, medications, transportation to and from transplant facilities, and routine medical follow-up. Employment-related problems are associated with financial stress, in addition to being stressful in their own right. Cancer survivors report difficulties including non-supportive work environments, changes in work schedules and relationships with colleagues, perceived employer discrimination, and reductions in perceived work ability, all of which may be persistent areas of concern with implications for their return to work, financial standing, and overall well-being [16]. Among HSCT survivors, enduring physical effects of transplant can prevent or substantially delay return to work [6]. One study found that approximately 40% of HSCT survivors had not returned to work 1-year post-transplant, and approximately 30% had not returned 2-years post-transplant [17]. Caregivers also lose income due to missed work, and incur substantial out-of-pocket expenses in order to stay at or near the treatment center [18]. Finally, many transplant survivors struggle with health insurance claims, policy caps, and obtaining future coverage. In one study approximately 32% of survivors reported that obtaining insurance was problematic, and 31% reported concerns about changing jobs for fear of losing health insurance coverage [19]. In a study of 10-year survivors of HSCT, 24% reported a history of health insurance denial compared to 0% of age-, sex-, and race-matched controls [5]. In addition to being a source of stress and frustration, insurance problems may increase financial burden among survivors who require ongoing surveillance. The role of insurance stress in cancer survivors' HRQOL has not been explored, although health insurance status has been shown to predict HRQOL in some studies. For instance, lack of insurance coverage has been associated with poorer HRQOL among survivors of prostate cancer [20]. However, insurance status was unrelated to HRQOL in a sample of Hispanic and African-American cancer patients [21]. The present study investigated these economic survivorship stressors and their association with HRQOL among survivors of HSCT. Participants were 181 men and women who had undergone HSCT 9–36 months prior to assessment. First, we examined survivors' post-transplant perceptions of financial, employment, and insurance stressors. Second, we investigated these perceived stressors as predictors of survivors' HRQOL, hypothesizing that greater economic survivorship stress would be associated with poorer HRQOL. Because stress and coping theory posits that people's perceptions of a situation (as opposed to the situation's objective characteristics) are most important in determining health [22], we predicted that associations between economic survivorship stress and HRQOL would remain even after controlling for objective indicators of socioeconomic position including income, education, and employment status. We also examined potential confounding effects of survivors' sociodemographic and medical characteristics on the hypothesized associations. A final, exploratory aspect of this study was based on the fact that people's social environments and personal resources influence how they appraise and respond to a stressor [22]. Informed by both relative deprivation theory [23–24], which predicts that greater financial disparities are associated with poorer health in part because people experience distress when they perceive their economic standing as worse than others, and social comparison theory [25], which posits that people compare themselves to others when evaluating themselves on a particular dimension, we reasoned that survivors would appraise economic survivorship stressors differently depending on their economic standing relative to others in their social environment. We investigated the effects of the financial crisis that occurred during this study, which led to a sudden, profound shift in the economic well-being of many Americans. We hypothesized that, compared to survivors who completed the study before the crisis, those who completed it after the crisis would appraise each of these stressors as less dire because of the knowledge that many people were experiencing similar problems. Although pinpointing the exact timing of the recession is difficult, experts identify the very public failures in the financial sector in September 2008 as a pivotal turning point [26–27]. We also examined whether the portion of survivors' transplant paid by health insurance, which varies across individuals and affects how much of the treatment costs they bear, would moderate the association between economic survivorship stress and HRQOL. This situational factor may influence how people appraise their financial demands; thus, we predicted that the adverse effects of each economic survivorship stressor on HRQOL would be amplified among those participants whose insurance covered the smallest portions of their transplant expenses.

Pain and anxiety are closely associated with bone marrow aspirates and biopsies. To determine whether hypnosis administered concurrently with the procedure can ameliorate these morbidities, the authors randomly assigned 80 cancer patients undergoing bone marrow aspirates and biopsies to either hypnosis or standard of care. The hypnosis intervention reduced the anxiety associated with procedure, but the difference in pain scores between the two groups was not statistically significant. The authors conclude that brief hypnosis concurrently administered reduces patient anxiety during bone marrow aspirates and biopsies but may not adequately control pain. The authors explain this latter finding as indicating that the sensory component of a patient's pain experience may be of lesser importance than the affective component. The authors describe future studies to clarify their results and address the limitations of this study.

We compared the outcomes of patients age 60-70 years with acute myelogenous leukemia receiving reduced-intensity allogeneic hematopoietic cell transplantation (HCT) in first remission (CR1) reported to the Center for International Blood and Marrow Research (n = 94) with the outcomes in patients treated with induction and postremission chemotherapy on Cancer and Leukemia Group B protocols (n = 96). All patients included had been in CR1 for at least 4 months. The HCT recipients were slightly younger than the chemotherapy patients (median age, 63 years vs 65 years; P < .001), but there were no significant between-group differences in the proportion with therapy-related leukemia or in different cytogenetic risk groups. Time from diagnosis to CR1 was longer for the HCT recipients (median, 44 days vs 38 days; P = .031). Allogeneic HCT was associated with significantly lower risk of relapse (32% vs 81% at 3 years; P < .001), higher nonrelapse mortality (36% vs 4% at 3 years; P < .001), and longer leukemia-free survival (32% vs 15% at 3 years; P = .001). Although overall survival was longer for HCT recipients, the difference was not statistically significant (37% vs 25% at 3 years; P = .08). Our findings suggest that reduced-intensity conditioning allogeneic HCT in patients age 60-70 with acute myelogenous leukemia in CR1 reduces relapse and improves leukemia-free survival. Strategies that reduce nonrelapse mortality may yield significant improvements in overall survival.

We examined the effect of donor characteristics on graft failure (95% donor chimerism, 145 patients were 5% to 95%, and 63 patients were

Cancer and Leukemia Group B conducted a phase II study to evaluate the safety and efficacy of a reduced-intensity conditioning regimen with allogeneic transplantation to treat patients with recurrent low-grade B cell malignancies. Patients over age 18 with a diagnosis of relapsed, chemotherapy-sensitive disease underwent transplantation with a matched sibling donor, and conditioning with cyclophosphamide (1 g/m(2)/day × 3) and fludarabine phosphate (25 mg/m(2)/day × 5). Graft-versus-host prophylaxis included cyclosporine or tacrolimus plus low-dose methotrexate. Forty-four evaluable patients with a median age of 53 and median of 2 prior regimens were accrued. Sixteen patients had follicular non-Hodgkin lymphoma and 28 had histologies including 7 indolent B cell lymphomas, 4 mantle cell, 15 chronic lymphocytic leukemia (CLL), and 2 prolymphocytic leukemia (PLL) patients. The 6-month treatment-related mortality (TRM) was 2.4% and 3-year TRM was 9%. Three-year event-free and overall survival were 0.75 and 0.81 for the follicular patients, 0.59 and 0.71 for the CLL/PLL patients, and 0.55 and 0.64 for the other histologies. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 29%, and extensive chronic GVHD was 18%. This report demonstrates that allogeneic sibling transplantation with a reduced-intensity conditioning regimen is safe and efficacious for patients with advanced indolent B cell malignancies enrolled on a Cooperative Group study.

Hematopoietic stem cell transplant (HSCT; also commonly known as bone marrow transplant) is an aggressive treatment for hematological malignancies that causes numerous physical and psychological difficulties, including significant distress and poor quality of life [1, 2]. Although previously a treatment of last resort, HSCTs are now indicated early in the course of many diseases. This shift in treatment strategy has resulted in improved survival rates [3, 4], but has also led to a greater focus on lingering side effects found among survivors. Researchers have recently begun to examine the potential neurotoxic effects of HSCT as well as the deleterious neurological impact of the cancers it treats. There are two ways in which such cognitive impairments have been measured: neuropsychological assessment (objective) and self-report measures of cognitive functioning (subjective). HSCT patients have impaired cognitive function using both forms of measurement [5–7]. However, in general, objective neuropsychological test results are not correlated with subjective cognitive functioning [7, 8]. Thus, patients may demonstrate deficits on neuropsychological tests but perceive little impairment in daily functioning, or they may demonstrate relatively normal neuropsychological test results despite perceiving considerable daily impairment. Despite the fact that subjective cognitive functioning is often not correlated with objective neuropsychological impairment, it is associated with poorer psychological adjustment and quality of life. For instance, Booth-Jones and colleagues [7] investigated HSCT patients who were 6-months post-discharge and found that poorer subjective cognitive functioning was associated with greater depressive symptomatology as well as poorer physical and mental quality of life. Similar associations have also been found in women receiving adjuvant therapy for breast cancer for whom self-reports of memory and concentration difficulties were associated with psychological distress and poorer quality of life [9]. Mechanisms through which subjective cognitive impairment affects distress and quality of life are not currently well-defined, but they are worth clarifying because they may be good targets for psychosocial interventions. One possible mechanism is suggested by Bandura’s social cognitive theory and its emphasis on self-efficacy, or “belief in one’s capabilities to organize and execute the courses of action required to manage prospective situations” [10]. HSCT survivors’ self-efficacy for managing symptoms is particularly likely to have implications for their well-being because of their high physical and psychosocial symptom burden after treatment [1]. Indeed, low self-efficacy has been associated with elevated psychological distress and poorer quality of life in other cancer patients [e.g., 11–13]. Thus, experiencing difficulties such as memory problems and poor concentration may cause survivors to doubt their ability to manage symptoms, which in turn may adversely affect their psychological adjustment and quality of life. Evidence from other patient populations supports the plausibility of such a mechanism. For example, in chronic pain patients, self-efficacy has been shown to mediate the relationship between self-reported pain intensity and outcomes such as disability and depression [14]. Self-efficacy for managing cognitive symptoms has also been found to mediate the relationship between community integration and global life satisfaction in patients with traumatic brain injury [15]. If self-efficacy were similarly conceptualized as a mediator among HSCT survivors suffering from subjective cognitive impairment, it might explain the link between subjective cognitive impairment and distress and poor quality of life. Thus, the purpose of the present study was to examine whether self-efficacy for symptom management mediates relations between subjective cognitive functioning and the following outcomes: psychological adjustment (i.e., depressed mood and anxiety), and health-related quality of life. We hypothesized that among HSCT survivors, poorer subjective cognitive functioning would be associated with lower levels of self-efficacy for symptom management, which would in turn be associated with poorer adjustment and quality of life.

Several risk factors are associated with increased mortality in patients with chronic graft-versus-host disease (cGVHD), but there is considerable variability in the reported factors. Therefore, we evaluated patient, transplantation, and cGVHD characteristics to develop a risk score in 5343 patients with cGVHD. Ten variables were identified as being significant in multivariate analysis of overall survival and nonrelapse mortality (NRM): age, prior acute GVHD, time from transplantation to cGVHD, donor type, disease status at transplantation, GVHD prophylaxis, gender mismatch, serum bilirubin, Karnofsky score, and platelet count. These 10 variables were used to build a cGVHD risk score, and 6 risk groups (RGs) were identified. The 5-year NRM was 5% (1%-9%) in RG1, 20% (19%-23%) in RG2, 33% (29%-37%) in RG3, 43% (40%-46%) in RG4, 63% (53%-74%) in RG5, and 72% (59%-85%) in RG6. The 5-year overall survival was highest at 91% (95% confidence interval [CI]:85%-97%) in RG1, followed by 67% (65%-69%) in RG2, 51% (46%-55%) in RG3, 40% (37%-43%) in RG4, 21% (12%-30%) in RG5, and 4% (0%-9%) in RG6 (all P < .01). This analysis demonstrates the usefulness of data from a large registry to develop risk-score categories for major transplantation outcomes. Validation of this cGVHD risk score is needed in a different population to ensure its broad applicability.

Objectives: The precise role of positron emission tomography (PET/CT) for predicting relapse/progression in multiple myeloma remains uncertain. We compared the predictive values of PET/CT, concurrent laboratory testing (labs), and their combination in prediction of 12-month progression, as determined by current International Myeloma Working Group (IMWG) criteria. Methods: PET/CT and labs (serum chemistry, β2-microglobulin, immunofixation, bone marrow biopsy, serum free light chains) were reviewed, and date of relapse/progression was determined by IMWG criteria. Results: The median time from therapy to PET/CT imaging was 12.0 months (1.0–110) and median time to progression (TTP) was 29.8 months (1.6–130+). Overall survival and survival-without-progression at last follow-up were 84% and 49%, respectively. Sensitivity of PET/CT for predicting relapse/progression was lower than that of labs (0.67 vs. 0.89, ns), but PET/CT was more specific (0.89 vs. 0.79, ns). When labs and PET/CT data were combined, a positive result for either test was 89% sensitive and a positive result for both tests was 100% specific for predicting 12-month progression of disease. Kaplan–Meier analysis showed significantly greater TTP for those with a negative vs. positive PET/CT (P = 0.0005), negative vs. positive labs (P

Objective: Hematopoietic stem cell transplant (HSCT) survivors who are 1 to 3 years posttransplant are challenged by the need to resume valued social roles and activities—a task that may be complicated by enduring transplant-related psychological distress common in this patient population. The present study investigated whether transplant survivors who receive adequate social support from their spouse or intimate partner experience lower distress. Method: Effects of receiving a greater quantity of partner support (a common approach to studying enacted support) were compared with effects of receiving more effective partner support (i.e., support that more closely matches their needs in terms of its quantity and quality). Men and women (N 230) who were 1 to 3 years posttransplant completed measures of partner support quantity (Manne & Schnoll, 2001), partner social support effectiveness (Rini & Dunkel Schetter, 2010), and psychological distress (Brief Symptom Inventory; Derogatis & Spencer, 1982). Potential medical and sociodemographic confounds were controlled in analyses. Results: As hypothesized, survivors reported less distress when they received more effective partner support (p .001). Quantity of partner support was not associated with distress (p .23). An interaction revealed that when partner support was effective, the quantity of support survivors received was not associated with their distress (p .90); however, when partner support was ineffective, receiving a greater quantity of partner support was associated with substantially elevated distress (p .002). Conclusions: Findings suggest that clinical approaches to addressing or preventing enduring distress after HSCT should target features of partner support related to its appraised effectiveness.

Background: In July of 2016, CMMI started a five year bundled payment program called OCM. Beneficiaries are attributed to practices providing their cancer care for a 6 month episode triggered by the administration or distribution of specified cancer drugs. The model provides risk adjustments to the target price based on risk factors such as age, chemotherapy and the receipt of certain treatments (radiation or bone marrow transplant). Target prices are adjusted by geographic region, novel therapy use, and a trend factor. Multiple Myeloma was identified in our practice as a cancer type with high variance on expenditures after the first Performance Period within the model (July 2016-December 2016). Chemotherapy represented 52% of total episode expenditures with oral chemotherapy and hormone therapy representing 24%. The average cost of lenalidomide for one year is $115,000. The model adjusts for novel therapies, including new drugs approved by the FDA after December 31, 2014 with status lasting two years. However, literature demonstrates that this does not fully adjust for the high costs of novel therapies (Muldoon et at., Health Affairs, 2018). Unlike solid tumors, Multiple Myeloma staging may not improve risk adjustment and target price. Methods: We analyzed the total cost of care of beneficiaries who triggered an OCM episode for Performance Period 1 (PP1). Beneficiaries were identified by diagnosis of Multiple Myeloma, and then segregated into cohorts of those who received lenalidomide and/or pomalidomide and those who did not. Observed vs. Expected (O/E) target price for each episode was determined for both cohorts comparing the actual episode expenditures and the target price per episode calculated by the Oncology Care Model. A two sample t-test was conducted followed by a linear regression to determine relation between drug days prescribed and O/E. Results: There were 125 attributed beneficiaries with a Multiple Myeloma diagnosis who triggered an episode during PP1. The average O/E of the cohort which received the chemotherapy, Cohort A, was 1.624 compared to 0.986 for those that did not, Cohort B. The difference in average O/E in the two cohorts was 39% higher in Cohort A, p Discussion: This is the first report on the impact of lenalidomide and pomalidomide on the total cost of care in an OCM practice. The results demonstrate the lack of adequate adjustment to the CMS target price for episodes in which one or both of these drugs were prescribed. Lenalidomide and pomalidomide are first and second line drugs used both for induction and maintenance. Both drugs are frequently used for prolonged periods of time in patients and trigger more than one episode in OCM. Therefore, the use of these agents greatly affects the total cost of care against a target price that is not adequately adjusted. Academic Medical Centers that care for larger populations of multiple myeloma patients may be disproportionately affected and this will impede their success under the OCM methodology. Additional analysis similar to this will inform CMMI as to further refinements to the OCM adjusters. Disclosures No relevant conflicts of interest to declare.

Failure to engraft donor cells is a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We describe the results of 122 patients reported to the National Marrow Donor Program between 1990 and 2005, who received a second unrelated donor HCT after failing to achieve an absolute neutrophil count ofor=500/microL without recurrent disease. Patients were transplanted for leukemia (n = 83), myelodysplastic disorders (n = 16), severe aplastic anemia (n = 20), and other diseases (n = 3). The median age was 29 years. Twenty-four patients received second grafts from a different unrelated donor. Among 98 patients who received a second graft from the same donor, 28 received products that were previously collected and cryopreserved for the first transplantation. One-year overall survival (OS) after second transplant was 11%, with 10 patients alive at last follow-up. We observed no differences between patients who received grafts from the same or different donors, or in those who received fresh or cryopreserved product. The outcomes after a second allogeneic HCT for primary graft failure are dismal. Identifying risk factors for primary graft failure can decrease the incidence of this complication. Further studies are needed to test whether early recognition and hastened procurement of alternative grafts can improve transplant outcomes for primary graft failure.

Purpose Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Patients and Methods We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS). Results Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and ≥ 65 years had 2-year survival rates as follows: 44% (95% CI, 37% to 52%), 50% (95% CI, 41% to 59%), 34% (95% CI, 25% to 43%), and 36% (95% CI, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% CI, 35% to 49%), 35% (95% CI, 27% to 43%), 45% (95% CI, 36% to 54%), and 38% (95% CI, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P > .3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. Conclusion With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.

46 Background: Hospitalization is a major contributor to cost in oncology. Minimizing avoidable admissions can lead to substantial savings. Methods: We studied Medicare claims data from 160 admissions for prostate cancer (PCa) patients from 1/2012 to 5/2015. Admissions with the lowest 50th percentile of charges were assessed for being potentially avoidable by 2 independent chart reviews; remaining admissions were assumed to be unavoidable due to medical complexity. Common admitting diagnoses were targeted by theoretical care pathways designed to minimize avoidable admissions via expedited outpatient follow-up. We compared the cost of the avoidable admissions to that of implementing 3 such pathways then estimated the financial impact. Results: Total cost for all 160 admissions was $1,979,200. 25% of these admissions, accounting for $494,800, were deemed potentially avoidable. Our model exchanged each of these admissions for a routine clinic visit which led to an estimated $464,800 in savings, or a 23% improvement in total cost. The most common admitting diagnoses were fever (18%), pain (12%), and dehydration (8%). On review, 3/9 fever admissions in this set were deemed avoidable with 1 extra clinic visit, 3 with 3 visits, and 3 were unavoidable, yielding a 53% reduction in cost for this diagnosis. Similar analyses led to cost reductions of 75% and 66% for pain and dehydration admissions, respectively. Combining just these 3 theoretical interventions led to an estimated savings of $146,955, or a 7.4% improvement in total cost. Conclusions: A sizable portion of PCa admissions can be avoided, with ample savings, if a system is in place to provide the additional care that often exceeds the capabilities of a busy practice. [Table: see text]

Summary This study examined barriers to mental health service use and their demographic, medical, and psychosocial correlates among hematopoietic stem cell transplant (HSCT) survivors. A sample of 253 HSCT survivors who were 1- to 3-years post-transplant completed measures of demographic, physical, psychological, and social characteristics as well as a newly modified measure of barriers to mental health service use. Only 50% of distressed HSCT survivors had received mental health services. An exploratory factor analysis of the barriers to mental health service use scale yielded four factors: Scheduling Barriers, Knowledge Barriers, Emotional Barriers, and Illness-related Barriers. Patients with higher social constraints (perceived problems discussing the illness experience with significant others) reported higher levels of all four types of barriers. General distress and transplant-related posttraumatic stress symptoms were positively associated with emotional, knowledge, and illness-related barriers to mental health service use, whereas physical and functional well-being were inversely associated with these barriers. Having more knowledge barriers and more emotional barriers predicted a lower likelihood of receiving mental health services, as did lower levels of education and general distress. Results suggest that a significant number of HSCT survivors may benefit from education about mental health services that is tailored to individual barriers.

Adult T-cell leukemia/lymphoma (ATLL) is a rare T-cell neoplasm caused by the human T-cell lymphotropic virus type-1 (HTLV-1), a retrovirus endemic in Japan, sub-Saharan Africa and the Caribbean ba...

We report the retrospective outcomes of unrelated donor (URD) transplants in 169 patients with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) who received transplants between 1995 and 2004. Median age was 33 years (range, 16-59 years). A total of 50% had a white blood cell count (WBC) more than 30 × 109/L, 18% extramedullary disease, 42% achieved CR more than 8 weeks from diagnosis, 25% had adverse cytogenetics, and 19% had T-cell leukemia. A total of 41% were HLA well-matched, 41% partially matched with their donors, and 18% were HLA-mismatched. At 54-month median follow-up, incidences of acute grade 2-IV, III to IV, and chronic graft-versus-host disease were 50%, 25%, and 43%, respectively. Five-year treatment-related mortality (TRM), relapse, and overall survival were 42%, 20%, and 39%, respectively. In multivariate analyses, TRM was significantly higher with HLA-mismatched donors and T-cell depletion. Relapse risk was higher if the diagnostic WBC was more than 100 × 109/L. Factors associated with poorer survival included WBC more than 100 × 109/L, more than 8 weeks to CR1, cytomegalovirus seropositivity, HLA mismatching, and T-cell depletion. Nearly 40% of adults with ALL in CR1 survive 5 years after URD transplantation. Relapse risks were modest; TRM is the major cause of treatment failure. Selecting closely HLA-matched URD and reducing TRM should improve results.

Background We previously showed that antithymocyte globulin (ATG) given with total body irradiation (TBI) 200 cGy and fludarabine results in high rate of donor engraftment. Its influence on acute and chronic graft versus host disease (GVHD) and on graft versus tumor effect is less known. Methods Sixty-five patients underwent nonmyeloablative stem cell transplant with ATG, TBI 200 cGy, and fludarabine. GVHD prophylaxis was mycophenolate mofetil and cyclosporine. Forty-two patients (pts) (65%) had match related donors, 18 (27%) match unrelated, 1 (1.5%) mismatch related, and 4 (6%) mismatch unrelated donors. Results At a median follow-up of 862 days, 24 patients (37%) developed GVHD. The median age of the patients with and without GVHD was 56 years respectively. Acute GVHD grade II-IV developed in 19 pts (29%). Fatal GVHD of liver and/or gut occurred in nine pts (14%). Forty-one pts survived more than 100 days. Five pts (12%) had chronic GVHD, two had extensive, and three had limited involvement. Relapsed disease was observed in 22 pts (34%). Infections occurred in 15 pts (23%) and were fatal in 13 (20%). Conclusions The addition of ATG to TBI 200cGy and fludarabine resulted in a modest incidence of GVHD. The best transplant outcomes were observed in pts with lymphoid malignancies.

We previously reported a risk score that predicted mortality in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (HCT) between 1995 and 2004 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We sought to validate this risk score in an independent CIBMTR cohort of 1128 patients with CGVHD who underwent transplantation between 2005 and 2007 using the same inclusion criteria and risk score calculations. According to the sum of the overall risk score (range, 1 to 12), patients were assigned to 4 risk groups (RGs): RG1 (0 to 2), RG2 (3 to 6), RG3 (7 to 8), and RG4 (9 to 10). RG3 and RG4 were combined, as RG4 accounted for only 1% of the total cohort. Cumulative incidences of nonrelapse mortality (NRM) and probability of overall survival were significantly different between each RG (all P

In this study, we explored dermal dendritic cell (DC) homeostasis in mice and humans both in the steady state and after hematopoietic cell transplantation. We discovered that dermal DCs proliferate in situ in mice and human quiescent dermis. In parabiotic mice with separate organs but shared blood circulation, the majority of dermal DCs failed to be replaced by circulating precursors for >6 mo. In lethally irradiated mice injected with donor congenic bone marrow (BM) cells, a subset of recipient DCs remained in the dermis and proliferated locally throughout life. Consistent with these findings, a large proportion of recipient dermal DCs remained in patients' skin after allogeneic hematopoietic cell transplantation, despite complete donor BM chimerism. Collectively, our results oppose the traditional view that DCs are nondividing terminally differentiated cells maintained by circulating precursors and support the new paradigm that tissue DCs have local proliferative properties that control their homeostasis in the steady state. Given the role of residual host tissue DCs in transplant immune reactions, these results suggest that dermal DC homeostasis may contribute to the development of cutaneous graft-versus-host disease in clinical transplantation.

Objectives. Noninvasive evaluation of fibrosis is an on-going effort in the management of chronic hepatitis C. This study was planned to noninvasively evaluate fibrosis staging. Design. We evaluated the biochemical, functional [aminopyrine breath test (ABT)] and ultrasonographic variables of 75 chronic hepatitis C patients. Results. Clinical [body mass index (BMI)], biochemical [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets (PLT)] and ratio indexes, together with the ABT, showed a higher relationship with fibrosis: initial (score ≤ 2) versus evident (score > 2) fibrosis: BMI (24 ± 2 vs. 26 ± 2, P = 0.0007), AST (56 ± 36 vs. 88 ± 65, P = 0.0159), ALT (92 ± 54 vs. 139 ± 108, P = 0.0290), PLT (220 ± 64 vs. 173 ± 61, P = 0.0007), PLT/spleen diameter ratio (PLT/SPD) (2133 ± 786 vs. 1540 ± 681, P = 0.0003), AST/platelet count ratio index (APRI) (0.80 ± 0.87 vs. 1.51 ± 1.47, P = 0.0010), ABT%d/h30 min (10.8 ± 4.5 vs. 7.6 ± 3.8, P = 0.0007), ABT%d/cum120 min (8.9 ± 3.3 vs. 6.5 ± 3.1, P = 0.0007). Considering the differences between fibrosis score 2 and 3 patients, BMI, ABT and PLT/SPD ratio proved to be statistically significant. Multivariate stepwise analysis (with and without BMI) identified two models for distinguishing between initial and evident fibrosis: Model 1: −0.569 +(BMI × 0.107) + (APRI × 0.169)−(PLT/SPD × 0.304), and Model 2: 2.376 + (APRI × 0.152)−(ABTd/h30 × 0.043)−(PLT/SPD × 0.249). These models showed concordance in identifying or ruling out evident fibrosis in 76% and 78.7% of the patients respectively. The PLT/SPD ratio also showed 78.7% concordance with the histological score. Conclusion. These results suggest that noninvasive evaluation of fibrosis in chronic hepatitis C may be considered an effective tool thanks to the use of an inexpensive, reproducible ratio index.

Nonmyeloablative allogeneic peripheral blood progenitor cell transplantation with low-dose total body irradiation (TBI; 200 cGy) plus fludarabine followed by cyclosporine and mycophenolate mofetil results in modest graft rejection rates. Acute and chronic graft-versus-host diseases (GVHD) are also seen and may not differ substantially from those that occur after fully ablative transplantation. Adding antithymocyte globulin (ATG) to pretransplant conditioning produces substantial immunosuppression. Because of its persistence in the circulation, ATG can achieve in vivo T-cell depletion. Twenty-five patients who were not eligible for conventional fully ablative allogeneic stem cell transplantation by virtue of age or comorbidities underwent nonmyeloablative allogeneic transplantation with ATG 15 mg/kg/d days -4 to -1, TBI 200 cGy on a single fraction on day -5, and fludarabine 30 mg/m(2)/d on days -4 to -2. Oral mycophenolate mofetil 15 mg/kg every 12 hours and cyclosporine 6 mg/kg every 12 hours were started on day -5. Grafts were unmanipulated peripheral blood progenitor cells mobilized with filgrastim 10 microg/kg/d and collected on day 5. The median age of the recipients was 57 years (range, 30-67 years); diagnoses were non-Hodgkin lymphoma (n = 11), acute myeloid leukemia (n = 6), multiple myeloma (n = 3), acute lymphoblastic leukemia (n = 2), severe aplastic anemia (n = 1), paroxysmal nocturnal hemoglobinuria (n = 1), and myelodysplastic syndrome (n = 1). The median CD34(+) and CD3(+) contents of the grafts were 7.6 x 10(6)/kg and 1.6 x 10(8)/kg, respectively. Five patients received voluntary unrelated donor grafts. Three patients, 2 with voluntary unrelated donor grafts and 1 with a sib donor, received a 1 antigen-mismatched graft. The rest were fully matched. Twenty-two of 25 patients were evaluable for chimerism. Sixteen had/=95% donor chimerism. Four patients displayed 80% to 90% donor chimerism, 1 displayed 78%, and 1 displayed 64%. Eleven patients relapsed with their original disease. One patient rejected the graft at 180 days. The median hospital stay was 27 days. Complications included GVHD in 6 patients (3 patients had grade I or II GVHD of skin and liver, and 3 patients had grade III or IV GVHD of liver and gut). Two of the patients with GVHD had mismatched grafts. Transplant-related toxicity was seen in 4 patients and infection in 5 patients. The median length of follow-up was 162 days (range, 17-854 days). Complete remissions were seen in 10 patients. Four patients remained in complete response (CR) at 280 to 595 days. One patient relapsed with non-Hodgkin lymphoma after a CR of 728 days. Of the 25 patients, 16 died (6 of relapsed disease, 4 of GVHD, 3 of infection, and 3 of transplant-related toxicity) and 9 are alive (6 with CR-2 of them after donor leukocyte infusion-and 3 with relapsed disease). The addition of ATG to low-dose TBI and fludarabine nonmyeloablative conditioning was well tolerated and resulted in80% donor engraftment in this small cohort. As in other series of truly nonmyeloablative transplantation, a high rate of relapse was observed. Donor engraftment may be facilitated by the addition of ATG to low-dose TBI and fludarabine conditioning.