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Increasingly, patients age ≥65 years are undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Although age alone is a well-documented predictor of overall survival (OS) and nonrelapse mortality (NRM), growing evidence suggests that poor functional status and frailty associated with aging may have roles as well. Our goal in the present study was to identify and improve these and other aging-related maladies by developing a multimodal supportive care program for older allo-SCT recipients. We designed and implemented a multimodal supportive care program, Enhanced Recovery in Stem Cell Transplant (ER-SCT), for patients age ≥65 years undergoing allo-SCT. The ER-SCT program consists of evaluation and critical interventions by key health care providers from multiple disciplines starting before hospital admission for transplantation and extending through 100 days post-allo-SCT. We determined the feasibility of implementing this program in a large stem cell transplantation center. After 1 year of ongoing process improvements, multiple evaluations, and enrollment, we found that a dedicated weekly clinic was necessary to coordinate care and evaluate patients early. We successfully enrolled 57 of 64 eligible patients (89%) in the first year. Our data show that a multimodal supportive care program to enhance recovery for older patients undergoing allo-SCT is feasible. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Ethical challenges are inherent in oncology clinical practice. Ranging from transitions in care to code status and treatment decisions, these ethical challenges can have an acute effect on nurses, with well-established connections to moral distress and other psycho-emotional sequelae. The availability of a nurse ethicist can provide invaluable resources to support nurses in awareness of ethical challenges and support for ethical decision making in practice.

Nursing care of blood and marrow transplantation (BMT) patients is complicated. Nursing considerations of BMT patients with GVHD require an additional set of skills and knowledge that include side effects, both expected and less common, assessment skills, treatment administration, both standard and novel, and acute or intensive care. Nursing care of BMT patients with skin GVHD will be determined by the degree of skin alteration with distinct decisions made about hygiene, both topical and systemic treatment, infection prevention, relief of discomfort, functional ability (ADL) and body image alteration.The nurse needs to have knowledge about assessment criteria for acute and chronic (NIH) assessment with special attention to skin (presence of rash, texture, mobility), joint mobility, mouth care, dressings, and skin care products. Nursing consideration of gastrointestinal GVHD includes importance of accurate intake and output, obtaining culture, fluid and electrolyte imbalance, nutrition, treatment, and skin care. Complication of GVHD treatment, namely effects of steroids require experts from many disciplines to provide comprehensive care. Caring and advocating for GVHD patients may include preparing for outcomes that are undesirable and impact the patient’s quality of life and mortality. BMT survivorship programs are a major source of patient education about chronic GVHD for patients after treatment. Caring for BMT patients, especially those experiencing GVHD, takes a knowledgeable, committed, and caring team of healthcare providers. Workshops like this are vital in providing information and networking to keep providers around the region and globe engaged in this critical work. Keywords: Graft versus host disease, Nursing care, Skin care, Multidisciplinary team

A projected shortage of hematopoietic cell transplantation (HCT) health professionals was identified as a major issue during the National Marrow Donor Program/Be The Match System Capacity Initiative. Work-related distress and work–life balance were noted to be potential barriers to recruitment/retention. This study examined these barriers and their association with career satisfaction across HCT disciplines. A cross-sectional, 90-item, web-based survey was administered to advanced practice providers, nurses, physicians, pharmacists, and social workers in 2015. Participants were recruited from membership lists of 6 professional groups. Burnout (measured with the Maslach Burnout Inventory subscales of emotional exhaustion and depersonalization) and moral distress (measured by Moral Distress Scale—Revised) were examined to identify work-related distress. Additional questions addressed demographics, work–life balance, and career satisfaction. Of 5759 HCT providers who received an individualized invitation to participate, 914 (16%) responded; 627 additional participants responded to an open link survey. Significant differences in demographic and practice characteristics existed across disciplines (P < .05). The prevalence of burnout differed across disciplines (P < .05) with an overall prevalence of 40%. Over one-half of pharmacists had burnout, whereas social workers had the lowest prevalence at less than one-third. Moral distress scores ranged from 0 to 336 and varied by discipline (P < .05); pharmacists had the highest mean score (62.9 ± 34.8) and social workers the lowest (42.7 ± 24.4). In multivariate and univariate analyses, variables contributing to burnout varied by discipline; however, moral distress was a significant contributing factor for all providers. Those with burnout were more likely to report inadequate work–life balance and a low level of career satisfaction; however, overall there was a high level of career satisfaction across disciplines. Burnout, moral distress, and inadequate work–life balance existed at a variable rate in all HCT disciplines, yet career satisfaction was high. These results suggest specific areas to address in the work environment for HCT health professionals, especially the need for relief of moral distress and a greater degree of personal time. As the creation of healthy work environments is increasingly emphasized to improve quality care and decrease costs, these findings should be used by HCT leadership to develop interventions that mitigate work-related distress and in turn foster recruitment and retention of HCT providers.

Background Research suggests that patients experience increased fatigue, reduced physical activity, and diminished quality of life (QOL) after hematopoietic stem cell transplantation (HSCT). Structured exercise during hospitalization has been shown to maintain or improve fatigue. Incentive-based interventions have not been tested to encourage physical activity maintenance. Objectives The study's aim was to evaluate the effect of participation in an incentive-based mobility program on fatigue, physical conditioning, performance status, and QOL in individuals undergoing allogeneic HSCT. We hypothesized that program participation would affect these variables and that time spent engaged in physical activity would correlate with improved outcomes. Methods A 1-group repeated-measures design used the Brief Fatigue Inventory, 6-minute walk test, and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale to assess study variables. Repeated-measures models assessed the effect of participation time on these variables. Results Individuals with higher participation (minutes) significantly increased 6-minute walk test scores throughout hospitalization but had no significant changes in Brief Fatigue Inventory and Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale scores. Fatigue and QOL decreased over hospitalization but improved by discharge. Subjects who demonstrated higher participation averaged fewer hospital days (R = 1.65; P = .005). Conclusions This study is unique in examining the impact of an incentive-based mobility program, participation in which may decrease length of hospital stay for HSCT patients. Randomized trials are needed to further validate these findings and assess additional variables that can influence outcomes. Implications for practice An incentive-based mobility program during hospitalization for HSCT has the potential to minimize fatigue and stabilize, if not improve, QOL.

Topic Significance & Study Purpose/Background/Rationale Nursing care of BMT patients is complicated. Trends in BMT demonstrated improved survival with patients experiencing better quality of life (QOL) during treatment, early recovery and long term because of expanding pool of stem cell sources, more effective less toxic regimens, new supportive care drugs, maintenance therapy and specialized medical and nursing care. Nonetheless, disease recurrence, graft versus host disease (GVHD), organ failure and secondary cancer are common causes of late death. Nursing considerations of HSCT patients with GVHD requires an additional set of skills and knowledge that include side effects both expected and less common, assessment skills, treatment administration both standard and novel, and acute or intensive care. Nursing care of patients with acute and chronic GVHD also require symptom recognition and knowledge of treatment modalities, management and care of both physical and psychosocial elements, and requires consistent coordination of care for possible prolonged period of time. The nurses' role is to advocate for the HSCT patient and that may include preparing for end of life if the patient's disease is refractory to treatment for GVHD. Methods, Intervention, & Analysis Specialized GVHD clinics have been set up at many larger centers. This is a multidisciplinary clinic that includes the clinic nurse, APP, BMT physician who specializes in GVHD, dermatologist and other experts in the field of gynecology, physical therapy, occupational therapy, GI medicine, pulmonary, pathology, symptom research, infectious disease, endocrinology, dental and ophthalmology. The patient is always in the central in the clinic focus. Findings & Interpretation Nursing care of BMT patients with skin GVHD will be determined by the degree of skin alteration with distinct decisions made about hygiene, both topical and systemic treatment, infection prevention, relief of discomfort, functional ability (ADL) and body image alteration. Care of the patient with chronic GVHD will also focus on prevention and early detection. Discussion & Implications Patient education about such aspects as sun protection, skin assessment, and recognition of risk for skin and oral cancer are important and covered in our survivorship program patient visit at or around day 100. A one-page handout on "Nursing Care Consideration of Skin GVHD" will be discussed.

Topic Significance & Study Purpose/Background/Rationale Patients of advancing ages represent a significant proportion of allogeneic hematopoietic stem cell transplants (HSCT). In recent years, up to 30% of patients receiving an allogeneic HSCT are older than 60 with about 5% greater than 70. This trend is also occurring at our large (over 700 HSCT per year) program at a major Southwest comprehensive cancer center. As a result, a multi-departmental and multidiscipline effort was formed to evaluate HSCT patients aged 65 and older for conditions which can lead to increase frailty, cognitive impairments, and malnutrition potentially leading to increased morbidity and mortality. Methods, Intervention, & Analysis Our team approach assesses for early identification of these conditions to minimize, prevent, and mitigate the HSCT complications in the pre-transplant phase and follow the patients’ progress throughout their first 100 days post-HSCT. We applied the principles of Enhanced Recovery after Surgery (ERAS) programs which have shown to impact outcomes related to decreased opiate use and pain levels, shortened average length of stay, increased patient satisfaction, and reduce cost. Literature is limited for enhanced recovery pathway within the HSCT population. Our program, entitled Enhanced Recovery Stem Cell Transplant (ER-SCT), has utilized similar approaches of ERAS. This includes evaluation by Prehabilitation (Physical Therapist (PT), Occupational Therapist (OT) and Rehabilitation MD evaluation), Gerontologist, Clinical Nutritionist, clinical pharmacist, and by our Advanced Practice Providers (APPs) and nursing coordinators. Additionally, ER-SCT patients are followed by our inpatient RNs, APPs, PT/OT and nutrition teams, with discharge follow-up with Prehabilitation and Clinical Nutrition. Findings & Interpretation Feasibility of the applying ERAS principles, foundation, and elements was established through a quality improvement (QI) project. Through application of the Model of Improvement (part of the QI program), a need was discovered to improve scheduling, care coordination, and multidisciplinary approaches to patient care; resulting in the creation of an ER-SCT clinic. This was shown to reduce patient appointments and decrease time from enrollment in ER-SCT to completion of pre-HSCT visits. Discussion & Implications ER-SCT is currently looking evaluating program outcomes through the development of an research protocol. There is discussion about broadening this program to younger HSCT patients at higher risk for prolonged recovery and to the autologous HSCT population.

Topic Significance & Study Purpose/Background/Rationale Nursing care for hematopoietic stem cell transplantation (HSCT) patients has always presented ethical challenges throughout the care continuum. Recent research indicates HSCT nurses frequently experiencing moral distress in situation related to diminished patient care quality due to poor team communication; provider giving false hope to patient or family; following family wishes to continue life support even when not in best interest of patient; patient care suffering due to lack of provider continuity; and initiating extensive life-saving actions when it is likely to only prolong death. With the addition of new cellular therapies, HSCT nurses find themselves caring for patients with hematologic and solid tumor malignancies with advanced or progressive disease. The promise of these new therapies with possible profound adverse effects promotes nursing concerns of unrealistic or uncertain patient expectations; questionable benefit versus harm in view of adverse events which have occurred in early clinical trials; and questionable patient understanding of the efficacy of phase 1 trials. Unresolved ethical issues may also contribute to team members’ burnout, compassion fatigue, and moral distress affecting recruitment and retention of healthcare team members. Methods, Intervention, & Analysis To assist nurses managing with these additional challenges the nursing leadership teams on the HSCT, leukemia and lymphoma units requested regular nursing ethics rounds to provide clinical nurses the opportunities to openly discuss their experience and distress with difficult patient situations. Nursing ethics rounds have been conducted monthly or every other month on different units for both days and night shift nurses. Clinical nurses have discussed concerns about patient selection, patient preparation for all possible outcomes, and their participation in administering treatment with uncertain or adverse outcomes. Current literature is presented on a relevant topic and continued education units are provided. Nurses are reminded of the resources available for immediate situational assistance (ethics consult) and individual assistance (employee assistance program). Findings & Interpretation Clinical nurses have discussed concerns about patient selection, patient preparation for all possible outcomes, and their participation in administering treatment with uncertain or adverse outcomes. Current literature is presented on a relevant topic and continued education units are provided. Nurses are reminded of the resources available for immediate situational assistance (ethics consult) and individual assistance (employee assistance program). Discussion & Implications Informal feedback has been positive and nurses have expressed appreciation for the opportunity to discuss their feelings about these new challenges.

The National Marrow Donor Program, in partnership with the American Society for Blood and Marrow Transplantation, sponsored and organized a series of symposia to identify complex issues affecting the delivery of hematopoietic cell transplantation (HCT) and to collaboratively develop options for solutions. "Hematopoietic Cell Transplantation in 2020: A System Capacity Initiative" used a deliberative process model to engage professional organizations, experts, transplant centers, and stakeholders in a national collaborative effort. Year 2 efforts emphasized data analysis and identification of innovative ideas to increase HCT system efficiency, address future capacity requirements, and ensure adequate reimbursement for HCT programs to meet the projected need for HCT. This report highlights the deliberations and recommendations of Year 2 and the associated symposium held in September 2011.

Hematopoietic cell transplantation (HCT) is the only known curative therapy for many patients with life-threatening hematologic and oncologic diseases. It is estimated that the National Marrow Donor Program(®) (NMDP) will facilitate 10,000 transplants by 2015, double the current number. To better understand the existing personnel and center infrastructure for HCT in the country and to address system capacity challenges to the future growth of HCT, the NMDP convened a diverse group of stakeholders and thought leaders representing HCT physicians, physician assistants, nurse practitioners, nurses, pharmacists, other healthcare providers, HCT program directors, hospital administrators, payors, and professional organizations. Working groups were formed to identify: capacity issues because of shortages in human resources, structural constraints, and patient access barriers including diversity and healthcare disparity challenges; recommendations to address challenges; and stakeholders to engage. This report details the deliberations and recommendations of a national symposium, "Hematopoietic Cell Transplantation in 2020: A Health Care Resource and Infrastructure Assessment," held in September 2010.

Background: As the advent of genomic technology accelerates personalized medicine and complex care, multidisciplinary care is essential for management of breast cancer. Objectives: To assess whether healthcare delivery systems are related to patients’ perceptions of care in breast cancer treatment institutions. Methods: We conducted a cross-sectional nationwide study of breast cancer treatment institutions approved by the Japanese Breast Cancer Society in Japan. From 128 of the 457 institutions, 1,206 patients were included in the analysis. Each patient completed a questionnaire regarding perceptions of care that consisted of a multidisciplinary care subscale and a patient-centered care subscale. Results: Multiple regression analysis revealed that the multidisciplinary care subscale was significantly related to implementation of patient-based medical record system that was paper-based (p

Hemorrhagic cystitis is a common cause of morbidity after allogeneic stem cell transplantation, frequently associated with BK virus infection. We hypothesized that patients with positive BK viruria before unrelated or mismatched related donor allogeneic hematopoietic stem cell transplantation have a higher incidence of hemorrhagic cystitis.To test this hypothesis, we prospectively studied 209 patients (median age 49 years, range 19-71) with hematologic malignancies who received bone marrow (n=78), peripheral blood (n=108) or umbilical cord blood (n=23) allogeneic hematopoietic stem cell transplantation after myeloablative (n=110) or reduced intensity conditioning (n=99). Donors were unrelated (n=201) or haploidentical related (n=8).Twenty-five patients developed hemorrhagic cystitis. Pre-transplant BK viruria detected by quantitative PCR was positive in 96 patients. The one-year cumulative incidence of hemorrhagic cystitis was 16% in the PCR-positive group versus 9% in the PCR-negative group (P=0.1). The use of umbilical cord blood or a haploidentical donor was the only significant predictor of the incidence of hemorrhagic cystitis on univariate analysis. There was also a trend for a higher incidence after myeloablative conditioning. Multivariate analysis showed that patients who had a positive PCR pre-transplant and received haploidentical or cord blood grafts with myeloablative conditioning had a significantly higher risk of developing hemorrhagic cystitis (58%) than all other recipients (7%, P0.001).Hemorrhagic cystitis is the result of a complex interaction of donor type, preparative regimen intensity, and BK viruria.

Acute graft-versus-host disease (GVHD) is a major limiting factor in allogeneic hematopoietic stem cell transplantation (HSCT), and the timing of acute GVHD may affect patient outcomes. We evaluated the incidence, risk factors, clinical manifestations, and outcomes of hyperacute GVHD, defined as that occurring within 14 days after transplantation, among 809 consecutive HSCTs at the University of Texas M. D. Anderson Cancer Center. Of 265 patients with grade II-IV acute GVHD, 27% had biopsy-proven hyperacute GVHD. Skin involvement was significantly more common (88% versus 44%) and more severe (stage III-IV, 88% versus 66%) in the hyperacute group compared with acute GVHD diagnosed after day 14. On multivariate analysis, significant risk factors for hyperacute GVHD included a mismatched related or matched unrelated donor, a myeloablative conditioning regimen, more than 5 prior chemotherapy regimens, and donor-recipient sex mismatch. Hyperacute GVHD was associated with a significantly lower response rate to first-line therapy and a higher rate of nonrelapse mortality in patients with a mismatched related or matched unrelated donor graft. In conclusion, hyperacute GVHD accounts for a substantial proportion of grade II-IV acute GVHD after HSCT. Patients at high risk or with a diagnosis of hyperacute GVHD should be included in clinical studies.

Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality in haematopoietic transplant recipients. Sirolimus is a macrocyclic triene antibiotic with immunosuppressive, antifungal and antitumour properties, that has activity in the prevention and treatment of acute GVHD. We conducted a phase II trial of sirolimus combined with tacrolimus and methylprednisolone in patients with steroid-resistant cGVHD. Thirty-five patients who developed GVHD after day 100 post-transplant were studied. Six patients had a complete response and 16 a partial response with an overall response rate of 63%. Major adverse events related to the combination of tacrolimus and sirolimus were hyperlipidaemia, renal dysfunction and cytopenias. Four patients had thrombotic microangiopathy (TMA) and 27 (77%) had infectious complications. The median survival for the whole group was 15 months. A significantly better outcome was observed in patients with a platelet count > or = 100 x 10(9)/l, as well as in those with true chronic manifestations of GVHD compared to those with acute GVHD beyond day 100. Controlled trials comparing this approach with alternative strategies to determine which can best achieve the goal of GVHD-free survival are warranted.

Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44% versus 16%, P = .006), patients in first CR (28% versus 3%, P = .008), and HLA-matched sibling donors (81% versus 40%, P = .001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P = .036), and lower cumulative incidence of relapse-related mortality (P = .029). Relapse rate after FAI and FM was 61% and 30%, respectively. Actuarial 3-year survival rate was 30% after FAI and 35% following FM. In a multivariate analysis of patient- and treatment-related prognostic factors, progression-free survival was improved after FM, for patients in CR at transplantation, and for those with intermediate-risk cytogenetics. Survival was improved for patients in CR at transplantation. In conclusion, FM provided better disease control though at a cost of increased TRM and morbidity.

In this study, we evaluated the influence of nonmyeloablative and ablative conditioning regimens on the occurrence of acute and chronic graft-versus-host disease (GVHD). One hundred thirty-seven patients undergoing matched-related sibling transplantations received the same GVHD prophylaxis. Myeloablative regimens included intravenous busulfan/cyclophosphamide (n = 45) and fludarabine/melphalan (n = 29). Patients in the nonmyeloablative group (n = 63) received fludarabine/idarubicin/cytarabine, cisplatin/fludarabine/idarubicin, and fludarabine/cyclophosphamide. The actuarial rate of grade II to IV acute GVHD was significantly higher (hazard ratio, 3.6; 95% confidence interval, 1.5–8.8) in patients receiving ablative regimens (36%) compared with the nonmyeloablative group (12%). The cumulative incidence of chronic GVHD was higher in the ablative group (40%) compared with the nonmyeloablative group (14%). The rates were comparable within the first 200 days and were significantly higher in the ablative group beyond day 200 (hazard ratio, 5.2; 95% confidence interval, 1.2–23.2). Nonrelapse and GVHD-related mortality were relatively low in both groups. The use of the described nonmyeloablative preparative regimens was associated with a reduced incidence of grade II to IV acute GVHD and chronic GVHD compared with the busulfan/cyclophosphamide and fludarabine/melphalan transplant regimens. It is interesting to note that nonrelapse mortality with nonmyeloablative regimens in older and more debilitated patients was low (14%) and comparable to that achieved with standard high-dose regimens in younger patients

Introduction Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Perturbations in immune reconstitution following allo-HSCT are believed to be integral to the pathophysiology of cGVHD. We hypothesized that skewing in T cell repertoire around day 80 would be predictive of cGVHD, while maintenance of a broad repertoire would be protective. One method used to assess skewing is the Gini Index, a conventional measure of income inequality. In this prospective study, we utilized a rapid FACS based method of TCR Vβ repertoire analysis within CD4+ and CD8+ in patients at day 80-110 post allo-HSCT to determine whether preferential TCR skewing predicts the development of cGVHD. Methods Peripheral blood samples were obtained from 79 consented patients at day 80-110 following allo-HSCT at The University of Texas MD Anderson Cancer Center from October 2012 to November 2015. All patients were in remission of their disease at the time of blood sampling. Fresh PBMC were analyzed by FACS after staining for CD3, CD4, CD8 and IOTest Beta Mark 24 TCR Vβ kit. The TCR Gini Index scores (GS) were calculated for the T cell subsets, and ranged from 0 to 100. Low GS indicate more equal distribution of TCR-Vβ families (i.e. broad repertoire), whereas high GS reflect unequal distribution of TCR-Vβ families (i.e. repertoire skewing). Predictive thresholds of GS were identified in quartiles analysis and confirmed by Receiver Operating Characteristic (ROC) curve.The association between GS and the rate of cGVHD since the date of blood sampling was evaluated using competing-risks regression analysis. The diagnosis of cGVHD was based on the 2014 National Institutes of Health guidelines. Results The median age at transplant was 53 years (range 21-75) and 60% of patients were male. The most common transplant indication was AML/MDS (52%) followed by lymphoma (16%), ALL (14%), and other (18%). Graft source was peripheral blood (54%), bone marrow (43%) and umbilical cord blood (UCB) (3%) with donors being matched unrelated (65%), matched-related (24%), mismatch related (9%) and UCB (3%). Forty three (54%) patients were not in remission at the time of transplant. At the time of enrollment, 47% had history of grade II-IV acute GVHD and 44% were on systemic steroids. At a median follow up of 2 years since blood sampling, 16 patients developed cGVHD (cumulative incidence (CI) 23%; 95% Confidence Interval: 15-35). The median time from HSCT to cGVHD was 174 days (range 111-551 days). None of the clinical or demographic characteristics listed above, except history of acute GVHD, was significantly associated with the incidence of cGVHD. GS were significantly predictive of the incidence of cGVHD. The 2 year %CI of cGVHD was 47% in patients who had CD4+ TCR GS >55% (n=19) compared with 16% in those with CD4+ GS ≤55% (n=60) (hazard ratio (HR) =3.4, P=0.01). In contrast to CD4+, lower CD8+ GS predicted for higher incidence of cGVHD. The 2 year %CI of cGVHD was 39% in patients (n=34) with CD8+ GS ≤60% compared with 10% in patients (n=45) with CD8+ GS >60% (HR=4.5, P=0.009). When both CD4+ and CD8+ GS were considered in combination, the 2 year incidence of cGVHD was highest in patients (n=6) with both low CD8+ (≤60%) and high CD4+ (>55%) GS, and lowest in patients (n=32) with high CD8+ (>60%) and low CD4+ (≤55%) GS (%CI: 83% vs 4%, P=0.001). The combined effect of high CD4+ and low CD8+ TCR skewing was more pronounced in patients with a history of grade II-IV acute GVHD. Low CD8+ (≤60%, n=28) or high CD4+ (>55%, n=13) GS occurring separately were associated with comparable rates of cGVHD (%CI: 31% and 27%, p=0.8), irrespective of history of grade II-IV acute GVHD (Figure). Conclusions High CD4+ and low CD8+ TCR Gini indices were independent predictors of cGVHD. Our results indicated that the higher skewing of CD8+ TCR appeared to be protective of cGVHD and the opposite for CD4+. Our study is the first to test the usefulness of FACS-based TCR measurement and Gini Index score in a clinical setting to help predict the development of cGVHD and provide greater insights into the pathogenesis of cGVHD. Using this convenient FACS-based method to identify patients who are at risk of developing cGVHD could be beneficial from development of effective preventive or therapeutic strategies. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Introduction The hematopoietic cell transplantation comorbidity index (HCT-CMI) at the time of transplant has previously been shown to predict the development of grade 3/4 acute GVHD (aGHVD) and higher non-relapse mortality (NRM) for patients with a high CMI (≥3). It has been postulated that inflammatory cytokines associated with many of the conditions accounted for in the CMI may contribute to GVHD development, severity, and ultimately mortality. Because of concerns for corticosteroid toxicities in frail or elderly patients, some clinicians will attempt to rapidly taper steroid doses. We hypothesized that patients with a high CMI and/or advanced age (>60 yo) are treated differently with respect to systemic steroids, and this results in a higher likelihood of progression to more severe aGVHD, increases the need for second-line GVHD therapy, and increases NRM. In order to test this hypothesis, we examined steroid tapering patterns in patients who received systemic steroids for aGVHD in order to determine the influence of age and/or CMI on the rate of taper, and whether this impacted treatment outcome. Methods Patients who underwent a first allogeneic HCT at MD Anderson Cancer Center between January 2010 and 2015 were retrospectively identified in our HCT database. All patients ≥18 years old that developed aGVHD in the first 100 days and required systemic therapy were evaluated. Detailed information on GVHD therapy, steroid tapering, indication for taper, response, and outcomes were collected retrospectively from the medical records using standard criteria. Competing risks analyses were used to estimate the incidence of second line therapy and NRM, and to evaluate predictors of early (≤5 days) taper, need for second line therapy, and non-relapse mortality. Incidence of second line therapy and NRM were estimated in landmark analysis starting on the date of initial taper. Results A total of 417 patients met the eligibility criteria for this analysis (Table 1). Median age of patients was 53 (range 18-75; 28% >60 yo), median CMI was 1 (0-10). Grade of aGVHD at the initiation of therapy was ≤ 2 in 87% of patients and grade 3/4 in 13% of patients with a median time to initiation of therapy of 2 days (0-58). The time from aGVHD diagnosis to initiation of therapy, initial aGVHD grade, and median starting steroid dose, (mg/kg/day) in methylpred equivalents, were comparable in patients ≤60 yo vs >60 yo (Table 1). However CMI>3 was higher in patients >60 yo as would be expected. The median time to initial taper was 5 days (1-26). Predictors for early taper (≤ 5 days) on multivariate analysis included CMI>3 in patients older than 60 yo (HR=1.6, p=0.02) and starting steroid dose >1.5 mg/kg/day (HR=1.5, p=0.001). In the subset of patients with grade 2-4 aGVHD (N=276) who were initially tapered for response, the median steroid dose on day 14 was significantly lower in patients >60 yo with a CMI>3 (0.4 [range 0.05-1.5] vs 0.7 [range 0-9]; p= 0.02) in all other patients. In responding patients, early taper was significantly predictive for cumulative incidence of second line therapy within the first month from the time of first taper (14% vs 6%, HR=2.5, p=0.04). The highest incidence of second line therapy (29%) was in patients >60 yo with CMI>3 who were tapered within the first 5 days (HR 2.8, CI 1.03-7.5, p=0.04). Importantly, none of the patients >60 yo with CMI>3 (n=8) who were tapered after 5 days required second line therapy (n=8). In patients >60 yo with CMI>3, those who were tapered early had a 6-month NRM of 47% vs 25% in those tapered after 5 days (p= 0.1). Conclusions These results confirm earlier reports implicating the impact of a high CMI at the time of transplant on aGVHD-related mortality. Our data offers evidence that tapering practices differ according to age and CMI and that this directly impacts GVHD outcomes. Investigating alternative (steroid sparing) strategies to prevent under-treatment of aGVHD is thus essential to improving survival outcomes in these patients. Disclosures Ciurea: Spectrum Pharmaceuticals: Other: Advisory Board; Cyto-Sen Therapeutics: Equity Ownership.

Few trials exist regarding the antiemetic efficacy of granisetron in bone marrow transplant (BMT) recipients conditioned with high-dose chemotherapy and total body irradiation (TBI). In this single-center, open-label, prospective, trial, the antiemetic efficacy and safety of granisetron plus dexamethasone were evaluated in 26 patients conditioned with cyclophosphamide-containing regimens (the majority receiving 60 mg/kg per day on 2 consecutive days), and TBI (12 Gy divided over 4 days). Daily intravenous doses of granisetron 1 mg plus dexamethasone 10 mg were given 30 min prior to chemotherapy or radiation, and continued for 24 h after the last conditioning treatment for a median of 6 days (range 3-9). Emetic control was defined by the number of emetic episodes occurring within a 24 h period, or the requirement for rescue medication for nausea or vomiting. A total of 25 patients completed 186 evaluable treatment days. Response (emetic control by treatment days) was complete in 50% of patients, major in 48%, minor in 2%, and there were no failures. Adverse effects were minor, with diarrhea (15%), headache (14%), and constipation (11%) reported most often. Based on these results, the antiemetic regimen of granisetron plus dexamethasone appears effective and well tolerated during BMT conditioning with high-dose cyclophosphamide and TBI.

OBJECTIVE To assess the effectiveness of a multifaceted infection control strategy in limiting the nosocomial transmission of respiratory syncytial virus (RSV) infection to patients in a bone marrow transplant (BMT) unit. DESIGN Before/after trial. SETTING University-affiliated tertiary cancer center. PATIENTS Adult BMT recipients hospitalized during two consecutive wintertime community outbreaks of RSV infection. INTERVENTIONS An infection control strategy against nosocomial RSV infection was implemented in the BMT unit in February 1993. The strategy involved prompt identification, isolation, and cohorting of RSV-infected patients; prompt therapy with aerosolized ribavirin; use of masks and gloves by anyone entering an infected BMT patient's room; screening visitors for respiratory symptoms; restricting visitation by all children under 12 years of age and all family members and other visitors with RSV symptoms; and restricting symptomatic hospital staff from working in the BMT unit. RESULTS After implementation of the multifaceted infection-control strategy, there were four cases of nosocomial RSV infection in 3,870 patient days (incidence density, 1.0 case/1,000 patient days) compared with 14 cases of nosocomial RSV infection in 3,152 patient days (incidence density, 4.4 cases/1,000 patient days) during the 1992-1993 RSV season (rate ratio, 4.4; 95% confidence interval [CI95]. 1.4-17.9: P < .01). This decrease in incidence occurred despite a comparable prevalence of community-acquired RSV cases between the two seasons (2.2% vs 3.2% in 1992-1993 and 1993-1994, respectively; prevalence ratio, 0.7; CI95, 0.2-2.1; P = 0.5). CONCLUSION Institution of a multifaceted infection control strategy significantly reduced the frequency of nosocomial RSV infection in a high-risk group of adult BMT recipients.

Objectives To determine the minimal active dose and extent of activity of intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. Methods Twenty-four adults with grade 3 or 4 hemorrhagic cystitis were treated. All but 2 had failed other local therapy. Treatment was initiated at a median of 32 days post-transplant. Eleven patients received carboprost intravesicularly at 0.2 mg/dL for 60 minutes every 6 hours, and the dose was escalated every 24 hours until a dose of 1.0 mg/dL was reached unless a response was achieved. Thirteen additional patients were treated at an initial dose of 0.8 mg/dL, with escalation to 1.0 mg/dL after four doses in the absence of a response. Results Overall, 15 of the 24 patients responded. In the dose-escalation setting, 0.8 mg/dL was the minimal active dose. The total response rate was 62% with doses at or above 0.8 mg/dL and 18% at lower doses. All but one response occurred with 7 or fewer days of therapy, and 9 patients relapsed later. Four additional patients were salvaged following cystoscopy with clot evacuation with or without alum or formalin instillation. In all but 1 patient, bladder spasms developed during treatment with carboprost, but were not sufficiently severe to discontinue therapy. Conclusions Intravesicular carboprost at 1.0 mg/dL every 6 hours for no more than 7 days should be considered or a randomized study for treatment of refractory hemorrhagic cystitis. Cystoscopic examination and evacuation of clots prior to therapy may be required to achieve the full benefit of this treatment.

Context Symptoms and quality of life (QOL) are critically important in hematopoietic stem cell transplantation (HSCT). However, few studies have examined these factors by transplant type among diverse cultures.

Acute Graft-vs.-Host Disease (aGVHD) is the major cause of mortality and morbidity following allogeneic hematopoietic cell transplantation (AHCT). Steroids are the standard initial therapy yet only ~50-60% will achieve a response. Strategies to improve response and minimize steroid-exposure are needed. We report the results of a randomized trial of extracorporeal photopheresis (ECP) plus steroids vs. steroids- alone as initial therapy for aGVHD. Methods: This was a Phase II, randomized, adaptive Bayesian design. Patients with histologically confirmed aGVHD and who received 0.80, that arm would be declared the preferred treatment. Pts and Results: Between 2008 and 2014 eighty-one (81) pts were randomized to ECP + MP (51 pts) or MP-alone (30 pts). Median age was 54 yrs (range, 17-75); 42% had AML/MDS and 62% were male. HCT was performed with myeloablative conditioning in 69% and 63% had an unrelated donor. At enrollment, 90% of patients had aGVHD grade II, 10% had grade III/IV. Organ Involvement was: skin (86%), upper GI (22%), lower GI (22%) and liver (10%). The treatment arms were balanced for all baseline characteristics. The probability that ECP+MP had a higher success rate than MP-alone was 0.815 which exceeded the protocol-specified threshold of 80%, declaring ECP-arm the preferred treatment. The ECP-arm was more beneficial in pts with skin-only aGVHD (72% vs. 57% response rate) whereas visceral-organ involvement response rates were similar (47% vs. 43%). By day 56, 43% of the evaluable patients randomized to the ECP were on physiologic doses of steroids (≤0.1mg/kg) versus 30% for MP-alone arm (p=0.34). To study the immunologic effects of ECP, we examined the recovery of T-cell subsets by multi-parameter flow cytometry in a subset of pts randomized to the ECP+MP and MP-alone arm at enrollment and study conclusion. ECP+MP was associated with more robust recovery of CD4+ and CD8+ cells and significantly higher absolute number of regulatory T-cells (p=0.043), figure 1. Conclusions: The results of this randomized, phase II trial indicate that the addition of ECP to steroids results in higher GVHD response and facilitates steroid-tapering in pts with newly diagnosed aGVHD. This combination appears most efficacious for pts with skin-involvement. Correlative studies implicate expansion of regulatory T-cells as a possible mechanism of action through which ECP exerts its immunologic effect. Figure 1. Patient Characteristics and Outcomes Figure 1. Patient Characteristics and Outcomes Figure 2. Mean Absolute Regulatory T-cell Count in subset of patients randomized to ECP+MP (red) vs. MP-alone (green) p-value= 0.043. Figure 2. Mean Absolute Regulatory T-cell Count in subset of patients randomized to ECP+MP (red) vs. MP-alone (green) p-value= 0.043. Disclosures Alousi: Therakos, Inc: Research Funding. Off Label Use: Extracorporeal Photopheresis is FDA approved for the treatment of cutaneous lymphoma. It is commonly used in the treatment of patients with acute and chronic graft-versus-host disease. There are no FDA approved therapies for this indication and all therapies are given as an "off-label" indication..

Respiratory syncytial virus (RSV) is a common community-acquired virus that causes upper and lower respiratory tract infections in children, hematologic malignancy patients, and hematopoietic stem cell transplant (HSCT) recipients. Nosocomial transmission of RSV in immunocompromised patients can significantly affect morbidity, mortality, and duration of hospitalization. Stringent infection control measurements are needed to control further hospital transmission. Prophylactic palivizumab was found to result in a significant reduction in hospitalization rates in high-risk children. In this article, we report a nosocomial outbreak of RSV in an adult HSCT unit (4 pods) from January 16 to February 4, 2004, including the infection control interventions used and the prophylactic administration of palivizumab in high-risk patients. Active surveillance identified 5 cases, a substantial increase from previous seasons (2 or 3 cases per season). All infected patients were isolated to 1 nursing pod and placed on contact isolation. All patients on the HSCT unit underwent rapid RSV antigen screening using nasal washes; this was repeated 1 week later, and 1 additional RSV case was identified. Patients identified to be at increased risk for RSV infection received prophylactic palivizumab. Routine screenings of the staff and visitors were undertaken. All patient and visitor areas were thoroughly cleaned with bleach. We educated health care workers about RSV transmission, highlighting proper hand hygiene and contact precautions. Four of 6 patients with RSV infection developed RSV pneumonia, and 2 of these patients died. Staff and visitors with upper respiratory symptoms were screened, and all were negative for RSV. Prophylactic palivizumab was administered in 16 patients who tested negative for RSV, but were considered to be at increased risk for RSV infection. None of these patients developed RSV infections. An RSV outbreak was controlled using prompt preventive measures, including cohorting patients, with a dedicated health care staff; contact isolation of patients; strict adherence to hand hygiene; and screening of visitors, family members, and health care staff for upper respiratory infection symptoms. Immunoprophylaxis with palivizumab, administered to high-risk patients, complemented strict infection control intervention. Thus, the role of palivizumab in the control of RSV hospital outbreaks merits further investigation.

Hematopoietic stem-cell transplantation (HSCT) is associated with high rates of gonadal failure, which is distressing for younger patients desiring to start a family. The perceived importance and optimal timing of discussing fertility- and menopause-related information with women undergoing aggressive treatment such as HSCT is not well defined. Questionnaires were sent to 532 patients who underwent HSCT between January 1987 and September 2004 at the ages of 16 to 50 years. The questionnaire assessed demographic data, the need for fertility- and menopause-related information at various times during treatment, and standardized measures of anxiety, quality of life, and menopausal symptoms. The return rate was 40.2%, with 196 patients participating. Of these, 38% reported that they had discussed fertility-related issues with health-care providers since their diagnosis; 54% had discussed menopause-related issues. At the time of diagnosis, participants considered receiving information on fertility and menopause as being of equal importance. However, after HSCT, information about menopause was considered more important than information on fertility (P ≤ .0001). Being

Patients who undergo autologous peripheral blood stem cell (PBSC) transplantation experience multiple symptoms that adversely affect quality of life. We assessed symptoms during the acute phase of autologous PBSC transplantation to determine the severity of individual symptoms and to determine overall symptom profiles in 100 patients with multiple myeloma or non-Hodgkin's lymphoma. Study subjects completed the blood and marrow transplantation module of the M. D. Anderson Symptom Inventory before hospitalization, during conditioning, on day of transplantation, at nadir (the time of lowest white blood cell count) and on day 30 post-transplantation. Additional symptom, quality-of-life and medical status measures were collected. Symptom means were mild at baseline, intensified during conditioning, peaked at nadir and decreased by day 30. At nadir, the most severe symptoms for the entire patient sample were lack of appetite, fatigue, weakness, feeling sick, disturbed sleep, nausea and diarrhea. Cancer diagnosis was a significant predictor of changes in symptoms over time. The patterns of fatigue, pain, sleep disturbance and lack of appetite were significantly different for patients with multiple myeloma as compared with patients with non-Hodgkin's lymphoma.

High-dose steroids are the first line of treatment for acute graft-versus-host disease (aGVHD). Steroid myopathy is a debilitating steroid-induced complication that significantly impairs a patient's performance status. To determine the frequency and severity of steroid myopathy and other steroid related complications in patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) who developed grade >or=2 aGVHD after allogeneic hematopoietic stem cell transplantation (HSCT), we performed a retrospective analysis. Patients were included in the analysis if they had a diagnosis of AML/MDS, underwent an allogeneic HSCT between January 1996 and December 2001 and developed grade >or=2 aGVHD that was treated with 2 mg/kg of methylprednisolone and survived at least 100 days post transplant. A total of 70 patients fulfilled our inclusion criteria. Steroid myopathy was identified in 29 (41%) patients. Steroid myopathy was generally of moderate severity with severe debilitating steroid myopathy seen in only 3% of patients. We concluded that steroid myopathy is a common complication of high-dose steroid therapy after allogeneic HSCT in AML/MDS. Interventions aimed at preventing and treating this complication are warranted and need to be explored in prospective clinical trials.

Chronic graft-versus-host disease (GVHD) is a major limitation of successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photochemotherapy (ECP) has been tested extensively in small cohorts of patients with chronic GVHD. In this study, we retrospectively evaluated 71 patients with severe chronic GVHD treated with ECP. Response rate was 61% (n = 43), and 14 patients had complete responses (CRs). The best responses were observed in skin, liver, oral mucosa, and eye. Factors affecting outcomes were assessed in the less heavily pretreated subgroup (n = 63). Thrombocytopenia was associated with a lower response rate (P = .04), and there was a trend toward a higher response rate in de novo chronic GVHD. At 6 months, a total of 27 (69%) of 39 patients who were alive continued to have a sustained response (CR 4 [10%] of 39, and partial response [PR] 23 [59%] of 39). The cumulative incidence of steroid discontinuation at 1 year was 22%. The overall survival since initiation of therapy was 53% at 1 year. Response to ECP and platelet count at initiation of therapy were the strongest predictors of nonrelapse mortality (NRM) on univariate analysis. Objective responses were observed in a substantial number of patients with both skin and visceral chronic GVHD failing corticosteroids and other immunosuppression.

Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in blood and marrow transplant (BMT) recipients. In some subsets of these immunocompromised patients, RSV upper respiratory illnesses frequently progress to fatal viral pneumonia. The frequency of progression to pneumonia is higher during the pre-engraftment than during the post-engraftment period. Once pneumonia develops, the overall mortality is 60-80%, regardless of the treatment strategy. We performed a pilot trial of therapy of RSV upper respiratory illnesses using aerosolized ribavirin and IVIG (500 mg/kg every other day), with the goal of preventing progression to pneumonia and death. Two dosages of ribavirin were used: a conventional regimen (6 g/day at 20 mg/ml for 18 h/day) and a high-dose short-duration regimen (6 g/day at 60 mg/ml for 2 h every 8 h). Fourteen patients were treated for a mean of 13 days (range: 7-23 days). In 10 (71%) patients, the upper respiratory illness resolved. The other four (29%) patients, three of whom were in the pre-engraftment period, developed pneumonia, which was fatal in two. The most common adverse effect was psychological distress at being isolated within a scavenging tent. In conclusion, prompt therapy of RSV upper respiratory illnesses in BMT recipients with a combination of aerosolized ribavirin and IVIG was a safe and promising approach to prevent progression to pneumonia and death.

This is a report of six cases of Clostridium difficile-associated diarrhea (CDAD) that occurred among cancer patients undergoing bone marrow transplantation in a tertiary-care cancer hospital. Specific infection control measures that were taken to minimize the nosocomial spread of CDAD also are discussed.