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Hematopoietic stem cell transplantation (HSCT) patients can suffer from various musculoskeletal problems resulting in long-term functional incapacity. Physical therapy (PT), as a part of the healthcare team, has been historically advocated for regaining functional capacity and improving quality of life post-HSCT. Because of the nature of this condition and the burden of post-transplant complications, this patient group requires a unique approach toward their rehabilitation that takes into account their complex musculoskeletal presentation ranging from fascia, muscle, tendons, bones, and ligaments. However, to our knowledge there is no universal standardized PT protocol or pathway to help guide rehab specialists to achieve optimal gains for this patient group, and anecdotal evidence suggests that these patients do not always receive the PT care they require. Hence, in collaboration with the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation, the Survivorship Special Interest Group of the American Society of Blood and Marrow Transplantation, and the Quality of Life Committee of the Eastern Mediterranean Blood and Marrow Transplantation, herein the Physical Therapy Association for Graft Versus Host Disease provides a brief review on role of PT in mitigating musculoskeletal complications in HSCT patients and makes evidence-based recommendations for incorporation of PT into routine HSCT care. ispartof: Biol Blood Marrow Transplant vol:25 issue:6 pages:e191-e198 ispartof: location:United States status: published

Topic Significance & Study Purpose/Background/Rationale Data managers auditing infusion forms consistently found incomplete source documentation. Incomplete source documentation places the hospital at risk during audits necessary for accreditation, and is contrary to the institution's goal of submitting quality data to optimize clinical decision making for the benefit of its patients. Methods, Intervention, & Analysis For six months, data managers used paper data collection tools to document six different types of incomplete source documentation. Colorful, high-impact charts were designed to present data on the frequency of missing documentation and incomplete documentation types by hospital unit. Hospital program leadership reviewed the charts weekly. Unit nurse managers reviewed the charts after the initial three months and identified a data collection improvement. The data managers’ supervisor contacted hospital nurse educators and offered to provide an educational in-service for floor nurses to understand the types of incomplete documentation. Then, an educational in-service was provided to one of the three hospital units. Data managers continued to collect data for an additional three months. Findings & Interpretation The project was limited in duration and data managers did not collect data long enough to measure a significant change in source documentation quality after the education in-service on the nursing unit. Senior leadership did not provide direction on what steps should be taken after the project to improve source documentation quality. Data managers expressed frustration with their inability to improve the data collection process themselves and also with the difficulty of initiating change across hospital units and management levels. Discussion & Implications Data managers created custom paper data collection tools to track incomplete source documentation over a six-month period. Not enough data existed after an educational intervention to make meaningful statistical conclusions. The lack of involvement from hospital leadership stakeholders and key nurse managers was a major limitation. Because auditing source documentation for submission to the CIBMTR was already part of data managers’ workflow, the quality project required minimal time and required few materials. Paper data collection tools could be easily replicated for use at other institutions.

s / Biol Blood Marrow Transplant 21 (2015) S114eS126 S124 Sarah Thirlwell , Kim Amtmann-Buettner . 1 BMT, Moffitt Cancer Center, Tampa, FL; 2 Professional Nursing Development, Moffitt Cancer Center, Tampa, FL; 3 Inpatient BMT, Moffitt Cancer Center, Tampa, FL; 4 Supportive Care Medicine, Moffitt Cancer Center, Tampa, FL; 5 Patient and Family Services, Moffitt Cancer Center, Tampa, FL Topic Significance & Study Purpose/Background/Rationale: BMT nurses deliver the treatments that can lead to patient and family acute and chronic suffering, and sometimes death, for the hope of cure and control of disease. In 2010, staff of our BMT Unit began demonstrating severe compassion fatigue (CF) with an increase in moral distress, nurse turnover rate, medical leave usage, conflict among staff, patients and families, and increased requests to Psychosocial Care for debriefing. Nursing Leadership, in partnership with other disciplines, recognized the need to address CF and create a plan to alleviate burnout and to increase nurses’ resiliency. Methods, Intervention, & Analysis: In 2011, the ProQOL5 survey, a valid CF assessment tool, was distributed to inpatient BMT nurses. The nurse manager then partnered with staff, Organizational Development, Social Work, Chaplaincy and Supportive Care Medicine to identify strategies to decrease CF among inpatient BMT nurses. A strategic plan was implemented to provide education about CF, to offer debriefing support, to hold skill-building sessions for resiliency and stress reduction techniques, to promote quality end-of-life care, and to improve workflow to promote selfcare. After implementation of the interventions, the ProQOL5 survey was repeated in 2013. Findings & Interpretation: Comparison of the results of the ProQOL5 surveys from 2011 to 2013 revealed improvement in the survey sub-domains of Compassion Satisfaction, Burnout, and Secondary Trauma. The result suggests that, when compared to standard compassion fatigue scores, BMT inpatient nurses experience slightly above average compassion satisfaction, low burnout as opposed to average burnout, and a low level of secondary trauma. Discussion & Implications: BMT nurses can experience severe compassion fatigue as a result of the care they deliver on a daily basis. A strategic and multimodal approach to alleviate CF can have a positive impact. Although the survey results did show improvement from 2011 to 2013, compassion fatigue is an ongoing concern for BMT nurses. Next steps include creation of a staff respite room on the BMT unit and the formation of a Code Lavender Team.

The long-term care of hematopoietic stem cell transplantation (HSCT) survivors poses special challenges owing to a myriad of possible chronic and/or late complications. Survivorship care plans (SCPs) have been proposed as tools to communicate information on the late effects of treatment and recommended follow-up care to clinicians and survivors. The primary aims of this study were to determine SCP content and format, as well as to assess the preferred timing of SCP provision following HSCT. HSCT survivors and nontransplantation clinicians (oncologists and primary care physicians) were invited to participate in a survey evaluating the usefulness and utility of a sample HSCT-specific SCP with a treatment summary generated by autopopulation from an electronic health record (EHR). All participating HSCT survivors (n = 29) and clinicians (n = 18) indicated a desire to receive an SCP. More than 85% of the participants perceived information about treatments received, recommended follow-up and health maintenance including vaccinations, survivor and clinician resources, and graft-versus-host disease and other late/chronic side effects to be useful. The majority of survivors also believed that care team contact information was useful. In addition, >85% of survivors and clinicians agreed that the SCP increased their understanding of treatments and chronic/late side effects, improved health care provided, and were satisfied with the SCP and found it understandable and easy to use. The majority of survivors indicated that additional information should be added to the SCP, whereas some clinicians deemed the SCP too long. Survivors preferred to receive the SCP as a paper document at the end of a regular follow-up visit and review it with a cancer clinician, whereas clinicians preferred to receive the SCP through the EHR. These findings will help improve the design of future SCPs for use by HSCT survivors and clinicians. Future work will include leveraging the EHR to ease the burden of creating user-centered documents.

Background Survivors of hematopoietic stem cell transplants (HSCTs) face many chronic and late complications that pose challenges to future survivorship care. The provision and review of Survivorship Care Plans (SCPs) has been proposed as a method to improve knowledge of these complications as well as screening and treatment recommendations among survivors and their non-transplant clinicians. Creating SCPs can be work intensive, however, using the electronic health record (EHR) can reduce the time and personnel resources required to generate SCPs and complement efforts to discretely capture HSCT data. Objectives Our objectives were to determine what content should be included in HSCT-focused SCPs for these diverse users as well as format and preferred timing of SCP provision. Results will be used to create HSCT-focused SCP templates generated by and integrated with an EHR. Methods Eligible HSCT survivors were ≥18 years and received a HSCT > 12 months ago. Non-transplant primary care and oncology clinicians were eligible if they provided care to HSCT patients. Those eligible were invited to complete a survey evaluating a HSCT-focused SCP with treatment summary data generated by an EHR. The usefulness of content, format and utility of the document, and timing of provision were considered especially pertinent. The survey utilized both 5-point Likert scales and open-ended questions. Results Survey response rate exceeded 80% (n=29/36 survivors; n=18/22 clinicians). Our survivor respondents were a median age of 59 (range 32-73), White (100%), mostly female (52%) and educated (52% held an associate degree or higher). Clinician respondents were predominately female (67%), White (78%) and providing primary care (56%). Over 85% of survivors and clinicians perceived information about treatments received, recommended follow-up and health maintenance including vaccinations, survivor and clinician resources, graft versus host disease and other late/chronic side effects to be useful or very useful. The majority of survivors also found care team contact information useful or very useful. Additionally, over 85% of survivors and clinicians agreed or strongly agreed that the SCP would improve follow-up care and increase their understanding of treatments and chronic/late side effects. Overall, 88% were satisfied with the SCP and found it understandable and easy to use. All respondents indicated a desire to receive SCPs. Survivors (93%) prefer to receive the SCP as a paper document at the end of a regular follow-up, and most would like to receive the SCP immediately after transplant (70%) or two to three months after transplant (67%). Clinicians (89%) would prefer to receive the SCP through the EHR. Conclusion These results will help improve future HSCT-focused SCP templates to meet the needs of these users. Future work will include leveraging the EHR for creation and provision of SCPs with ease.

The Patient Protection and Affordable Care Act requires that health care insurers cover routine patient costs associated with participating in clinical trials for cancer and other life-threatening diseases. There is a need to better define routine costs within the context of hematopoietic stem cell transplantation (HSCT) clinical trials. This white paper presents guidance on behalf of the American Society for Blood and Marrow Transplantation for defining a standard HSCT episode and delineates components that may be considered as routine patient costs versus research costs. The guidelines will assist investigators, trial sponsors, and transplantation centers in planning for clinical trials that are conducted as a part of the HSCT episode and will inform payers who provide coverage for transplantation.

Severe combined immunodeficiency (SCID) is 1 of the most common indications for pediatric hematopoietic cell transplantation (HCT) in patients with primary immunodeficiency. Historically, SCID was diagnosed in infants who presented with opportunistic infections within the first year of life. With newborn screening (NBS) for SCID in most of the United States, the majority of infants with SCID are now diagnosed and treated in the first 3.5 months of life; however, in the rest of the world, the lack of NBS means that most infants with SCID still present with infections. The average survival for SCID patients who have undergone transplantation currently is >70% at 3 years after transplantation, although this can vary significantly based on multiple factors, including age and infection status at the time of transplantation, type of donor source utilized, manipulation of graft before transplantation, graft-versus-host disease prophylaxis, type of conditioning (if any) utilized, and underlying genotype of SCID. In at least 1 study of SCID patients who received no conditioning, long-term survival was 77% at 8.7 years (range out to 26 years) after transplantation. Although a majority of patients with SCID will engraft T cells without any conditioning therapy, depending on genotype, donor source, HLA match, and presence of circulating maternal cells, a sizable percentage of these will fail to achieve full immune reconstitution. Without conditioning, T cell reconstitution typically occurs, although not always fully, whereas B cell engraftment does not, leaving some molecular types of SCID patients with intrinsically defective B cells, in most cases, dependent on regular infusions of immunoglobulin. Because of this, many centers have used conditioning with alkylating agents including busulfan or melphalan known to open marrow niches in attempts to achieve B cell reconstitution. Thus, it is imperative that we understand the potential late effects of these agents in this patient population. There are also nonimmunologic risks associated with HCT for SCID that appear to be dependent upon the genotype of the patient. In this report, we have evaluated the published data on late effects and attempted to summarize the known risks associated with conditioning and alternative donor sources. These data, while informative, are also a clear demonstration that there is still much to be learned from the SCID population in terms of their post-HCT outcomes. This paper will summarize current findings and recommend further research in areas considered high priority. Specific guidelines regarding a recommended approach to long-term follow-up, including laboratory and clinical monitoring, will be forthcoming in a subsequent paper.

There is a lack of published data on personnel time required to complete CIBMTR forms. Therefore, calculating the Full Time Employees (FTE) needed to complete Transplant Essential Data (TED) or Comprehensive Report Forms (CRF) is challenging. Reporting center supervisors are required to generate business justifications for the number of FTEs needed to meet the required data submission. Intuition or estimates are what guide FTE justification without quantified data. Barnes Jewish Hospital/Washington University School of Medicine performed a time analysis to determine actual personnel hours needed to complete forms, giving us the ability to calculate FTEs needed to meet current reporting burden and to anticipate future FTE needs. An opening meeting with Data Managers was scheduled to discuss the project and determine relevant forms to track. A paper data collection tool was created utilizing the feedback from this meeting. Time was recorded using a simple kitchen timer. Any time applied to complete the form was counted i.e. reviewing chart, completing form, and resolving any issues. No breaks or interruptions were counted. Reporting centers interpreting the data should take into account several considerations. The period of data collection was only six months. During data collection, Data Managers utilized both electronic and paper health records and had a specific transplant software to collect, integrate, and submit data through AGNIS. Other centers applying the data should make appropriate adjustments, depending on the institution's software and reporting practices. Despite the limitations, the time analysis data can provide a platform for reporting center supervisors to justify current FTEs and project future personnel requirements based on growth projections.

The American Society for Transplantation and Cellular Therapy (ASTCT) published its first white paper on indications for autologous and allogeneic hematopoietic cell transplantation (HCT) in 2015. It was identified at the time that periodic updates of indications would be required to stay abreast with state of the art and emerging indications and therapy. In recent years the field has not only seen an improvement in transplantation technology, thus widening the therapeutic scope of HCT, but additionally a whole new treatment strategy using modified immune effector cells, including chimeric antigen receptor T cells and engineered T-cell receptors, has emerged. The guidelines review committee of the ASTCT deemed it optimal to update the ASTCT recommendations for indications for HCT to include new data and to incorporate indications for immune effector cell therapy (IECT) where appropriate. The guidelines committee established a multiple stakeholder task force consisting of transplant experts, payer representatives, and a patient advocate to provide guidance on indications for HCT and IECT. This article presents the updated recommendations from the ASTCT on indications for HCT and IECT. Indications for HCT/IECT were categorized as (1) Standard of care, where indication is well defined and supported by evidence; (2) Standard of care, clinical evidence available, where large clinical trials and observational studies are not available but have been shown to be effective therapy; (3) Standard of care, rare indication, for rare diseases where demonstrated effectiveness exists but large clinical trials and observational studies are not feasible; (4) Developmental, for diseases where preclinical and/or early-phase clinical studies show HCT/IECT to be a promising treatment option; and (5) Not generally recommended, where available evidence does not support the routine use of HCT/IECT. The ASTCT will continue to periodically review these guidelines and update them as new evidence becomes available.

Topic Significance & Study Purpose/Background/Rationale Successful developments in disease control and management of early toxicity have seen outcome improvements in allogeneic bone marrow transplant (AlloBMT) resulting in increased numbers of patients transitioning to long term follow up (LTFU) care. LTFU care has traditionally been provided in quaternary centres by a dedicated LTFU team. A successful Victorian (Australia) Cancer Survivorship Program grant was utilised to pilot a shared survivorship model of care for eligible patients post AlloBMT. The Breaking Good shared survivorship care project built on the success in establishing a dedicated hospital based LTFU clinic by extending and modifying our service to be appropriate for and inclusive of primary care providers (PCP). Aim 1. To assess the feasibility & acceptability of shared survivorship care after AlloBMT in an established hospital based LTFU service. 2. To pilot a shared survivorship model for eligible patients Methods, Intervention, & Analysis 1. 250 patients and PCP pairs were surveyed to determine feasibility and acceptability of shared survivorship care. 16 patients consented to semi structured interviews that were analysed by thematic content analysis. An eligibility tool based on post allograft complexity criteria was tested and utilised to identify suitable patients for shared survivorship care. 2. 10 existing LTFU patients were identified as eligible to participate in a pilot to transition to shared survivorship care. Findings & Interpretation 1. Application of eligibility tool, patient and PCP surveys identified approximately 55% of patients suitable for & confident to receive shared survivorship care. 2. Pilot evaluation demonstrated high satisfaction with (a) quality of information provided in preparation for shared care review (b) confidence in provision of shared survivorship care by PCP (b) ongoing willingness of patient and PCP to participate in shared care Discussion & Implications This paper will discuss the feasibility & acceptability by patients and PCPs to participate in shared survivorship care. Resource development including eligibility tool, modified care plans, education video, clinical placements and rapid access portal will be described. Implementation of shared survivorship care into standard model of LTFU care will be discussed including communication & resource facilitators & barriers.

Patients who fail to adequately reconstitute the donor-derived immune system after allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk for infections and leukemia relapse. In the past, pan T-cell depleted haploidentical grafts were associated with delayed immune reconstitution (IR). Recently, the majority of patients receiving αβ T-cell/B-cell depleted haploidentical HSCT (αβhaplo-HSCT) reach a threshold of 200 CD3+ T cells/mcl by 100 days after HSCT (Bertaina A et al. Blood 2014 Jul 31;124(5):822-6). However, a proportion of patients experience a slower IR with consequent higher morbidity and mortality. Early prediction of delayed IR may permit prompt clinical intervention such as infusion of donor lymphocytes or of virus-specific cytotoxic T cells. Flow cytometry, the most widely applied approach for IR analysis, suffers from intrinsic limitations, such as high lymphocyte number requirement, degradation of samples, and insufficient standardization due to technical and operator variability. To overcome these limitations, we used a DNA methylation-based quantitative PCR that detects the epigenetic signature of different peripheral blood immune cell subsets (epigenetic quantification). This technique provides relative and absolute immune cell counts applicable to fresh, frozen, or paper-spotted dried blood. Epigenetic measurements are based on a per cell DNA copy number and provide a clear positive or negative signal rather than arbitrarily defined thresholds for "positivity" as in flow cytometry. We hypothesize that epigenetic quantification at day 15 after αβhaplo-HSCT could predict flow-based IR at day 100. Patients were consented at Lucile Packard Children's Hospital (Stanford, CA). Blood was collected between days 10-17 for epigenetic quantification and days 82-124 for flow cytometry. Bisulfite treated DNA underwent qPCR quantification of cell type-specific DNA regions of de-methylation (Baron U et al. Sci Transl Med 2018 Aug 1;10(452):eaan3508). Flow cytometry was performed using directly conjugated antibodies. Absolute cell counts were determined, plotted, and then analyzed using a linear regression model. In the first 5 αβhaplo-HSCT patients evaluated, we found a direct correlation between the epigenetic quantification at day 15 and flow cytometry at day 100 for CD4+ T cells (P=0.01), while the early epigenetic quantification of CD3+ and CD8+ T cells was not informative (Fig. 1). Preliminary data suggest that the use of epigenetic quantification early after αβhaplo-HSCT can predict the IR of CD4+ T cells at day 100 in αβhaplo-HSCT recipients. Ongoing analysis on a larger cohort of both αβhaplo-HSCT and unmanipulated HSCT recipients, will confirm if epigenetic quantification results obtained early post-HSCT can be used as a clinical biomarker of delayed IR and guide physicians in the use of post-HSCT adoptive immunotherapy.

Topic Significance & Study Purpose/Background/Rationale C. difficile is the most common organism to cause healthcare-associated infection (HAI) in the United States (Dubberke, Carling, Carrico, Donskey, Loo, McDonald, et al., 2014). C. diff infection (CDI) rates in Hematopoietic Stem Cell Transplant (HSCT) recipients are up to 9-fold higher than those in other inpatient units due to weakened immune systems, long hospitalizations and antibiotic treatments (Bruminhent, Wang, Hu, Wagner, Sunday, Hegarty, et al., 2014). The nursing team and Infection Prevention and Control (IPC) personnel on the HSCT unit noticed the cluster of HAI CDI. From January to June 2019 the unit had a total of 10 cases; 6 cases alone were in May 2019, raising concern about daily practice. Evidence-based strategies have been implemented to reduce environmental contamination and increase education of patients, visitors, and staff. This paper describes how the unit established a “ZERO Harm” comprehensive plan to reduce the number of HAI CDI by 20% in six months on a 16-bed HSCT inpatient unit. Methods, Intervention, & Analysis Established meetings with Environmental Service (EVS) and Food & Nutrition (F&N) and nursing team to discuss action plan. • Implemented double cleaning of room, adenosine triphosphate (ATP) inspection for isolation rooms. • Educated staff regarding sending stool specimens for polymerase chain reaction (PCR) testing. • Utilized disposable food trays, stethoscopes and pillows. • Implemented a “No sharing” rule for mobile equipment such as weight scales. • Validated on proper cleanliness of shared equipment such as glucometers by the fluorescent dye. • Educated clinicians in the proper practice of PPE and hand hygiene. Findings & Interpretation The HSCT unit had 13 cases of HAI CDI in 2017, 25 cases in 2018 and 10 cases from January to June 2019. The intervention started in July 2019 and HAI CDI data will be collected until December 2019 for post-intervention evaluation. Discussion & Implications Environmental cleanliness, proper precautions, and education are vital to reduce CDI. Collaboration between nurses, IPC, EVS, and F&N is essential to stop CDI transmission. Utilizing ATP testing and the fluorescent dye method helps to validate proper cleanliness of the environment. Despite reducing HAI CDI to one case in August 2019, there were opportunities identified related to equipment cleanliness and educational gap. Obtaining disposable curtains and additional weight scales is considered. The future implementation of a “clean protocol” for nursing is next step.

Background CIBMTR previously showed that centralized PRO collection from patients treated at multiple transplant centers (TC) was feasible; however, consenting by sites and the paper mode of collection were logistically challenging. CIBMTR built an electronic system (ePRO), and we report our initial experience. Methods This was a cross-sectional study of patients ≥55 years old with MDS who underwent allogeneic transplant. Additional inclusion criteria were: ≥6 months from transplant, English/Spanish speaking, an active email address. Lists of potentially eligible patients were sent to TCs to confirm eligibility and provide contact details. All further patient contact (email/phone) was then made by the CIBMTR Survey Research Group (SRG). SRG contacted patients by phone to describe the study, then obtained consent electronically. PRO measures were delivered using computerized adaptive testing (CAT). Results TCs provided contact information on 188/273 (69%) potentially eligible patients. The biggest reason for lack of confirmation of eligibility was an inability by the TC to contact the patient (Figure 1). Of the 188, SRG contacted and confirmed eligibility in 164 (87%). 90/164 (55%) enrolled, and 80 (89%) have completed PROs. A median time of 15 minutes (IQR 11.3-20.7) was required for PRO completion. 62 patients did not enroll: 28 lost to follow-up after initial contact and 34 actively declined to participate. Reasons for declining to participate included: lack of interest in research, technology issues, health reasons and study specific concerns. SRG made fewer contact attempts for those who participated (Table 1). Conclusions We show that while the ePRO system is an efficient mechanism to consent patients and collect PRO, many patients do not reach the enrollment stage. The biggest reason for this is lack of initial or subsequent contact, which was noted at every stage (both TC and SRG). It is unknown whether this is due to passive decline by the patient, or to incorrect contact details. Additionally, relying on the TC to provide contact details (engaging TCs as IRB approved-research sites) was time-consuming and inefficient. CIBMTR has moved to central IRB study approval, and begun to collect contact details proactively, achieving a truly centralized mechanism which should allow CIBMTR to establish contact with patients early in the transplant process. Maintaining engagement through the ePRO may help to address ongoing logistic challenges.

Topic Significance & Study Purpose/Background/Rationale Transplant centers that maintain membership in the Center for International Blood & Marrow Transplantation Research (CIMBTR) are required to submit clinical treatment and patient outcome data. To ensure data integrity, the CIMBTR performs audits of submitted data. The audit benchmark is to have a data reporting error rate that is less than or equal to three percent (≤3%) on Transplant Essential Data (TED) and other selected forms. Adverse consequences are instituted if repeated audit failures occur. Audits at our center in 2007, 2011, and 2015 all exceeded the CIMBTR benchmark (>3%). Corrective action plans were implemented after each audit; however, they were not fully completed or successful. Methods, Intervention, & Analysis After the third audit failure in 2015, a systemic review of the data reporting process was performed by the BMT Clinical Nurse Specialist, Research Nurse and Data Manager. Deficiencies were identified in numerous areas: inadequate staffing for data management, lack of ongoing training/development of the data manager, lack of retention of critical documents in the shadow charts, infrequent consultation with content experts, poor design of physical space for storage, and conversion from a paper-based medical records system to an electronic medical record (EMR). A comprehensive corrective action/preventive action plan (CAPA) was implemented to improve the data reporting process and decrease the error reporting rate. The following actions influenced a reduction in errors: structured shadow charts; additional data management support, expansive training of a new data manager, robust internal audit process, and re-commitment by medical staff as content experts for disease-based and GVHD reporting. Findings & Interpretation Internal audits demonstrated improvement over the next three years. A formal audit by CIMBTR in 2019 demonstrated an overall audit error rate of less than one percent ( Discussion & Implications We found the focused use of TED form instructions, extensive auditing and real time audit feedback to be beneficial. The key factor of success for improvement in the data reporting process and subsequent decreased error rate was collaborative work of multiple team members from multiple disciplines within the transplant program.

Topic Signficance & Study Purpose/Background/Rationale We initially conducted a quality review of patients treated with CAR-T therapies and noted inconsistencies in cytokine release syndrome (CRS) and neurotoxicity grading due to data located in various areas within our EMR and fragmented documentation between the EMR and paper record. Consistent documentation of CAR T-cell toxicity amongst providers is important for assesment and management of toxicities post-infusion in cellular therapy programs. EMR flowsheets facilitate tracking and communication within the healthcare team and ensuring proper clinical documentation. Method, Interventions, & Analysis Key members from the Informatics and Adult Stem Cell Transplant Program collaborated to develop a flowsheet to capture all elements to grade, identify symptoms and toxicities. To enhace clinical documentation, we created a tool that brings in several flowsheet enteries to the notes and to guide providers for accruate grading of CRS and neurotoxicity related to CAR T-cell infusions for the Epic® EMR. Findings & Interpretation These electronic tools were developed during the planning phase of the CAR T-cell program. Two flowsheets were used by nurses to document CRS (Figure 1) and neurotoxicity (Figure 2) based on practice guidelines established by program leaders. The flowsheet enteries were added to provider's daily documentation through “smart phrases” (Figure 3) that captured grading of toxicities and guided clinical decision making. Discussion and Implications Development of tools to standardize symptomology reporting and effectively capture data is imperative for CAR T-cell therapy programs. EMR tools can facilitate management and streamline data collection for reporting of toxicities. As more patients receive this novel immunotherapy, it will be important to have tools in place to assist with tracking patient outcomes. The future goal is to have grading auto-generated to enhance real time care delivery with alert based warnings for worsening CRS or neurotoxicity, and for these tools to reflect current standards of care, including revised consensus criteria for grading and reporting of CAR-T toxicities currently being developed by the ASBMT.

The 2006 National Institutes of Health (NIH) Consensus paper presented recommendations by the Ancillary Therapy and Supportive Care Working Group to support clinical research trials in chronic graft-versus-host disease (GVHD). Topics covered in that inaugural effort included the prevention and management of infections and common complications of chronic GVHD, as well as recommendations for patient education and appropriate follow-up. Given the new literature that has emerged during the past 8 years, we made further organ-specific refinements to these guidelines. Minimum frequencies are suggested for monitoring key parameters relevant to chronic GVHD during systemic immunosuppressive therapy and, thereafter, referral to existing late effects consensus guidelines is advised. Using the framework of the prior consensus, the 2014 NIH recommendations are organized by organ or other relevant systems and graded according to the strength and quality of supporting evidence.

Adequate hematopoietic stem cell (HSC) mobilization and collection is required prior to proceeding with high dose chemotherapy and autologous hematopoietic stem cell transplant. Cytokines such as G-CSF, GM-CSF, and peg-filgrastim, alone or in combination with plerixafor, and after chemotherapy have been used to mobilize HSCs. Studies have shown that the efficiency of HSC mobilization and collection may vary when different methods of mobilization are used. No studies have shown that survival is significantly affected by the method of mobilization, but some studies have suggested that cost and resource utilization may be different between different mobilization techniques. After the FDA approval of plerixafor with G-CSF to mobilize HSCs many transplant centers became concerned about the cost of HSC mobilization. A panel of experts was convened ant this paper reviews the current literature on the pharmacoeconomics of HSC mobilization. (C) 2013 American Society for Blood and Marrow Transplantation.

Adequate hematopoietic stem cell (HSC) mobilization and collection is required prior to proceeding with high dose chemotherapy and autologous hematopoietic stem cell transplant. Cytokines such as G-CSF, GM-CSF, and peg-filgrastim, alone or in combination with plerixafor, and after chemotherapy have been used to mobilize HSCs. Studies have shown that the efficiency of HSC mobilization and collection may vary when different methods of mobilization are used. No studies have shown that survival is significantly affected by the method of mobilization, but some studies have suggested that cost and resource utilization may be different between different mobilization techniques. After the FDA approval of plerixafor with G-CSF to mobilize HSCs many transplant centers became concerned about the cost of HSC mobilization. A panel of experts was convened ant this paper reviews the current literature on the pharmacoeconomics of HSC mobilization. (C) 2013 American Society for Blood and Marrow Transplantation.

Patient-reported outcomes (PROs), including symptoms and health-related quality of life (HRQOL), provide a patient-centered description of hematopoietic cell transplantation (HCT)-related toxicity. These data characterize the patient experience after HCT and may have prognostic usefulness for long-term outcomes after HCT. We conducted a study of 32 patients after HCT (10 autologous HCT recipients, 11 full-intensity conditioning allogeneic HCT recipients, and 11 reduced-intensity conditioning allogeneic HCT recipients) to determine the feasibility of weekly electronic PRO collection from HCT until day (D) +100. We used questions from the PRO version of the Common Terminology Criteria for Adverse Events to capture symptoms, and the Patient-Reported Outcomes Measurement Information System Global Health scale to measure physical and mental HRQOL. The vast majority (94%) of patients used the electronic PRO system, with only 6% opting for paper-and-pencil only. The median weekly percentage of participants who completed the surveys was 100% in all cohorts through hospital discharge, and remained 100% for the autologous HCT and reduced-intensity allogeneic HCT cohorts through D+100. Patients were satisfied with the electronic system, giving high marks for readability, comfort, and questionnaire length. Symptom severity varied by absolute level and type of symptom across the 3 cohorts, with the full-intensity allogeneic HCT cohort exhibiting the greatest median overall symptom severity, peaking at D+7. Median physical health HRQOL scores decreased with time in the 3 cohorts, and HRQOL was generally correlated with overall symptom severity. Our results demonstrate the feasibility of frequent electronic PROs in the early post-HCT period. Future studies in larger populations to explore predictive models using frequent PRO data for outcomes, including long-term HRQOL and survival, are warranted.

Informed consent is essential to ethical research and is requisite to participation in clinical research. Yet most hematopoietic cell transplantation (HCT) informed consent forms (ICFs) are written at reading levels that are above the ability of the average person in the United States (U.S.). The recent development of ICF templates by the National Cancer Institute, National Institutes of Health, and the National Heart Blood and Lung Institute have not resulted in increased patient comprehension of information. Barriers to creating Easy-to-Read ICFs that meet U.S. federal requirements and pass institutional review board (IRB) review are the result of multiple interconnected factors. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) formed an ad hoc review team to address concerns regarding the overall readability and length of ICFs used for BMT CTN trials. This paper summarizes recommendations of the review team for the development and formatting of Easy-to-Read ICFs for HCT multicenter clinical trials, the most novel of which is the use of a 2-column format. These recommendations intend to guide the ICF writing process, simplify local IRB review of the ICF, enhance patient comprehension, and improve patient satisfaction. The BMT CTN plans to evaluate the impact of the Easy-to-Read format compared with the traditional format on the informed consent process.

The purpose of this paper is to describe the outcome of patients who underwent double allogeneic hematopoietic stem cell transplantation (AHSCT) with reduced-intensity conditioning regimens (RIC). Forty-five patients who received double RIC-AHSCT between 1997 and 2006 were retrospectively studied. The predominant diagnosis was acute myeloid leukemia (AML) (n = 17). Other diagnoses were aplasic anemia (AA) (n = 5), myelodysplasic disorder (n = 5), acute lymphoblastic leukemia (ALL) (n = 4), chronic myelomonocytic leukemia (CML) (n = 3), myeloma (n = 3), non-Hodgkin lymphoma (NHL) (n = 3), chronic lymphocytic leukemia (CLL) (n = 2), Hodgkin's disease (HD) (n = 2), and chronic myelomonocytic leukemia (n = 1). Main indications for RIC-AHSCT 2 were relapse (n = 25, 56%) and early (n = 8, 18%) or late (n = 12, 26%) graft failure. Median delays to reach a neutrophil count of 0.5 × 10(9)/L and platelet counts of 50 × 10(9)/L were significantly smaller after the second AHSCT. Among 25 patients who relapsed after RIC-AHSCT 1, 14 patients (56%) presented a response improvement after RIC-AHSCT 2. In this group, 9 patients sustained a complete response and 5 patients a partial response. Moreover, among the 20 patients who had early or late graft failure following RIC-AHSCT 1, 9 (45%) finally reached an engraftment. Disease-free survival (DFS) was significantly improved after RIC-AHSCT 2. Thirteen patients (28%) died of transplant-related mortality (TRM) at a median delay of 69 days (range: 0-451) after RIC-AHSCT 2. Double RIC-AHSCT is a feasible procedure that allows a response or engraftment not observed after RIC-AHSCT 1. The main indication is relapse. However, TRM remains high.

Hematopoietic stem and progenitor cells (HSPC) for bone marrow transplantation are currently obtained directly from living voluntary donors or from cord blood units. However, a suitable donor is not always found. Because HSPC are known for their relative resistance to hypoxia, using an experimental murine model, we explored cadaveric bone marrow (BM) as their alternative source. After donor mice were sacrificed, BM was left in intact femurs at 37°C, 20°C, or 4°C under ischemic conditions, resulting in combined oxygen and metabolic substrate shortage and the accumulation of metabolic waste products. BM cells were harvested after a set time period ranging from 0 to 48 hours. To determine the impact of delayed harvesting on the transplantability of HSPC, a competitive repopulation assay using a murine Ly5.1/Ly5.2 congenic model in 2 different settings was used: after submyeloablative (6 Gy) or myeloablative (9 Gy) total-body irradiation, Ly5.2 hosts received cadaveric Ly5.1 cells or a mixture of cadaveric Ly5.1 cells and fresh Ly5.2 cells in a 1:1 ratio. Chimerism resulting from cadaveric donor cells, followed up to 6 months after transplantation, proved that the long-term repopulation ability of HSPC was fully preserved for 2 hours, 6 hours, and 12 hours at 37°C, 20°C, and 4°C of ischemia, respectively. A colony-forming unit-spleen (CFU-S) clonogenic assay revealed a higher sensitivity of proliferating hematopoietic progenitors to ischemia compared to repopulating cells (STRC and LTRC). Flow cytometry analysis of apoptosis in cadaveric BM demonstrated that the LSK (Lin(low)Sca-1(+)c-Kit(+)) subpopulation, enriched in HSPC, contained less apoptotic and dead cells than the BM as a whole. Furthermore, the number of LSK SLAM (CD150(+)CD48(-)) and LSK SP (side population) cells (fractions highly enriched in hematopoietic stem cells) decreased in parallel with BM transplantability. As well as cadaveric BM cells, we also tested the transplantability and survival of BM cells after storage in a suspension in vitro without specific hematopoietic growth factors. HSPC did not display any decrease in transplantability after 2 days of storage at 37°C or 4 days at 4°C. A higher sensitivity of progenitors to unfavorable conditions was observed again using CFU-S and granulocyte macrophage-colony forming cell (GM-CFC) assays, especially at 37°C. This paper shows that HSPC survive the cessation of circulation for a considerable time and maintain their engraftment potential. This time is significantly extended with in vitro storage compared to the cadaveric BM.

Although allogeneic hematopoietic progenitor cell transplant (HPCT) is curative therapy for many disorders, it is associated with significant morbidity and mortality, which can be related to graft-versus-host disease (GVHD) and the immunosuppressive measures required for its prevention and/or treatment. Whether the immunosuppression is pharmacologic or secondary to graft manipulation, the graft recipient is left at increased risk of the threatening opportunistic infection. Refractory viral diseases in the immunocompromised host have been treated by infusion of virus-specific lymphotyces and by unmanipulated donor lymphocyte infusion (DLI) therapy. L-leucyl-L-leucine methyl ester (LLME) is a compound that induces programmed cell death of natural killer (NK) cells, monocytes, granulocytes, most CD8(+) T cells, and a small fraction of CD4(+) T cells. We have undertaken a study of the use of LLME-treated DLI following T cell-depleted allogeneic HPCT, specifically to aid with immune reconstitution. In this ongoing clinical trial, we have demonstrated the rapid emergence of virus-specific responses following LLME DLI with minimal associated GVHD. This paper examines the pace of immune recovery and the rapid development of antiviral responses in 6 patients who developed viral infections during the time period immediately preceding or coincident with the administration of the LLME DLI.

We read with great interest the recently published article by Torlen et al., in which the authors analyzed a large population of patients with acute myeloid leukemia and myelodysplastic syndrome who underwent reducedintensity conditioning (RIC) allogeneic hematopoietic cell transplantation. The authors found that a peripheral blood progenitor cell (PBPC) CD34þ dose > 4 106 CD34þ/kg and > 6 106 CD34þ/kg was associated with lower mortality in HLA-matched sibling and unrelated donor hematopoietic cell transplantation, respectively, in the setting of RIC. The authors concluded that their data offer the opportunity to establish standards for PBPC collection [1]. However, we believe that the eligibility criteria in this paper fail to explain whether the CD34þ dose estimation was based on the actual body weight, ideal body weight (IBW), or adjusted ideal body weight (AIBW) of the patients. In this study, obese patients represented 28.4% of the overall population. An estimation based on actual weight may explain why there were more obese patients in the group of CD34þ low dose and related donor, and why body mass index did not affect mortality. There are data suggesting that IBW and/or AIBW may be a better basis for calculating

The 2nd International Conference on High Dose Chemotherapy: Innovation and Evolution was held April 9-12, 2002, in Banff, Alberta, Canada. It was the follow-up conference to the successful EBMT International Conference on High Dose Chemotherapy in Breast and Ovarian Cancer which was held in Florence, Italy, in September 2000. In the last two years, the transplantation for solid tumors has been experiencing a major shift in thinking. Only randomized prospective Phase III studies representing level I evidence will be taken into consideration in the future. Data derived from such studies will change clinical practices. It is expected that survival benefit must be identified in a magnitude that is exceeding the usual. Statistical significance will not be sufficient and major clinical impact must be identified. Due to such a shift in thinking about high dose chemotherapy for solid tumors, our subtitle ″Innovation and Evolution" was chosen to identify the new developments of the transplantation concept. At our conference, three topics were covered by the distinct international faculty. The first session dealt with high dose chemotherapy and reports on phase III trials in metastatic breast cancer, high-risk early breast cancer, and ovarian cancer from North America, Europe, Australia, and Japan. The second session dealt with immunotherapy using the cellular product (allogeneic and autologous) or monoclonal antibodies. Finally, the third session focused on targeted therapeutics which have experienced a tremendous boom over the last three years. The identification and sequencing of the human genome with its logical consequence proteonomics has allowed researchers to identify molecular pathways that are instrumental in tumorgenesis. Whether or not we can use these targets for therapy and how to deal with the novel molecules in clinical studies was the topic concluding the scientific sessions. On the following pages, please find the abstracts of papers that were presented along with the abstracts that were accepted for the poster session. I trust that the goal to identify the status of high dose chemotherapy as well as its innovation and evolution was met. We will reconvene for the 3rd International Conference on High Dose Chemotherapy in Ankara, Turkey, in September 2004. Biol Blood Marrow Transplant 2002;8(6):336-47.

s from the 2012 BMT Tandem Meetings. Poster presentation in San Diego, CA. This paper is posted at ScholarlyCommons. http://repository.upenn.edu/dental_papers/34 For more information, please contact repository@pobox.upenn.edu. Recommended Citation Vogl, D. T., Mick, R., Stoopler, E. T., Davis, L. E., Paul, T. M., Salazar, G., Raguza-Lopez, M., Porter, D. L., Luger, S. M., & Stadtmauer, E. A. (2012). Effect of Body Composition and Renal Function on the Pharmacokinetics of High-Dose Melphalan for Multiple Myeloma. Biology of Blood and Marrow Transplantation, 18 (2), S248-. http://dx.doi.org/10.1016/j.bbmt.2011.12.131 Effect of Body Composition and Renal Function on the Pharmacokinetics of High-Dose Melphalan for Multiple Myeloma Disciplines Biological Factors | Other Pharmacy and Pharmaceutical Sciences | Pharmaceutical Preparations | Surgical Procedures, Operative Comments Abstracts from the 2012 BMT Tandem Meetings. Poster presentation in San Diego, CA. Author(s) Dan T. Vogl, Rosemarie Mick, Eric T. Stoopler, Lisa E. Davis, Thomas M. Paul, German Salazar, Maria Raguza-Lopez, David L. Porter, Selina M. Luger, and Edward A. Stadtmauer This other is available at ScholarlyCommons: http://repository.upenn.edu/dental_papers/34

Survival following hematopoietic stem cell transplantation (HSCT) has improved and the number of allogeneic HSCTs performed annually in the United States is expected to reach 10,000 by 2015. The National Marrow Donor Program created the System Capacity Initiative to formulate mechanisms to care for the growing number of HSCT recipients. One proposed method to increase capacity is utilization of pharmacists to manage drug therapy via collaborative practice agreements (CPAs). Pharmacists have managed drug therapy in oncology patients with CPAs for decades; however, there are limited HSCT centers that employ this practice. Engaging in collaborative practice and billing agreements with credentialed pharmacists to manage therapeutic drug monitoring, chronic medical conditions and supportive care in HSCT recipients may be cost-effective and enable physicians to spend more time on new or more complex patients. The goal of this paper is to provide a framework for implementation of a CPA and address how it may improve HSCT program capacity.

Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, or of a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include the following: (1) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity; (2) prognostic risk to develop chronic GVHD; and (3) prediction of response to therapy. Sample collection for chronic GVHD biomarkers studies should be well documented following established quality control guidelines for sample acquisition, processing, preservation, and testing, at intervals that are both calendar and event driven. The consistent therapeutic treatment of subjects and standardized documentation needed to support biomarker studies are most likely to be provided in prospective clinical trials. To date, no chronic GVHD biomarkers have been qualified for use in clinical applications. Since our previous chronic GVHD Biomarkers Working Group report in 2005, an increasing number of chronic GVHD candidate biomarkers are available for further investigation. This paper provides a 4-part framework for biomarker investigations: identification, verification, qualification, and application with terminology based on Food and Drug Administration and European Medicines Agency guidelines.

Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are performed in the United States annually. With advances in transplantation technology and supportive care practices, HCT has become safer, and patient survival continues to improve over time. Indications for HCT continue to evolve as research refines the role for HCT in established indications and identifies emerging indications where HCT may be beneficial. The American Society for Blood and Marrow Transplantation (ASBMT) established a multiple-stakeholder task force consisting of transplant experts, payer representatives, and a patient advocate to provide guidance on "routine" indications for HCT. This white paper presents the recommendations from the task force. Indications for HCT were categorized as follows: (1) Standard of care, where indication for HCT is well defined and supported by evidence; (2) Standard of care, clinical evidence available, where large clinical trials and observational studies are not available but HCT has been shown to be effective therapy; (3) Standard of care, rare indication, for rare diseases where HCT has demonstrated effectiveness but large clinical trials and observational studies are not feasible; (4) Developmental, for diseases where preclinical and/or early phase clinical studies show HCT to be a promising treatment option; and (5) Not generally recommended, where available evidence does not support the routine use of HCT. The ASBMT will periodically review these guidelines and will update them as new evidence becomes available.

Chronic graft-versus-host disease (cGVHD) has the potential to cause significant morbidity and mortality in people who undergo allogeneic hematopoietic stem cell transplantation. Management of complications due to cGVHD can be challenging because of multiorgan involvement and variable presentation of the disease. This paper outlines the diagnosis and management of musculoskeletal, neurologic, and cardiopulmonary manifestations of cGVHD that have the potential to cause profound functional impairment and that may significantly impact quality of life and lifespan. Expert evaluation by a physical medicine and rehabilitation physician and multidisciplinary team may be beneficial in the treatment of the disease sequelae, and examples of specific rehabilitation interventions are described.

Blood and marrow transplantation (BMT) is a potentially curative therapy for a number of malignant and nonmalignant diseases. Multiple variables, including age, comorbid conditions, disease, disease stage, prior therapies, degree of donor-recipient matching, type of transplantation, and dose intensity of the preparative regimen, affect both morbidity and mortality. Despite tremendous gains in supportive care, BMT remains a high-risk medical therapy. A critically ill BMT recipient may require transfer to an intensive care unit (ICU) and the specialized medical and nursing care that can be provided, such as mechanical ventilation and vasopressor support. Mortality for BMT recipients requiring care in an ICU is high. This paper will describe the experience of the Stanford Blood and Marrow Transplant Program in developing and implementing guidelines to maximize the benefit of intensive care for critically ill BMT recipients.