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Rapid advances in the field of hematopoietic cell transplantation (HCT), as well as the advent of immune effector cell therapy (IEC), have resulted in an increasing number of patients undergoing these therapies and an increasing level of expertise required to manage them. Previous guidelines for the training of HCT physicians were last published in 2012. In recognition of the expanding knowledge base and increasing skill set essential to the delivery of these treatment modalities, the American Society for Transplantation and Cellular Therapy Committee on Education has updated these guidelines to reflect nearly a decade of new knowledge in the field of HCT, as well as the evolution of IEC from an experimental modality to a widely used and mainstream therapy. The resulting document reflects the Committee on Education's recommended educational structure for programs engaged in the training, evaluation, and mentorship of HCT/IEC trainees.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a severe and potentially life-threatening complication. HSCT-TMA is often underdiagnosed due to multifactorial pathophysiology and a historic lack of standard diagnostic criteria. Identification of the multi-hit hypothesis and the key role of the complement system, particularly the lectin pathway of complement, has led to development of treatments targeting the underlying pathogenesis of HSCT-TMA. Additional research is ongoing to investigate the efficacy and safety of these targeted therapies in patients with HSCT-TMA. Advanced practice providers (APPs; nurse practitioners and physician assistants) and pharmacists are critical members of the multidisciplinary HSCT team and ensure management of patients throughout the continuum of care. Additionally, pharmacists and APPs can improve patient care through medication management of complex regimens; transplant education for patients, staff, and trainees; evidence-based protocol and clinical guideline development; assessment and reporting of transplant-related outcomes; and quality improvement initiatives to improve outcomes. Understanding the presentation, prognosis, pathophysiology, and treatment options for HSCT-TMA can improve each of these efforts.

Key Points Shingrix is poorly immunogenic following allogeneic hematopoietic cell transplantation independent of age, CD4, and B-cell recovery. In hematopoietic cell transplantation recipients with antibody response to the vaccine, varicella zoster virus reactivation risk is not null.

Chimeric antigen receptor (CAR) T-cell therapy represents an exciting innovation in the treatment of cancer. With the approval of two revolutionary anti-CD19 CAR T-cell therapies (axicabtagene ciloleucel [Yescarta] and tisagenlecleucel [Kymriah]) for relapsed/refractory large B-cell lymphoma, health-care providers must consider how to prepare for the future of cancer care. While these therapies have been shown to provide clinical benefit to many patients, they are associated with a range of adverse events (AEs) that will need to be identified, assessed, and managed. Widespread education of health-care providers, patients, and caregivers will also be essential to ensure the success of this novel treatment. This supplement aims to provide practical information to the advanced practitioner on a number of considerations relating to the implementation and expansion of CAR T-cell therapy, including CAR T-cell biology and mechanism of action, how to identify, grade, and manage treatment-related AEs, as well as best practices for educating patients and caregivers about this type of therapy.

During JADPRO Live Virtual 2020, Maritza Alencar, DNP, MBA, APRN-BC, BMTCN, described advances in the management and prevention of infectious disease complications and graft-vs.-host disease following transplant. Dr. Alencar also emphasized the role of advanced practitioners in post-transplant care.

When South Florida became a hotspot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists and administrators, who rapidly built a multi-platform, PCR- and serology-based detection program, established drive-thru facilities and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and to multiple diagnostic laboratory companies and government officials enabled us to implement both FDA authorized and laboratory developed testing (LDT)-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers, to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity, to testing hundreds of healthcare workers and patients daily, within three weeks. We believe our experience can inform the efforts of others, when faced with a crisis situation.

When South Florida became a hot spot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists, and administrators who rapidly built a multiplatform, polymerase chain reaction- and serology-based detection program, established drive-through facilities, and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and multiple diagnostic laboratory companies, and government officials enabled us to implement both Food and Drug Administration authorized and laboratory-developed testing-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity to testing hundreds of health care workers and patients daily, within 3 weeks. We believe our experience can inform the efforts of others when faced with a crisis situation.

Formal training is an important mechanism to assist the new generation of nurse practitioners (NPs) entering the complex field of oncology. The growing number of patients with cancer and the expansion of treatment options demand structured oncology training to support the transition of novice advanced practice nurses to the field. Oncology NP fellowships are a potential solution for those seeking training centered on the management of patients with cancer. This article discusses the process of implementing an NP fellowship program at an academic cancer center, including benefits and barriers.

The use of haploidentical or HLA-mismatched unrelated donors (MMUD) allows allogeneic hematopoietic cell transplantation in individuals without suitable matched donors. Post-transplantation cyclophosphamide (PTCy) is used routinely for prevention of graft-versus-host disease in recipients of haploidentical transplants, and its use has been recently explored in MMUD transplantation. We compared the incidence of cytomegalovirus (CMV) reactivation and rate of lymphocyte recovery between PTCy MMUD and alternative transplantation modalities. Single-center retrospective study of 22 consecutive PTCy MMUD recipients transplanted between April 2017 and January 2019. Patients undergoing anti-thymocyte globulin (ATG) MMUD (n = 37) and PTCy haploidentical transplantation (n = 19) between January 2015 and July 2018 served as historical controls. We assessed the incidence of CMV (any viremia) and clinically significant CMV reactivation (cs-CMVi; defined as CMV disease or CMV viremia leading to preemptive treatment) in these 3 groups. Immune reconstitution was assessed by absolute lymphocyte count (ALC) at days 30, 90, 180, and 360 after transplantation. Statistical analyses included Kaplan-Meier plots with a log-rank test, Kruskal–Wallis test, and Fisher's exact test where appropriate, and logistic regression analyses. For PTCy MMUD, PTCy haploidentical and ATG MMUD groups, the 100-day and 200-day incidence of CMV (any viremia) were 41%, 63%, and 77% (P = .02), and 64%, 68%, and 86% (P = .049), respectively. The rate of cs-CMVi was also lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (14% versus 53% and 54% at day 100 [P = .01] and 25% versus 53% and 58% at day 200 [P = .03]). There was a trend toward lower 200-day incidence of cs-CMVi in PTCy MMUD compared to ATG MMUD, even after excluding letermovir-treated patients from the analysis (25% versus 58% [P = .06]). The association between PTCy MMUD and lower risk of cs-CMVi remained significant even after adjusting for letermovir prophylaxis (odds ratio = 0.23, 95% confidence interval, 0.07-0.81 [P = .02]). Day 30 ALC was lower in PTCy MMUD compared to PTCy haploidentical and ATG MMUD (0.14, 0.33, 0.44 × 109/L, respectively [P = .005) but similar across groups at other time points. PTCy MMUD transplantation was associated with lower incidence of CMV events, independent of the use of CMV prophylaxis. Larger studies are needed.

Background Many patients are referred to chimeric antigen receptor (CAR) T-cell therapy programs from outside their primary oncology setting and community. Collaboration between the referring and treating providers is required to coordinate safe and effective care. Objectives This article presents an overview of key considerations for referring providers and institutions prior to and following CAR T-cell therapy. Methods Definitions of the consultation and workup, leukapheresis, bridging, lymphodepleting chemotherapy, infusion and monitoring, and long-term follow-up phases are presented, along with specific considerations for referring centers. Findings Although CAR T-cell therapy is limited to select centers, the process of supporting and educating patients and their caregivers requires a partnership between referring and treating providers. As CAR T-cell indications expand, management of patients in diverse settings requires a collaborative and evidence-based approach to support safe and effective care.

Background Hematopoietic cell transplant (HCT) recipients are at high risk for Varicella zoster virus (VZV) reactivation. Shingrix, the adjuvanted recombinant zoster vaccine, is a new alternative to the live-attenuated VZV vaccine for immunocompromised individuals. Post-marketing data on its immunogenicity and safety in HCT is limited. Objectives To assess the safety and immunogenicity of Shingrix vaccine in HCT recipients. Methods Single center retrospective study of 134 consecutive adult allogenic and autologous HCT recipients who received the full series (two doses) of Shingrix vaccine. Primary study end points were safety and immunogenicity defined as either seroconversion in previously seronegative individuals or 4-fold increase from baseline VZV IgG titers in previously exposed patients. Results Among the 134 patients who completed vaccine series, 39 patients including 25 allogeneic and 14 autologous HCT recipients (Figure), had serological data available at baseline and after completion of vaccine series. The median age of patients at the time of HCT was 61 years (IQR, 53-67). The median time from HCT to first dose of Shingrix vaccine was 9 months (IQR, 7-14) for the entire cohort, but it was significantly shorter in autologous versus allogeneic HCT recipients: 7 (IQR, 6-8) vs. 12 (IQR, 9-16) months (P=0.003 by Mann Whitney test), respectively. Vaccine administration was very well tolerated, out of 134 patients only two (1.4%) had documented adverse events following Shingrix (and other vaccines co-administered), including injection site reaction after second dose and flu-like syndrome with fatigue and non-productive cough after the first dose (n=1 each). Both reactions occurred in autologous HCT recipients. The median time from the second Shingrix dose to post-vaccination VZV IgG titer assessment was 3.5 (IQR, 2-6) months. A total of 16 (41%) patients had documented humoral vaccine responses as measured by post vaccination VZV IgG levels including 8/14 (57%) autologous HCT recipients compared to 8/25 (32%) allogeneic HCT recipients (P=0.18 by Fisher's exact test). Among the 16 responders, the VZV IgG antibody concentration index increased from 179 (2.1-559) to 3,868 (2,232-4,000) (P Conclusions A 2-dose course of adjuvanted recombinant zoster vaccine was well tolerated among adult HCT recipients. Vaccine humoral responses occurred in less than half of the patients although vaccine seems to be more immunogenic following autologous HCT and among seronegative patients. Although Shingrix vaccine is currently only licensed for VZV seropositive patients, our data indicate that this recombinant vaccine may also be useful for primary VZV immunization. Larger studies are needed.

Background The use of haploidentitical or HLA mismatched unrelated donors permits allogeneic hematopoietic cell transplantation (HCT) in individuals with otherwise no donors available. Post-transplantcyclophosphamide(PTCy) is used for prevention graft-vs.-host disease (GVHD) in recipients of mismatched donors. We hypothesized that type and incidence of infectious complications following allogeneic HCT would vary according to the type of transplant. Methods We systematically assessed viral kinetics and reactivation rates for cytomegalovirus (CMV) in a prospective cohort of mismatched unrelated donor (MMUD) HCT recipients who had PTCy at our center (April 2017–March 2019). In addition, we evaluated the incidence of invasive aspergillosis (IA), invasive candidiasis (IC), bloodstream infection (BSI), pneumonia, Clostridium difficile (CDI), and community-acquired respiratory virus. Haploidentical donor and anti-thymocyte globulin (ATG) treated MMUD recipients were served as historical control groups. Results A total of 81 patients were analyzed in 3 groups (Table 1): PTCy MMUD (group 1; n = 22), ATG MMUD (group 2; n = 40) and haploidentical (group 3; n = 19). Whereas the 1 year incidence of CMV viremia was similar across groups, the rate of clinically significant (requiring preemptive therapy) CMV viremia was lower in group 1, compared with groups 2 and 3 (18 vs 53%; P = 0.02). The 1 year incidence of CDI was 47% in group 3 vs. 18% in groups 1 and 2 (P = 0.01). There was no significant difference in the incidence of IA (5–18%), pneumonia (30–42%), BSI (32–55%) and CARVs (28–53%) between groups. There were no cases of IC in this cohort. 1 year infection attributable mortality was lower in group 1 (figure), compared with groups 2 and 3, (9%, 62% and 39%, respectively; P = 0.005). Conclusion Compared with ATG MMUD and haploidentical donor, PTCy MMUD HCT was associated with lower incidence of clinically significant CMV and lower infection attributable mortality. These findings might be related to the contemporary prophylactic strategies used in this patient population. Larger studies are needed. Disclosures All authors: No reported disclosures.

Introduction Thrombocytopenia after HCT is multifactorial in etiology and frequently requires prolonged transfusions to minimize bleeding risks. Eltrombopag (TPO) is a thrombopoietin agonist that is FDA-approved for use in the setting of ITP. Given encouraging studies in aplastic anemia, TPO is increasingly used after HCT in the setting of poor engraftment and thrombocytopenia; however, published data is limited to small retrospective cases/series. We present our single institution experience. Methods We retrospectively reviewed HCT patients and identified the clinical characteristics and outcomes of those who received TPO post HCT from 1/1/13 to 10/1/18. We excluded patients with documented relapses at the time of TPO initiation. Results 17 patients were identified; 9 had primary failure of platelet recovery ( 30K without transfusion preceding 7 days). Of 7 responders, 5 were started as outpatients. Median time to response was 39 days (range 10 – 118). In 5 patients with unidentified relapse at TPO start, TPO preceded diagnosis of relapse by median 62 days (range 22-281). Of the 9 patients who started TPO as inpatient, 7 subsequently died with median time from TPO to death 195 days (range 18-398). No significant toxicities to TPO were identified. The median time from TPO outpatient prescription to start was 22 days due to insurance delays (range 8-40). Conclusion While causality is difficult to establish, TPO was associated with improvement of platelet counts in a subset of patients, with responses most likely to occur in outpatients with viral reactivation, GvHD, or primary poor engraftment. In 5 patients with unidentified relapse, start of TPO preceded a diagnosis of relapse by median 62 days. This should alert clinicians to assess for relapse when considering TPO. The start of TPO in inpatients generally reflects grave clinical outlook given low response rates and high number of subsequent deaths.

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.

Topic Significance & Study Purpose/Background/Rationale Inconsistencies on the nurses’ interpretation of neutropenic diet can lead to patients obtaining misinformation on food safety standards and foods permitted on the diet. The purpose of this quality improvement project (QIP) is to identify University of Miami Hospital and Clinic's (UMHC) nurses’ understanding of the neutropenic diet, safe food handling, and to provide cohesive education to the nurses. Methods, Intervention, & Analysis Identical, 17-question pre and post surveys were created to ascertain nurse's knowledge on foods allowed on the facility's neutropenic diet and USDA's food safety standards. The pre-survey was administered to 46 UMHC oncology nurses from inpatient stem cell transplant and hematology/oncology. Subsequent education was provided by the nurse practitioner and dieticians on both topics, followed by a post-survey. Findings & Interpretation Among the UMHC's oncology nurses the averaged overall pre-survey's score revealed that 56.3% of questions were answered correctly based on the facility's neutropenic diet and national standards of food safety, compared to the post survey's 85.2% (Figure 1). Nurses had more difficulty correctly answering which foods are allowed on neutropenic diet, general food safety and temperature control questions versus cross contamination and preparation/wash questions (Table 1). Discussion & Implications Inconsistencies of UMHC nurse's knowledge regarding foods allowed on neutropenic diets and food safety standards were identified. Providing education improved nurses’ knowledge which could decrease patient misinformation and potentially minimize patient's risk. It is important to implement routine education to nurses to decrease risk of food borne illnesses to this vulnerable population.

The optimal viral load threshold at which to initiate preemptive cytomegalovirus (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to be defined. In an effort to address this question, we conducted a retrospective study of 174 allogeneic HCT recipients who underwent transplantation at a single center between August 2012 and April 2016. During this period, preemptive therapy was initiated at the discretion of the treating clinician. A total of 109 patients (63%) developed CMV viremia. The median time to reactivation was 17 days (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia ≥150 IU/mL was strongly associated with a reduced probability of spontaneous clearance (relative risk, .16; 95% confidence interval, .1-.27), independent of established clinical risk factors, including CMV donor serostatus, exposure to antithymocyte globulin, and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV350 IU/mL (19 days; IQR, 11-35 days) compared with those who started antiviral therapy at higher viremia thresholds (33 days; IQR, 21-42 days; P = .02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started preemptive therapy at CMV350 IU/mL and those who started at CMV350 IU/mL (44% versus 57%; P = .42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32% versus 0%; P = .001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR], .26; 95% confidence interval [CI], .1-.8; P = .02), whereas therapeutic failure was associated with a significant increase in the probability of 1-year NRM (adjusted HR, 26; 95% CI, 8-87; P .0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150 IU/mL is associated with a80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive therapy. Delaying initiation of therapy until a CMV value ≥350 IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.

Topic Significance & Study Purpose/Background/Rationale Nurse practitioner (NP) graduate programs mainly focus on primary care and lack specialty training. It is important that new NPs entering the field of hematology are prepared to manage the complexity of patient care involved with the transplant and immunotherapy population. Inadequate training and mentoring can lead to poor job satisfaction, burnout, high turnover and suboptimal proactive care assessment and interventions impacting patient outcomes. Methods, Intervention, & Analysis In 2017, the Oncology NP fellowship was initiated. With the FDA approval of chimeric antigen receptor T-cell therapy came the vision to expand the fellowship to include a designated track for the transplant program. The NP fellow spends one year immersed in managing stem cell transplant and cellular therapy patients in the inpatient and outpatient setting under the guidance of a senior transplant NP and mentor. The program includes didactic and clinical experiences with a curriculum based on national guidelines and clear endpoints for successful completion (Figure 1). Findings & Interpretation It is critical to the development for NPs interested in practicing in specialty services have a standardized framework for training. This allows the NP the opportunity to gain the necessary knowledge and confidence to manage transplant and cellular patients effectively, provide quality care and become valuable members of the multidisciplinary team. Discussion & Implications The role of the transplant NP continues to evolve. It is vital to establish training programs to support the growing complexity of cancer care. Development of specialty training programs promotes a structural framework (Figure 2) and smooth integration of the new NP into transplant and cellular therapy programs.

Double-stranded DNA (dsDNA) viral infections constitute a major complication following solid organ and stem cell transplantation. Few therapeutic options are currently available for the treatment of such infections in highly immunocompromised hosts. Brincidofovir is an oral investigational drug with broad antiviral activity against dsDNA viruses in vitro, but clinical experience is limited. Here we report a young female who developed a mixed infection with adenovirus, cytomegalovirus, Epstein-Barr virus and BK polyomavirus after an allogeneic stem cell transplant, and was successfully treated with brincidofovir.

101 Background: Oncology infusion centers play a crucial role in detection of malnutrition. In one month, the Sylvester Comprehensive Cancer Center chemotherapy infusion center in Miami (SCCC CTU) treats over 400 oncology patients. Research shows that 40-80% of patients with a cancer diagnosis are malnourished (Isenring et al., 2006). In April, 1.89% of patients seen at the Miami CTU were referred to an oncology nutritionist. The goal was to increase the percentage of patients referred by 2% by June through adequate screening and referral. Methods: SCCC Miami CTU nursing staff’s knowledge on the use of the Malnutrition Screening Tool (MST) and the referral process were assessed through a survey. The survey also functioned as an educational instrument. Additionally, one-on-one discussions about the referral process were conducted with the SCCC CTU nurse practitioners. Results: The survey was available to CTU RNs with a 35% completion rate. Results portrayed that 82.35% were aware of the MST screening tool; however, 88.25% were unaware of the appropriate code to refer patients to nutritionist. Therefore, if nutritional consults were placed, it was unlikely that the nutritionist would receive the request. Identified obstacles included having to call a provider to initiate a consult, lack of time for proper assessment and the availability of a nutritionist. Conclusions: Although results did not yield a significant increase of referrals through the use of the appropriate code, there was a 1.22% increase on the overall referrals placed. Lack of training and knowledge on the MST, improper use of the referral code, and the intricacy of the workflow, were contributing factors to the inadequacy in screening and referral process. Participation of all staff in education initiatives and interventions should be a vital component in improving quality care of oncology patients. [Table: see text]