Blood And Marrow Transplantation Research Articles

Virtual Teaching Modules - the Future of Blood and Marrow Transplantation (BMT) Patient Education.

Virtual Teaching Modules - the Future of Blood and Marrow Transplantation (BMT) Patient Education.

Code Heat: Integrating a New Rapid Response in a Blood and Marrow Transplant (BMT) Unit for Febrile Neutropenia Patients to Decrease Time to Antibiotic Administration

Code Heat: Integrating a New Rapid Response in a Blood and Marrow Transplant (BMT) Unit for Febrile Neutropenia Patients to Decrease Time to Antibiotic Administration

Development of a Patient Itinerary for Chimeric Antigen Receptor T Cell (CAR-T) Therapy and Blood and Marrow Transplant (BMT) Recipients and Donors

Development of a Patient Itinerary for Chimeric Antigen Receptor T Cell (CAR-T) Therapy and Blood and Marrow Transplant (BMT) Recipients and Donors

Supporting data driven translational patient-centered care using network analysis to visualize symptom distress in children with serious illness.

There are an increasing number of techniques and tools to improve the capacity for children to relay their perceptions of their symptom experience while undergoing blood and marrow transplant (BMT). Network analysis (NA) is a tool that can illustrate associations between symptoms and the distress they cause. We aimed to develop a biopsychosocial assessment clinical analytic tool to examine symptom relationships for children undergoing BMT to find actionable relationships for intervention to improve clinical outcomes including mood. This pilot study used an analytical mobile application tool to support a wide scope of 15 biopsychosocial symptom distress levels and five mood assessments. Children recorded their symptom distress and mood using the app. NA was used to explore relationships between symptom distress and mood. Four children, 11-14 years old, undergoing BMT used the app daily during hospitalization. We found a strong presence of emotional distress and its associations symptom distress and mood. Multiple symptom associations were identified including associations between the set of symptoms difficulty breathing and fever (0.557), sad and worried (0.429). Of note, pain distress had a strong capacity to bridge other symptoms and was connected directly to many symptoms. We found the significance of patient struggles with emotional and symptom distress and the importance of this relationship to other clinical outcomes. This provides valuable insights and an improved understanding of the child's symptoms. Our findings support early assessment, intervention, and improved symptom communication to enhance sense of well-being and the child's care experience.

Post-Autologous Hematopoietic Cell Transplant Care in the "Home Sweet Home" Setting: A Treatment Paradigm Shift.

Multiple myeloma (MM) is the second most common hematologic malignancy, with 34,470 estimated new cases in 2022. High-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) remains a standard treatment for MM even in the era of novel therapies. This is usually performed in hospital-based settings, either in the inpatient or outpatient units. Advanced Care at Home (ACH) represents a virtual hybrid hospital-at-home program that combines a virtual provider-staffed command center with a vendor-mediated supply chain capable of delivering high-acuity care in the comfort of the patients' own homes. In our program, we used the existing ACH platform to deliver post-HCT care for recipients of auto-HCT. Four patients (female = 2, 50%) with MM, with a median age of 60 (range, 40-74) years, were admitted to the inpatient Blood and Marrow Transplant (BMT) unit. The conditioning regimen consisted of melphalan 200 mg/m2, administered on day -2. All patients received stem cell infusion (day 0) in the inpatient setting, with a median dose of 3.64 (range, 2.92-8.22) × 106/kg CD34 cells. Patients were discharged to their homes after completing the infusion on day 0 or day +1 at the latest. Post-infusion care was provided by the ACH team in coordination with the BMT team. The median time intervals to absolute neutrophil count and platelet engraftment were 12 (range, 11-13) and 11 (range, 9-16) days, respectively. All patients were successfully discharged from the ACH program at a median of day +14 (range, day +14 to day +15). Our results highlight the feasibility of delivering post-HCT care for auto-HCT recipients in the home setting and confirm the generalizability of this approach.

MP18-14 ASSESSMENT OF THE UROLOGICAL NEEDS OF ADOLESCENTS AND YOUNG ADULTS SURVIVING CANCER AND/OR BLOOD AND MARROW TRANSPLANTATION AT A SINGLE TERTIARY CENTER

You have accessJournal of UrologyCME1 Apr 2023MP18-14 ASSESSMENT OF THE UROLOGICAL NEEDS OF ADOLESCENTS AND YOUNG ADULTS SURVIVING CANCER AND/OR BLOOD AND MARROW TRANSPLANTATION AT A SINGLE TERTIARY CENTER Kathryn Trandem, Julie Nichols, Kathryn Tomlinson, Rachel Phelan, and Jonathan S. Ellison Kathryn TrandemKathryn Trandem More articles by this author , Julie NicholsJulie Nichols More articles by this author , Kathryn TomlinsonKathryn Tomlinson More articles by this author , Rachel PhelanRachel Phelan More articles by this author , and Jonathan S. EllisonJonathan S. Ellison More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003238.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: As more children survive childhood cancer and blood and marrow transplantation (BMT), focus on genitourinary survivorship including fertility but also urinary and sexual function has become increasingly important in recent years. As children survive these treatments and enter into adulthood, quality of life questions exist with regard to fertility and genitourinary function. Because such sensitive topics may not be volunteered in routine follow-up care, we sought to standardize a process to elicit such concerns within our oncology and BMT survivorship clinic. METHODS: Surveys regarding genitourinary symptoms were co-developed by a multidisciplinary survivorship team. Surveys were administered to all adolescents and young adults (AYA, age 15+) that attend our Children’s Wisconsin Next Steps survivorship clinic yearly. These are AYA patients that have a history of treatment for childhood cancer or BMT and have completed their full respective treatment courses a minimum of 2 years prior. The fifteen survey questions asked the patients about various genitourinary symptoms that they may have experienced since their treatment, including specific questions about fertility, sexual function, and lower urinary tract symptoms (LUTS). RESULTS: A total of 142 unique responses were received between March 2021 to June 2022. The average age of respondents were 19 years old (15-33 years) and 72 self-identified as men (50%). Forty seven percent were interested in learning more about fertility now or in the near future and 28% had already met with a fertility specialist. Ten (7%) complained of new onset LUTS. Six (4%) complained of difficulty with sexual function with 50 other patients saying they haven’t been sexually active yet. Seventy two (50%) were aware of possible fertility, sexual and/or LUTS side effects of their treatments. CONCLUSIONS: While fertility remains a critical issue with high interest in the AYA survivorship group, over 10% of survivors have issues with sexual and/or urinary function and control. The majority of survivors responded they were aware of possible fertility, urinary, and/or sexual side effects from their cancer and/or BMT. In addition to fertility preservation, discussions regarding genitourinary function need to be had with all AYA survivors. Genitourinary side effects in survivors of pediatric cancer treatments and BMT remains an understudied field. These patients may benefit from directed questions regarding symptomatology to help facilitate appropriate referral and treatment. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e228 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kathryn Trandem More articles by this author Julie Nichols More articles by this author Kathryn Tomlinson More articles by this author Rachel Phelan More articles by this author Jonathan S. Ellison More articles by this author Expand All Advertisement PDF downloadLoading ...

Demographics, Motivations, and Experiences of Participants in Transplantation or Cellular Therapy Fellowships

Recent American Society for Transplantation and Cellular Therapy guidelines have sought to establish clinical and research expectations for participants in blood and marrow transplantation (BMT) and cellular therapy (CT) fellowships. However, little is known about participants in BMT/CT fellowships and the value they find from this additional training. We wanted to characterize the demographics, motivations, and experiences of recent participants in BMT/CT fellowships. We developed a 27-item online survey addressing backgrounds, application processes, training experiences, and perceived benefits among physicians who had started a clinical U.S.-based BMT/CT fellowship between 2012 to 2021. Anonymous responses were solicited through program director outreach, society website postings, targeted emails, and social media. Of 105 respondents (44% pediatric trainees), 4% were URMs and 39% were non-U.S. IMGs. The most important motivations for applying were comfort with allogeneic BMT, improved career prospects, and opportunities for research and publication. Almost all respondents (92%) attended donor selection meetings, whereas smaller proportions visited cell processing facilities (65%), HLA laboratories (57%), or good manufacturing practice facilities (22%). Most respondents reported ≥1 publication (26% reported 4+) based on research or experiences during their fellowship. Respondents reported improved post-fellowship comfort with all queried BMT/CT-related competencies. Seventy percent of respondents stated that they would recommend their fellowship highly to others; this corresponded to a Net Promoter Score of +65%, consistent with a strongly positive experience. Most respondents reported currently being in clinical practice (89% at academic centers), with a median of 70% of time currently spent caring for BMT/CT recipients. Although limited by recruitment methods and recall bias, our study demonstrated that BMT/CT fellowships are effective at increasing comfort with BMT/CT management and that most participants would highly recommend this BMT/CT training to others. Nevertheless, our study identified substantial heterogeneity in clinical responsibilities and BMT/CT-related laboratory exposure. The high representation of non-U.S. IMGs underscores the distinct role of BMT/CT fellowships for this group, whereas improved URM recruitment remains an important future direction for the field. Whether advanced fellowships will ever become required for the future BMT/CT workforce, analogous to the additional training required for solid organ transplantation in other medical and pediatric subspecialties, remains uncertain.

Management of patients with germline predisposition to haematological malignancies considered for allogeneic blood and marrow transplantation: Best practice consensus guidelines from the UK Cancer Genetics Group (UKCGG), CanGene-CanVar, NHS England Genomic Laboratory Hub (GLH) Haematological Malignancies Working Group and the British Society of Blood and Marrow Transplantation and cellular therapy (BSBMTCT).

Germline predisposition to haematological cancers is increasingly being recognised. Widespread adoption of high-throughput and whole genome sequencing is identifying large numbers of causative germline mutations. Constitutional pathogenic variants in six genes (DEAD-box helicase 41 [DDX41], ETS variant transcription factor 6 [ETV6], CCAAT enhancer binding protein alpha [CEBPA], RUNX family transcription factor 1 [RUNX1], ankyrin repeat domain containing 26 [ANKRD26] and GATA binding protein 2 [GATA2]) are particularly significant in increasing the risk of haematological cancers, with variants in some of these genes also associated with non-malignant syndromic features. Allogeneic blood and marrow transplantation (BMT) is central to management in many haematological cancers. Identification of germline variants may have implications for the patient and potential family donors. Beyond selection of an appropriate haematopoietic stem cell donor there may be sensitive issues surrounding identification and counselling of hitherto asymptomatic relatives. If BMT is needed, there is frequently a clinical urgency that demands a rapid integrated multidisciplinary approach to testing and decision making involving haematologists in collaboration with Clinical and Laboratory Geneticists. Here, we present best practice consensus guidelines arrived at following a meeting convened by the UK Cancer Genetics Group (UKCGG), the Cancer Research UK (CRUK) funded CanGene-CanVar research programme (CGCV), NHS England Genomic Laboratory Hub (GLH) Haematological Oncology Malignancies Working Group and the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT).

The Impact of Graft CD3+ T-Cell Dose on the Outcome of T-Cell Replete Human Leukocyte Antigen-Mismatched Allogeneic Hematopoietic Peripheral Blood Stem Cells Transplantation.

Data on whether the graft CD3-positive (CD3+) T-cell dose in T-cell-replete human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic peripheral blood stem cells transplantation (PBSCT) influences post-transplant outcomes are controversial. Using King Hussein Cancer Center (KHCC) Blood and Marrow Transplantation (BMT) Registry database, 52 adult subjects, receiving the first T-cell-replete HLA-mismatched allogeneic hematopoietic PBSCT for acute leukemias or myelodysplastic syndrome, were identified, from January 2017 to December 2020. The cutoff value of graft CD3+ T-cell dose was identified using the receiver operating characteristic (ROC) formula and Youden's analysis. Subjects were divided into two cohorts: cohort 1 with low CD3+ T-cell dose (n = 34) and cohort 2 with high CD3+ T-cell dose (n = 18). Correlative analyses were performed between CD3+ T-cell dose and the risk of graft-versus-host disease (GvHD), relapse, relapse-free survival (RFS), and overall survival (OS). P-values were two-sided and considered significant when P < 0.05. Subject covariates were displayed. Subject's characteristics were comparable, except for higher nucleated cells and more female donors in the high CD3+ T-cell cohort. The 100-day cumulative incidence of acute GvHD (aGvHD) was 45±7% and 3-year cumulative incidence of chronic GvHD (cGvHD) was 28±6.7%. There was no statistically significant difference between the two cohorts in aGvHD (50% vs. 39%, P = 0.4) or cGvHD (29% vs. 22%, P = 0.7). The 2-year cumulative incidence of relapse (CIR) was 67.5±16.3% for low compared with 14.3±6.8% for high CD3+ T-cell cohort (P = 0.018). Fifteen subjects relapsed and 24 have died, 13 due to disease relapse. There was an improvement in 2-year RFS (94% vs. 83%; P = 0.0022) and 2-year OS (91% vs. 89%; P = 0.025) in low CD3+ T-cell cohort compared with high CD3+ T-cell cohort. Graft CD3+ T-cell dose is the only significant risk factor for relapse (P = 002), and OS (P = 0.030) in univariate analysis which was maintained in multivariate for relapse (P = 0.003), but not for OS (P = 0.050). Our data suggest that high graft CD3+ T-cell dose is associated with lower risk of relapse, and might improve long-term survival, but has no influence on the risk of developing aGvHD or cGvHD.

102 - Incorporating Simulation Based Training in the Initial Training of New Graduate Registered Nurses in a Blood and Marrow Transplant (BMT) Unit

102 - Incorporating Simulation Based Training in the Initial Training of New Graduate Registered Nurses in a Blood and Marrow Transplant (BMT) Unit

Post-Transplant Cyclophosphamide, Abatacept and Short Course of Tacrolimus (CAST) for Graft-Versus-Host Disease Prevention Following Haploidentical Peripheral Blood Stem Cell Transplantation

Background: Haploidentical blood and marrow transplantation (BMT) substantially expands the pool of potential hematopoietic stem cell donors, including for minority groups. However, the outcomes of haploidentical transplantation remain inferior to matched unrelated donor (MUD) transplants when a standard post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GvHD) prophylaxis regimen is employed in both settings. To address this issue, we sought to develop a more effective GvHD prevention regimen in haploidentical transplantation. While abatacept (Aba) seems to decrease the incidence of acute GvHD, PTCy is particularly effective in the prevention of chronic GvHD. Therefore, we designed a regimen that combines the merits of both agents and examined whether such approach can allow early withdrawal of tacrolimus (Tac). Methods: We enrolled 46 adult patients with hematological malignancies receiving haploidentical transplantation from a relative in a prospective single center pilot phase Ib-II clinical trial. Patients received non-myeloablative, reduced-intensity or myeloablative preparative regimens followed by G-CSF mobilized peripheral blood transplants and a combination of PTCy (50mg/kg on days +3 and +4), Aba (10mg/kg on days +5, +14 and +28) and Tac at a dose adjusted based on blood level. Tac taper was initiated on day +60 and completed by day +90. After treating 30 patients, the study was amended to administer an additional dose of Aba on day +56 based on the noted timing of acute GvHD development and Aba terminal ½ life. Patients received standard supportive care by institutional practice including G-CSF and anti-microbial prophylaxis. Serologically CMV positive patients also received letermovir prophylaxis. Results: Patient characteristics are summarized in table 1. Importantly, 19 out of 46 (41.3%) patients were from racial or ethnic minorities. The data cutoff date was July 29th, 2022. Three patients were excluded from this analysis due to short follow-up. For the remaining patients, median follow-up was 8.9 months. Median time to neutrophil engraftment was 18 days (13-30). One patient died before achieving platelet (plt) engraftment and 2 patients have not yet achieved plt engraftment. For the remaining 40 patients, median time to plt engraftment was 29 days (16-52). All patients achieved full donor chimerism at the time of count recovery. Tac was successfully tapered off as planned in all but 5 patients. Cumulative incidence of acute GvHD grades II-IV, III-IV and IV with death as competing event was 12.8%, 5.1% and 0%, respectively. One-year (y) cumulative incidence of moderate to severe chronic GvHD was 17.1%. All cases of acute GvHD except 1 grade II acute GvHD were observed in the first 30 patients. Cases of chronic GvHD included 2 cases of overlap syndrome. There was no case of steroid-refractory acute GvHD or GvHD-related death. One-y cumulative incidence of relapse (non-relapse mortality as competing event) was 8.3% (95% CI 0%-17.1%). KM estimates of 1-year relapse-free survival (RFS), overall survival (OS) and GRFS (composite end point of grade III-IV acute GvHD-, chronic GvHD requiring systemic therapy- and relapse-free survival) were 91.7% (95% CI 83%-100%), 90.6% (95% CI 80.9%-100%) and 71.8% (95% CI 57.2%-90%), respectively. None of the safety stopping rules was triggered. There was 1 case of thrombotic microangiopathy due to Tac and 2 cases of sinusoidal occlusive disease, 1 requiring treatment with defibrotide; all 3 patients recovered. There were 2 cases of respiratory failure of undetermined etiology. One-y cumulative incidence of non-relapse mortality (relapse as competing event) was 2.6% (95% CI 0%-7.8%). The incidence of CMV and EBV reactivation was 39.5% and 2.3%, respectively. There was no case of adenovirus or HHV-6 virus reactivation. BK viruria occurred in 27.9% of patients with limited symptomatology (1 patient required treatment with cidofovir). Immune reconstitution results are summarized in figure 1. Conclusion: CAST is a new GvHD prevention regimen that seems safe and effective, yielding excellent outcomes. CAST also allows early discontinuation of Tac. Outcomes with longer follow-up will be presented at the meeting. If the results are confirmed, CAST might be a step forward toward closing an important health disparity gap in BMT, equalizing the outcomes of haploidentical transplantation and MUD transplants. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cellular Therapy Product Viability during Long Term Cryopreserved Storage

Introduction Cryopreservation of human cellular therapy products (CTPs) is integral for modern blood and marrow transplant (BMT) programs. However, there is limited data available regarding CTP stability during long-term storage, particularly beyond ten years. Our policy assigns a 20-year expiration to cryopreserved HPC(A) and HPC(M) products. To support the 20-year expiration period, a validation program was developed and assessed. Methods Cryopreserved samples and products stored in vapor phase liquid nitrogen tanks were tested using two sample groups. HPC(A) or HPC(M) specimens from deceased patient samples stored over 15 years were the initial group tested. A second group was added from an ongoing Prospective Stability Program (PSP). Post-thaw viability testing was performed by flow cytometry per our validated procedure based on the ISHAGE gating strategy, producing a percent viability for CD34+ cells (CD34v) and CD3+ cells (CD3v). Acceptance criteria was defined as ≥ 75% viability for both cell populations. Simple linear regression was used to predict the 75% threshold. After initial analysis, data from the PSP was included for an expanded analysis. This provided an additional 14 CD34v and 13 CD3v results, ranging in age from < 1 week (e.g., soon after cryopreservation) to 8 years; all PSP results are from cryovial specimens. Results Twenty-six collections were identified for testing, collected 15 to 31 years prior. The 25 HPC(A) specimens ranged in age from 15 to 26 years. The single HPC(M) collection was 31 years old (yo). Initially, 11 cryovials, 12 sample bags and 3 product bags from 26 different patients were tested. All but two specimens <20yo were cryovials; one product and one sample bag were also <20yo. All but three specimens >20yo were sample bags; the remainder were products. A second product from the HPC(M) collection was tested four months after the initial test for an additional HPC(M) data point. All specimens < 20yo and both HPC(M) specimens met the acceptance criteria. Of the 13 HPC(A) over 20yo, nine met the 75% CD34v acceptance criteria (range = 66 - 95%) and four met the 75% CD3v acceptance criteria (range = 42 - 80%). Notably, two HPC(A) only days over 20yo failed to meet CD3v, with results of 52% and 74%; CD34v was 79% and 90%, respectively. However, several 21-22yo met both acceptance criteria. Both HPC(M) results of the 31yo product met acceptance criteria; CD34v mean ± SD = 95% ± 0.4 and CD3v mean ± SD = 86% ± 3.9. Linear regression analysis of the initial HPC(A) dataset predicts CD34v would reach 75% after more than 30 years and CD3v would reach 75% after 21 years. Similar evaluation of the expanded dataset (which includes stability program samples up to 8 years old as well as both results from the retested HPC(A) and the HPC(M)) predicts reaching 75% CD34v at almost 48 years and CD3v at about 24 years. The accompanying CD34v and CD3v graphs show the expanded dataset and include 95% confidence interval bands for the linear regression analysis. Conclusions CD34+ cells appear to maintain viability well during cryopreserved storage. CD3+ cell viability is maintained adequately but less robustly compared to CD34+ cells and may begin to decline more dramatically after 20 years of cryopreserved storage. The linear regression analysis supports our current 20-year expiration date. We plan to expand the dataset as the PSP specimens continue to age. We are evaluating viable cell recovery to ensure viability is not artificially high due to cell loss. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Blood and Marrow Transplantation (BMT) within Four Weeks of Sars-Cov-2 Infection Is Associated with Increased Risk of Mortality: A National COVID Cohort Collaborative Study

Blood and Marrow Transplantation (BMT) within Four Weeks of Sars-Cov-2 Infection Is Associated with Increased Risk of Mortality: A National COVID Cohort Collaborative Study

The Impact of Pharmacogenomic CYP3A5 Variants on Calcineurin Inhibitor Metabolism and SLCO1B1 Variants on Methotrexate in Adult Allogeneic BMT Patients

Allogeneic blood and marrow transplant (BMT) is used to transplant a new immune system in patients with hematologic malignancies or immune-mediated disease. BMT patients require initial immune suppression to prevent graft rejection and graft versus host disease (GVHD). Tacrolimus and cyclosporine are calcineurin inhibitors (CNI) and methotrexate is an antimetabolite used to mitigate this immune response. Tacrolimus has data supporting oral dose variation based on pharmacogenomic (PGx) studies for Intermediate Metabolizers (IM) and Poor Metabolizers (PM) on studies done in kidney transplant patients. There are fewer studies on BMT patients in this field, and even less on the variability of IV to oral conversion dosing and first pass metabolism effect based on PGx profiles. Methotrexate has been shown to have PGx mutations affecting its metabolism at higher dosing used for chemotherapy, but its impact on BMT patient dosing is not well-defined. Based on our study, we found statistically significant variability in Tacrolimus concentration based on drug assay levels compared with dosing for Intravenous (IV) and oral formulation based on PGx predicted phenotypes. We further noted a profound effect on first pass metabolism when transitioning between IV and oral dosing of Tacrolimus based on PGx predicted phenotypes. The average oral dose in predicted IM phenotypes divided by the IV dose was 2.68. For the predicted PM phenotype, the average oral dose divided by the IV dose was 1.18. The p-value in a two-tailed nonparametric T-test with equal variance assessing the conversion factor from IV to oral dosing in predicted IM versus PM phenotypes was significant with a p-value of 0.002. Methotrexate metabolism did not seem to be affected by PGx mutations at the doses used for BMT GVHD prevention.

Oral Cryotherapy for Oral Mucositis in Patients Receiving Busulfan: A Retrospective/Prospective Descriptive Study.

To determine whether oral cryotherapy (OC) mitigates oral mucositis (OM) resulting from busulfan chemotherapy. Electronic health records of patients undergoing busulfan conditioning for blood and marrow transplantation were reviewed for this descriptive study. The post-OC group received OC with busulfan, but the pre-OC group did not. Demographic and disease characteristics for both groups were summarized using descriptive statistics. Wilcoxon rank-sum test was performed for continuous and ordinal measures, and chi-square tests were performed for categorical outcomes between the two groups. This study found a decrease in the severity of OM as assessed by the World Health Organization OM scale. This study also found a reduction of total parenteral nutrition and opioid pain medication use, as well as a decrease in length of stay and airway protection-related intensive care unit transfers. An increase in day 11 methotrexate administration for graft-versus-host disease prophylaxis was observed in the post-OC group. OC is a safe and easily implemented intervention that can decrease OM in patients receiving busulfan chemotherapy.

Hematopoietic Stem Cell Transplantation in Nepal: International Partnership, Implementation Steps, and Clinical Outcomes

Blood and marrow transplantation (BMT) is rarely available in many low- to middle-income countries (LMICs). In 2012, Civil Service Hospital, a government hospital in Kathmandu, partnered with the University of Illinois at Chicago to consult on the establishment of BMT in their hospital, train staff, and promote educational activities. The implementation of BMT occurred in 3 phases over 4 years and included regular onsite visits, training of personnel in Chicago, continuous remote communication, and co-organization of educational events in Kathmandu. The Nepalese government funded the construction of a state-of-the art BMT unit and stem cell laboratory inside Civil Hospital. Autologous (auto) hematopoietic stem cell transplantation (HSCT) was started in 2016, and allogeneic (allo) HSCT from matched related donors (MRDs) or haploidentical (haplo) donors was initiated in 2017. The cost of transplantation was $5200 for auto-HSCT, $10,000 for MRD HSCT, and $13,300 for haplo HSCT. The major socioeconomic determinants reported by Nepalese BMT providers were the cost of transplantation, loss of revenue of the patient and/or caregiver, and cost of transportation. All patients (n=66) received peripheral blood stem cell grafts, and all allo-HSCT recipients were given post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis. Among recipients of auto-HSCT (n=30), with a median follow-up of 1029 days (range, 130 to 1653 days), 87% were alive, and transplantation-related mortality (TRM) was 10%. Among allo-HSCT recipients (n=36), all patients engrafted, and at a median follow-up of 204 days (range, 12 to 1131 days), 75% of them were alive (MRD, 71%; haplo, 83%), with a TRM of 19%. Only 3 of 36 patients developed acute GVHD grade II-IV. The median overall survival in auto-HSCT recipients was 1610 days and was not reached in allo-HSCT recipients. The long-lasting partnership with University of Illinois at Chicago helped build capacity and allowed the Civil Service Hospital team to establish a BMT program in Nepal that has high quality standards at an affordable cost for the majority of patients.

Hand hygiene among nurses in pediatric blood and marrow transplantation setting: a best practice implementation project.

The aim of this project was to promote evidence-based best practice regarding hand hygiene among nurses in a pediatric blood and marrow transplantation (BMT) setting. Healthcare-associated infections (HAI) represent important complications of healthcare with potentially major impact on patient outcomes. Most HAI are transmitted through the hands of healthcare professionals (HCP) and therefore hand hygiene is the simplest, most effective and proven method for preventing HAI. However, the overall compliance rate of HCP with hand hygiene remains at a very low level. In this case, it is necessary to implement strategies to improve the compliance with hand hygiene of the HCP with the purpose of reducing HAI rates, mortality and costs, all the more so as it is known that patients with BMT have an increased risk of HAI. This best practice implementation project was based on the JBI methodological approach and included three phases of activity: a baseline audit, implementation of strategies and a follow-up audit. The project was conducted in the pediatric BMT setting of a large university hospital located in Bucharest, Romania, and the sample included 10 nurses and five relatives of pediatric patients from this ward. As a result of the implementation of strategies, improvements were observed across seven audit criteria, given that for two audit criteria out of a total of nine audit criteria compliance was maximum (100%) since the baseline phase. Moreover, the post implementation audit showed a complete compliance (100%) for six audit criteria. However, for the other three audit criteria the compliance in follow-up audit was high: 92, 85 and 80%, respectively. The strategies applied within this evidence implementation project were appropriate, so the project was a success. However, permanent actions are required to sustain changes in practice and improvements made.

Reducing Central Line Associated Bloodstream Infections in Allogeneic Hematopoietic Stem Cell Transplant Patients

Background: The blood and marrow transplant (BMT) unit at Cleveland Clinic had an increased rate of central line associated bloodstream infections (CLABSIs) in 2020 for allogeneic transplant admissions from an expected average of 1 per month to 4 in August of 2020. We aimed to reduce the number of CLABSIs in allogeneic BMT patients during their transplant admission to an average of 1 per month.Patientsand Methods: We formed a multidisciplinary team with nursing, advanced practice providers (APPs), infection prevention, fellows, residents, BMT staff, and Taussig quality improvement staff. We underwent training through the SolVE (Solutions for Value Enhancement) program, with biweekly meetings for training and coaching sessions to help design and support the quality improvement project.Results: We performed an initial data review of CLABSIs from January 2020 until September 2020 with a total of 13 cases identified. 53% of cases were female, 76% of patients were neutropenic, 53% of patients had mucositis, 61% of patients had diarrhea and 7% of patients had graft versus host disease. Patients had the following underlying diagnoses: myelodysplastic syndrome (4), acute myeloid leukemia (3), acute lymphoblastic leukemia (4) and diffuse large B-cell lymphoma (1). Central line data revealed that all lines were placed at Cleveland Clinic. 76% of lines were removed after identification of infection, 46% of lines had signs of infection or malfunction. Microbiologic data culture revealed that 7 cases were Pseudomonas aeruginosa, 3 Staphylococcus epidermidis, 1 vancomycin-resistant Enterococcus faecalis, 1 Streptococcus mitis and 1 Stenotrophomonas maltophilia.To build our process map we performed a Gemba walk where we observed central line use and access on the BMT unit. We conducted a root cause analysis and identified the following factors as drivers of the rise in CLABSIs: severe immunocompromised state, pre-existing infections, long duration of line present, frequent access, excessive line manipulation, and poor hand hygiene.The changes that were implemented on the unit included: retraining of all nurses on central line care, central line care being added as a topic to the annual competency review, site and tubing checks were to be performed at the time of bedside handoff at shift change, increasing Shine Audits to 40 per week from 10 on average and deep clean of nursing unit by EVS following outbreak of pseudomonas.Following the above interventions, we decided to form a CLABSI review meeting to review each CLABSI in real time and to be able to have a longitudinal comprehensive data collection of factors contributing to each case. These meetings involve nursing, infection prevention, APPs, and physicians directly involved with the patient's care. Data is stored in Redcap and includes patient factors (admission date, conditioning regimen, type of transplant, disease data), line factors (placement date, location, infection date, line removal date), microbiologic data (organism, reason for culture collection), personnel factors, maintenance/environmental factors and space for other comments. Data is presented at regular quality meetings with the section chair to develop further quality improvement projects.Initially the reduction of CLABSI rates did not reach our objective: we had 5 CLABSIs from January to February 2021. However, in the following months (March to June, 2021) we were able to reach our objective of 0-1 CLABSI's per month.ConclusionWe continue to work as a team to reduce the number of infections in the BMT unit. Next steps include continuing CLABSI review meetings, discussions with ICU to better understand indications and process of blood culture collections, discussion with infectious disease for input on other strategies for CLABSI reduction and examining central line processes in other institutions. DisclosuresSobecks: CareDX: Membership on an entity's Board of Directors or advisory committees.

Impact of Center Experience with Donor Type and Treatment Platform on Outcomes: A Secondary Analysis BMT CTN 1101

BACKGROUND: Our group recently reported on the results of Blood and Marrow Transplant (BMT) Clinical Trials Network (CTN) 1101 a randomized comparison between double umbilical cord blood (dUCB) and haploidentical bone marrow (haplo) with post-transplant cyclophosphamide (ptCy) in the nonmyeloablative setting that showed similar progression free survival (PFS) between the two treatment groups, but lower non-relapse mortality (NRM) and better of overall survival (OS) in the haplo arm. In this secondary analysis we sought to investigate if transplant center experience with haplo and or cord blood HCT had an impact on outcomes.PATIENTS AND METHODS: All patient randomized in BMT CTN 1101 were included. In order to determine the transplant center experience with either haplo or dUCB we queried the Center for International Blood and Marrow Transplant Research (CIBMTR) for number of transplants with each platform in the year prior to initiation of the study. Centers were then grouped as dUCB center (> 10 dUCB, n=117, 10 centers), Haplo center (>10 haplo and ≤10 dUCB, n=110, 2 centers), and ≤10 haplo and ≤10 dUCB HCTs (other center, n=140, 21 centers). Further analysis considered the alternative cut-off for haplo (> 5 vs ≤ 5) experience, and considered the outcomes based on the donor experience vs. others (e.g. dUCB > 10 vs. ≤ 10; haplo > 5 vs. ≤ 5).RESULTS: The effect of center experience on HCT outcomes shown in Figure, below . After adjusting for age, Karnofsky performance score and, disease risk index we found that there was no difference in outcomes between haplo and dUCB for centers that were experienced with dUCB or had limited to no experience with either dUCB or haplo. In contrast, in centers that were primarily experienced with haplo had better outcomes with this donor type, as compared to dUCB. The higher risk of treatment failure (relapse or death) and overall mortality in dUCB in haplo experienced centers was driven by significantly higher risk of relapse. We then considered the transplant experience with each of the donor types separately. In transplant centers that had performed > 10 dUCB, there were similar outcomes for recipients of both dUCB and haplo. Similarly, centers that had ≤ 5 haplo HCTs had no difference in outcomes between donor types suggesting an overlap with centers that had performed > 10 dUCB HCTs. Overall mortality was higher among dUCB recipients in centers that had performed ≤ 10 dUCB. Notably, the hazard ratio of non-relapse mortality favored haplo in all four donor experience type of transplant center, albeit not statistically significant.CONCLUSION: Except for dUCB recipients in centers with < 10 dUCB/year had worse overall mortality, primarily driven by relapse, the transplant center experience in the year prior to the initiation of BMT CTN 1101 had limited impact on the outcomes of this randomized clinical trial. [Display omitted] DisclosuresBrunstein: NANT: Research Funding; FATE: Research Funding; GamidaCell: Research Funding; BlueRock: Research Funding; AlloVir: Consultancy. Costa: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria. Cutler: Deciphera: Consultancy; Cimeio: Consultancy; Editas: Consultancy; Kadmon: Consultancy; Pfizer: Consultancy; Mallinckrodt: Consultancy; CareDx: Consultancy; Incyte: Consultancy; Omeros: Consultancy; Syndax: Consultancy; Mesoblast: Consultancy; Jazz: Consultancy. Horowitz: Sobi: Research Funding; Regeneron: Research Funding; Orca Biosystems: Research Funding; Tscan: Research Funding; Xenikos: Research Funding; Miltenyi Biotech: Research Funding; Stemcyte: Research Funding; Medac: Research Funding; Vor Biopharma: Research Funding; Kite/Gilead: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding; Kiadis: Research Funding; Seattle Genetics: Research Funding; Mesoblast: Research Funding; GlaxoSmithKline: Research Funding; Sanofi: Research Funding; Pfizer, Inc: Research Funding; Omeros: Research Funding; Magenta: Consultancy, Research Funding; Jazz Pharmaceuticals: Research Funding; Vertex: Research Funding; Genentech: Research Funding; Takeda: Research Funding; Novartis: Research Funding; Shire: Research Funding; Gamida Cell: Research Funding; Daiicho Sankyo: Research Funding; CSL Behring: Research Funding; Chimerix: Research Funding; Bristol-Myers Squibb: Research Funding; bluebird bio: Research Funding; Astellas: Research Funding; Amgen: Research Funding; Allovir: Consultancy; Actinium: Research Funding. Horwitz: Gamida Cell: Research Funding. McGuirk: Novartis: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; EcoR1 Capital: Consultancy; Pluristem Therapeutics: Research Funding; Novartis: Research Funding; Bellicum Pharmaceuticals: Research Funding; Astelllas Pharma: Research Funding; Gamida Cell: Research Funding; Fresenius Biotech: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau. Rezvani: US Department of Justice: Consultancy; Kaleido: Other: One-time scientific advisory board; Nohla Therapeutics: Other: One-time scientific advisory board; Pharmacyclics-Abbvie: Research Funding. Rybka: Spark Therapeutics: Consultancy; Merck: Consultancy. Vasu: Kiadis, Inc.: Research Funding; Boehringer Ingelheim: Other: Travel support; Seattle Genetics: Other: travel support; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees.

Symptom Correlates Using Network Analysis in Pediatric Patients Undergoing Blood and Marrow Transplant

Introduction: Youth undergoing blood and marrow transplantation (BMT) experience significant distress. The widespread and mainstream use of mHealth technologies such as smartphone applications offer a unique opportunity to collect patient-generated health data that can enhance patients' and clinicians' understanding of symptom onset, trajectories, and inter-relationships. Network analysis (NA) is a useful tool that can illuminate inter-relationships between symptoms, leading to better collective understanding of the symptom experiences of these youths. This knowledge can lead to enhanced patient-caregiver interactions/collaborations, treatment management, and potentially support improved inference around adverse clinical outcomes.Objective: To determine the feasibility of using network analysis to evaluate mHealth symptom data in patients undergoing BMT.Aim 1. Estimate the network by creating a graphic model that depicts symptom inter-relationships.Aim 2. Identify influential symptoms in the network by evaluating centrality indices and assessing the stability of edges and centrality results.Methods: Study participants undergoing BMT recorded daily symptoms via a smartphone app from preconditioning through 120 days. Patients report their symptom experience (intensity and distress on a scale of 0-10). NA was conducted on the initial patients (n=3) to evaluate inter-relationships between reported symptoms. Each symptom is represented by a circle (node), while associations (regularized partial correlations coefficients) between symptoms are depicted as lines (edges). Stronger associations among symptoms present as thicker lines in the network and a higher value in the weighted matrix table.Centrality indices identify and quantify symptoms that exert more influence in the network. These symptoms are influential in the network due to their strength (sum of absolute values of its connections with other nodes), betweenness (number of times a node lies on the shortest path between two other nodes), or closeness (the summed average distance of a node to all other nodes). Other centrality measures also exist. Centrality tests aimed to evaluate symptoms for their reported importance to the youth and association of those symptoms with other reported symptoms. The more “central” a symptom, the higher the potential to transmit effects to and from other symptoms in the network. This can make them important foci for intervention. Stability testing was used to assess the network's accuracy.Results/Discussion: Descriptive statistics are summarized in Table 1. The estimated network (Fig. 1) provided details on the eight most often reported symptoms; nausea, tired (intensity and distress), vomiting, pain, mouth pain, and sore throat (intensity). The network shows strong mutual associations (regularized partial correlations) between the intensity and distress of nausea (.596) and being tired (.722). There was also a strong relationship between mouth pain and sore throat (.791). A less strong relationship was noted between nausea intensity and tired intensity (.145), and tired intensity and pain intensity (.187). A slight negative relationship was noted between vomiting intensity and pain intensity (-.086).The centrality indices (Fig. 2) revealed vomiting intensity (-1.917) as the strongest symptom with the highest closeness (-1.715). The symptom with the highest betweenness centrality was equal for both nausea intensity and tired intensity at 1.286. To assess confidence in the network estimation we replicated this test 1000 times (non-parametric bootstrapping, n=1000) on the edge stability and centrality results (Fig. 3). Results indicate areas with wide confidence intervals (instability) especially in the edge between vomiting intensity and mouth pain.Conclusion: It is feasible to use mHealth data from youth who experience symptom distress during BMT. However, efforts to obtain more data is necessary if we hope to make accurate inferences from the data. Future work will focus on enriching data collection, examining clinically important sign and symptom patterns and interrelationships, and to explore feasibility of using mHealth data for individualized/precision care and possible predictive uses. [Display omitted] DisclosuresShah: Novartis: Research Funding, Speakers Bureau; GBT: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy; Guidepoint Global: Consultancy; Alexion: Speakers Bureau; Bluebird Bio: Consultancy; Emmaus: Consultancy; GLG: Consultancy.