Bone Marrow Transplant Patients Research Articles

Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial

Although severe haemoglobinopathies can be cured with allogeneic blood or bone marrow transplantation, availability of matched donors and toxic effects can be problematic. We previously found that non-myeloablative haploidentical related bone marrow transplantation with post-transplantation cyclophosphamide expanded the donor pool while limiting graft-versus-host disease (GVHD). However, graft failure-albeit with full host haemopoietic recovery-occurred in 50% of patients. In this study, we investigated whether increasing total body irradiation from 200 cGy to 400 cGy would improve engraftment while maintaining the safety profile. This study was done at Johns Hopkins Hospital (Baltimore, MD, USA). Patients aged 2-70 years receiving their first bone marrow transplant were eligible for inclusion in the study. Patients received rabbit-derived intravenous anti-thymocyte globulin 0·5 mg/kg on day -9 and 2 mg/kg on days -8 and -7, intravenous fludarabine 30 mg/m2 on days -6 to -2, intravenous cyclophosphamide 14·5 mg/kg on days -6 and -5, and total body irradiation 400 cGy administered as a single fraction on day -1. We collected unmanipulated bone marrow and infused on day 0. GVHD prophylaxis comprised intravenous cyclophosphamide 50 mg/kg per day on days 3 and 4 after transplantation, oral mycophenolate mofetil 15 mg/kg per dose (maximum 1 g) every 8 h on days 5 to 35, and oral sirolimus to maintain a level of 5-15 ng/dL for at least 1 year starting on day 5. The original planned primary objectives of this phase 2 clinical trial were transplant-related mortality and progression-free survival. However, the coverage decision by the Centers for Medicare and Medicaid Services to only provide payment for allogeneic bone marrow transplantation for patients with sickle cell disease on a clinical trial that had a comparison arm with patients not receiving bone marrow transplantation prompted the closure of this trial to accrual in 2017. Therefore, as we were unable to perform our planned statistical analysis, the primary objective was modified to evaluate engraftment, assessed by chimerism. This trial is registered with ClinicalTrials.gov, number NCT00489281. The study is closed to new participants and this is the primary analysis. Between Sept 24, 2014, and Aug 1, 2017, we enrolled 17 consecutive patients: 12 (71%) with sickle cell disease and 5 (29%) with β-thalassaemia major. The median patient age was 16 years (range 6-31, IQR 7·7-27·5). One (6%) of 17 patients had primary graft failure with recovery of host haemopoiesis. 13 (76%) of 17 patients achieved full donor chimerism and three (18%) had mixed donor-host chimerism. Five (29%) of 17 patients developed grade 2-4 acute GVHD, including four (24%) with maximal grade 2 GVHD and one (6%) with grade 3 GVHD. Chronic GVHD developed in three (18%) patients. As of their last follow-up visit, GVHD had resolved in all patients and no patients were receiving systemic GVHD therapy. All patients remained alive as of Aug 4, 2019, and the median follow-up duration was 705 days (range 355-1294; IQR 398-943). Only one (6%) of the 16 engrafted patients remained transfusion dependent, and 14 (88%) discontinued immunosuppression. Increasing total body irradiation to 400 cGy substantially reduced graft failure while maintaining the safety of haploidentical bone marrow transplantation with post-transplantation cyclophosphamide. These results suggest that engraftment after haploidentical bone marrow transplantation for haemoglobinopathies is possible, and primary graft failure-the main problem previously reported-might be addressed by this strategy. Therefore, this curative approach should no longer be restricted to patients with HLA-matched donors. Maryland Stem Cell Research Fund and US National Institutes of Health.

Investigating the mechanisms of BK polyomavirus egress and virus-host interactions

BK polyomavirus (BKPyV) is a small, non-enveloped dsDNA virus that can establish a lifelong, silently persistent infection in the kidney and is estimated to infect 70–90 % of the world’s population. In immunocompromised individuals, particularly bone marrow and kidney transplant patients, increases in BKPyV replication can result in significant pathological conditions. In the case of kidney transplant patients, this can result in nephropathy, which in severe cases can result in the deterioration of allograft function and loss of the transplanted organ. There are currently no antiviral treatments with strong evidence of clinical efficacy against BKPyV. Though little is known about BKPyV egress from infected cells, we have evidence showing that BKPyV can be released in a non-lytic manner by an unconventional cellular secretory pathway that bypasses the Golgi apparatus. Here, we investigate the mechanisms behind BKPyV non-lytic egress through studying the effects of knocking out candidate host proteins involved in unconventional secretory pathways on BKPyV release, examining the effects of BKPyV infection on host cell protein secretion, and ascertaining which host proteins are essential for the BKPyV life cycle via a whole-genome CRISPR screen. These experiments are uncovering novel virus-host interactions that, when targeted, could lead to antiviral effects.

Cardiac Complications in the Adult Bone Marrow Transplant Patient.

Due to advancements in oncologic treatment strategies and techniques, the number of survivors who have undergone hematopoetic stem cell transplant (HCT) continues to increase in the United States; this number is projected to reach 502,000 by the year 2030. There is significant interest within the field of cardio-oncology to identify cardiotoxicity and cardiovascular disease in the HCT population. Epidemiologic studies analyzing both short- and long-term cardiovascular effects, risk stratification modeling, cardioprotective strategies, and expert consensus documents for cardiotoxicity surveillance recommendations are reviewed. Patients who have undergone HCT are at increased risk of cardiovascular events and mortality compared to matched controls. The type of cardiotoxicity and the incidence rates vary based on specific therapeutic regimens and pre-existing cardiovascular risk factors. Life-threatening cardiotoxicity can present during HCT as acute heart failure, arrhythmias, pericardial tamponade, or cardiac arrest; or it can present late after treatment as cardiomyopathy, ischemic heart disease, vascular disease, stroke, or comorbid conditions, such as hypertension and diabetes mellitus that are associated with cardiac events. HCT is associated with excess cardiovascular risk partially due to exposure to cardiotoxic chemotherapy and radiation, as well as indirect and direct detrimental effects on cardiovascular reserve. This review discusses the epidemiology and the known cardiotoxic effects of historical chemoradiation agents in addition to newer targeted therapies. Recent expert consensus statements from cardiology and hematology/oncology societies are reviewed in regard to risk stratification of the cancer patient based on the type of treatments. Finally, gaps in knowledge are identified with proposed avenues of research that will allow for more accurate risk assessment, prediction, and potential treatment of the HCT patient in attenuating the risk of developing both short- and long-term cardiovascular comorbidities.

Human cord blood-derived viral pathogens as the potential threats to the hematopoietic stem cell transplantation safety: A mini review.

Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) and potential alternative for bone marrow transplantation for patients who lack human leukocyte antigen (HLA)-matched donors. The main practical advantages of UCB over other HSC sources are the immediate availability, lower incidence of graft-versus-host disease, minimal risk to the donor, and lower requirement for HLA compatibility. However, the use of UCB is limited by delayed engraftment and poor immune reconstitution, leading to a high rate of infection-related mortality. Therefore, severe infectious complications, especially due to viral pathogens remain the leading cause of morbidity and mortality during the post-UCB transplantation (UCBT) period. In this context, careful screening and excluding the viral-contaminated UCB units might be an effective policy to reduce the rate of UCBT-related infection and mortality. Taken together, complete prevention of the transmission of donor-derived viral pathogens in stem cell transplantation is not possible. However, having the knowledge of the transmission route and prevalence of viruses will improve the safety of transplantation. To the best of our knowledge, there are few studies that focused on the risk of virus transmission through the UCB transplant compared to other HSC sources. This review summarizes the general aspects concerning the prevalence, characteristics, and risk factors of viral infections with a focus on the impact of viral pathogens on cord blood transplantation safety.

Evaluation of Cardiac Parameters in Bone Marrow Transplant Patients: Effect of Pulmonary Artery Pressure on Survival

Objective:Hematopoietic stem cell transplantation (HSCT) is a choice of treatment for malignant and non-malignant diseases. After HSCT, some complications may develop in patients. Cardiac complications are particularly important. The aim of this study was to investigate whether systolic pulmonary artery pressure (PAP) is a marker for overall survival (OS) in HSCT patients.Materials and Methods:In our study, 428 HSCT patients were evaluated. Ejection fraction (EF) and PAP values were investigated during symptom-oriented echocardiography in the pre-HSCT and post-HSCT periods.Results:Pre-HSCT EF values were similar between the groups. In patients with autologous HSCT (auto-HSCT) (PAP >25 mmHg), it was found that the 5-year mortality rate was 48.6%, while in the other group (PAP <25 mmHg) the 5-year mortality was 25.5%. There was a significant association between 5-year mortality rate and PAP level (p<0.046) in the auto-HSCT group. OS was 38% in the pre-auto-HSCT period with PAP values of >25 mmHg, while OS was 61% in the pre-auto-HSCT period with PAP values of <25 mmHg (p<0.001). We determined that there was a statistically significant difference between OS and PAP levels in patients with auto-HSCT. Five-year mortality rate and OS were not significantly different in patients undergoing allogeneic HSCT (allo-HSCT) (p>0.05).Conclusion:Our results suggest that pre-HSCT PAP value is an important risk factor for mortality and OS in patients undergoing auto-HSCT.

BK-virus and pathophysiology of associated diseases

BK virus (BKV) is a widely distributed polyomavirus in the world population. It is the causative agent of BKV-associated nephropathy in kidney transplant recipients and hemorrhagic cystitis in bone marrow transplant patients. To date, there is no specific antiviral treatment against BKV. A better understanding of the pathophysiology of BKV-associated diseases, especially in immunocompromised patients, may contribute to the development of novel preventive and therapeutic strategies. After a detailed description of the genomic characteristics of the virus, its replication cycle and available model systems, the pathophysiological and immune mechanisms involved in BKV infection are developed and discussed in this review.

Pharmacokinetic-Pharmacodynamic Analyses of Dose Selection for Rezafungin Prophylaxis Against Invasive Fungal Infections in Bone Marrow Transplantation

Background Rezafungin (RZF) is a novel echinocandin in development for prevention of invasive fungal infections caused by Candida, Aspergillus, and Pneumocystis spp. in patients at high risk of infection. RZF has demonstrated in vivo prophylaxis efficacy and low risk of drug-drug interactions. Furthermore, the stability and PK profile of RZF allow for once-weekly dosing. RZF is also in development for treatment of candidemia and invasive candidiasis using a dosing regimen of RZF 400 mg followed by 200 mg once-weekly, which achieved >90% target attainment against Candida. While lower doses might be useful to prevent Candida and Pneumocystis, invasive aspergillosis is a different challenge. We evaluated RZF dosing for prophylaxis against Aspergillus fumigatus in bone marrow transplant (BMT) patients using PK/PD simulations of the treatment dosing regimen. Methods A previous population PK model was refined using data from Phase 1 and Phase 2 trials of IV RZF (NONMEM Vers 7.2). Stepwise forward selection (α = 0.01) and backward elimination (α = 0.001) were used to assess for relationships between interindividual PK variability and covariates, such as age, sex, BSA), albumin, liver and renal function markers, and infection status. The final model was validated by comparing model-based predictions to observed data. The model and demographic data from BMT recipients at Stanford Medical Center (Table 1) were used for Monte Carlo simulation (n=2,000) of expected RZF concentration-time profiles in BMT patients receiving IV RZF 400 mg on Week 1 followed by 200 mg weekly x 11. Free-drug concentration-time profiles were evaluated (97.4% human protein-binding) relative to the A. fumigatus minimal effective concentration required to inhibit 100% of isolates tested (MEC100; JMI 2014-2017 SENTRY international surveillance data). Results The population PK model was a linear, 4-compartment model with zero order IV input. Albumin was a statistically significant predictor of interindividual variability. Non-significant relationships were found with sex, BSA, presence of cirrhosis, and infection status. The model provided precise, unbiased fits to the observed data (r2=0.993 observed vs individual-predicted). RZF plasma free-drug concentrations at weeks 1, 2, and 12 were above the A. fumigatus MEC100 (0.03 mg/L) for the entire dosing interval in 98.4%, 93.3%, and 91.9% of simulated patients, respectively, and in ≥99.9% for all 12 weeks based on the MEC90 (0.015 mg/L). Conclusions These data modeled from BMT patients support the RZF dosing regimen of 400 mg IV followed by 200 mg once-weekly for prophylaxis against A. fumigatus. Current antifungal prophylaxis may be limited by toxicity, DDIs, or patient factors such as mucositis. The PK of RZF and its spectrum, safety, tolerability, and lack of DDIs may address challenges in IFI prophylaxis for BMT and other immunocompromised patients.

A Pilot Study Using EMR (Electronic Medical Record) and BMT (Bone Marrow Transplant) Registry Data to Evaluate Health Service Utilization in BMT Patients with Depression and Comorbid Conditions at an Academic Cancer Center

Introduction and Objectives Depression has been shown to increase health service utilization in cancer patients. Using data from EMR and BMT Registry we evaluated the impact of depression and comorbidity in BMT patients at our center. Methods A retrospective review of EMR of autologous (AUTO) and allogeneic (ALLO) stem cell transplant patients in UCSD Moores Cancer Center from 2012 to 2017. All diagnoses were defined by ICD-9/ICD-10 codes. Between group differences were assessed by t-test and chi-square test. Negative binomial modeling was performed to evaluate predictors of length of stay in the hospital (LOS) and clinic visits. The analyses were adjusted for age, gender, cancer diagnosis, comorbid conditions, GVHD status (for ALLO patients only) and Charlson Comorbidity Index (CCI). Results A total of 731 patients of whom 22.3% had depression were identified: AUTO Patients (N = 472; 18% Depressed [85]); ALLO patients (N = 259; 30.1% depressed [78]). For the entire population, we compared depressed patients (n = 540) to non-depressed patients (n = 158). Significant differences were observed for LOS (days), clinic visits, and CCI: 59.58+/-49.48 vs. 40.28 (p For AUTO patients, the corresponding LOS, clinic visit, and CCI were 35.31+/-26.14 vs. 25.40+/-22.89 days (p = 0.002), 16.3+/-11.87 vs. 10.77+/-7.29 (p For AUTO patients, depression and infection were significant predictors for increased LOS and frequent clinic visits. For ALLO patients, significant predictors for increased LOS includes COPD and chronic GVHD which was a significant predictor for frequent clinic visits (Table 1). Conclusion Depression and comorbidities had a significant impact on health service utilization. Clinicians and health systems should recognize the importance of providing care in BMT patients with depression and managing comorbid conditions.

Bridging the GAP: How to Maintain Continuity of Care for Our BMT Patients While Maintaining a High Quality of Life for Our Nurses

Topic Significance & Study Purpose/Background/Rationale At our academic comprehensive cancer center (CCC) we perform approximately 450 bone marrow transplants (BMT) a year. Much of the care for BMT patients is delivered in the ambulatory clinic with few hospitalizations. It is imperative to have specialized BMT nurses to manage these high acuity patients with multiple comorbidities. The clinical care mandates triaging phone calls, performing critical assessments, medication management, monitoring lab values, and assessments of psychosocial and spiritual needs. Patients are assigned a team upon arrival, comprised of an attending physician, an advanced practice provider, and the nurse. The nurse remains constant throughout the trajectory of BMT acting as the primary contact for the patient. Work life balance is crucial for BMT nurses who are caring for patients often undergoing their last line of therapy and requiring immense clinical and psych-social support. It is imperative for our team nurses to have flexible schedules and the ability to take time off to recuperate and rejuvenate. Methods, Intervention, & Analysis Our patients spend 1-4 months on the BMT team. To facilitate BMT nurses’ quality of life without sacrificing the continuity of care of our patients, we have developed a role for a “float” or “vacation relief” nurse for sick, or vacation coverage. Findings & Interpretation These “vacation relief” nurses are full time nurses specialized and experienced in transplant. The intense training and orientation undergone by “vacation relief” nurses is months in duration with Team nurses fulfilling the role of preceptors. Along with this training, we have weekly team meetings between team nurses and the vacation relief nurses to address challenges and care issues. This communication ensures that our BMT patients are safely cared for and experience the best possible outcomes. Discussion & Implications The “vacation relief” role is one that maintains continuity of care of our patients. It also provides flexibility in schedules and appropriate time off work, without compromising our patients’ safety. The results of this role have been an increase in retention of our nurses, thus, creating a team of exceptionally experienced and expert BMT nurses, ultimately, promoting the highest quality of care for BMT patients.

Enhancement of Early Recognition in the Deteriorating Pediatric Bone Marrow Transplant Patient By Incorporating Blood Pressure As a Clinical Indicator

Topic Significance & Study Purpose/Background/Rationale Hematopoietic stem cell transplantation provides a curative alternative for malignant and non-malignant diagnoses, and Texas Children's Hospital's (TCH) Pediatric Bone Marrow Transplant (BMT) unit performs over 100 of these curative alternative transplants annually. Patients frequently experience clinical deterioration that results in increased morbidity and/or mortality. The purpose of this quality improvement project is to determine if the integration of blood pressure into the Pediatric Advanced Warning Score (PAWS) assessment would be an earlier predictor of initial clinical deterioration with patients in the conditioning, aplastic, engraftment and post discharge phases of treatment. Methods, Intervention, & Analysis TCH implemented the (PAWS) scoring system in 2009 as a validated and reliable scoring tool. The PAWS scoring system uses three categories of clinical indicators: behavior, cardiovascular status and respiratory status (Bell et al, 2013). BMT added blood pressure as a fourth clinical indicator for the PAWS assessment, validated the new scoring system through staff education and scoring patient scenarios and implemented in August 2018. When the early recognition algorithm triggered a score of four, the charge nurse, bedside nurse, attending physician and fellow completed a huddle to debrief on the current phase of treatment and abnormal clinical indicators to formulate a treatment plan based on the phase of transplant. Findings & Interpretation From October 2017 to July 2018, 70% (n=33) of BMT patients who required a Rapid Response Team (RRT) call were transferred to the Pediatric Intensive Care Unit (PICU). After project implementation, only 57% (n=14) of patients who required an RRT call were transferred to the PICU. Adding the blood pressure to the PAWS score decreased the initial recognition time to an average of 45 hours (range 17-62). Discussion & Implications The revised PAWS scoring tool and early recognition algorithm has demonstrated increased sensitivity to the identification of initial clinical deterioration, promoting better outcomes and decreased morbidity and mortality for our patients. We are continuing to monitor the BMT PAWS tool and patient outcomes.

The Mindfulness Pilot Project: The Effects of a Body Scan Activity on Bone Marrow Transplant Patients

Topic Significance & Study Purpose/Background/Rationale Patients with hematological malignancies, particularly those with acute diagnoses requiring immediate treatment and hospitalization, often experience high levels of distress. Mindfulness has been shown to alleviate symptoms of distress in cancer patients, but there is limited research on the effects of mindfulness on distress in this inpatient population. The purpose of this pilot study is to determine the effects of a mindfulness intervention on symptoms of distress during inpatient hospitalizations for patients with hematological malignancies (HM). Methods, Intervention, & Analysis A convenience sample of 30 patients with HM admitted to an oncology floor in a large, Midwestern hospital participated in this study. Participants completed the Rotterdam Symptom Checklist (RSCL): 30 physiological and psychological symptoms of distress, rating how much the symptoms bothered them during the past week on a Likert-type scale. Patients completed a 20-minute mindfulness activity including breathwork and the Body Scan in their rooms. Participants were given a summary sheet and practice log. The RSCL was again completed at two weeks. Patients were asked open-ended questions regarding their experience. Findings & Interpretation A Wilcoxon Signed Rank Test revealed a statistically significant reduction in physiological and psychological distress at the two-week follow-up, z=4.12, p Discussion & Implications Patients expressed the desire for their care to include mindfulness interventions. This intervention is low-risk and low-cost and might be extended to include recorded mindfulness exercises or informal classes. Future studies might explore the use of different media such as audio recordings or phone apps for inpatient self-practice. After initial education of the Body Scan, nurses might encourage patients to utilize it while waiting for as-needed medications to be administered, before or during inpatient procedures, or in conjunction with medication to alleviate side effects of treatment. Doing so could empower patients during the course of their hospitalization, improving the patient experience.

Rezafungin Prophylactic Efficacy in a Mouse Model of Pneumocystis Pneumonia

Background The risk of Pneumocystis pneumonia often warrants antifungal prophylaxis for bone marrow and solid organ transplantation patients. However, complications such as myelosuppression, nephrotoxicity, and intolerance with the existing standard, TMP/SMX, may hinder or interrupt prophylaxis. Rezafungin (RZF) is a novel echinocandin in development for prevention of invasive fungal infections caused by Candida, Aspergillus, and Pneumocystis species in patients at high risk of infection. RZF has a favorable safety and tolerability profile and a low risk of drug-drug interactions. Furthermore, the stability and pharmacokinetics of RZF allow for once-weekly dosing and broad distribution to the lung and other target organs. RZF was shown to prevent in vitro Pneumocystis biofilm formation and to reduce the viability of mature biofilms. A previous prophylactic study was conducted using a broader range of RZF doses. In the current study, the efficacy of RZF was evaluated to better understand the minimum doses necessary to prevent Pneumocystis growth in a mouse model. Methods C3H/HeN mice were immunosuppressed (dexamethasone 4 mg/L in acidified drinking water) and then infected intranasally with P. murina (2 × 106/50 µL). Given the slow growth of P. murina, test agents were administered at the same time mice were inoculated to test for prophylactic efficacy. Mice received intraperitoneal injections of either vehicle (control/steroid [C/S]), TMP/SMX 50/250 mg/kg/3x/week (wk), caspofungin 5 mg/kg once daily, or RZF 5 mg/kg or 0.5 mg/kg once daily, 1x, or 2x/wk. After a 6-week dosing period, mice were sacrificed and lung homogenates were processed for analysis to quantify the nuclei (trophic) and asci (cyst) forms of Pneumocystis. Prophylaxis efficacy was based on reduction of organism burden compared with C/S. Nuclei and asci counts were log transformed and analyzed by ANOVA; individual groups were compared by the Student-Newman-Keuls t test. Survival rates were compared using GraphPad Prism v5. Results All mice in the RZF groups had significantly reduced nuclei and asci burdens compared with the C/S group, and all but the lowest doses of RZF (0.5 mg/kg 1x or 2x/wk) worked as well as TMP/SMX at reducing nuclei levels (Fig 1). Similarly, all RZF groups except for the 0.5 mg/kg 1x/wk group showed reductions in asci levels comparable to that of TMP/SMX (Fig 1). The survival rates were not statistically different between treatment groups. Conclusions RZF demonstrated potent in vivo efficacy as prophylaxis against Pneumocystis in an in vivo mouse infection model at dose regimens much lower than the human equivalent Ph3 regimen. These data support the development of RZF for the prevention of invasive fungal infections including Pneumocystis pneumonia.

Changes in the Stool Virome and Fungome of Children Undergoing Bone Marrow Transplant

Background Bacterial dysbiosis is associated with acute graft versus host disease (GVHD) and blood stream infections (BSI) after bone marrow transplant (BMT). Intestinal viral and fungal changes after BMT are unknown in children. Methods Metagenomic shotgun paired reads sequencing was performed for 56 patients who underwent a BMT at Cincinnati Children's Hospital Medical Center. Stool samples were collected pre BMT and at least one post BMT time point (range day+1-day+35). Metagenomics data were analyzed using DIAMOND / MEGAN6 CE and NCBI RefSeq database. Results Demographics are shown in Figure 1. A total of 180 stool samples were analyzed. Twelve of 56 patients had stool samples analyzed at 2 time points (pre BMT and post BMT) while 44 patients had stool analyzed at > 2 time points with one being a pre BMT sample. All patients were on fungal and viral prophylaxis. Fungome Fungi were detected in 19 of 56 patients' stool samples (Fig 2A). The most frequent fungi isolated from stool were Candida sp. Nine of 56 patients had evidence of clinical fungal infection after BMT (Candida N=7, Malassezia N=1, Rhizopus N=1). One patient with clinical Candida infection had Candida detected from stool pre BMT but the remaining patients did not have a fungal infection similar to the fungi isolated from stool. BSI occurred in 7/19 in patients with fungi isolated from stool compared to 11/37 in patients without fungi in stool. GI GVHD occurred in 7/16 (43%) in allogeneic BMT patients with fungi in stool compared to 5/35 (14%) patients without fungi isolated in stool. likely reflecting antibiotic exposure and resultant dysbiosis. Virome Viruses were identified in 31 of 56 patients' stool samples (Fig 2B). Caudalovirales (bacteriophages) were the most frequent organisms seen in stool (n=20). Interestingly Caudalovirales in stool were detected in 18 patients who were on human milk as their nutritional source. Mastadenovirus sp. (adenovirus in clinical practice) was observed in 5 patients. Mastadenoviruses in stool were seen with ATG (n=1) or alemtuzumab (n=4) exposure. Ten of 56 patients had clinical adenoviral reactivation. Four of the 10 patients with clinical adenoviral reactivation had adenovirus isolated in the stool prior to onset of clinical viremia (pre BMT n=1; day+1 n=2; day+13 n=1). Conclusion We observed that fungi were not frequently detected from stool, and presence of fungi did not always imply clinical fungal infection with the same organism but could reflect antibiotic exposure and contribute to intestinal dysbiosis leading to acute GVHD. Presence of bacteriophages in stool is a novel observation, which could be reflective of a diet of human milk. We have previously shown that human milk lowers intestinal inflammation after BMT and these findings will be explored in independent studies. Mastadenovirus was detected in stool before or early after BMT and frequently heralded clinical viral reactivation.

The Effectiveness of the Neutropenic Diet in Pediatric Bone Marrow Transplant Patients

Background Opportunistic infections are a significant cause of morbidity and mortality in children treated with chemotherapy. Historically, the neutropenic diet has been utilized to limit the incidence of infections by reducing exposure to potential pathogens. The neutropenic diet is utilized at our center for all allogeneic(allo) hematopoietic stem cell transplant (HSCT) patients at admission and restricts uncooked vegetables, fruits without thick peels, undercooked meats/seafood, and any restaurant food. Autologous (auto) HSCT patients follow a regular diet with food safety education according to Center for Disease Control (CDC) and Food and Drug Administration (FDA). The neutropenic diet is not endorsed by the CDC and FDA due to lack of evidence to support it. We hypothesize the neutropenic diet offers limited advantage over the FDA and CDC food safety guidelines in respect to rates of neutropenic fever or infection. Methods We performed a retrospective descriptive review of consecutive pediatric patients >1 year of age that underwent HSCT between June 2016 and February 2017 to assess fever and infectious complications occurring before engraftment. All patients were placed on prophylactic antibiotic therapy (cipro and pen VK) on admission until fever or engraftment. Results A total of 72 HSCT procedures were conducted on our inpatient unit (Auto, 24 and Allo 48). Median age at HSCT was 6 years (Range 1-24 years). Of 72 total transplants, 56 (78%) had at least one fever episode from the start of conditioning until engraftment. The median day of fever was day -2. 6 of 57 episodes of fever were due to blood steam infection (3 allogeneic; 3 autologous), Organisms included Bacillus species, Enterobacter cloacae, acid fast bacilli, Streptococcus oralis and Staph epidermidis. Twenty-eight patients had diarrhea, five had identified stool pathogens to include C.difficile (n=2), Adenovirus (n=3), Norovirus (n=1), E.coli (N=1), of note 2 patients had 2 concurrent infections present. Sixty seven(89%) patients received TPN for a median of 41 days (ranging from 9-233 days) for allogeneic and median of 20 days (ranging from 6-170 days) for autologous recipients. Thirty seven (49%) patients had clinically documented mucositis (see Table 1). Discussion Fevers were commonly chemotherapy related and infectious causes were rare for both auto HSCT on a regular diet and allo HSCT on a neutropenic diet. Antibiotic practices may contribute to outcomes. Further investigation evaluating the safety of the FDA diet during the neutropenic period of HSCT is warranted to improve overall nutrition and quality of life.

Impact of Non-Compliance with the Beers Criteria on Post-Stem Cell Transplant Health Outcomes

Purpose The impact of non-compliance with the Beers Criteria on the health outcomes of elderly patients undergoing Stem Cell Transplant (SCT) has not previously been examined. Studies have evaluated the effect of polypharmacy in solid malignancies; however, compliance with the Beers criteria was not assessed in these studies. The purpose of this study is to determine if patients 65 years or older who undergo SCT had medication lists consistent with the Beers criteria. The study will examine if there is a relationship between Beers compliance and incidence of adverse drug reactions and/or the need for physical rehabilitation services post-SCT. Methods The study will consist of a retrospective chart review of patients who underwent SCT between November 1, 2007 and July 1, 2017 in a community hospital. The information will be accessed via electronic medical records. The inclusion criteria consist of patients 65 to 88 years of age who underwent SCT at a comprehensive cancer center in South Florida. The exclusion criteria includes non-treatment-related death while undergoing the SCT. The data to be reviewed includes home medication list, hospital discharge medication list, laboratory parameters (SCr, CrCl, among others), discharge disposition (rehabilitation center vs home), and other pertinent parameters. Descriptive statistics will be used for demographics and outcomes. Results A total of 102 patients received SCT between the study period; 78 patients did not meet inclusion parameters and 7 more had insufficient data, therefore a total of 85 patients were excluded and only 17 patients were included in this study. The data compiled shows that 76% of the patients were admitted to the SCT unit with a pre-SCT medication list that is not compliant with BEERs criteria. This percentage of non-compliance does not change with the discharge medication list. The majority of patients who were not compliant with the criteria were discharged home and one was discharged to a physical rehabilitation center. All the patient with list that adhere to the BEERs criteria were discharged home. The population that received an evaluation from the physical therapy team included only 2 patients (11.8%); however there is documentation that evidences the physical deconditioning of 4 patients. Additional results are still pending. Conclusion Better compliance with Beers criteria and methodology to improve that goal should be a priority in elderly bone marrow transplant patients. Pharmacists should be involved during admission and at discharge of patients. Outcomes in the long term need to be analized to assess impact of non compliance on bone marrow transplant outcomes.

Longitudinal Utility of Peripheral Airway Function Tests in Pulmonary Graft Vs. Host Disease in Pediatric Bone Marrow Transplant Patients

Introduction Pulmonary graft versus host disease is a pathological process arising in peripheral airways causing significant morbidity and mortality post-Bone Marrow Transplantation (BMT). Current screening and diagnosis focuses on spirometry change from baseline to identify Bronchiolitis Obliterans Syndrome (BOS), and an at-risk pre-BOS stage BOS0p (≥10% fall FEV1). Sensitive peripheral airway function tools exist but remain under-utilized and utility is unclear. Aim To investigate longitudinal peripheral airway function change, detected by Multiple Breath Washout (MBW) and Forced Oscillation Technique (FOT), in pediatric BMT subjects with/without BOS and BOS0p. Methods Children aged ≥3 years were recruited. Testing occurred at baseline, monthly during 1st year and 6-monthly to 3yrs: MBW (LCI, Scond and Sacin, ExhalyserD®, Ecomedics), FOT (Rrs and Xrs at 5Hz, AX, Fres, tremoFlo®, Thorasys) and, if feasible, spirometry, plethysmography and DLCO. Groups (BOS, BOS0p, unaffected) compared at baseline, 12, 24 and 36 months. Results Of 24 recruited subjects (mean±SD (range) age 10.2±4.2 (3.3-18.1) years at BMT, 54% AML/ALL diagnosis, 71% male), 1 withdrew and 6 died (5 within 12 months). BOS and BOS0p alone were detected in 3 (12.5%) and 8 (33.3%), respectively. BOS was associated with pattern of marked abnormality, significant increases from baseline were observed in LCI, Scond, Sacin, Xrs, AX and Fres. One subject developed BOS3 at 105 days (1st feasible post-BMT test). MBW/FOT abnormality was detected 26 and 207 days prior to BOS≥1 in other cases. LCI trajectory increased with increasing BOS severity. At 3 years, statistically significant differences between BOS0p vs unaffected were observed for LCI (p=0.009), Sacin(p=0.03), Xrs (p=0.004) and approached significance for AX (p=0.09) and Fres (p=0.09). Conclusion BOS and its earlier at-risk stage BOS0p were associated with significant peripheral airway abnormality detectable on MBW and FOT. MBW and FOT abnormality predated BOS≥1 in 2/3 BOS cases.

Comparison of Parenteral Nutrition Usage in Pediatric Bone Marrow Transplant Patients with and without Gastrostomy Tubes

Purpose To determine whether placement of gastrostomy tubes (GT) in pediatric bone marrow transplant patients prior to transplant and provision of enteral nutrition (EN) can decrease the duration/necessity of parental nutrition (PN) usage during time of treatment related mucositis and nausea/vomiting. Methods We retrospectively reviewed the medical records of pediatric bone marrow transplant patients admitted to the Medical University of South Carolina (MUSC) Children's Hospital from July 2014 through July 2018. We collected data on type of transplant, chemotherapy regimen, presence of GT, PN initiation and duration, diagnosis of veno-occlusive disease (VOD), and hospital length of stay (LOS). Results We analyzed 63 transplant occurrences in 53 patients including 23 allogeneic, 35 autologous and 5 haplo-identical stem cell transplants. In 28 of 63 (44%) transplant occurrences, the patients had a GT placed prior to admission. PN was administered in 22 of 28 (79%) in the GT group and 28 of 35 (80%) in the no GT group. The average duration of PN was 10 days in the GT group (range 4 to 20 days) and 17 days in the no GT group (range 1 to 65 days). The incidence of VOD was 14% in both GT and no GT groups. The average length of stay was 36 days (range 23 to 59) in the GT group and 44 days (range 23 to 83) in the no GT group. Conclusion Placement of gastrostomy tubes and provision of EN in pediatric bone marrow transplant patients did not eliminate the need for PN but decreased the number of days patients require PN during the transplant process. Our data did not show a decrease in the incidence of VOD in patients with GT. Though many factors play a role, we demonstrated an association between GT placement and decreased length of stay.

Utilization of a BMT Nursing Symposium to Standardize Education of BMT Staff

Topic Significance & Study Purpose/Background/Rationale To support our mission and provide our patients competent and professional care, we realized that we have to provide our nurses and support staff with comprehensive education. With increasing complexity of care, rapid development of immunotherapies and cellular therapies, and a significantly growing transplant program, it is imperative for not only BMT staff, but also staff from other BMT ancillary services, to have the knowledge and skills to successfully care for this patient population. Methods, Intervention, & Analysis A comprehensive BMT Nursing Symposium with interactive audio-visual presentation and question & answer session was developed by the BMT program. The day-long symposium covered a wide variety of topics including overviews of autologous and allogeneic transplants, as well as post-transplant complications including graft versus host disease, febrile neutropenia, CMV reactivation, and veno-occlusive disease. Additional topics regarding support services included nutrition, social work, stem cell collection and processing, and histocompatibility testing. All topics are presented by experts in the field including BMT physicians, pharmacists, and nurse practitioners. The symposium also included a portion on nursing care of the BMT patient. Two identical sessions of the symposium were offered in order to accommodate all staff's schedules while still allowing coverage off the inpatient and outpatient areas. All BMT nursing staff including inpatient, outpatient, and infusion areas are required to attend. The symposium is also offered to nursing staff in the Intensive Care Unit's (ICU) and Emergency Department's (ED) as these departments treat BMT patients. A seven hour Continuing Education Unit (CEU) credit was offered to the participants. Findings & Interpretation The BMT team recently held the third annual BMT Nursing Symposium. Attendance at the symposium has increased each year with the most recent symposium reaching 80 attendees, a 25% increase from year one. After the symposium, surveys are distributed to determine how effective the presentations were. Overall, the symposium receives positive reviews. Staff also has the opportunity to suggest new topics for future years. Discussion & Implications Nurses have a great impact on the quality of care bone marrow transplant patients receive. By standardizing education for our staff, we hope to give our new hires a solid foundation, while at the same time reaffirming the foundation in our seasoned employees. Patients also interact with our support staff, so it is important for us to educate our entire multidisciplinary team so the patient can have uniform and consistent care throughout the whole treatment process. In the next few years, we hope to cover additional topics including cellular therapy. Also, if needed, we would like to explore the idea of having two tracks for the symposium – one for new employees and one for more experienced employees. Institutions should consider implementing a similar symposium to standardize staff education on the complexities of treating the BMT patient.

The use of 2-Dimensional Strain Imaging for the Detection of Right Ventricular Dysfunction After Bone Marrow Transplantation Involving Anthracycline Chemotherapy

Background: 2D strain imaging detects subclinical myocardial dysfunction in a range of disease states; however strain analysis has largely been applied to the left ventricle. Aims: We sought to evaluate RV function in bone marrow transplant (BMT) patients who have received anthracycline chemotherapy. Due to its thinner wall, we hypothesised that the right ventricle (RV) may show evidence of toxicity earlier, thus allowing earlier diagnosis. Method: 68 BMT patients were retrospectively analysed; 47 patients had received anthracyclines. BMT patients were compared to 31 age and gender matched healthy controls. RV systolic function was assessed using conventional parameters including TAPSE, s’ and RV fractional area change (FAC), as well as 2-dimensional RV free wall strain. Results: TAPSE (21.1±3.7 vs 24.5±3.7 cm, p = 0.001), FAC (38.8±5 vs 43.8±5%, p < 0.0001) and RV free wall strain (28.1±2.8 vs 23.2±4.0%, p < 0.0001) were reduced in patients who had received anthracyclines compared with controls. Importantly, traditional RV function parameters failed to detect RV dysfunction as compared to RV free wall strain (i.e. 13 patients with preserved FAC and 12 patients with preserved TAPSE had reduced RV strain). Further, despite preserved LV function (LVEF >53% and GLS >17) a reduced RV GLS (<22%) was noted in 9 patients, all of whom had preserved FAC and TAPSE. Conclusion: Traditional parameters of RV dysfunction were less sensitive than RV GLS strain to identify RV dysfunction. Additionally, RV function using strain identified RV subclinical dysfunction even in the absence of LV dysfunction.

Alterations in Multiplanar Strain in Bone Marrow Transplant Patients Previously Treated with Anthracyclines

Background: Echocardiographic strain analysis can identify subclinical LV dysfunction in patients who have received chemotherapy and bone marrow transplant (BMT). Methods: 50 BMT patients, with previous anthracycline exposure, who underwent a transthoracic echocardiogram (TTE) [Nov 2016–Oct 2017] were compared to 50 age and gender matched controls (departmental database). Standard parameters of LV function (LVEF) and offline strain analysis were performed (GE Echopac). Results: Time from BMT to TTE was 7 ± 6 years. Based on current recommendations [[1]Plana J.C. et al.Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.J Am Soc Echocardiogr. 2014; 27: 911-939Abstract Full Text Full Text PDF PubMed Scopus (822) Google Scholar], a normal LVEF cutoff >53% was used. 40 BMT patients had an LVEF > 53%. Global longitudinal strain (GLS) was significantly lower versus controls (18.4 ± 3 vs 20.5 ± 2%; p = 0.001), as was global circumferential strain (GCS) (15.9 ± 4 vs 19.3 ± 4%; p = 0.002). 29 BMT patients and 48 controls had “normal” LV function (LVEF > 53% and GLS > 17). Even in this subgroup, GCS was significantly lower in the BMT group (16.9 ± 4 vs 19.1 ± 4%, p = 0.04) and suggests that it could be an additional marker to detect pre-clinical stage B heart failure. Limitations: This is a single centre cross-sectional study with a limited sample size; lack of serial measurements preclude evaluation of within patient changes over time. Conclusions: Our results provide new insights for the use of multiplanar strain imaging for detection of sub-clinical cardiac dysfunction that may be present in patients after a BMT despite preserved LVEF. Their prognostic value to identify adverse events require further evaluation.