History Of Bone Marrow Transplantation Research Articles

Low-risk pneumatosis intestinalis in the pediatric surgical population.

Pneumatosis intestinalis (PI, presence of air in bowel wall) develops in a variety of settings and due to a variety of insults which is then characterized by varying severity and clinical course. Anecdotally, many of these cases are benign with few clinical sequelae; however, we lack evidence-based guidelines to help guide management of such lower-risk cases. We aimed to describe the clinical entity of low-risk PI, characterize the population of children who develop this form of PI, determine if management approach or clinical outcomes differed depending on the managing physician's field of practice, and finally determine if a shortened course of NPO and antibiotics was safe in the population of children with low-risk PI. We performed a retrospective review of all children over age 1year treated at Children's Hospital Colorado (CHCO), between 2009 and 2019 with a diagnosis of PI who did not also have a diagnosis of cancer or history of bone marrow transplant (BMT). Data including demographic variables, clinical course, and outcomes were obtained from the electronic medical record. Low-risk criteria included no need for ICU admission, vasopressor use, or urgent surgical intervention. Ninety-one children were treated for their first episode of PI during the study period, 72 of whom met our low-risk criteria. Among the low-risk group, rates of complications including hemodynamic decompensation during treatment, PI recurrence, Clostridium difficile colitis, and death did not differ between those who received 3days or less of antibiotics and those who received more than 3days of antibiotics. Outcomes also did not differ between children cared for by surgeons or pediatricians. Here, we define low-risk PI as that which occurs in children over age 1 who do not have a prior diagnosis of cancer or prior BMT and who do not require ICU admission, vasopressor administration, or urgent surgical intervention. It is likely safe to treat these children with only 3days of antibiotic therapy and NPO. Level III.

Steady-State Hemoglobin Is Associated with Self-Reported Ability to Perform Challenging Physical Function Activities, but Not Global Physical Function in Individuals with Sickle Cell Anemia

Introduction People living with sickle cell disease (SCD) need high levels of physical function to support independent living. Researchers should prioritize identifying modifiable targets that improve physical function. People with SCD who have physical limitations and low muscular capacity are at risk of poor function and lower quality of life. This abstract describes domain-specific and global self-reported physical function among adults living with SCD and identifies cross-sectional associations between hemoglobin and physical function. Methods Respondents consented to chart abstraction and completed the PROMIS Physical Function Short Form 8b survey. We operationalized domain-specific function as binary variables indicating no impairment versus any impairment in 8 activities. We calculated participants' global physical function using PROMIS' HealthMeasures web tool calibrated to the US population and converted to t-scores (range: 20.3 [worst] to 60.1 [best]). Eligible participants met the following criteria: age 18+ when surveyed,labs drawn during a non-acute encounter within +/- 30 days of the survey, no pregnancy-related outcome the year before survey, no history of bone marrow transplant, and available covariate data. We estimated cross-sectional associations between hemoglobin and 8 physical function sub-domains using multivariable logistic regression. We fit heteroscedastic tobit regressions to estimate the association between hemoglobin and global physical function. We adjusted the models for age, sex, recruitment site, history of renal damage, disease-modifying therapy (DMT) use, body mass index, and lactate dehydrogenase (LDH). We used STATA/SE 18.0 to perform the analyses separately by SCD subtype: sickle cell anemia (SCA) - HbSS/HbSβ 0, versus other subtypes (variant SCD). Results Between 2016 and 2023, 331 people with SCD at 7 GRNDaD sites completed the survey; 119 adults met eligibility criteria (52% female). The median age was 31 years (IQR: 24 , 39 years); 95% identified as Black, and 65% had SCA [Table 1]. Seventeen percent reported no limitation in any domain. Those with While For those with SCA, the hardest activity was heavy housework (74% reported limitation), while the easiest was running errands (39% reported limitation). For those with variant SCD, the hardest activity was heavy housework (88% reported limitation), while the easiest was climbing stairs (64% reported limitation). In adjusted logistic regression models among those with SCA, higher steady state hemoglobin was associated with higher odds of full function when carrying groceries (OR = 1.59, 95% CI = 1.05 , 2.41), performing 2 hours of labor (OR = 2.17, 95% CI = 1.29 , 3.65), and heavy housework (OR = 1.78, 95% CI = 1.04 , 3.06) [Figure 1]. Hemoglobin was not associated with any function sub-domains for individuals with variant SCD. In adjusted tobit regression models, hemoglobin was not associated with global physical function for those with SCA (β= 0.23 95% CI = -0.99 , 1.45) nor with variant SCD (β= -0.10, 95% CI= -0.77 , 0.58). Conclusions People with SCA reported better age-adjusted subjective function than those with variant disease, perhaps reflecting availability of treatments for SCA. In SCA, hemoglobin was positively associated with higher function in the 3 PROMIS sub-domains that respondents ranked as most challenging. Hemoglobin was not associated with global physical function for either SCD subtype. research in larger longitudinal samples is needed to explicate potential mechanisms linking hemoglobin to self-reported function sub-domains, corroborate the observed patterns of self-reported function by subtype, investigate associations between hemoglobin and objectively measured physical function, and identify how within-person changes in hemoglobin may contribute to changes in performing challenging everyday physical function activities.

What is the role of neutropenia in pediatric cancer patients with pneumatosis intestinalis?

We aimed to identify prognostic indicators in pneumatosis intestinalis (PI) in a pediatric oncology population. We hypothesized that neutropenia would be an independent risk factor for adverse outcomes, including the need for abdominal operation to treat PI and for the development of recurrent PI. We performed a retrospective review of all patients treated for PI between 2009 and 2019 with a diagnosis of cancer or history of bone marrow transplant (BMT). Sixty-eight children were treated for their first episode of PI; 15 (22%) were not neutropenic at presentation; eight underwent urgent abdominal operation (12%). Patients with neutropenia were more likely to receive TPN, had a longer course of NPO, and received a longer course of antibiotics. Neutropenia at presentation was associated with a decreased risk of PI recurrence (40% vs 13%, p = 0.03). Children who required an abdominal operation were more likely to require vasopressors at diagnosis (50% vs 10%, p = 0.013). Among pediatric cancer patients, need for vasopressors at the time of PI is a marker of severe PI, with increased likelihood of requiring operative intervention. The presence of neutropenia is associated with lower rates of PI recurrence. Level III.

(174) Sexual Health in Young Adult Survivors of Childhood Cancer: A Project REACH Study

Abstract Introduction Sexual health, a key component of general well-being, relies on the successful interplay of physical, psychological, and social development. Although we know cancer treatment early in life disrupts many of these processes, it remains unclear exactly how treatment leads to sexual dysfunction in young adult childhood cancer survivors (YACCS). Our previous research found that approximately one third of YACCS report two or more sexual dysfunction symptoms using five sexual health items on a larger health-related quality of life survey. This research suggests that sexual dysfunction is related to late effects (e.g., fatigue) but not specific cancer treatments (e.g., chemotherapy). However, additional research using validated sexual health measures is required to understand these relationships more fully. Objective To build on previous research by examining the relationship between cancer treatment and sexual dysfunction in YACCS using validated sexual health measures. Methods 252 YACCS enrolled in Project REACH, a prospective cohort study, completed self-report measures on sexual functioning, psychological distress, and physical functioning. To examine proportion of participants experiencing clinically significant sexual dysfunction, participants were classified as a sexual dysfunction “case” if they scored ≥ 19 on the Female Sexual Function Index (FSFI-6) or ≥ 24 on the International Index of Erectile Function (IIEF). Relationships between sexual dysfunction, cancer type, cancer treatment, psychological distress (Brief Symptom Inventory-18; BSI-18), and health-related quality of life (i.e., Short Form-12; SF-12) were examined. Results Almost half (43%) of participants were classified as a sexual dysfunction case, with females significantly more likely (51%) to be a case than males (34%, p=.007). Brain tumor survivors were significantly more likely to be a case (53%) than participants with other types of cancers (36%, p=.009). Participants with a history of bone marrow transplant (BMT) were more likely to be a case (61%) than those without (41%, p=0.061), although this finding was only marginally significant. There were no significant differences in case vs. non-case by age, time since diagnosis, chemotherapy, radiation, or surgery. Sexual dysfunction cases reported significantly worse anxiety and depression (BSI-18) and overall mental and physical health (SF-12) than non-cases. Conclusions Our findings extend previous research by confirming that YACCS, particularly female YACCS, have significant sexual dysfunction according to validated sexual health measures. Findings also confirm strong ties between sexual dysfunction and other common late-effects (e.g., anxiety). Unlike previous research, our current findings link a history of brain cancer and BMT to more significant sexual dysfunction. Additional research is required to understand whether higher rates of sexual dysfunction are related to the more significant disruptions to physical, psychological, and social development during treatment in these two groups. Nevertheless, findings suggest that sexual health screening and treatment is clearly warranted in YACCS, particularly with those who have experienced brain cancer or BMT. Disclosure No

Head and neck carcinoma in children: A clinicopathological study of 42 cases

Background/purposeCancer is an important part of the global burden of childhood diseases. Head and neck carcinoma in children is rare and related research is limited. This study aimed to investigate the clinicopathological features of childhood head and neck carcinoma. Materials and methodsForty-two cases of childhood head and neck carcinoma treated in our institution were reviewed and analyzed. ResultsMedian age overall was 11 years. Twenty-three patients (54.8%) were male and 19 (45.2%) were female. Parotid gland location was most common (54.8%). Mucoepidermoid carcinoma and squamous cell carcinoma were the most common histological types (57.1% and 11.9%, respectively). Two patients had a history of bone marrow transplantation and two had a history of odontogenic keratocyst. The recurrence rate after treatment was 8.6%. ConclusionEarly diagnosis and treatment and close follow-up of childhood head and neck carcinoma are warranted to prevent recurrence and improve clinical outcome.

1052. Characteristics and Outcomes in Hospitalized Adult Patients Infected with the SARS-CoV-2 Omicron Variant at a Large Healthcare System in South Florida, January 1–14, 2022

Abstract Background The SARS-CoV-2 Omicron variant has been rapidly spreading worldwide. We aimed to characterize Omicron severity by assessing in-hospital deaths and intensive care admissions in a large healthcare system in South Florida during an Omicron predominant surge. Methods Laboratory-confirmed COVID-19 adult patients hospitalized during January 1—14, 2022 were retrospectively reviewed. Risks of in-hospital mortality and intensive care admission were estimated using logistic regression models. Analyses were stratified by age ≥ 65 years and vaccination status, and further adjusted for sex, comorbidities, and history of a previous COVID-19 infection. Results 500 consecutively hospitalized COVID-19 Omicron patients were included. The median age was 69 (IQR, 53-80) years, and 271 (54.2%) were women. The most common comorbidities were hypertension (65.5%), diabetes (32%), and chronic kidney disease (24%). 260 (52%) patients were fully vaccinated (defined as a patient who received 2-dose vaccines), and 32 (6.4%) were previously infected with COVID-19. 252 (50.4%) patients required supplemental oxygen, 54 (10.8%) required intensive care unit (ICU) admission, and 44 (8.8%) patients required mechanical ventilation. At study closeout of March 7, 2022, case fatality rates among patients aged 18–29 years, 30–39 years, 40-49 years, 50-59 years, 60-69 years, 70-79 years, and ≥ 80 years were 0%, 2.2%, 6.4%, 5.3%, 8.0%, 5.7%, and 15.4% respectively (p< 0.001), with the median time from hospital admission to death being 13 days (IQR, 6.5-20.5) (Figure 1). Patients aged ≥ 65 years had 2.6 times higher rates for in-hospital mortality (OR, 2.63; 95% CI, 1.29-5.33; p=0.007) than those aged < 65 years, but were comparable for ICU admission (OR, 0.85; 95% CI, 0.49-1.52; p=0.586). Past vaccination offered no protection against in-hospital mortality (OR, 1.18; 95% CI, 0.64-2.19; p=0.599) or ICU admission (OR, 1.16; 95% CI, 0.66-2.06; p=0.6) (Figure 2). In multivariable-adjusted models, patients aged ≥ 65 years had a higher in-hospital mortality than those aged < 65 years (Figure 2). Figure 1.Left: Distributions of survivors and non-survivors among hospitalized COVID-19 Omicron patients at different age groups; Right: Death curve of non-survivors with COVID-19 omicron in the South Florida area, January 1-14, 2022.Figure 2.Forest plots showing association of age and vaccination status with COVID-19 Omicron patient outcomes. Results were reported as odds ratios (OR,•) with 95% confidence intervals (CIs, horizontal lines), adjusted for sex-, diabetes, hypertension, COPD, chronic kidney disease, coronary heart disease, active malignancy, history of malignancy, history of solid organ transplantation, history of bone marrow transplantation, HIV, and previous SARS-CoV-2 infection. A-B. In-hospital mortality (death); C-D. ICU admission. ICU, intensive care unit. Conclusion This case series provides characteristics and outcomes of hospitalized adult patients with COVID-19 Omicron variant. Past COVID-19 vaccination did not impact ICU admission rate nor in-hospital mortality. Disclosures All Authors: No reported disclosures.

The utility of procalcitonin for diagnosing bacteremia and bacterial pneumonia in hospitalized oncology patients.

Procalcitonin (PCT) is an inflammatory marker elevated in bacteremia and bacterial pneumonia. We aimed to assess the real-world diagnostic accuracy of PCT in hospitalized patients with malignancy. A retrospective cohort of 715 patients with cancer who had PCT measured during 750 admissions was analyzed. Diagnosis of bacteremia was determined using blood culture data. Diagnosis of bacterial pneumonia was based on radiographic infiltrate and/or sputum culture. PCT's performance was assessed using receiver operating characteristic (ROC) curves, sensitivity, and specificity. Patients had bacteremia, bacterial pneumonia, or both during 210 admissions (28%). PCT elevation above 0.5ng/mL was significantly associated with diagnosed infection in the overall population (p < 0.0001) and in subgroups with solid tumor malignancies (p < 0.0001) and hematologic malignancies (p = 0.008). PCT was associated with infectious status in patients with any metastases, but not those with primary lung cancer, lung metastases, neuroendocrine tumors, febrile neutropenia, or history of bone marrow transplant (BMT). The area under the ROC curve for PCT in the overall population was 0.655. An ideal cutoff of 0.21ng/mL led to a sensitivity of 60% and specificity of 59%. At cutoffs of 0.5ng/mL and 0.05ng/mL, PCT's sensitivity was 39% and 94%, while specificity was 79% and 17%, respectively. In this large cohort of hospitalized oncology patients, PCT elevation was associated with diagnosed bacteremia and/or bacterial pneumonia. However, specificity was limited, and PCT elevation was not associated with diagnosed infection in some subpopulations. While PCT may have some diagnostic utility for hospitalized oncology patients, values must be interpreted cautiously and considering clinical context.

Inflammatory infiltration of the cardiac conduction system in acute lymphocytic myocarditis.

A 53-year-old man with prior history of bone marrow transplant after acute myeloblastic leukaemia was admitted in the acute cardiac care unit due to suspected acute myocarditis. At admission, his electrocardiogram (ECG) showed right bundle branch block and left anterior fascicular block (Panel A). Previously, he had been assessed regularly in a dedicated cardio-oncology clinic, with normal ECG and transthoracic echocardiography (see Supplementary material online, Videos S1 and S2). Despite high-dose pulses of methylprednisolone, he developed both complete atrio-ventricular (AV) block and progressive left ventricular systolic dysfunction (see Supplementary material online, Videos S3 and S4), leading to cardiogenic shock requiring temporary transvenous pacing and mechanical circulatory support with VA-ECMO. However, he died on day 9 due to multiorgan failure. Gross examination of the heart (Panel B) was normal, but histopathology and immunohistochemistry showed significant infiltration of the ventricular myocardium (Panel C), AV node (Panel D) left anterior fascicle (Panel E), and right bundle branch (Panel F) by mononuclear CD3 + T cells, consistent with the diagnosis of lymphocytic myocarditis. High-definition images S1-S8 are included in the Supplementary material online.

The Diagnostic Dilemma of a Nodule Appearing as a Mass

<h3>Introduction</h3> Posttransplant lymphoproliferative disorder (PTLD) after lung transplantation (LT) occurs due to immunosuppressant therapy that limits antiviral host immunity and permits Epstein-Barr viral (EBV) replication and transformation of B cells. <h3>Case Report</h3> We present the case of a 61-year-old man with history of bone marrow transplant (08/2009) for non-Hodgkin's lymphoma and bilateral LT (04/2021) for idiopathic pulmonary fibrosis - EBV status: D+/R+. The transplant was complicated by prolonged duration of ECMO and a lengthy post-LT hospital stay for renal failure, significant deconditioning, and acute on chronic respiratory failure requiring tracheostomy and fiberoptic bronchoscopic airway stent placement to limit atelectasis. He also required a muscle flap for right bronchial anastomotic dehiscence in this time course. After 4 months, he was finally discharged to home with tracheostomy in place, requiring oxygen supplementation based only on physical demands. On his return to clinic, an inspection bronchoscopy was performed to assess the airway stent, which was found to have purulent secretions concerning for infection. Bronchoalveolar lavage was positive for pan-sensitive <i>Pseudomonas</i> requiring intravenous antibiotic therapy. At the same time, a chest CT revealed multiple pulmonary nodules in the right lung base, the largest measuring 2.8 cm in diameter. A CT-guided biopsy confirmed EBV-positive polymorphic PTLD. Immunostaining yielded positive results for CD20, CD138, CD79a, MUM1, and EBV-encoded RNAs (EBER) (<b>Figure 1</b>). Notably, this patient never had a positive EBV-viral load. Given his undetectable EBV levels, a decision was made to reduce immunosuppression and follow imaging and blood counts as appropriate. <h3>Summary</h3> EBV-positive PTLD with negative EBV viremia is an unusual combination in an EBV-seropositive recipient with donor non-mismatch. The patient's tenuous respiratory status requiring intensive corticotherapy likely contributed significant risk for PTLD in this case.

Etiologies of hearing loss in Fanconi Anemia

ObjectivesWe aim to describe types of hearing loss associated with Fanconi anemia patients who underwent a bone marrow transplant (BMT) to identify possible etiologies of hearing loss. Additionally, we hope to investigate hearing loss early in life as a potential predictor of needing a BMT surgery. Fanconi anemia is a rare autosomal recessive disease that is the most common inherited bone marrow failure syndrome, characterized by bone marrow failure and multiple congenital anomalies, including hearing loss. This is the largest study to date reviewing types of hearing loss in patients with Fanconi anemia, specifically in those who have undergone BMTs. MethodsA retrospective chart review of patients diagnosed with Fanconi anemia at a single institution, tertiary, referral-based children's hospital with a bone marrow transplant team specializing in Fanconi anemia was conducted from 4/19/1976 to 10/19/2015. History, physical examination, audiometry, and imaging findings were reviewed in patients with and without history of bone marrow transplant. Patient hearing levels, as measured by pure tone audiometry at 500 Hz, 1, 2, and 4 kHz, were evaluated. Patients were grouped by transplant status and results and were assessed to determine type and degree of hearing loss. Statistical analysis was performed to compare the likelihood of bone marrow transplant procedures in Fanconi anemia patients with normal and abnormal hearing. ResultsThere were 252 patients with Fanconi anemia identified via diagnosis search in institutional electronic medical records using CPT codes and cross referencing with the Fanconi Anemia database, 58 of whom had available audiometric data. Of the 58 Fanconi anemia patients with available audiograms, 21 (36%) had abnormal audiograms; 37 patients had normal audiograms. Twenty out of 21 (95%) patients who had abnormal audiograms had undergone bone marrow transplants. Thirty-one of 37 (84%) patients with normal audiograms had received bone marrow transplants. Statistical analysis showed that patients with hearing loss were more likely to require a BMT in the future (OR = 3.87, p = 0.05). Of the patients with abnormal audiograms and a bone marrow transplant (n = 20), 14 (70%) had conductive hearing loss, 5 (25%) had mixed hearing loss, and 1 patient (5%) had sensorineural hearing loss. 13 of 20 patients (65%) had bilateral hearing loss and eight of 20 (40%) had unilateral hearing loss. Of those patients with conductive hearing loss (n = 15), the most common etiologies were Eustachian tube dysfunction (47%), external auditory canal stenosis (33%), and abnormal middle ear anatomy (13%). ConclusionsHearing loss is a common finding in Fanconi anemia patients who have undergone BMTs with conductive hearing loss being the most common audiologic manifestation in our cohort of patients. This demonstrates the necessity of frequent hearing screenings in this population and close collaboration with audiology throughout patient care. Our study indicates that hearing status early in life may be a predictor of needing a bone marrow transplant in the future. Further studies should explore the long-term impact of BMT surgery on hearing status.

Osmotic demyelination syndrome after bone marrow transplantation

A 14-year-old boy with a past medical history of bone marrow transplantation (BMT) was referred to the emergency department with the loss of consciousness and seizure. On admission, the blood test indicated strict hyponatremia with hypokalemia, hypomagnesemia, hypophosphatemia, hypoglycemia, and low-serum low-density lipoprotein cholesterol (LDL-C). After six days, the patient suffered from dysarthria, dysphagia, behavioral disturbances, disorientation, and obtundation. Based on the physical examination, hyperreflexia and upward bilateral plantar reflexes were outstanding. Lumbar puncture, spiral brain CT scan, and MRI were normal. Hence, MRI repeated 2 weeks later, and the T2-weighted image indicated the bilateral symmetric hyperintense lesions in the basal ganglia. The osmotic demyelination syndrome (ODS) is a scarce and serious neurologic complication of the quick correction of chronic strict hyponatremia.

Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort.

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p<.001), hypertension (69% vs. 44%, p=.001), HIV (7% vs. 1.4%, p=.024), and peripheral vascular disorders (19% vs. 8%, p=.018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p=.13), length-of-stay (sHR: 0.9 1.11.4 , p=.5), or mortality (sHR: 0.1 0.41.6 , p=.19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3-4]) (p=.042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.76 0.810.86 , p<.001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.

COMMODORE Cohort: A Novel, Real-World, Noninterventional Cohort Study Using a Patient-Centered Approach to Evaluate the Safety and Effectiveness of C5 Inhibitors in Patients with Paroxysmal Nocturnal Hemoglobinuria

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disease of dysregulated complement activation characterized by hemolysis and thrombosis and is associated with bone marrow failure. PNH can also impair patient quality of life and negatively impact the ability to work. PNH is a rare disease with an estimated incidence of 1 to 1.5 cases per million people globally. Inhibition of complement component 5 (C5) has been shown to reduce intravascular hemolysis, stabilize hemoglobin, reduce the need for blood transfusion, and improve quality of life for patients with PNH. C5 inhibitors eculizumab and ravulizumab are approved in the United States and other countries for treatment of PNH, yet there are limited data on the real-world use of these agents, especially in populations not eligible to participate in registrational clinical trials. Here we describe the COMMODORE Cohort study, which will use a novel patient-centered study design to collect both retrospective and prospective patient data on the real-world use, safety, and effectiveness of eculizumab and ravulizumab, as well as disease burden and outcomes, in patients with PNH in the United States. Study Design and Methods This noninterventional cohort study will collect data using the PicnicHealth digital personal health record platform. This platform uses a novel human-in-the-loop machine learning system to integrate, harmonize, and structure patient data, including clinical notes, medications, laboratory results, and diagnostic reports contained in medical records collected from any healthcare facility in the United States. This study was designed in collaboration with patient advocacy groups to ensure that data generated will answer questions important to the patient community. In contrast to many studies, patients will be directly recruited to participate through multiple avenues, including working with patient advocacy groups and societies as well as outreach through social media and other communication tools. All patients must complete an informed consent form to participate. Patient data is anonymized, and the study complies with the Health Insurance Portability and Accountability Act data security standards. The study will be submitted to IntegReview for institutional review board approval. Patients who report a diagnosis of PNH within the past 5 years and have subsequently been treated with eculizumab or ravulizumab can be included in this study (Figure). Data extracted by the platform will confirm that the patient meets study criteria. The study has 3 arms: arm A is comprised of patients who initiated therapy with eculizumab, arm B is patients who initiated therapy with ravulizumab, and arm C is patients who initiated therapy with eculizumab and later switched to ravulizumab. Exclusion criteria for patients in arms A and B includes treatment with a complement inhibitor prior to PNH diagnosis and treatment with eculizumab or ravulizumab for &amp;gt; 25 weeks. Exclusion criteria for all patients include platelet count &amp;lt; 30,000/μL, absolute neutrophil count &amp;lt; 500/μL, and history of bone marrow transplant. The primary objective is to describe the proportion of patients who do not receive packed red blood cell transfusion. Secondary objectives are to determine the proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and a thromboembolic event and the change in normalized lactate dehydrogenase. Safety objectives are to determine the rates and proportions of selected adverse events. Primary, secondary, and safety objectives will be evaluated from week 5 to 25 of treatment. The effectiveness and safety analyses will be conducted in all patients who fulfill entry criteria and have a minimum of 25 weeks of accrued person-time from treatment initiation. Exploratory analyses assessing long-term experiences and outcomes and will be conducted in all patients who fulfill entry criteria with no minimum treatment duration requirement. Descriptive statistics will be provided. Summary The COMMODORE Cohort study will use a novel, patient-centered approach to data generation including collaborating with patient groups to ensure that the study answers questions important to the PNH community. This approach may serve as a model for future studies evaluating other rare diseases with limited real-world data. Disclosures Shang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Faghmous:Kite Pharma: Current Employment; F. Hoffmann-La Roche Ltd: Ended employment in the past 24 months, Other: All authors received medical writing support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . Drozd:PicnicHealth: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Katz:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland..

Percutaneous Lung Biopsy in Immunocompromised Pediatric Patients.

To determine the diagnostic yield and safety of image-guided lung biopsies in immunocompromised pediatric patients. This was a retrospective pediatric cohort study conducted from June 2000 to April 2017. Subjects were 0-17 years of age (median, 10 years of age). There were 46 males (48%). A total of 73 consecutive image-guided lung biopsies were performed in 68 patients (weight range, 4.9-97.3 kg [median, 25.3 kg]). The indication for biopsy was to isolate an organism to tailor medical therapy. All patients were immunocompromised with an underlying history of bone marrow transplantation (n= 50), primary immunodeficiency (n= 14), and solid organ transplantation (n= 4). Patient and technical factors were analyzed for rates of complication. Overall diagnostic yield was 43 of 73 patients (60%). There were 14 minor (19%) and 8 major (11%) complications. Major complications included pneumothorax or hemoptysis requiring intervention (n= 6), and death (n= 2). The histological diagnosis was an infectious cause in 5 of 8 major complications (63%). There were statistically significant differences between the rates of complications with the imaging modality used (P= .02) and the use of fine needle aspiration (P= .02). Image-guided percutaneous lung biopsy can be helpful in isolating an organism to tailor therapy. Biopsies performed in immunosuppressed patients result in an elevated complication risk of up to 30% and demonstrate lower diagnostic yield and increased mortality, which should warrant detailed discussion with the primary team and family.

Incidence and Outcomes of Pneumocystis pneumonia When Utilizing PCR-Based Diagnosis in Patients with Hodgkin Lymphoma Receiving Intensive Chemotherapy

Background: The overall incidence of Pneumocystis Pneumonia (PJP) in lymphoma varies according to diagnosis, host factors and treatment rendered.(Carmona, et al. 2011) A meta-analysis suggested that prophylaxis is appropriate when the chance of incurring PJP is 3.5% or greater.(Green, et al. 2007) Accurately characterizing the incidence of PJP is further complicated by a transition in diagnostic methods from direct immunofluorescence assay (DFA) to a DNA-based polymerase chain reaction (PCR) technique.(Caliendo et al., 1998, Wilson JW, et al., 2011) The incidence of PCR-based diagnosis of PJP and the need for anti-Pneumocystis prophylaxis in patients diagnosed with Hodgkin lymphoma receiving chemotherapy requires further investigation. Methods: This single center, retrospective, observational study was approved by the Mayo Clinic Institutional Review Board and performed in accordance with the ethical standards of the 1964 Declaration of Helsinki. Consecutive adult patients with a diagnosis of Hodgkin lymphoma receiving chemotherapy between January 2006 and August 2018 were evaluated. Patients with history of bone marrow transplant were excluded. Kaplan-Meier estimation was used to calculate the cumulative incidence of PJP with a 95% confidence interval. Cox proportional hazard models were used to demonstrate the strength of association between the independent variables and PJP rate. Results: The 506 included patients had a median (IQR) age of 40.3 (28.6, 59.7) years, 287 (56.7%) were male, and 470 (92.9%) were Caucasian. Further baseline demographics and clinical characteristics are described in table 1 with no significant differences between those diagnosed and those free from PJP. Chemotherapy combined with radiation therapy was prescribed for 163 (32.3%) patients while 342 (67.7%) patients received chemotherapy alone. Chemotherapy regimen distribution included 356 patients (70.4%) receiving bleomycin-containing chemotherapy. Median (IQR) total Bleomycin dose was 122 (IQR: 78, 178) Units. Bleomycin-containing combination chemotherapy regimen was not significantly associated with a higher risk for PJP when compared to other combination regimens (HR=1.59, 95% CI 0.55-4.62 p=0.40). Bleomycin-related lung compromise was suspected in 130 (25.7%) patients. Anti-pneumocystis prophylaxis was provided for 97 patients (n=39 a priori, 58 after chemotherapy initiation) and this was not significantly associated with a decreased incidence of PJP (HR=0.51, 95% CI 0.15-1.71, p=0.28). The cumulative incidence of PJP 1 year after start of chemotherapy was 6.2% (95% CI 3.8%-8.5%) and is shown in figure 1. Diagnosis of PJP occurred most commonly during the 2nd (n=8, 30.7%), 3rd (n=8, 30.7%), and 4th (n=7, 26.9%) cycles of chemotherapy. Trimethoprim-sulfamethoxazole was the only agent prescribed as PJP management. There were 10 (38%) patients with PCP that required ICU admission with 9 needing mechanical ventilation, 4 necessitating vasopressor support, and none requiring dialysis. Mortality 30-days from PJP diagnosis was 8% (n=2) with one death attributable to PJP infection. Conclusion: Cumulative incidence of PJP was 6.2% in patients receiving intensive chemotherapy for Hodgkin lymphoma. As the incidence is above the 3.5% threshold previously described, the clinician should consider the potential value of prophylaxis. Defining the overall utility of universal vs. targeted anti-pneumocystis prophylaxis requires further prospective, randomized investigation. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Trimethoprim/Sulfamethoxazole, Pentamidine isethionate, and dapsone will be discussed as prevention of Pneumocystis Pneumonia in the HIV-negative population

64 Acute Pancreatitis Outcomes May Not Be Worse in Post-Transplant Patients

INTRODUCTION: The average incidence of acute pancreatitis (AP) in patients with a history of solid organ transplant ranges from 2 to 8%. Patients with a history of bone marrow transplant are reported to have an incidence of 4%. Presentations include “chemical” pancreatitis with enzymes elevation only and clinical pancreatitis according to the revised Atlanta criteria. A few previous studies have shown that multi-organ failure and death are frequent complications of AP in transplanted patients. Most of the studies individualize their findings based on a specific organ transplanted (such as kidney or heart or liver, etc.) The aim of our study was to evaluate the outcomes of patients with acute pancreatitis with a history of any solid organ or bone marrow transplant using a national database. METHODS: We performed a retrospective cross-sectional analysis using the National Inpatient Sample (NIS) database from 2014. We included all patients with acute pancreatitis (ICD 9 Code: 577.0). Next, we divided the AP patients into two groups - one with history of a transplant and those without a history of transplant. We compared the outcomes of both groups. Both univariable and multivariable analyses were performed to assess the risk factors and outcomes of patients with acute pancreatitis in post transplant patients. RESULTS: We analyzed more than 35 million US hospitalizations in 2014 out of which 279,145 were acute pancreatitis related hospitalizations. There were 1,265 hospitalizations for acute pancreatitis in previously transplanted patients, an incidence of 4.53%. The mortality rate of AP was similar in non-transplanted patients (0.66%) than in transplanted patients (0.4%). The mean length of stay (4.62 days vs. 4.61 days) and mean total charges ($35,723 vs. $31,202) were similar in acute pancreatitis for transplant and non-transplant patients. Multivariable regression analysis showed that multiorgan dysfunction risk among AP patients was significantly higher if they had a history of transplant (OR of 2.27; P &lt; 0.01). CONCLUSION: Our study showed that AP generally has similar outcomes in transplant and non-transplant patients even with a higher risk of multiorgan failure. More data is needed to determine if this holds true for subjects who develop AP in the immediate post transplant period.

P033 Cytomegalovirus colitis: Does concomitant inflammatory bowel disease lead to worse clinical outcomes? Descriptive study from a single-centre experience

BACKGROUND: The association between cytomegalovirus (CMV) colitis and inflammatory bowel diseases (IBD) is well documented. Current studies estimate a 2% risk of CMV reactivation in the gastrointestinal tract of IBD patients. The effect of CMV colitis on clinical outcomes of IBD patients remains unclear. Our aims are to compare the clinical characteristics of CMV colitis patients with IBD compared to those without IBD and to determine if CMV colitis leads to worse clinical outcomes amongst IBD patients compared to those patients with no IBD. METHODS: All patients diagnosed with CMV colitis based on colonic tissue biopsies between 1/2002 and 5/2018 were included in this retrospective study. Patient demographics were obtained from patient's medical charts including age, gender, presence of concomitant IBD, other comorbid illnesses, review of medication list, namely current or recent steroid use, as well as patient symptoms that prompted the colonoscopy. Outcomes pertaining to length of hospital stay, need for colectomy, escalation of IBD medications, readmission rates, and mortality rates were obtained. Duration of anti-viral therapy was also recorded for those patients. Simple statistics (percentages and means) were reported for the descriptive data, the student's t-test was used to assess associations for continuous variables. RESULTS: A total of 22 patients were found to have CMV colitis based on colonic tissue diagnosis. Most of these patients (n = 14; 63.6%) were males, and the mean age of the sample was 52 ± 19 years. Only 5 (22.7%) of the 22 patients had concomitant IBD; 4 patients had ulcerative colitis while 1 patient had Crohn’s disease. Of the remaining 17 patients with CMV colitis, 10 had a history of bone marrow transplantation, 1 had acute lymphoblastic leukemia, 1 had chronic lymphocytic leukemia, 1 had common variable immunodeficiency, and 4 suffered from a chronic illness such as diabetes mellitus, Parkinson’s disease, and iatrogenic Cushing's syndrome, amongst others. Of the 22 patients, 8 (36.4%) developed CMV colitis during their hospitalization for an unrelated issue while the remaining 14 (63.6%) were admitted for the management of symptomatic CMV colitis. Most of the patients were receiving an immunosuppressive medication including an immunomodulator such as azathioprine or cyclosporine (n = 9; 40.9%), or corticosteroid therapy (n = 9; 40.9%). Most of the patients had been receiving valacyclovir prior to admission (66.7%). The average length of hospital stay for CMV colitis patients was 35 ± 23 days. Comparing IBD to non-IBD patients, IBD patients tend to have a shorter hospital stay (17 ± 8.5 vs 39.5 ± 23.9; P = 0.077). When comparing the 2 groups, those with IBD were more likely to be on 5-ASA or immunomodulators. CONCLUSION(S): CMV reactivation in the gastrointestinal tract is a common condition in IBD patients due to their immunosuppressed status. From this series, it was found that non-IBD patients who developed CMV colitis were also immunosuppressed due to a different co-morbid condition strengthening the available data that associates concomitant CMV of the gastrointestinal tract with immunosuppression.

A Call for Fertility and Sexual Function Counseling in Pediatrics.

* Abbreviation: AAP — : American Academy of Pediatrics During a pediatric endocrinology clinic visit, a 16-year-old boy presented with his family for evaluation of his endocrine axes due to history of bone marrow transplantation. He had previously been followed elsewhere; transfer records stated his family had been told that his fertility was likely to be impaired, but his parents had not shared this with him. It was also unclear from review of the notes whether any discussions regarding sexual function had occurred. Historically, reproductive health in pediatrics has focused primarily on contraception and prevention of sexually transmitted infections. However, there is now a growing body of literature discussing the long-term impact of many pediatric conditions and treatments on fertility and sexual function, such as oncologic therapy, hematologic or autoimmune conditions requiring bone marrow transplantation, renal and rheumatologic disorders in which alkylators are used, cross-sex hormonal therapy used in the care of transgender youth, disorders of sex development, and other genetic syndromes such as galactosemia. Pediatric providers face dilemmas about the optimal approaches for assessing and discussing fertility and sexual function with patients and families, the type of guidance to give to parents about related communications with their children at each developmental stage, and ethical obligations regarding disclosure when parents are opposed to sharing sensitive information with their children. Decades ago, the nondisclosure approach to sensitive … Address correspondence to Leena Nahata, MD, Nationwide Children’s Hospital, 700 Children’s Dr, Columbus, OH 43205. E-mail: leena.nahata{at}nationwidechildrens.org

Safety and Efficacy of Intravitreal Ganciclovir Injections More than 10 Times for Cytomegalovirus Retinitis

Purpose: To study the treatment outcomes in patients who were administered multiple intravitreal ganciclovir injections more than 10 times alone without systemic anti-cytomegalovirus therapy for cytomegalovirus retinitis. Case summary: A 64-year-old man who underwent immunosuppressive therapy after thymectomy due to an invasive thymoma and pure red-cell aplasia, a 60-year-old woman who underwent chemotherapy after diagnosis of diffuse large B-cell lymphoma, a 49-year-old man with a history of bone marrow transplantation due to acute myeloid leukemia, a 29-year-old woman with dermatomyositis treated with oral steroids and cyclosporine, and a 47-year-old woman who received intravitreal dexamethasone implant injections, intravitreal and subtenon steroid injections due to Behcet's disease were diagnosed with cytomegalovirus retinitis. All patients showed systemic complications such as pancytopenia after systemic anti-cytomegalovirus therapy, and therefore, they were administered multiple intravitreal ganciclovir injections alone. Best-corrected visual acuities improved in all patients, except in one case, where viral lesions were observed in the fovea. Retinal hemorrhaging and infiltrative lesions decreased in all patients. No severe complication was observed during the injection and in the follow-up period. Conclusions: Multiple intravitreal ganciclovir injections alone can be used as a treatment modality for cytomegalovirus retinitis to avoid the systemic side effects of systemic anti-cytomegalovirus therapy. J Korean Ophthalmol Soc 2016;57(2):316-323

Prognostic Markers in Cardiac Non-Hodgkin Lymphoma: A Retrospective Review

Introduction: Cardiac involvement by Non-Hodgkin lymphoma (NHL) occurs by several distinct mechanisms: primary extra-nodal disease, direct extension, hematogenous or lymphatic spread. While it is not an uncommon autopsy finding, it is rarely deemed to be clinically significant. By contrast, extranodal involvement by NHL is associted with inferior outcomes. Here we performed a retrospective review of 91 published cases of NHL with biopsy-proven cardiac disease to evaluate its clinical significance and impact on outcomes.Methods: A literature search using Pubmed was performed between 1990 and 2015. Inclusion criteria were biopsy proven lymphoma, age greater than or equal to 18, no history of bone marrow transplant and direct involvement of the pericardium and or myocardium. Survival data was only analyzed from patients without HIV/AIDS. Log-rank (Mantel-Cox) test was used to calculate survival. Age comparisons were calculated using an unpaired t-test with a two-tailed p-value and one-way ANOVA.Results: Ninety-one cases met inclusion criteria for the review. The mean age was 55 years (range 19-90 years). Patients with Burkitt lymphoma and HIV/AIDS were younger (p=0.016). Of patients with pathological evidence of cardiac involvement, diffuse large B-cell lymphoma (DLBCL) was the most common NHL subtype (52% of cases), followed by T-cell lymphoma (16%), Burkitt Lymphoma (8%) and small lymphocytic lymphoma (SLL, 6%). Chest pain was the most frequent presenting symptom (Table).TableN=91 (%)Age: 18-60 >60 (60-90)48 (53) 43 (47)Sex: Male Female60 (66) 31 (34)Lymphoma type: Burkitt SLL DLBCL Follicular T-Cell Not specified8 (9) 6 (7) 52 (57) 2 (2) 15 (16) 8 (9)Treatment: Chemotherapy Chemo and radiation Radiation Surgery None Unreported25 (28) 6 (6) 1 (1) 4 (4) 11 (12) 44 (49)HIV/AIDS: Infected Non-infected17 (19) 74 (81)Presenting clinical syndrome: Arrhythmia Chest pain CHF/Dyspnea Constitutional symptoms SVC syndrome Heart Block Stroke Sudden Death Other Unreported2 (2) 10 (12) 31 (34) 6 (7) 4 (4) 4 (4) 3 (3) 3 (3) 8 (9) 20 (22)Forty-eight patients had primary cardiac lymphoma, which was defined as de novo lymphomatous involvement confined to the myocardium and/or pericardium, 41 patients had secondary disease and two were indeterminate. Patients with primary cardiac lymphoma were older (60 years, 95% CI, 55-59 years, versus 50 years, 95% CI, 47-53 years, p=0.006).Survival data were available for 54 patients. Of note, ~50% of patients did not receive therapy. Median survival was 3 months for all patients. The median survival of patients with T-cell lymphoma was 2 months, versus 4 months in the B-cell lymphoma subgroup (p=0.20). The median survival of patients with indolent B-cell lymphoma (SLL) was 37.5 months versus 4 months in patients with aggressive lymphoma (DLBCL and Burkitt, p=0.77). We found that female sex was associated with a trend towards improved outcome (median survival of 12 versus 3 months, p=0.63). Furthermore, patients diagnosed with primary (de novo) cardiac lymphomas also had better survival, 4 versus 2 months (p=0.23), possibly reflecting the more aggresive nature of relapsed disease.On further analysis, patients who were alive one month after diagnosis had a median survival of 18 months versus 3 months for all patients in this cohort (p=0.032). Furthermore, patients with primary B-cell lymphoma had superior survival to patients with T-cell lymphoma and/or secondary disease (median survival not reached vs 2.5 months, p=0.027). We also found that patients who received chemotherapy had a median survival of 18 months versus 1 month for those who did not (p=0.003).Discussion: Symptomatic cardiac involvement by NHL is rare. While it appears to be more common in DLBCL, it is seen across multiple indolent and aggressive NHL subtypes and is more common in men, typically presenting in the 6th decade of life. The outcomes of patients with NHL with cardiac involvement are poor, particularly among those with aggressive subtypes. However, patients who are candidates for chemotherapy and who survive beyond one month, particularly those with de novo (primary) cardiac B-cell lymphoma, are more likely to achieve long-term survival. Pathological lymphomatous involvement of cardiac tissue needs to be considered as part of differential diagnosis during work-up of patients with NHL. DisclosuresNo relevant conflicts of interest to declare.