A 68-year-old male was admitted for evaluation of an endobronchial mass obstructing the right middle lobe (RML) and right lower lobe (RLL) of the lung. Flexible bronchoscopy revealed a notable endobronchial lesion in the bronchus intermedius that completely obstructed the RML and the RLL. Argon plasma coagulation (APC) at 30 watts and gas flow at 0.8 liters/minute to 1 liter/minute were applied to the tumor. In the recovery room, the patient was discovered to have a left-sided facial droop and left-sided weakness. The initial computed tomography (CT) scan of the brain and an angiogram of the head and neck were normal, but a repeat CT scan of the head several hours later was remarkable for an area of hypoattenuation in the right frontoparietal lobe concerning for infarct. A magnetic resonance imaging (MRI) brain scan confirmed acute to sub-acute cortical infarcts. Given the direct temporal relation between the onset of neurologic symptoms and the usage of APC with bronchoscopy, a cerebral air embolism (CAE) was thought to be the cause of the patient’s acute stroke.

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Introduction Acute graft versus host disease (aGVHD) is a leading cause of morbidity and mortality in patients who undergo allogeneic hematopoietic stem cell transplant (SCT). aGVHD is thought to be initiated when donor T cells encounter recipient antigen presenting cells (APC) such as dendritic cells (DC) and become activated. Preclinical studies have shown that vitamin D (VD) inhibits DC maturation biasing T cell proliferation towards tolerating rather than alloreactive T cell populations [Rosenblatt et al. BMT 2010]. A study of 53 patients who underwent myeloablative (ABL) SCT showed pre-SCT VD <25 ng/mL was associated with increased cumulative incidence (CI) of chronic GVHD but not for aGVHD [Glotzbecke et al. BMT.2013]. Another study evaluating day-30 VD levels post-SCT in 54 patients showed that VD < 20 ng/mL was associated with increased risk of acute skin GVHD, but only in patients who underwent reduced intensity conditioning (RIC) [Ganetsky et al. Abstract # 416. BBMT. 2014]. Given the conflicting data of the effect of VD on the incidence of aGVHD, and small sample size of prior studies, we performed a retrospective analysis to evaluate whether pre-HSCT serum vitamin D levels were associated with acute skin GVHD in patients undergoing both ABL and RIC SCT. Methods One hundred fifty-four patients at the University of Texas Southwestern (UTSW) Medical Center who had serum samples banked prior to RIC or ABL conditioning and then underwent matched related (MRD) or unrelated (MUD) SCT from December 2007 to December 2014, were included in the analysis. CI of acute skin GVHD grade II-IV (asGVHD) was assessed within 100 days post-SCT. VD cutoff of 25 ng/mL was chosen based on receiver operating curve (ROC) analysis from a prior study [Glotzbecke et al. BMT.2013]. The shape and distribution of continuous variables was examined. Mean and standard deviations were calculated for continuous variables and percent's calculated for categorical data. The χ2-test and Fisher's exact test were used to compare categorical variables and Student's t-test was used to compare parametric data and calculate p values. Stratified analysis was performed to evaluate for presence of interaction between dichotomous VD variable and other covariates. Statistically significant interaction was found between VD levels and ABL vs. RIC regimens. We therefore stratified analysis of our primary endpoint, CI of grade II-IV asGVDH, into RIC and ABL groups. Kaplan-Meir (KM) curves for CI of asGVHD were constructed with death and relapse and competing factors. Difference between CI curves was tested using the Gray method. Results Out of 154 patients, 93 (60.3%) were male, mean age was 51 (range 20-72) and mean VD was 22.6 (range 7.6-63.6). Overall CI of asGVHD was 24%. Most patients (112, 72.7%) had with VD <25 ng/mL (VD<25). On bivariate analysis, conditioning regimen (ABL vs RIC), donor type (MRD vs MUD), cell source (peripheral blood vs bone marrow), age at SCT, and ABO compatibility were similar among those with VD levels <25 and ≥25. CI of asGVHD was 22.0% and 25.0% in VD≥25 and VD<25 groups, respectively (p=0.696). Patients were then analyzed separately with respect to type of conditioning regimen they received (ABL and RIC). The ABL group had 79 patients with CI of asGVHD of 29.1% versus 18.6% in the 75 patients of the RIC group (p=0.12). In the ABL group, CI of asGVHD with VD≥25 was 40% versus 27.1% in VD<25 (p=0.4). In RIC group, CI of asGVHD with VD≥25 was 4.8% versus 24.1% with VD <25 (p=0.095). Figure 1A shows that in the ABL group the CI of asGVHD appears increased in patient with VitD≥25 (40% vs 27.1%, p=0.27). In contrast, Figure 1B shows that in the RIC group, the CI of asGVHD is higher for those with VD<25 (4.8% vs 24.1%, p=0.05). Conclusion Pre-SCT VD level was not associated with asGVHD, however there was a trend toward significance in patients who underwent RIC with a VD<25mg/mL. After accounting for competing factors, KM analysis showed that in patients who undergo RIC, VD level < 25 ng/mL is associated with a statistically significant increased risk of developing asGVHD. Interestingly, VD > 25 may be associated with increased risk of asGVHD in patients who underdo ALB conditioning, although these results were not statistically significant. This is the largest study analyzing the association of peri-SCT VD levels and GVHD to date. Further studies to clarify the interaction between VD status, conditioning regimen and development of asGVHD are warranted. Disclosures No relevant conflicts of interest to declare.

Introduction: Graft-versus-host disease (GVHD) remains the most common cause of morbidity and transplant-related mortality after allogeneic hematopoietic stem cell transplantation, despite significant advances in prophylaxis and treatment. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy for which cutaneous T cell lymphoma is currently the only FDA-approved indication; it is, however, increasingly used as a second-line therapy for acute and chronic GVHD patients who are steroid-refractory or -dependent. Evidence suggests overall response rates of 60-80%, with better response rates among patients with cutaneous manifestations. This retrospective analysis reports our experience using ECP to treat adults with acute and chronic GVHD over a 5-year period. Methods: We identified 67 patients (age 21-69, 70% males) who underwent ECP therapy for GVHD between November 1, 2010 and June 2, 2016. Eleven patients were excluded based on exclusion criteria of fewer than 8 procedures, any part of ECP course performed at an outside institution, and inadequate documentation regarding GVHD response. Among the remaining 56 patients, 6 underwent more than one course of ECP, resulting in a total of 62 courses of ECP included in final analysis. Charts were reviewed for each of these 62 courses to obtain relevant demographic and transplant-related data, type of GVHD, and organs involved. Response was assessed separately for each involved organ using strict response criteria and was censored on the date of last ECP procedure. Hematology notes were reviewed for noted worsening or improvement of GVHD, and a response was counted only if it was maintained throughout the remainder of the ECP course, including the date of last procedure. Results: Results are summarized in Table 1. Tapering of immunosuppressive therapy by end of ECP course, defined as steroid tapering by at least 50% from baseline or steroid withdrawal and tapering of other immunosuppressive therapy, was successful in 43 out of 62 (69%) ECP courses. Overall response rate, defined as complete or partial response, was highest for skin GVHD (73%) and lowest for lung GVHD (27%). However, 6 out of 11 (54%) patients with lung involvement experienced no progression of disease, which may be considered a successful response in these difficult-to-manage patients. Twenty-two out of 62 courses did have a new immunosuppressive agent, such as mycophenylate mofetil, tacrolimus, or rituximab, introduced at the start of or during the ECP course, and 11 of these 22 courses achieved a response that may not reflect therapeutic effect of ECP alone. Four patients developed new progressive liver or lung involvement by GVHD even as other involved organs in these patients, such as skin, showed complete response. Conclusion: Response rates to ECP at our institution are similar to those reported in the literature; it is a useful therapeutic option in patients with acute or chronic GVHD, particularly those with skin involvement. ECP allows successful tapering or withdrawal of immunosuppressive therapy in the majority of patients, even in those who are steroid-refractory or steroid-dependent. Disclosures Sarode: CSL Behring: Consultancy, Honoraria.

Background: Bendapudi et al. (Lancet Hematol. 2017) have recently developed and validated a clinical scoring system, the "PLASMIC score," to aid in assessing the risk of thrombotic thrombocytopenic purpura (TTP) in the absence of ADAMTS13 activity (Table 1). Although a few external validations describe good to excellent discriminatory value (Table 2), our experience using the PLASMIC score has not been helpful overall. We sought to perform our own validation of the PLASMIC score for clinical prediction of severe ADAMTS13 deficiency. Methods: We evaluated 323 patients who had ADAMTS13 testing performed between January 1, 2006 and June 20, 2018. We excluded patients who did not meet criteria for thrombotic microangiopathy (TMA), defined as schistocytes noted on peripheral blood smear within 2 days prior to ADAMTS13 testing and platelet count ≤ 100 x 109/L on the day of ADAMTS13 testing. We also excluded patients who were seen as outpatients, had PLEX elsewhere prior to admission, presented with a known TTP history, had possible interferences with the ADAMTS13 assay, or had irretrievable records. A total of 186 patients were excluded, including 9 "missing data" patients for whom all 7 components of the PLASMIC score were not available to calculate a score. 137 patients were included in the final analysis, 90 with an initial ADAMTS13 activity >10% and 47 with a severe deficiency (≤10% activity). We calculated a PLASMIC score for each patient, using the earliest admission laboratory values if initial ADAMTS13 testing was within Day 3 of admission. If initial ADAMTS13 testing occurred on or after Day 4 of admission, we used the closest laboratory values within 5 days prior to ADAMTS13 testing. This methodology was used in previous external validations of the PLASMIC score. We also experimented with two modifications on the original methodology. Our first modified PLASMIC score ("Mod 1") was designed to maximize the PLASMIC score, in order to err on the side of caution and help avoid missing potential TTP. Rather than just the earliest or closest laboratory value, any eligible laboratory value within 5 days prior to ADAMTS13 testing could be used to assign 1 point for a given category. Our second modified score ("Mod 2") assigns 1 point for serum creatinine <2.5 mg/dL rather than <2.0 mg/dL. With <7% of patients with missing data, we were able to use complete-case analysis for logistic regression. Results: The original PLASMIC score model predicted severe ADAMTS13 deficiency with a concordance "c" statistic of 0.88, where a value of 1 would indicate perfect prediction. The Mod 1 and Mod 2 models had a c statistic of 0.87 and 0.88, respectively. Sensitivity, specificity, and positive and negative predictive value for each of these 3 models, when PLASMIC score was dichotomized at high (score 6-7) versus low-intermediate risk (score ≤ 5), are summarized in Table 3. Almost 20% of patients with ADAMTS13 activity >10% had high scores, and the majority had a score of intermediate (score = 5) or higher (Table 4). We performed chi-square testing for each original PLASMIC score parameter; there was no statistically significant relationship between presence of severe ADAMTS13 deficiency and mean corpuscular volume <90 fL (z-score, p = 0.236). Among those patients with a high risk PLASMIC score by original methodology, we found a significant improvement in overall survival for those patients who received PLEX versus those who did not (log rank, p =0.0003), while no such difference was found among those with a low-intermediate risk score (log rank, p =0.3085). Conclusion: Our study uses a sample size similar to previously published external validations and shows a lower predictive value (c = 0.88) of the PLASMIC score for identifying a severe ADAMTS13 deficiency. Across all 3 of our models the specificity is also lower than previously published (81%, vs. 92%). Our first modification increased sensitivity while decreasing specificity compared to the original model, while the second modification had results similar to the original model. Overall our results suggest that the PLASMIC score may not show the same diagnostic performance across all populations and may cause an increase in unnecessary PLEX. Disclosures No relevant conflicts of interest to declare.