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Background In patients with bloodstream infections (BSI), the BioFire blood culture identification (BCID2) multiplex PCR panel is associated with decreased time to organism identification and antimicrobial susceptibility results needed to guide optimal therapy. While the performance of BCID2 has been evaluated in the general population, data for transplant recipients are limited. We sought to identify the utility of the BCID2 panel in transplant recipients. Methods A retrospective chart review was conducted to identify all solid organ recipients (SOTR) and bone marrow transplant recipients (BMTR) within 2 years of transplantation with BSI for whom BCID2 was performed from 06/2021 to 01/2022. Demographic and microbiological data were collected. Positive blood cultures for the same patient and same organism(s) occurring within 14 days of the initial test were considered a single BSI event. Descriptive statistics were performed. Results A total of 29 transplant recipients with 45 positive blood cultures underwent BCID2 testing. Mean age was 54 years, 69% were BMTR and 53% of cultures were from peripheral sites. A total of 51 organisms were recovered from 45 blood cultures. Organisms identified by blood cultures included Enterobacterales (45%), Enterococcus spp (20%), Candida spp (8%), non-Enterobacterales gram negative rods (14%), Streptococcus spp (8%), and other gram positives (5%). No anaerobic organisms were isolated. BCID2 did not detect 7/51 (14%) organisms identified by blood cultures including monomicrobial (n=6/39) and polymicrobial (n=1/6) cultures. All 7 organisms not identified by BCID2 were not in the BCID2 database. All occurred in BMTR; 4 were considered pathogenic and treated with antimicrobials vs. 3 contaminants (Table 1). BCID2 detected CTX-M or Van A/B in all 15 samples with ceftriaxone (n=9) or vancomycin resistance(n=6). Conclusion In transplant recipients, BCID2 detected 86% of organisms and 100% of resistance markers identified by conventional testing. All 7 (14%) missed cases involved off-target organisms, of which 4 were considered pathogenic. BCID2 is a useful tool for BSI detection in transplant recipients, but providers should consider the possibility of off-target pathogens when clinically appropriate. Disclosures David Peaper, MD, Tangen Biosciences: Stocks/Bonds Maricar F. Malinis, MD, Aicuris: Primary Investigator of Clinical Trial at Yale Site|Takeda: Primary investigator of clinical trial at Yale Site Maricar F. Malinis, MD, Aicuris: Primary Investigator of Clinical Trial at Yale Site|Takeda: Primary investigator of clinical trial at Yale Site.

Objective:Methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs are utilized to guide the discontinuation of empiric MRSA therapy. In multiple studies, MRSA nasal swabs have been shown to have a negative predictive value (NPV) of ~99% in non-oncology patients with pneumonia and other infections. We evaluated the performance characteristics of a negative MRSA nasal swab in the acute myeloid leukemia (AML) populaion to determine its NPV.Design:Retrospective chart review.Patients:This study included adult AML patients with a suspected infection and a MRSA nasal swab collected between 2013 and 2018.Methods:MRSA nasal swab and culture-documented infections were identified to determine the sensitivity, specificity, NPV, and positive predictive value of the MRSA nasal swabs.Results:In total, 194 patients were identified, and 484 discrete encounters were analyzed. Overall, 468 (97%) encounters had a negative MRSA nasal swab upon admission with no cultured documented MRSA infection during their hospitalization. However, 3 encounters (0.6%) had a negative MRSA nasal swab with a subsequent cultured documented MRSA infection during their admission. Identified infections were bacteremia (n = 2) and confirmed pneumonia (n = 1). MRSA nasal swab had a sensitivity of 62% (95% CI, 0.24–0.91), specificity of 98% (95% CI, 0.96–0.99), positive predictive value of 38% (95% CI, 0.21–0.6), and NPV of 99% (95% CI, 0.98–1).Conclusions:A negative MRSA nasal swab has a 99% NPV for subsequent MRSA infections in AML patients with no prior history of MRSA colonization or infection. Based on these findings, a negative MRSA nasal swab can help guide de-escalation of empiric MRSA antibiotic therapy.

Introduction: The cost of acute myeloid leukemia (AML) treatment is substantial and increasing. Inpatient treatment costs for allogeneic hematopoietic stem cell transplant (HSCT) and intensive chemotherapy are the main cost drivers in AML, however this pattern may change as new, expensive oral therapies enter the market. Areas covered: The authors provide an overview of the healthcare costs in patients with AML treated with various modalities (intensive chemotherapy, allogeneic HSCT, low-intensity treatment and supportive care only). The authors review both the impact of the recently approved novel AML agents and an increasingly personalized treatment approach on healthcare resources. Finally, the authors discuss whether these treatments are cost-effective from a societal perspective and how the increase in AML-associated costs can potentially be slowed. Expert opinion: The direct healthcare costs of AML are substantial and vary depending on the treatment approach, the country studied, and in the United States, a patient's insurance status. Treatment costs have increased out of proportion to general inflation and this trend is likely going to continue or even accelerate. Societal consensus on cost-effectiveness is essential. It remains to be seen how advances in diagnostic techniques and the incorporation of novel agents will impact medical outcomes, costs and influence health policy.

Background Ibrutinib is a small molecule tyrosine kinase inhibitor that blocks the activity of B cells and other immune effectors and is used in a variety of hematologic malignancies. There have been numerous reports of increased frequency of serious infections including invasive fungal infections (IFI) in patients on ibrutinib. Methods Demographic and clinical features of all patients receiving ibrutinib at a single tertiary care center were collected from electronic medical records. Univariate and multivariate statistical analyses were performed to find out the factors associated with infection. Results A total of 244 patients received ibrutinib for hematologic malignancies, of which 44 (18.0%) experienced ≥ 1 serious infection including 5 (2.0%) with IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis), 39 (16.0%) with bacterial infections and 8 (3.3%) with viral infections. Ten patients (4.1%) experienced multiple infections or co-infections while on ibrutinib and 10 (4.1%) expired or were transferred to hospice as a result of infection. In multivariate analysis risk factors that were less common in uninfected versus infected patients included advanced age (73 years vs. 77 years), Eastern Cooperative Oncologic Grade (ECOG) performance score ≥ 2 (6.5% vs. 31.8%) and concurrent use of steroids (4.5% vs. 20.5%) or other cytotoxic agents (0% vs. 4.6%). Conclusions There was a high rate of serious infection but relatively few IFI in patients receiving ibrutinib. Most patients who developed serious infections while on ibrutinib had additional predisposing risk factors including concurrent use of steroids or other cytotoxic agents, advanced age and frailty.

Hyperleukocytosis may lead to multiple medical emergencies. Hydroxyurea, intensive chemotherapy, and leukapheresis are used for cytoreduction. However, there is little data regarding the best approach. Here, we report on the efficacy and safety of high dose cyclophosphamide (HDCy; 60 mg/kg). 27 patients with acute myeloid leukemia or blast phase chronic myeloid leukemia who presented with white blood cell count (WBC) of ≥50x10

We report results on 23 patients with cutaneous T cell lymphoma (7 primary cutaneous γδ T cell lymphoma [PCGDT], 16 mycosis fungoides/Sézary syndrome [MF/SS]) who underwent allogeneic stem cell transplantation. All pts had skin involvement, 14 had total skin electron beam before conditioning. Donors were 10/10 HLA matched related (13), 5/10 haploidentical (4), and matched unrelated (5) or mismatched unrelated (1). Thirteen were in a clinical complete remission at the time of transplant. The 100-day transplant related mortality for the MF/SS and PCGDT patients was 12% and 29%, respectively. At a median follow up of 5.5 years, the overall survival and disease-free survival for MF/SS patients was 75% and 64%, respectively, and 6 of 10 MF/SS pts in long term complete response had a partial response at the time of transplant. Of seven PCGDT patients, four of seven are alive at a median follow up of 5 years and three are disease-free.

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has a high death rate in patients with comorbidities or in an immunocompromised state. We report a mild and attenuated SARS CoV-2 infection in a patient who is 17 months post stem cell transplantation and maintained on the JAK/STAT inhibitor ruxolitinib, a proposed novel therapy for SARS CoV-2 pneumonia.

Background Voriconazole is an azole antifungal utilized for prophylaxis and treatment of invasive fungal infections in hematologic patients. Previous studies have revealed decreased efficacy and increased toxicity with subtherapeutic 4 mcg/mL levels. A voriconazole dose modification guideline was introduced in July 2014 based on a retrospective analysis. Objective The primary objective was to evaluate the voriconazole dose modification guideline. Secondary objectives were to identify patient-specific characteristics that contribute to inadequate levels, adverse effects, and breakthrough invasive fungal infections. Methods This prospective study included 128 patients with 250 admissions who received voriconazole from July 2014 to February 2016. Eligible adult patients receiving voriconazole for prophylaxis or treatment with at least one trough level, drawn appropriately, were included. Demographics, adverse effects, and breakthrough invasive fungal infections were documented. Results Voriconazole use was categorized as: new start, new start with loading dose, or continuation of home therapy. The median initial levels were 1.5, 3.5, and 1.7 mcg/mL with 62% (73/119), 55% (6/11), and 60% (72/120) within the therapeutic range, respectively. Using the voriconazole dose modification guideline, 80% were within goal by the second dose adjustment. Age ≤ 30 and BMI ≤ 25 kg/m2 had higher rates of subtherapeutic levels in the new start cohorts ( p = 0.024 and p = 0.009). Approximately 7.6% of patients experienced an adverse effect with neurologic/psychological being the most common. A total of 8.5% of patients had a possible, probable or proven breakthrough invasive fungal infections while on voriconazole. Conclusion Using the voriconazole dose modification guideline, the number of patients that reached therapeutic range improved from 36% to 80% by the second dose adjustment ( p = 0.007). This voriconazole dose modification guideline can be utilized to help dose and adjust voriconazole in order to achieve therapeutic levels.

Patients with primary refractory or relapsed-acute myeloid leukemia (RR-AML), particularly older adults, have dismal outcomes and limited therapy options [1]. Given the tolerability of hypomethylat...

Background Ibrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib. Methods We performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection. Results A total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p < 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p < 0.001), neutropenia (OR 3.6, p < 0.01), lymphopenia (OR 2.4, p < 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p < 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments. Conclusion The incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib. Disclosures All Authors: No reported disclosures

Background Treatment of GvHD with steroids increases the risk of infection in HSCT patients due to additive immunosuppression and may delay the diagnosis of infection due to lack of symptoms. Outpatient surveillance blood cultures in HSCT with GvHD being treated with HD steroids has demonstrated a blood culture positivity rate of 3.5%. Currently, the utility of surveillance cultures in patients receiving LD steroid therapy is unknown. Our practice includes weekly outpatient surveillance cultures for all GvHD patients treated with steroids regardless of the dose. The primary endpoint of this study was to assess the incidence of positive surveillance blood cultures in GvHD patients receiving HD or LD steroids. Secondary endpoints included number of patients treated, hospitalization, 30 day mortality due to infection, and organisms isolated. Methods This was a single-center, retrospective review of GvHD patients at Yale New Haven Hospital between January 2013 and May 2019. Patients were excluded if: lack of signs or symptoms of GvHD, treatment with steroids for any indication other than GvHD, and active GvHD without central line. Cultures from patients receiving antibiotics for concurrent infection were also excluded. Results A total of 71 patients met criteria with 901 blood cultures. On HD, eight patients (14%) had 12 positive cultures (4%), and on LD, 16 patients (25%) had 22 positive cultures (4%) (p=0.15). Treatment occurred in six patients (75%) with four (24%) requiring hospitalization on HD, and 12 patients (75%) with 10 (83%) requiring hospitalization on LD (p=0.45). The median duration of steroid therapy was 93 and 236 days with a median dose of steroids of 1mg/kg/day and 0.15mg/kg/day, respectively. The number of positive cultures/1000 steroid days was 1.2 on HD and 0.5 on LD (RR 2.2). 30 day mortality was only noted in one patient (8%) on LD. The most common organism in both groups was Coagulase-negative staphylococci with all six cultures on HD classified as contaminants and 6/10 cultures requiring treatment on LD. Conclusion Although the relative risk of positive surveillance blood cultures in HD patients compared to LD was twofold higher, there were clinically significant infections identified in the LD group. Disclosures All Authors: No reported disclosures

Background Ibrutinib, a tyrosine kinase inhibitor used for treatment of hematologic malignancies, is associated with an increased risk of infection including invasive fungal infections (IFI). However, the risk of infection may vary across different types of malignancies. The primary aims of our study were to determine the incidence of serious infection and associated risk factors in different hematologic malignancies while on ibrutinib. Methods We performed a retrospective analysis of patients prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital between January 2014 and July 2019 by chart review. We collected demographic, and clinical data along with oncologic history, and identified serious infections defined as those requiring inpatient management. Chi-squared tests were used to determine characteristics associated with an increased risk of infection. Results A total of 254 patients on ibrutinib were identified including 156 with CLL, 89 with NHL including 20 with Mantle Cell Lymphoma (MCL) and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. Of 51 patients with serious infections, 10 (20%) had MCL, 11 (20.3%) had other NHLs, 28 (54.9%) had CLL and 2 (3.9%) had other malignancies. The relative frequency of serious infections was higher in MCL than non-MCL (50% vs. 17.1%). More MCL patients experienced IFI (1 pulmonary cryptococcosis, 2 pulmonary aspergillosis), compared to non-MCL patients (2 pulmonary aspergillosis; 15% vs. 0.9%). Risk factors associated with serious infection in MCL included maximum ibrutinib dose of 560 mg (OR 16.4, p < 0.001), other concurrent chemotherapy (OR 8.2, p < 0.001), prior HSCT (OR 5.9, p < 0.001), concurrent steroid use (≥ 10 mg prednisone for ≥ 2 weeks; OR 2.4, p < 0.05), lymphopenia (OR 2.4, p < 0.05) a history of prior chemotherapy (OR 0.2, p < 0.05) and ECOG score ≥ 2 (OR 3.2, p < 0.01). Conclusion In this study of hematologic malignancy on ibrutinib, MCL patients had a greater risk of serious infection. This increased risk in MCL could be associated with more prolonged and intense immunosuppression rather than underlying disease pathogenesis. Antimicrobial prophylaxis should be considered in MCL patients on ibrutinib to mitigate risk of infection. Disclosures All Authors: No reported disclosures

Peripheral CD34+ cells may be mobilized using filgrastim alone or in combination with chemotherapy. The addition of plerixafor can be efficacious, though guidelines for repeat dosing are lacking.This quality improvement project was initiated to generate guidelines for repeat plerixafor dosing after retrospective evaluation of data in adult patients undergoing autologous peripheral blood stem cell mobilization and collection.Analysis included 195 patients: 119 (61 %) with multiple myeloma and 76 (39 %) with lymphoma. Patients given at least one dose of plerixafor (n = 109) were further divided: Group 1) (A) goal of 3 × 10E6/kg and day 1 peripheral blood CD34+ count30 × 10E6/L, vs (B) ≥ 30 × 10 E6/L; Group 2) (A) goal of 6 × 10E6/kg and day 1 peripheral blood CD34+ count50 × 10E6/L or50 % of collection goal after day 1, vs (B) ≥ 50 % of collection goal after day 1. Ninety five percent of cases in Group 1B and 88 % of cases in Group 2B did not receive additional plerixafor doses and all of them achieved their collection goals. In contrast, those in Groups 1A and 2A required additional plerixafor dosing and some mobilizations/collections were futile.Based on these data, with consideration of collection goal, peripheral blood CD34+ count, and CD34+ cell bag count on collection day 1, we have generated institutional guidelines for collection initiation and repeat plerixafor dosing. Long term, we predict these guidelines will optimize pharmacy, apheresis, and stem cell processing resources while improving the patient experience.

Purpose Carmustine (BCNU) is used in the conditioning regimens BEAM and CBV for autologous stem cell transplantation. Carmustine-related infusion reactions, while not described in the BEAM literature, occurred in 95 % of patients who received CBV. The most common symptoms include flushing, facial pain, headache, and hypotension. These reactions have been attributed to the absolute ethanol that is used in the reconstitution process or alternatively by a direct effect of carmustine. It is currently recommended that carmustine 300 mg/m2 be infused over at least 100 min (3-5 mg/m2/min). Prior to October 2014, carmustine infusions were given over 90 min but were changed to 120 min based on the above recommendation. We compared the two infusion rates in patients receiving BEAM to see if lengthening the infusion decreased the frequency of reactions. Methods Overall, 100 patients received BCNU as part of BEAM or Zevalin BEAM and were equally divided between 90 and 120 min infusion times. The primary outcome was the incidence of infusion-related reactions which were graded based on CTCAE 4.03 descriptions of flushing and infusion-related reactions. We also evaluated the impact of premedication as well as the efficacy of medications used to treat infusion reactions. Results Between the years 2013-2016, there were 50 patients who received BCNU over 90 min and 50 patients over 120 min. There were no significant differences observed for diagnosis, age and gender between the two groups. Twenty-eight (56 %) in the 90-min and 26 (52 %) in the 120-min infusion intervals developed a reaction (p = 0.6882). Of the patients that developed a reaction, 19 patients (67 %) in the 90-min and all 26 patients (100 %) in the 120-min infusion were given premedications predominately acetaminophen, in addition to dexamethasone. Among reacting patients, 57 % of the 90-min and 65 % of the 120-min groups received additional intervention (p = 0.53). Conclusion Infusion reactions during high-dose BCNU are common and are not clearly reduced by modestly extending the duration of infusion or giving premedications.

Background Autologous stem cell transplantation remains important in the treatment of myeloma and relapsed lymphoma. Plerixafor has been shown to significantly enhance stem cell mobilization but is very expensive. Patients and Methods We evaluated plerixafor use in the 3-year period after its approval in December 2008. Results A total of 277 patients with myeloma and lymphoma had stem cell mobilization; 97.5% were successfully mobilized, including 41.5% who received plerixafor. Plerixafor was generally used for rescue after suboptimal granulocyte-colony stimulating factor (G-CSF) mobilization ("just in time") or for remobilization after an unsuccessful attempt with chemotherapy plus G-CSF. In addition, 10% of patients received planned G-CSF plus plerixafor because of high risk factors for inadequate collection. Rescue plerixafor was more effective in patients with myeloma than lymphoma as after 1 dose of plerixafor; 85% versus 55% collected a minimum number of stem cells (2 × 10E6 CD34 cells/kg) for 1 transplant and 51% versus 15% collected > 5 × 10E6 CD34 cells/kg. After transplantation, there were no significant differences in engraftment as a consequence of plerixafor use. Among all patients, there were less platelet transfusions in patients provided ≥ 3.5 × 10E6 CD34 + cells/kg. Conclusion With the judicious use of plerixafor, nearly all patients can collect enough stem cells to proceed to transplantation. Further studies, including hematologic tolerance to posttransplantation therapy, are required to determine the cost-effectiveness of using plerixafor to convert adequate to more optimal mobilizers.

Mucormycosis is a life threatening infection caused by fungi in the order Mucorales. Mucormycosis can affect any organ system with rhino-orbital-cerebral and pulmonary infections being the most predominant infection types. Gastrointestinal mucormycosis is rare and accounts for only 4–7% of all cases. Here, we present a case of invasive gastrointestinal mucormycosis in an immunocompromised host treated with systemic and topical anti-mold therapy.

Background Fever is a common component of cytokine release syndrome (CRS) occurring in 90% of patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Fevers typically occur between the stem cell infusion (Day 0) and initiation of post-transplant cyclophosphamide and are often confused with febrile neutropenia (FN). Due to longer time to engraftment in Haplo-HSCT, CRS/FN exposes patients to prolonged courses of empiric broad spectrum antibiotic (BSA) therapy increasing the risk for multi-drug resistant organisms. Recently, at Yale New Haven Health, our practice has changed to now recommend antibiotic de-escalation to prophylaxis after 7 days of BSA if no infection is identified. The objective of this study was to assess the incidence of breakthrough infections with the de-escalation of BSA in CRS/FN. Secondary endpoints include rate of FN, rate of de-escalation, rate of recurrent fevers, duration of BSA, and positive blood culture data. Methods The patient population included those undergoing Haplo-HSCT between July 2016 and February 2020 and who developed CRS/FN between Day 0 and Day +5. Patients were excluded if they had prolonged hospitalization due to non-infectious complications or engraftment failure. Bacteremia was defined using NHSN definitions. Results Of the 53 Haplo-HSCTs assessed, 43 experienced CRS/FN. Thirty-five Haplo-HSCT (81%) with CRS/FN had negative cultures and 23 (66%) of these were de-escalated back to antibacterial prophylaxis. The median duration of BSA in the de-escalated group was 7 days (range 5–13) compared to 16.5 days range (13–21) in the non-de-escalated group (p< 0.001). Among those de-escalated, 7 (30%) had recurrent fever occurring at a median of 4 days (range 2–14) and were placed back on BSA. Two Haplo-HSCT (9%) that had fever after de-escalation developed a breakthrough bacteremia. No Haplo-HSCT after de-escalation had fever or re-admission for bacteremia 30 days after engraftment. Four Haplo-HSCT (9%) with CRS/FN had positive blood cultures; however, three (7%) were still able to be de-escalated from BSA to narrower agents based on susceptibilities. Conclusion De-escalation of BSA in FN/CRS in Haplo-HSCT patients reduced unnecessary, prolonged antibiotic exposure with a low incidence of breakthrough infections. Disclosures All Authors: No reported disclosures

Introduction T-NHL are associated with an aggressive clinical course and poor outcomes. The role of PET-CT at the time of SCT (pre-SCT), BM biopsy, and peripheral blood (PB) flow cytometry have not been well investigated. We retrospectively analyzed 83 pts with T-NHL undergoing auto or allo SCT to determine the predictive value of pre-SCT PET-CT scan, BM and PB flow for relapse-free survival (RFS) and OS. Methods PET CR was defined as the absence of any radiographic dz by PET-CT (5-pt score). Overall CR was defined as negative PET, BM and PB flow. Pre-SCT variables were assessed for their effects on RFS and OS: age, number of previous lines of therapy, CIBMTR dz risk, pre-SCT BM, pre-SCT PB flow, and pre-SCT PET-CT. Results Of 83 pts studied, 49 were autoSCT and 34 were alloSCT. Six pts who underwent alloSCT had received a prior autoSCT. Diagnosis was PTCL NOS 34, AITL 23, CTCL/Sezary syndrome 11, nasal NK-T 6, EATL 3, SPTCL 2, hepatosplenic 1, ALK-ALCL 1, HTLV-2 ATL 1, T-lymphoblastic 1. The majority of pts with AITL (16/23) underwent autoSCT upfront. Conditioning for autoSCT was BEAM. Conditioning for alloSCT was Pentostatin/TBI in all but 6 SCT. Median lines of therapy prior to SCT were 1 for auto and 4 (r 2-13) for alloSCT. Median age at SCT was 60 (r 20-75). A total of 6 out of 49 (12%) autoSCT and 8 out of 34 (24%) alloSCT had positive PET-CT (score 4-5) at the time of SCT. BM was positive in 8 out of 49 (16%) at the time of autoSCT and 7 out of 34 (21%) at the time of alloSCT. PB flow was positive in 9 out of 49 (18%) at the time of auto SCT and 6 out of 34 (12%) at the time of alloSCT. CIBMTR dz index was low in 57(69%), intermediate in 15(18%), and high in 11 (13%) of 83 SCT. The majority of allo-SCT were intermediate-high risk. The median follow-up 56 months (r 6 - 122). Twenty (24%) pts had expired. Univariate analysis of pre-autoSCT variables did not reveal statistically significant (SS) results for BM or PET positivity. Univariate analysis of pre-alloSCT variables identified positive BM and positive PET/CT scan as being SS. There was a SS lower incidence of relapse, longer RFS and OS in alloSCT pts with either negative pre-SCT PET-CT scan or negative pre-SCT BM. Other pre-SCT variables tested were not SS. In multivariate analysis, pre-alloSCT PET-CT alone retained SS. Pre-alloSCT PET-CT scan was a strong predictor of 2-yr RFS and 2-yr OS. Conclusion This data indicates that in heavily pretreated pts with T- NHL undergoing alloSCT, a negative pre-SCT PET-CT is a statistically significant predictor of long-term RFS and OS regardless of dz risk and number of lines of therapy. Due to the small number of autoSCT with positive PET-CT scans, BM biopsy, or PB flow at the time of SCT, no association between the above-mentioned variables and relapse was identified. Further studies with larger numbers of pts are warranted to determine the role of pre-autoSCT PET-CT, BM and PB flow as prognostic factors in T-NHL.

BACKGROUND Current guidelines recommend adding vancomycin to empiric treatment of FN in patients who meet specific criteria. After 48 hours, the guidelines recommend discontinuing vancomycin if resistant Gram-positive organisms are not identified. Based on these recommendations, a vancomycin stewardship team defined criteria for discontinuation of vancomycin at 48 hours and increased surveillance of vancomycin usage through a multimodal approach. The purpose of this retrospective analysis is to assess the impact of this multimodal approach on the discontinuation of empiric vancomycin at 48 hours in FN. METHODS This retrospective analysis included a pre- and post-intervention cohort of 200 HSCT recipients with FN from 2015 to 2018. Criteria for continued vancomycin use beyond 48 hours included culture-documented resistant Gram-positive infection, positive Methicillin-Resistant S aureus (MRSA) nasal swab with evidence of pneumonia, or hemodynamic instability with concern for sepsis. The following patient characteristics were collected: previous MRSA infection, MRSA nasal swab collection and results, culture results, duration of vancomycin use, rationale for continuation of vancomycin beyond 48 hours, and re-initiation of vancomycin. RESULTS In the post-intervention cohort, vancomycin discontinuation at 48 hours increased from 31% (95% CI 21.94-40.05) to 70% (95% CI 61.02-78.97; P

Patients with primary refractory or relapsed acute myeloid leukemia (RR-AML) have very poor prognosis. Due to limited treatment options, some patients are treated with hypomethylating agents (HMAs) due to their tolerability. Little is known about the role of allogeneic hematopoietic stem cell transplantation (HSCT) following HMA therapy in this setting. We retrospectively analyzed an international cohort of 655 RR-AML patients who received HMA therapy to study patterns and outcomes with HSCT. Only 37 patients (5.6%) patients underwent HSCT after HMA therapy. The conditioning regimen was myeloablative in 57% and nonmyeloablative in 43%. Patients received matched unrelated donor, matched sibling, haploidentical and mismatched unrelated HSCT in 56%, 24%, 16% and 4% of cases, respectively. Acute GvHD and chronic GvHD were observed in 40% and 17% of patients. While the median OS for the entire cohort of patients was 15.3 months (95% CI 9.5 - 21.7 months), OS reached 29.7 months (95% CI 7.01 - not-reached) for patients who achieved a complete remission (CR) to HMA and no intervening therapies between HMA therapy and HSCT. Our study suggests that HMA therapy can effectively bridge some patients with RR-AML to HSCT. (C) 2018 American Society for Blood and Marrow Transplantation.

Although hypomethylating agents (HMAs) are frequently used in the frontline treatment of older acute myeloid leukemia (AML) patients, little is known about their effectiveness in relapsed or primary treatment–refractory (RR)-AML. Using an international multicenter retrospective database, we studied the effectiveness of HMAs in RR-AML and evaluated for predictors of response and overall survival (OS). A total of 655 patients from 12 centers received azacitidine (57%) or decitabine (43%), including 290 refractory (44%) and 365 relapsed (56%) patients. Median age at diagnosis was 65 years. Best response to HMAs was complete remission (CR; 11%) or CR with incomplete count recovery (CRi; 5.3%). Additionally, 8.5% experienced hematologic improvement. Median OS was 6.7 months (95% confidence interval, 6.1-7.3). As expected, OS differed significantly by best response, with patients achieving CR and CRi having a median OS of 25.3 and 14.6 months, respectively. In multivariate analysis, the presence of ≤5% circulating blasts and a 10-day schedule of decitabine were associated with improved response rates, whereas the presence of >5% circulating blasts and >20% bone marrow blasts were associated with decreased OS. A significant subset of RR-AML patients (16%) achieved CR/CRi with HMAs and experienced a median OS of 21 months. Outside of a clinical trial, HMAs represent a reasonable therapeutic option for some patients with RR-AML.

Background Methicillin-Resistant Staphylococcus aureus (MRSA) nasal swabs are utilized to guide discontinuation of empiric MRSA therapy. In multiple studies, MRSA nasal swabs has been shown to have a negative predictive value (NPV) of ~99% in non-oncology patients with pneumonia and other infections. At Yale New Haven Hospital (YNHH), a negative MRSA nasal swab is utilized in acute myeloid leukemia (AML) patients to de-escalate empiric MRSA antibiotic therapy. The primary endpoint was to assess the percentage of patients with a negative MRSA nasal swab who developed a culture documented (CD) MRSA infection during their admission. Secondary endpoints included the number of MRSA nasal swabs that were initially negative but converted to positive, and the types of MRSA infections. Methods This was a retrospective chart review of AML patients with a suspected infection and a MRSA nasal swab collected at YNHH between 2013 and 2018. Patients were excluded if < 18 years old, prior confirmed MRSA infection or positive MRSA nasal swab within the past year. Results 194 patients were identified with 484 discrete encounters analyzed. Hematopoietic stem cell transplantation occurred in 83 (43%) patients. A total of 468 (97%) encounters had a negative MRSA nasal swab upon admission with no CD MRSA infection during their hospitalization. Three encounters (0.6%) had a negative MRSA nasal swab with a subsequent CD MRSA infection during their admission. Identified infections were bacteremia (2) and pneumonia (1). Median duration from the negative MRSA nasal swab to CD infection was 16 days. Thirteen encounters (3%) had a positive MRSA nasal swab, 5 of which had a CD MRSA infection. Infections included bacteremia (3), pneumonia (2), and sputum with negative chest X-ray (1). MRSA nasal swab had a sensitivity of 57% (CI 0.56–0.58), specificity of 98% (CI 0.98–0.98) positive predictive value of 31% (CI 0.3–0.32), and NPV of 99% (CI 0.99–0.99). Conclusion The results of this retrospective study demonstrate that a negative MRSA nasal swab has a 99% NPV for subsequent MRSA infections in AML patients with no prior history of MRSA colonization or infection. Based on these findings, a negative MRSA nasal swab can help guide de-escalation of empiric MRSA antibiotic therapy in this immunosuppressed population. Disclosures All authors: No reported disclosures.

Prolonged and profound neutropenia is common among hematology and hematopoietic stem cell transplant (HSCT) patients as a result of chemotherapy. The National Comprehensive Cancer Network (NCCN) and Infectious Diseases Society of America (IDSA) currently recommend antibacterial prophylaxis in patients who are deemed at intermediate or high risk for infection. Specifically, fluoroquinolone prophylaxis should be considered for high-risk neutropenic patients. However, with prolonged and frequent exposure to fluoroquinolones, these high-risk patients may develop resistance to these agents. Patients may also have allergies or other contraindications which prohibit the use of fluoroquinolones for antibacterial prophylaxis. Unfortunately, there is no standard recommendation for alternative antimicrobial therapy in this patient population, as well as there is a lack of data to support the use of potential alternative agents. Currently, Yale-New Haven Hospital utilizes fosfomycin for antibacterial prophylaxis in patients who are not eligible for fluoroquinolone therapy. The primary objective of this study was to assess the incidence of breakthrough infections in this population receiving fosfomycin. Secondary objectives included organisms identified, types of breakthrough infections, resistance patterns, and time from initiation to onset of fever. Of the 42 patients who received fosfomycin, 25 patients with 42 admissions met inclusion criteria. A total of 8 (19%) breakthrough infections occurred during the 42 admissions. Organisms included Klebsiella spp. (5), Streptococcus mitis/viridans (2), Pseudomonas aeruginosa (1), and coagulase-negative staphylococcus (1). Infections included the following: bacteremia (7), cellulitis (1), and urine (1). Given the low rate of breakthrough infections, fosfomycin may be a potential alternative option for antibacterial prophylaxis.

Background HSCT patients are at an increased risk of developing PJP after transplant due to treatment induced immunosuppression. Given the risk of cytopenias with co-trimoxazole, AP is utilized as an alternative for PJP prophylaxis. A prior study revealed a 0% (0/19 patients) incidence when AP prophylaxis was given for one year post autologous HSCT. Current guidelines recommend a duration of 3 – 6 months for PJP prophylaxis in autologous HSCT. The primary endpoint of this study was to assess the incidence of PJP infection within one year post autologous HSCT in patients who received 3 months of AP. Secondary endpoint was a cost comparison of 3 months compared with 6 months of AP. Methods A single-center, retrospective study of adult autologous HSCT patients at Yale New Haven Hospital between February 2013 and December 2017 was performed. Patients were excluded if: 3 months of AP, changed to alternative PJP prophylactic agent or received no PJP prophylaxis, received tandem HSCT, deceased prior to one year post-transplant from a non PJP-related infection, HIV positive, or lost to follow-up. Pentamidine was given as a 300 mg inhalation monthly for 3 months starting Day +15 after autologous HSCT. Results A total of 288 patients were analyzed, no PJP infections occurred within one year post HSCT. Additionally, 187 (65%) patients received treatment post HSCT with 135/215 (63%) receiving maintenance immunomodulatory drugs for myeloma and 40/288 (14%) patients developing relapsed disease. 43% of the chemotherapy regimens for relapsed disease included high dose corticosteroids. The cost difference of using 3 months vs. 6 months of AP is $790, reflecting the cost of drug and its administration. Applying our incidence of 0%, potential cost savings of 3 months vs. 6 months of AP would be $330,000 over 5 years or $66,000 per year. Conclusion Three months of AP for PJP prophylaxis in autologous HSCT patients is safe and effective as well as cost-effective compared with a 6 month regimen. Disclosures All authors: No reported disclosures.

Introduction T-cell lymphomas are heterogenous group of neoplasms associated with generally unfavorable outcomes. High dose chemotherapy and autologous stem cell transplant (SCT) consolidation is a standard approach in first remission while allogeneic SCT (alloSCT) is recommended in the relapsed/refractory setting. Data on outcomes after alloSCT are limited, particularly in the era of brentuximab. Methods We retrospectively analyzed data from patients (pts) with T-cell lymphomas who underwent alloSCT in our institution from 11/2010–6/2018. Patient and disease characteristics were summarized using median and range for continuous data, and frequency and percentage for categorical data. Kaplan-Meier analysis was used to estimate progression free survival (PFS) and overall survival (OS) from the day of receipt of transplant. Survival probabilities were expressed by 95% confidence limits (CI). Results Thirty-three pts received alloSCT. Median age at transplant was 57 years (range [R], 22-73). T-cell lymphoma types included: cutaneous T-cell lymphoma, n = 12; NK-T cell, n = 4; peripheral T-cell lymphoma subtypes, n = 9; angioimmunoblastic T lymphoma, n = 6; T-cell rich B-cell, n = 2. Median lines of therapy prior to alloSCT were 4 (R, 2-13), including six with prior autologous SCT. Sixteen pts were transplanted in CR1, five in CR2, and three in CR3. Pentostatin/TBI was the most common pretransplant conditioning regimen (n = 23) followed by haplo regimen of Flu/TBI/Cy (n = 4). Donor transplant sources were MRD (16), MUD (8); Haplo (4), MMUD (5). Median days to neutrophil and platelet engraftment were 12 (R, 10-19) and 13 (R, 10-30), respectively. Cumulative incidence of grade II-IV acute and chronic GVHD were 24.2% and 45.4%, respectively. One-year PFS and OS probabilities were 69.5% (95% CI, 54.7- 88.4) and 87.1% (95% CI, 54.7-88.4), respectively. With a median follow up of 53 months (R, 2-97), 25 (75%) are alive and 24 are disease free. Four died from transplant related mortality (TRM) and 3 from relapse. The median time to relapse was 3.9 months [R, 2.2-12.5]). The cumulative incidence of GVHD was higher among patients who were relapse-free (71% vs 22% in relapsed pts, p=0.02). Seven of the 9 who relapsed were treated with brentuximab vedotin; of these 4 responded, including two patients who had haplo transplants. Conclusions Results from our study suggest that alloSCT in T-cell lymphomas with reduced intensity regimens are associated with overall favorable outcomes. Treatment of post-transplant relapse with brentuximab is feasible and should be explored further in long-term prospective studies.

Background The Infectious Diseases Society of America and the National Comprehensive Cancer Network guidelines recommend adding vancomycin to the empiric treatment of NF in patients meeting specific criteria. After 48 hours, the guidelines recommend discontinuing vancomycin if resistant Gram-positive organisms are not identified. An analysis of vancomycin use for NF at our institution revealed 35% of patients had vancomycin discontinued appropriately at 48 hours. Based on these results, a vancomycin stewardship team defined criteria for continuation of vancomycin past 48 hours and increased surveillance of vancomycin usage through AST oversight. The objective of this study is to assess the incidence of vancomycin discontinuation at 48 hours with the new criteria of use and the addition of pharmacist led stewardship. Methods This study included NF patients who were treated with an antipseudomonal β-lactam and vancomycin from January to April 2017. Criteria for vancomycin continuation beyond 48 hours included culture-documented Gram-positive infection, positive Methicillin Resistant S.aureus (MRSA) nasal swab with evidence of pneumonia, or hemodynamic instability due to septic shock. Patients who received aztreonam, or a single dose of vancomycin were excluded. Patient characteristics, previous MRSA infection, MRSA nasal swab collection and results, culture results, fever status, duration of vancomycin, rationale for continuation of vancomycin past 48 hours, re-initiation of vancomycin, and AST recommendations were collected. Results Sixty-nine patients with 73 admissions were initiated on vancomycin for NF during the study period. Vancomycin was appropriately discontinued in 63% (46/73) compared with 35% (19/54) previously. An additional 8% (6/73) was discontinued between 48 and 72 hours, and 20% (15/73) was continued past 72 hours inappropriately. The most common reasons for continuation was lack of neutrophil recovery (5) and cellulitis (4). AST recommended discontinuation on 5 patients, all of which were accepted. Conclusion Establishing criteria for vancomycin use along with pharmacist led antibiotic surveillance, AST, and provider education improved the use of vancomycin with the discontinuation rate increasing from 35% to 63%.(P = 0.002) Disclosures All authors: No reported disclosures.

Background HSCT patients are at an increased risk of developing infections after transplant due to the loss of immunogenicity from prior vaccinations. Current national and international guidelines recommend routine revaccinations at a fixed dosing schedule for HSCT patients post-transplant. Although immunization adherence is vital to prevent infections, compliance with post-transplant vaccinations is unknown. The primary endpoint of this study was the completion rate of the post-transplant vaccination series. Secondary endpoints included identifying reasons for noncompliance, rates of breakthrough vaccine-preventable infections, and assessing post-vaccination antibody responses based on titers. Methods A single-center, retrospective study of adult HSCT patients at Yale New Haven Hospital between January 2010 and September 2015 was performed. Patients were excluded if

Arsenic trioxide has been established for use in both relapsed and front-line treatment of acute promyelocytic leukemia. Dose adjustments are recommended to be considered in severe renal impairment although dosage reduction guidelines are not provided. In addition, toxicities of arsenic are significant. The use of arsenic trioxide has not been well studied in dialysis patients and there is a paucity of data in the literature to support the use in such a situation. We describe an 81-year-old relapsed acute promyelocytic leukemia hemodialysis-dependent patient with a pre-existing cardiac condition who was treated with 10 mg arsenic trioxide three times weekly after dialysis. These findings provide support along with the marginal amount of currently published data for an arsenic trioxide dosing regimen in hemodialysis patients.

After allogeneic stem cell transplant, severe grade III-IV gastrointestinal (GI) acute GvHD is associated with significant morbidity and mortality, and generally results in poor outcomes. Salvage therapy for patients who fail steroid therapy is not well defined in the literature. In the current retrospective study, we reviewed our experience with the combination of basiliximab and infliximab in 21 patients with severe, grade III-IV GI acute GvHD of whom 16 met the definition for steroid-refractory disease. The overall response rate was 76%, with 43% CR at a median time of 21 days after beginning treatment. The survival at 1 year was 24%, with most deaths due to complications from GvHD and recurrence of primary disease. All five of the long-term survivors have chronic GvHD. On the basis of a review of the literature, this regimen does not seem to be significantly more effective than other strategies for severe GI GvHD and seems to be worse than the results reported for basiliximab alone. Future studies of single-agent basiliximab and newer agents are required.

Introduction: Patients with RR-AML, particularly older adults, have dismal outcomes and limited therapy options. Given low response rates and high toxicity with salvage intensive chemotherapy, and frequent ineligibility for allogeneic stem cell transplantation (alloSCT), many patients are treated with HMAs. Robust data regarding use of HMAs in AML predominates in the frontline setting, while their use in RR-AML has limited supportive data. Here wesought to analyze theoutcomes and their predictors in patients with RR-AML treated with HMAs. Methods:We collected data, spanning a period from 2006 to 2016, from 7 centers in the United States and 4 centers in Europe regarding patients treated with HMAs for RR-AML. Responses were defined by International Working Group criteria. Kaplan-Meier methods estimated overall survival (OS) from initiation of HMAs to death or end of follow-up. Multivariable logistic regression models estimated odds for response, and multivariable Cox Proportional Hazard (CPH) models estimated hazards ratios (HR) for OS. Covariates considered included HMA received, age at diagnosis (in years), AML classification at diagnosis (AML with myelodysplasia-related changes [AML-MRC], therapy-related [t]-AML), disease status (relapsed vs. refractory), number of therapy lines prior to HMA (1 vs. 2 vs. >=3), duration of first complete remission (CR1), white blood cell count, peripheral blood blast percentage, bone marrow (BM) cellularity ( 20%), BM blast percentage (20%), cytogenetic risk group, and the presence of complex or chromosome 7 abnormalities. Results: Of 514 patients, 217 patients (42.2%) had refractory and 297 (58%) had relapsed AML. By end of study, 415 patients (88.5%) had died. Median follow-up for living patients was 11.6 months.Median age at diagnosis was 64 years (range [R], 16-92). AML-MRC was diagnosed in 29.0% while 8.2% had t-AML. Median number of prior therapies was 2 (R, 1-7), with 48.3% receiving 1 prior line, 30.2% receiving 2 prior lines, and 21.5% receiving >=3 prior lines. Prior alloSCT was performed in 21.2%. Only 1.9% had good risk (core binding factor) karyotype, while 56.2% had intermediate risk karyotype, and 41.9% had poor risk karyotype. Azacitidine was used in 45.8% and decitabine in 54.2%; median number of azacitidine cycles was 4 (Interquartile range [IQR], 2-6) compared to 2 for decitabine (IQR, 1-4, p Conclusions: In this largest reported cohort of patients with RR-AML treated with HMAs, we found that HMAs are often used as alast line of therapy, with a minority of patients receiving subsequent treatment. Nonetheless, the minority of patients who achieve CR (11.7%) with HMA therapy had a median OS of 25.6 months. Therefore, use of HMAs for management of RR-AML is a reasonable intervention in the absence of clinical trial options. There appears to be no difference in OS or probability of achieving CR+CRi based on HMA used. Ongoing analyses in this dataset include further evaluations of predictors, including genetic mutations, and the development of prediction tools for clinical outcomes with HMA therapy. Figure 1. Figure 1. Disclosures Podoltsev: Ariad: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Ritchie:Novartis: Honoraria; Incyte: Speakers Bureau; Arian: Speakers Bureau; Pfizer: Honoraria; Celgene: Speakers Bureau. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Komrokji:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Speakers Bureau. Al-Kali:Onconova Therapeutics, Inc.: Research Funding; Celgene: Research Funding. Santini:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Onconova: Consultancy; Amgen: Consultancy; Astex: Consultancy. Roboz:Cellectis: Research Funding; Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy. Fenaux:Celgene, Janssen,Novartis, Astex, Teva: Honoraria, Research Funding. Prebet:celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Gore:celgene: Consultancy, Honoraria. Zeidan:Ariad: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

Purpose. The pharmacology, pharmacokinetics, dosage and administration, efficacy, safety, effects on quality of life, and place in therapy of romiplostim are reviewed. Summary. Romiplostim is a second- generation thrombopoietic agent that stimulates the thrombopoietin receptor and platelet production without inducing production of autoantibodies. Romiplostim, a peptibody, bears no structural resemblance to endogenous thrombopoietin, thus minimizing the risk for development of thrombopoietin autoantibodies. Clinical trials have shown that romiplostim increases platelet counts compared with placebo in both splenectomized and non-splenectomized adult patients with chronic idiopathic thrombocytopenic purpura (ITP). Clinical trials with romiplostim are ongoing for patients with myelodysplastic syndrome and those receiving chemotherapy for treatment of malignancies. Romiplostim may confer an increased risk of bone marrow reticulin formation or fibrosis, malignancy, thrombosis, and thrombocytopenia that is more severe than the level present before initiation of romiplostim. While all patients receiving romiplostim in clinical trials experienced at least one adverse event, most were mild to moderate in severity. The most frequent adverse effects were ecchymosis, headache, and petechiae. Romiplostim is initiated at a dosage of 1 μg/kg subcutaneously once weekly and titrated to achieve platelet counts between 50 and 200 × 109 platelets/L, with a maximum dose of 10 μg/kg. Romiplostim is only available through the manufacturer’s risk-management program. The current wholesale price of romiplostim is $1,062.50 for a single-use vial of 250 μg or $2,125 for a single-use vial of 500 μg. The extrapolated drug cost for weekly dosing for one year is approximately $55,250. Conclusion. Romiplostim is a novel thrombopoietic-stimulating agent for use in patients with chronic ITP who have not responded to other therapies.

At high latitudes, such as in Iceland, the daily photoperiod varies from almost continuous darkness in winter to virtually constant light in summer. Previous studies of detailed retinal structure in vertebrates have shown significant daily and annual effects of photoperiod. We sampled arctic charr in Iceland during the summer, including fish that were both light- and dark-adapted, during both day and night. We observed retinomotor responses characteristic of light- and dark-adaptation, but found no difference in the number of synaptic ribbons in the retina. The morpho-physiological changes, appearing as retinomotor responses, are thus not expressed at the synaptic level.