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Background and Purpose— Industry payments to physicians raise concerns regarding conflicts of interest that could impact patient care. We explored nonresearch and nonownership payments from industry to vascular neurologists to identify trends in compensation. Methods— Using Centers for Medicare and Medicaid Services and American Board of Psychiatry and Neurology data, we explored financial relationships between industry and US vascular neurologists from 2013 to 2018. We analyzed payment characteristics, including payment categories, payment distribution among physicians, regional trends, and biomedical manufacturers. Furthermore, we analyzed the top 1% (by compensation) of vascular neurologists with detailed payment categories, their position, and their contribution to stroke guidelines. Results— The number of board certified vascular neurologist increased from 1169 in 2013 to 1746 in 2018. The total payments to vascular neurologist increased from $99 749 in 2013 to $1 032 302 in 2018. During the study period, 16% to 17% of vascular neurologists received industry payments. Total payments from industry and mean physician payments increased yearly over this period, with consulting fee (31.1%) and compensation for services other than consulting (30.7%) being the highest paid categories. The top 10 manufacturers made the majority of the payments, and the top 10 products changed from drug or biological products to devices. Physicians from south region of the United States received the highest total payment (38.72%), which steadily increased. Payments to top 1% vascular neurologists increased from 64% to 79% over the period as payments became less evenly distributed. Among the top 1%, 42% specialized in neuro intervention, 11% contributed to American Heart Association/American Stroke Association guidelines, and around 75% were key leaders in the field. Conclusions— A small proportion of US vascular neurologists consistently received the majority of industry payments, the value of which grew over the study period. Only 11% of the top 1% receiving industry payments have authored American Heart Association/American Stroke Association guidelines, but ≈75% seem to be key leaders in the field. Whether this influences clinical practice and behavior requires further investigation.

Outcomes after allogeneic stem-cell transplantation (AHSCT) are influenced by both disease- and patient-related factors. Here, we developed a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), by combining the refined disease risk index (DRI-R) and hematopoietic stem-cell transplant comorbidity/age index (HCT-CI/Age) to predict post-transplant survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The analysis included 942 AML/MDS patients treated with AHSCT. Patients were stratified into 4 HCT-CR risk groups: Low-risk—patients with low/intermediate DRI-R and HCT-CI/Age ≤3 (N = 272); Intermediate-risk—patients with low/intermediate DRI-R and HCT-CI/Age >3 (N = 168); High-risk—patients with high/very high DRI-R and HCT-CI/Age ≤3 (N = 284); and Very high-risk—patients with high/very high DRI-R and HCT-CI/Age >3 (N = 184). Compared with the low-risk group, intermediate, high, and very high-risk groups had a significantly increased risk of death [adjusted HR of 1.37 (P

Ibrutinib, a Bruton's tyrosine kinase inhibitor has reformed the treatment of various B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Although generally well tolerated, here we describe our institutional experience of unique adverse effects encountered with the use of ibrutinib in patients with B-cell lymphomas.This is a retrospective observational study done at a tertiary care facility, to evaluate adverse events in patients with B-cell malignancies on treatment with ibrutinib between 2014 and 2018. Further details including type of malignancy, cytogenetics, interventions for treatment of the side effect, and outcomes were obtained through electronic health record.We found 10 patients with unique adverse events related to ibrutinib. Among those, six had chronic lymphocytic leukemia, two had Waldenstrom's macroglobulinemia, and two had mantle cell lymphoma. The events included palindromic rheumatoid arthritis, diffuse spongiotic dermatitis, bullous pemphigoid, recurrent hemorrhagic stroke, peripheral neuropathy, recurrent paronychia, intramedullary fibrosis, recurrent joint pains, pulmonary aspergillosis, dyspnea with exacerbation of atrial fibrillation, and resolution of autoimmune hemolytic anemia.Our case series illustrates the wide variety of unique events recognized in patients treated with ibrutinib, some of which required cessation and most had dose reduction of the treatment. Thus, stressing the importance of early identification and intervention for the events to avoid worsening of toxicity and inability to continue treatment in such patients.

TO THE EDITOR: Allogeneic hematopoietic stem-cell transplantation (ASCT) is curative treatment for patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), who otherwise have dismal outcomes.[1][1][⇓][2][⇓][3]-[4][4] The TP53 gene is located in the 17p13

7527 Background: Patients with Chronic Lymphocytic Leukemia (CLL) are susceptible to infections due to impaired humoral immunity as a complication of the disease, treatments received and age at diagnosis. Herpes zoster (HZ) is a painful, vesicular rash from reactivation of varicella-zoster virus that is common in immunocompromised patients. While HZ vaccines can reduce both varicella-zoster reactivation and post-herpetic neuralgia, vaccination rates are low. The aim of this study is to determine the effect of vaccination on rates of HZ infection in patients with CLL. Methods: We identified patients diagnosed with CLL between September 1999 and October 2015 using Veterans Administration Central Cancer Registry (VACCR). Pharmacy records were used to identify patients who received treatment for CLL and HZ. HZ events were defined as patients with International Classification of Diseases 9th Revision (ICD-9) codes for HZ infection (053) or prescriptions of acyclovir or valacyclovir at a dose of 1500 mg/day or higher or famciclovir at a dose of 1000 mg/day or higher without a diagnosis of Herpes simplex or Bell’s palsy, or an ICD-9 code and prescription above. Cox proportional hazards regression model was used to assess the association between vaccination as a time-varying exposure and developing HZ while controlling age at CLL diagnosis, co-morbidity score, and receipt of first and second line chemotherapy. The study was approved by the St. Louis VA Medical Center institutional review board. Results: A cohort of 7155 patients with CLL was identified using VACCR. 2640 patients (36.9%) and 1161 patients (16.2%) received first and second line chemotherapy respectively. Mean age at first chemotherapy was 69.5 years. We detected 1115 cases of HZ (15.6%) using ICD-9 codes, prescriptions or both. 615 patients (8.6%) received HZ vaccinations. Patients with HZ were younger (mean 68.0 vs. 69.8 years, p < 0.001), had similar co-morbidities, and were more likely to get treatment for CLL (58.1% vs. 33.0%, p < 0.001). Using a time-varying analysis, there was a trend for HZ vaccine to decrease the risk of developing HZ (HR 0.71, 95% CI 0.49-1.04, p = 0.082). When adjusting for age and co-morbidity, patients with CLL treated with first line chemotherapy had a higher risk of HZ (HR 2.34, 95% CI 2.02-2.71, p < 0.001) compared to those never receiving therapy. Second line chemotherapy increased risk of HZ (HR 1.32, 95% CI 1.13-1.55, p < 0.001) beyond first line treatment. Conclusions: HZ is prevalent in patients with CLL and affects younger patients who require chemotherapy. The risk of developing HZ increases in recipients of first and second line chemotherapy. In the time-varying analysis, there was a trend towards decreased infection in patients who received HZ vaccination. Further studies in a more modern cohort that assess infection risk using a larger vaccinated group with the newer and more effective HZ vaccine are warranted.

Clostridium perfringes is a gram-positive, rod-shaped, anerobic, spore-forming pathogenic bacterium. C. perfringes is commonly known to cause tissue necrosis and gas gangrene. However, severe life-threatening complications like hemolysis due to clostridium sepsis are rarely encountered. We present a case of a 35-year-old female presenting with endometritis complicated with severe hemolysis in the setting of sepsis secondary to C. perfringes . Her hospital course was complicated with multi-organ involvement, requiring broad-spectrum intravenous antibiotics. Eventually, she made an uneventful recovery by early recognition of these rare complications and prompt institution of appropriate therapy. J Hematol. 2017;6(2-3):59-61 doi: https://doi.org/10.14740/jh328w

Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome. It is categorized as familial or acquired, most commonly caused by infections, malignancies, rheumatologic and immunodeficiency disorders. Irrespective of the etiology, the age at the onset is the strongest prognostic factor, hence it is extremely important to have a high suspicion for HLH, diagnose it promptly and initiate treatment without any delay. We encountered a 70-year-old female patient who initially presented with left-sided facial weakness and pancytopenia, secondary to diffuse stage IV B diffuse large B-cell lymphoma with isolated bone marrow involvement with secondary HLH. J Hematol. 2017;6(2-3):49-51 doi: https://doi.org/10.14740/jh324w

Introduction Outcomes after allogeneic stem cell transplant (AHSCT) are influenced by both disease and patient related factors. We hypothesized that combining hematopoietic stem cell transplant comorbidity-age index (HCT-CI/Age) and the refined disease risk index (DRI-R) would better predict survival post-transplant and developed a hematopoietic cell Transplant-composite risk (HCT-CR) model, which we tested in a group of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treated at MD Anderson Cancer Center (MDACC). Methods The study included consecutively treated patients, 18 years of age or older, with AML and MDS who received first AHSCT at MDACC between 2005-2016. Donors were HLA-matched related (MRD), HLA-matched unrelated (MUD), 9/10 MUD (MMUD), haploidentical (HAPLO) and 9/10 MRD (MMRD). To develop this model, patients were assigned into 4 groups: 1. Patients with low/intermediate DRI-R and HCT-CI/Age 3 (intermediate-risk); 3. Patients with high/very high DRI-R and HCT-CI/Age 3 (very high-risk). Primary endpoint was 5-year overall survival (OS); other outcomes assess were progression-free survival (PFS), non-relapse mortality (NRM) and relapse rate. The stability of the HCT-CR model was tested by bootstrap resampling. The discrimination power of the HCT-CR model on OS was compared with that of the DRI-R, HCT-CI/Age and cytogenetic risk model by the Harrell C-concordance index. Results The analysis included 942 patients (492 male and 450 female) with a median age of 53 years (range 18-65 years). Cytogenetic data at diagnosis was available in 928 (98.5%) patients and was favorable, intermediate and adverse cytogenetic risk in 63 (7%), 523 (56%) and 342 (37%), respectively. Fifty-five (6%), 399 (43%), 392 (42%) and 82 (9%) patients had low, intermediate, high and very high DRI-R, respectively. The HCT-CI/Age was available in 922 (98%) patients with the median score of 3 (range 0-18). Donor types included MRD (n=377), MUD (n=416), MMUD (n=68), HAPLO (n=73) and MMRD (N=8). Using the HCT-CR model, patients were stratified into 4 risk groups: low (N=272), intermediate (N=168), high (N=284) and very high-risk (N=184), with significantly different survival. The 5-year OS rates for patients in low, intermediate, high and very high-risk group were 57%, 48%, 34%, and 26%, respectively (P Compared with the low HCT-CR risk group, patients with intermediate, high and very high-risk group had a significantly increased risk of death with HR of 1.42 (95%CI 1.06-1.91; P=0.02), 2.11 (95%CI 1.65-2.70; P The stability of the hematopoietic cell transplant - composite risk model was confirmed in a bootstrap resampling procedure. Among 500 new datasets, on average, patients in intermediate, high and very high-risk group had significantly increased risk of death after transplant when compared with low risk group with HR of 1.39, 2.11 and 2.98, respectively. Results from the concordance test showed that the HCT-CR model provided better discriminative capacity for prediction of OS when compared with DRI-R, HCT-CI/Age and cytogenetic risk group models with C-index of 0.62 versus 0.60, 0.54 and 0.55, respectively. The goodness of fit test showed that the HCT-CR model fit the data significantly better than the other models (P Conclusion Combining disease and patient-related factors provides better survival stratification for patients with AML/MDS receiving AHSCT. This novel HCT-CR model will be validated in patients with all diseases undergoing allogeneic hematopoietic stem cell transplantation and results will be presented at the meeting. Disclosures Oran: ASTEX: Research Funding; Celgene: Consultancy, Research Funding; AROG pharmaceuticals: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

e16532Background: Bleomycin has an established role in treatment of Hodgkin’s lymphoma (HL) and testicular germ cell tumors (tGCT). Bleomycin-induced pulmonary toxicity (BPT) remains a dose-limitin...

Background: There have been significant improvements in the outcomes for patients with multiple myeloma over the past 10 years. The course of the disease remains highly variable. While some patients experience 10-15 year survivals, others succumb to highly refractory disease within a few months. Many studies have focused on the description of prognostic factors capable of predicting this heterogeneity in survival. Baseline Serum free light chain concentration is a major prognostic indicator for plasma cell neoplasms and normalization of free light chain ratio with treatment has been reported as an indicator for favorable prognosis. High Baseline free light chain concentration at presentation indicates aggressive disease. Furthermore High serum free light chain ratio correlates with elevated serum creatinine, elevated LDH and extensive marrow infiltration. Objectives: To determine if serum free light chain concentration > 1000mg/dl at the time of diagnosis and at disease progression was an independent prognostic marker for multiple myeloma. Methods: The results of all the serum free light chain analyses of patients evaluated at western Pennsylvania hospital between 2007 -2015 were reviewed and patients with serum free light chain concentration >1000mg/dl at the time of initial diagnosis and disease progression were identified Retrospective chart review was done to study the survival in these patients. Results: Total of 15 patients in whom serum free light chain concentration was greater than 1000 mg/dl at diagnosis were identified. Median age at diagnosis was 60.81 years (45.2-77.3). The median survival in this population is 1.85 years (range 0.06-8.85 years), with 5 deaths. Of these 15, 9 patients received an autologous PBSCT as a part of their initial therapy. Six of them are alive with a median overall survival of 2.44 years and mean survival of 3.89 years (range 0.87-8.89). In the remaining 6 patients that did not undergo an auto PBSCT 3 of them are alive with median overall survival of 1.21 years and a mean survival 1.20 years (range 06-2.76 years). There is an overall trend toward very poor prognosis in this specific group of patients irrespective of the age, sex, stage at time of diagnosis, the immunoglobulin subtype and the free light chain subtype (kappa vs lambda). We also conducted a retrospective review of patients in whom serum free light chains concentration was greater than 1000mg/dl at disease progression. Twenty patients were identified all of whom are deceased with a median overall survival from the time of progression with serum free light chains greater than 1000 mg /dl was dismal at 0.27 years and mean survival was 0.53 years (range 0.04-2.52 years) Conclusion: Patients with multiple myeloma who presented with a serum free light chain concentration greater than 1000 mg/dl at diagnosis have very poor prognosis. These specific subgroups of patients should be identified and treated aggressively at the time of diagnosis to prevent complications from multiple myeloma and improve their overall survival. In our small cohort of patients those who underwent auto PBSCT as a part of their initial therapy tend to have better outcomes in terms of overall survival compared to patients who received therapy without auto PBSCT consolidation. Patients with serum free light chains greater than 1000 mg/dl at disease progression will need to be treated aggressively with perhaps a salvage auto PBSCT to improve their overall outcome. A larger study to evaluate elevated serum free light chains (greater than 1000 mg/dl) as a prognostic indicator at diagnosis and progression should be done to further validate these findings Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.

Objectives: To assess the efficacy and safety of da-EPOCH-R as frontline treatment for patients diagnosed with Stage III/IV Diffuse Large B-Cell Lymphoma. Methods: We conducted a retrospective study of newly diagnosed patients with advanced Diffuse Large B-Cell Lymphoma from January 2008 till September 2015, who received frontline da-EPOCH-R or R-CHOP at our Health System. We excluded patients with primary CNS lymphoma, primary testicular lymphoma and patients who received chemotherapy for a prior lymphoma. 25 patients who received da-EPOCH-R and 50 patients who received R-CHOP were identified. Da-EPOCH-R regimen consisted of Etoposide 50mg/m2/day, Doxorubucin 10mg/m2/day and Vincristine 0.4mg/m2/day given on Days 1-4, Cyclophosphamide 750mg/m2 on Day 5, Prednisone 60mg/m2 twice a day from Days 1-6 and Rituximab 375mg/m2given on Day 5. On Day 6 G-CSF was administered. Each cycle was given every 21 days for a total of 6 cycles. The dose of Etoposide, Doxorubucin and Cyclophosphamide was adjusted according to standard protocols. All patients on the da-EPOCH arm were on Acyclovir, Ciprofloxacin, Fluconazole and Trimethoprim-Sulfamethoxazole for anti-microbial prophylaxis during their treatment. The use of growth factors and anti-microbial prophylaxis was inconsistent in the R-CHOP arm. Results: When comparing the da-EPOCH-R arm versus the R-CHOP arm, the average age of the patients was 50 years (25-81) vs 60 years (19-84). High-risk IPI was similar in both arms (76% vs 74%). The percentage of non-germinal center type (non-GCB) was equal as well (36% vs 32%). The average number of cycles administered was 5.3 compared to 4.8. There were more dose reductions in the da-EPOCH-R arm (36% vs 24%), however fewer delays and cessations were noted (36% vs 54%). After a median follow up of 29.1 months, the age-adjusted overall survival (77% vs. 69%, p=0.093) and disease-free survival (76% vs. 55% p=0.54) was improved in the da-EPOCH-R arm. In the non-GCB variant da-EPOCH improved overall survival by 77% (p=0.024). The Overall Response Rate was higher in the da-EPOCH-R arm 80% (CR/CRU=64% and PR=16%) vs. 56% (CR/CRU=44% and PR=12%). The relapse rate was lower in the da-EPOCH-R arm (16% vs 28%), and it was lower in the non-GCB patients as well (11% vs 25%). There were more Grade 3-4 neutropenia in the da-EPOCH arm (72% vs 48%), however infectious complications were lower (24% vs 42%). There were fewer unplanned admissions in the da-EPOCH arm (32% vs 60%) and a significantly lower treatment related mortality (12% vs 22%). Other Grade 3-4 toxicities too were lower in the da-EPOCH-R arm (20% vs 30%). Conclusion: Our preliminary results suggest that da-EPOCH-R has a survival benefit especially in the non-GCB subgroup. Our data does show good survival data even for the GCB subtypes. There was a higher response rate, lower relapse rate and no added toxicities in patients who received da-EPOCH-R. A Phase III trial is currently ongoing and will provide us with answers regarding the efficacy and toxicities of this chemotherapy regimen. Disclosures No relevant conflicts of interest to declare.

8064Background: There have been significant improvements in the outcomes for multiple myeloma patients over the past 10 years. However, the prognosis of the disease remains highly variable. While s...

Background: The addition of a Tyrosine Kinase Inhibitor (TKI) to induction chemotherapy has improved the outcome of patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). However, the treatment related mortality and morbidity of intensive treatment increases with age. The use of a TKI alone for induction is less toxic and yields CR rates comparable to combined therapy. Eligibility for post remission hematopoietic stem cell transplantation is less likely to be compromised with TKI induction. We present a retrospective review of patients with Ph+ ALL treated at our institution with dasatinib and prednisone induction who subsequently underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) as post remission therapy. Methods: We retrospectively identified 15 patients with Ph+ ALL treated at our institution between February 2012 and June 2015. Patients received induction therapy with dasatinib at 100 mg or 140mg daily till complete hematological response. Prednisone 60 mg/m2/day (capped at 120 mg daily) was administered until day 24 and then tapered and stopped at day 32. Intrathecal chemotherapy with MTX and Ara-C were administered twice during the induction period. Dasatinib dose reduction/discontinuation was permitted for non-hematological toxicity. Patients who achieved remission proceeded to allo-HSCT if a suitable HLA-matched donor was available. Patients who did not have a suitable HLA matched donor received TKI + POMP maintenance. We calculated CHR, CCyR, disease-free survival (DFS) and overall survival (OS). Results: The median age of patients treated with dasatinib plus prednisone was 62 years (range: 19-73). Baseline patient and disease characteristics are summarized in Table 1. Median WBC count was 22.5 x 109/L. Fourteen of 15 patients treated with dasatinib achieved a CHR (93.3%), 1 patient did not undergo a bone marrow biopsy but had normal blood counts. Median time to CHR was 42 days (range: 22-69). CCYR was obtained in 11 patients (73%) and MMR was achieved in 5 patients (33%). No patient died during induction therapy. The 14 patients who were in CHR after induction, underwent allo-HSCT (n=7), are being evaluated for allo-HSCT (n=3), were unable to undergo allo-HSCT due to a high comorbidity index and/or lack of a suitable donor (n=3) or were lost to follow-up (n=1). Of the 3 patients who were unable to undergo allo-HSCT, 2 patients continue on dasatinib maintenance and 1 patient takes ponatinib. Of 8 patients not yet transplanted 3 relapsed, while only 1 relapse was seen in 7 patients who underwent allo-HSCT. Median DFS was 315 days (range: 57-1061) and median OS was 354 days (range: 107-1082) corresponding Kaplan Meier curves for OS and DFS are shown below. Conclusions: In our adult Ph+ ALL patients induction therapy with dasatinib and prednisone was effective and well tolerated. Patients achieving CHR were able to undergo allo-HSCT with curative intent. This strategy retrospectively appears equal or better than results with induction chemotherapy of conventional variety. Table 1. Patient characteristics Male sex, n (%) 5 (33.3) Age Figure 1. Overall Survival. Figure 1. Overall Survival. Figure 2. Disease Free Survival Figure 2. Disease Free Survival Disclosures Fazal: Novartis: Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Off Label Use: Dasatinib use for newly diagnosed Ph+ ALL.

inhibitor that may potentiate the efficacy of concurrent radiation therapy (RT) and docetaxel (D). A Phase 2 trial was conducted to determine the efficacy and toxicities of the combination in patients with LA-SCCHN. Materials/Methods: Patients (pts) with previously untreated Stage III-IVb SCCHN received daily RTwith IMRT using dose painting: 70 Gy at 2 Gy/ fx to the primary tumor and gross nodes, 63 Gy at 1.8 Gy/fx to the highrisk nodal levels, and 56 Gy at 1.6 Gy/fx to the elective neck. Daily E (150 mg) was started 2 weeks prior to beginning RT. Elrotinib and D (20 mg/ m/week) were given concurrently with RT and pts were maintained on daily E for up to two years following the completion of RT. Data was collected on site of failures and HPV status, RT schedules, and toxicities. Toxicity was scored using CTCAE v3. Probabilities of survivals were estimated by the Kaplan-Meier method. Differences in outcomes according to HPV status, were evaluated using the log-rank test. Results: 43 pts (33 male), median age 57 years (range 35-75), with Stage III or IV (81%) were enrolled. Median follow-up is now 29.1 months (range 1.4 60.5). The primary site of disease was as follows: oropharynx (28), larynx (11) and oral cavity (4). Mean RT dose was 69.9 Gy to the primary site (range 61.2-72.4 Gy) and the mean duration of RT was 53 days. One pt died during chemoRT from a narcotic overdose. HPV status was available for 36 pts (23 HPV+). For all pts, 3-year locoregional failure-free survival (LFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were 81.1%, 76.8%, 64.6%, 73.7% respectively. HPV positive status showed a trend toward improved LFFS at 3 yrs (95.7% vs 71.6%, pZ0.06), PFS (82.6% vs 43.6%, pZ0.06), and OS (77.0% vs 66.1%, pZ0.36). Grade 3 leukopenia was noted in a majority of pts. Grade 4 hematologic toxicity was observed in 13 pts and Grade 4 GI toxicity was noted in 2 pts. Conclusions: Erlotinib in combination with RT and docetaxel is an active and tolerable treatment regimen for pts with LA-SCCHN with acceptable toxicities. HPV positive status was associated with a trend toward improved LFFS, PFS, and OS. Acknowledgment: This reseach was supported in part by Genentech, NIH grants P30 CA43703 and M01 RR-000080. Author Disclosure: M. Yao: None. C. Woods: None. P. Savvides: None. P. Lavertu: None. R. Rezaee: None. C. Zender: None. P. Fu: None. M. Gibson: None. J. Wasman: None. M. Machtay: Q. Leadership; RTOG.