Search

Post-transplant cyclophosphamide (PTCy) combined with tacrolimus (TAC) as graft-versus-host disease (GvHD) prophylaxis post-hematopoietic cell transplantation (HCT) is safe and effective. Optimal serum levels of TAC in this combination remain undetermined. We hypothesized that TAC at initial steady state (TISS) of

Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate-day plasma exchange (PE), rituximab, intravenous γ globulin (IVIg) and an irradiated donor buffy coat for patients with DSAs at 2 institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSAs (n = 345). The majority of patients in the DSA group were female (83.8% vs 37.1% in controls, P < .001) and received stem cells from a child as the donor (67.6% vs 44.1%, P = .002). Mean DSA level before and after desensitization was 10 198 and 5937 mean fluorescence intensity (MFI), respectively, with mean differences of 4030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity, while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA > 20 000 MFI and persistent positive C1q after desensitization had a significantly lower engraftment rate, which resulted in significantly higher non-relapse mortality and worse overall survival (OS) than controls, whereas graft outcome and survival of patients with initial DSA < 20 000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSAs ≤20 000 MFI.

Background Post-transplant cyclophosphamide (PTCy) is a safe and efficacious graft-versus-host-disease (GvHD) prophylaxis following hematopoietic cell transplantation (HCT) from haploidentical (haplo) donors. Cytokine release syndrome (CRS) is a common complication of this platform. Early fever post-haplo HCT using bone marrow grafts is associated with higher CD3+ cell dose and CRS. However, the impact of CD3+ and CD34+ cell dose on CRS post-haplo HCT using peripheral blood stem cell (PBSCT) grafts is unknown. Objective Our goals were to evaluate the incidence of CRS following PBSCT and to identify factors that can be modified to prevent the development of severe CRS in this setting. Study Design In 271 patients, we investigated factors associated with development of CRS following haplo PBSCT and examined the impact of CRS on clinical outcomes. Results Ninety-three percent of patients developed CRS of any grade post-haplo PBSCT. In multivariate analysis, severe CRS (grade 3-4 vs. grade 0-1) was associated with higher non-relapse mortality (HR=6.42; 95% CI: 2.68-15.39; p Conclusions Overall, we observed that severe CRS (grade 3-4) negatively affected transplant outcome and that higher CD3 cell dose was associated with development of any grade and severe CRS.

BACKGROUND Blinatumomab has demonstrated encouraging activity in relapsed/refractory (r/r) and minimal residual disease-positive (MRD+) acute lymphoblastic leukemia (ALL). Extramedullary disease (EMD) relapse or relapse with CD19- disease has been observed after blinatumomab therapy in patients with r/r or MRD+ ALL. However, the pathophysiology and risk factors of treatment failure are not fully understood. METHODS This study retrospectively reviewed the outcomes of adult patients with B-cell ALL treated with blinatumomab (n = 132) for either r/r (n = 103) or MRD+ disease (n = 29) at the authors' center (2013-2021) and analyzed factors associated with treatment response and EMD failure. RESULTS The overall response rate was 64%. A lower marrow blast burden before blinatumomab (P = .049) and no history of previous EMD (P = .019) were significantly associated with a higher response. Among the patients who responded to blinatumomab, 56% underwent consolidation with allogeneic transplantation. Blinatumomab failure was observed in 89 patients; 43% of these patients (n = 38) either progressed or relapsed at extramedullary sites. A history of extramedullary involvement (53% vs 24%; P = .005) and retention of CD19 expression at the time of relapse/progression (97% vs 74%; P = .012) were associated with a higher risk for extramedullary failure. Central nervous system (CNS) failure after blinatumomab was encountered in 39% of the patients with EMD. CONCLUSIONS A history of EMD predicted an inferior response to blinatumomab therapy with a higher risk for relapse/progression at extramedullary sites (particularly CNS). Consolidation with allogenic transplantation in patients who primarily responded to blinatumomab did not abrogate the risk of extramedullary relapse. The incorporation of extramedullary assessment and the intensification of CNS prophylaxis may help in addressing extramedullary failure. LAY SUMMARY Extramedullary failure is common during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia. A history of extramedullary disease predicts an inferior response to blinatumomab therapy and a higher risk for relapse/progression at extramedullary sites. Most extramedullary failure cases retain CD19 expression.

Hemolytic anemia in the setting of malignancy is a rare manifestation of paraneoplastic syndrome with significant morbidity. Here we discuss a case involving metastatic breast cancer presenting with severe hemolytic anemia and renal failure secondary to thrombotic microangiopathy of malignancy. This case discusses the workup for secondary hemolytic anemia, a possible role for therapeutic plasma exchange in this setting, as well the current understanding of the management of microangiopathic hemolytic anemia of malignancy.

Acute myeloid leukemia (AML) is predominantly a disease of older adults and the majority of affected patients succumb to the disease. After decades of slow progress, the last 5 years have witnessed remarkable progress in AML therapy with the approval of multiple highly active and well-tolerated novel therapies. Notable among these are agents targeting driver mutations including FLT3, IDH1/2 as well as the Bcl-2 inhibitor venetoclax. The combination of hypomethylating agents with venetoclax is highly active in AML and has become the standard of care for older patients as well as those with comorbidities. As a result of these advances, a larger proportion of AML patients now achieve complete remissions enabling them to undergo allogeneic hematopoietic cell transplantation with curative intent. Progress is also being made in the field of monoclonal antibodies targeting leukemia antigens and other immunotherapies and many such agents are currently under active investigation.

Sarcomas are rare tumors with limited treatment options. Although chemotherapy is standard for certain subtypes, overall survival has not improved in several decades. Bupivacaine has been shown to induce apoptosis and prevent cell growth in multiple different types of malignancies but has not been studied in sarcoma. The current study evaluated the effects of bupivacaine on multiple patient-derived sarcoma cells and a commercial sarcoma cell line. Multiple patient-derived sarcoma cell subtypes and a commercial synovial cell sarcoma cell line were exposed to bupivacaine for different durations and at different concentrations. The patient-derived cells included a high-grade conventional osteosarcoma, a high-grade undifferentiated pleomorphic sarcoma of bone, and a high-grade synovial sarcoma. Flow cytometry and an MTT assay were used to evaluate whether a treatment effect was observed. Treatment of all the subtypes of sarcomas in this study with bupivacaine demonstrated a time- and dose-dependent increase in apoptosis and decrease in cell viability. A cell viability assay demonstrated that the IC50 was between 0.04 and 0.05% and that the treatment effect occurred at clinically relevant doses in vitro. Bupivacaine was toxic to both the patient-derived cells and the commercial cell line at doses commonly used in the clinical setting. These findings provide a foundation for further in vivo studies to evaluate whether these effects will translate to the clinical setting. Although further research is necessary, bupivacaine shows promise as not only an adjunct for pain management but as a treatment modality for sarcoma.

To the EditorExtramedullary disease (EMD) is not an uncommon presentation at the time of acute myeloid leukemia (AML) diagnosis and/or relapse, and can present either as an isolated disease (myeloi...

Background: Breast cancer (BC) is the leading cause of cancer death in Hispanic/Latina women nationwide. Hispanic women are more likely to be presented with advanced disease and might have adverse prognosis. Further, the Hispanics of Mexican-American origin might reflect different clinico-pathological characteristics as opposed to other Hispanics and ethnic groups. No previous largest studies comprised with Hispanics of Mexican-American origin explored tumor characteristics and compared to other ethnic groups. Thus, the aim of this study was to describe the clinico- pathological characteristics and disparities in breast cancer in this minority group at two tertiary care University- based medical centers in 2 states with a large Hispanic presence. Methods: After IRB approval, cancer registry was used to analyze the variables of 3,441 patients with breast cancer diagnosed and treated consecutively at two large tertiary University based medical centers in El Paso, TX and Loma Linda, CA between 2005-2015. Unadjusted and adjusted associations of race/ethnicity with cancer stage, hormone receptor status and treatment option were investigated, as well as comparison to other ethnic groups. Results: Overall 45.5% of the patients were Hispanic (n= 1566). Hispanics were more likely to be diagnosed at a younger age (57 years) compared to in non-Hispanic (NH) whites, more likely to have invasive ductal carcinoma type (82.7%) & triple negative disease (17.1%, 95%CI: 15% to 19%). 58.8% of Hispanics (95%CI: 56% to 61%) have HR+ & HER2- as opposed to 71% in NH whites. In addition, Hispanic individuals presented with advanced stages (III and IV) of BC (25.3%, 95% CI: 23% to 28%) similar to African Americans (25.4%), and had a lower proportion of lumpectomy versus mastectomy compared to NH whites (50%) but similar to African Americans (50%). Hispanic patients had the highest prevalence of triple negative BC (17.1% in Hispanics Versus 13.9 % in African Americans, versus 8.5% in NH whites). Hispanics also had significantly higher relative risk of HER2+/HR - disease (RRR=1.77, p Conclusions: This large multi-institutional study shows that Hispanics are diagnosed with breast cancer at a younger age, have a higher prevalence of triple negative and HER2 positive/HR- breast cancer, are diagnosed at more advanced stages of disease and undergo less lumpectomies compared to NH whites. Increased efforts geared toward early detection, improving awareness and access to health care is desperately needed in this rapidly increasing minority in the U.S. Citation Format: Otoukesh S, Nahleh Z, Mirshahidi HR, Nguyen AL, Botrus G, Badri N, Diab N, Alvarado A, Sanchez LA, Dwivedi A. “Disparities in breast cancer: A multi-institutional comparative analysis focusing on American Hispanics” [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-10-04.

Background Rearrangements of lysine methyltransferase 2A (KMT2A) gene, previously known as the MLL gene, occur in 3 to 5% of adult patients with de novo AML and are enriched in therapy-related disease after treatment with topoisomerase II inhibitors (Bill, M et al. PNAS. 2020). KMT2A encodes a histone H3 lysine 4 methyltransferase and KMT2A rearrangements result in fusion proteins that induce aberrant Hox gene expression. (Armstrong, SA et al. Nature. 2002) Among patients with KMT2A rearranged AML (rAML) receiving intensive chemotherapy, the fusion partner impacts prognosis, and KMT2A-MLLT3 is associated with an intermediate risk while other KMT2A rearrangements are associated with adverse risk in the ELN classification. (Dohner, H et al. Blood. 2017) Here we evaluate the outcomes of patients with newly diagnosed and relapsed or refractory (R/R) AML with KMT2A rearrangements receiving venetoclax and hypomethylating agents (HMA). Methods Medical records of 333 patients with newly diagnosed or R/R AML receiving venetoclax in combination with HMAs at City of Hope National Medical Center between 11/1/2015 and 4/15/2020 were reviewed. Criteria for inclusion were a pathologically confirmed diagnosis of AML, age > 18 years, treatment with either decitabine or azacitidine in combination with venetoclax. KMT2A rearrangements were detected by karyotype and confirmed by FISH or RNA sequencing. Responses were evaluated per the ELN criteria (Dohner, H et al. Blood. 2017) Minimal residual disease flow cytometry was performed at the University of Washington. Patient characteristics were summarized by frequency and associations between overall response and patient and disease characteristics were tested by Fisher's exact test. OS was evaluated by the Kaplan-Meier method and the difference between groups was determined by log-rank test. All statistical analyses were performed using SPSS and Prism. Results We identified 18 patients (5.4%) with KMT2A rAML who met criteria for inclusion. MLLT3 was the predominant fusion partner, occurring in nine patients followed by ELL (n=2), AFDN (n=2), MLLT6 (n=1), MLLT10 (n=1), AFF1 (n=1), CBL (n=1), and TET1 (n=1). The cohort included both newly diagnosed (n=10) and R/R (n=8) AML patients. 44% had therapy-related or secondary AML. NRAS or KRAS mutations occurred in 4 out of 13 patients (31%) with available sequencing prior to treatment. Decitabine was the predominant HMA used in combination with venetoclax and 56% of all patients received 10-day dosing during the first cycle. For the total cohort, 9 patients achieved an overall response (ORR 50%), including 8 patients with a complete remission (CR/CRi 44%) and 1 (6%) patient with a morphologic leukemia free state, Figure 1. All six of the responders who were tested for MRD were negative. For treatment naïve patients, we observed a CR/CRi rate of 70% and a median survival of 11 months. On univariate analysis, R/R disease was the only factor associated with a significant decrease in response (ORR 12.5% vs. 80%, p=0.015, Table 1). With a median follow-up of 14.4 months for responding patients, median OS for the cohort was 6.59 months and 19.15 months for responding patients (Figure 2). The presence of NRAS or KRAS mutations was the only factor significantly impacting survival (HR 6.04, log rank 0.05, Table 1). Notably, the KMT2A fusion partner type did not impact response or survival. Allogeneic stem cell transplant was performed in 4 out of 9 (44%) responding patients. Conclusion Here, we show that venetoclax in combination with HMA led to a high rate of response and prolonged survival in a high-risk KMT2A rAML population. The outcomes of newly diagnosed KMT2A rAML patients after treatment with venetoclax and HMA in this study are similar to chemotherapy outcomes in patients aged < 60 years (CR 68% and median OS 0.9 months; Bill, M et al. PNAS. 2020). Consistent with previous studies, we found that MLLT3 was the most common fusion partner, occurring in 50% of patients and that RAS mutations were also common (~30%). In contrast to what has been reported for chemotherapy outcomes and in the ELN classification, the KMT2A-MLLT3 translocation was not associated with improved outcomes when compared to other KMT2A translocations. While this study was limited in being retrospective and having a small and heterogeneous population, our findings suggest that venetoclax and HMA are effective in KMT2A rAML and warrant further investigation. Figure 1 Figure 1. Disclosures Koller: Novartis: Consultancy. Al Malki: Hansa Biopharma: Consultancy; Rigel Pharma: Consultancy; Neximmune: Consultancy; Jazz Pharmaceuticals, Inc.: Consultancy; CareDx: Consultancy. Aribi: Seagen: Consultancy. Ali: Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees. Marcucci: Novartis: Other: Speaker and advisory scientific board meetings; Agios: Other: Speaker and advisory scientific board meetings; Abbvie: Other: Speaker and advisory scientific board meetings. Pullarkat: AbbVie, Amgen, Genentech, Jazz Pharmaceuticals, Novartis, Pfizer, and Servier: Membership on an entity's Board of Directors or advisory committees; Amgen, Dova, and Novartis: Consultancy, Honoraria.

Low level of vitamin D (VD) has been linked with a higher risk of cancers. The aim of this study was to assess the prevalence of low VD in patients with breast cancer in a predominantly Mexican Hispanic/Latino patient population, a fast growing and relatively understudied population.We sought to evaluate the serum VD levels in breast cancer patients diagnosed at the Texas Tech University Breast Cancer Center in El Paso, TX, between May 2013 and May2014 via a retrospective chart review of the Electronic Medical Records.We identified a total of 83 consecutive breast cancer patients with available VD levels. Mean age 57 yr, 94% were Hispanics. VD was insufficient (30 ng/ml) in 86% of patients (95% CI: 0.76-0.92) and it was deficient (20 ng/ml) in 39% (95% CI: 0.28-0.50).VD deficiency is widely prevalent in Hispanic/Latino patients with breast cancer. This is quite alarming in view of possible increased risk of cancer with low VD and potentially worse cancer outcomes. This calls for increased efforts to screen for, diagnose, and treat VD deficiency in this patient population. Further pharmacogenomics studies are warranted to explore the underlying etiology of VD deficiency in this paradoxically sunny region.

Peripheral blood stem cell (PBSC) as a graft source compared to bone marrow has been reported to result in lower risk of relapse after haploidentical hematopoietic cell transplantation (haplo-HCT) with use of post-transplant cyclophosphamide (PTCy) as a graft-versus-host-disease (GvHD) prophylaxis. However, cytokine release syndrome (CRS) is a common complication of this platform that can affect the outcomes of patients after PBSC haplo-HCT. CRS occurs due to rapid activation and proliferation of alloreactive donor T cells resulting in the elevated secretion of inflammatory cytokines. In this study, we sought to examine the risk factors for CRS and the effect of CRS severity on outcomes of PBSC haplo-HCT. We identified total of 271 consecutive patients with hematological malignancies who received their first PBSC haplo-HCT with PTCy-based GVHD prophylaxis at City of Hope (n=157) or Moffitt (n=114) Cancer Centers between 2014 and 2019. The median patient age at HCT was 54 years (INQ range, 37-64) for the entire cohort and 48% of the patients had HCT-CI ³3. Close to 70% of the study cohort had acute leukemia and 33% of all patients had high/very high-risk disease risk index. Myeloablative conditioning was used in 52% of the cases and 81% of all HCT recipients were CMV seropositive. The median donor age at HCT was 33 years (INQ range, 26-43). The HLA -A, -B, -C, -DRB1, -DQB1, or -DPB1 mismatch between the recipient and the donor in the GVH direction was 5/10 in 51%, 4/10 in 29% and £3/10 in 20% of cases. Offspring donors were used in 54% of the patients, sibling donors in 35%, and parent/other relative donors in 11%. Female donors to male recipients were used in only 22% of patients. The median infused CD34 dose was 5.25 x106 cells/kg (range, 2.3-22.4x106) and the CD3 dose was 2.48x108 cells/kg (range, 0.002-8.88 x108). CRS of any grade by ASTCT criteria was observed in 92% of study patients within first 7 days of HCT: 54% had grade 1, 39% grade 2, and 5.2% grade 3-4. Infused cell doses of CD34 >5x106 cells/kg and of CD3 >2.5x108 cells/kg had no significant effect on grade 3-4 CRS. On multivariable analysis, the use of reduced-intensity conditioning (RIC) was associated with increased grade 2-4 CRS (HR = 1.6, 95% CI: 1.11.-2.33, p=0.01) and grade 3-4 CRS (HR = 14.7, 95% CI: 1.97-109.5, p=0.009) compared with the myeloablative conditioning. Donor 5/10 HLA-mismatch was also associated with increased grade 2-4 CRS (HR = 1.5, 95% CI: 1.05-2.18; p=0.03) and grade 3-4 CRS (HR = 3.50, 95% CI: 1.00-12.32; p=0.05) compared with £4/10 HLA-mismatch. Non-relapse mortality (NRM) at day 100, and 1-year overall survival (OS) by CRS severity is shown in Figure. Comparing with the grade 0-1 CRS in multivariable analysis (Table), increase in CRS severity was associated with lower probability of neutrophil engraftment (HR = 0.9 for grade 2 and HR = 0.4 for grade 3-4; p=0.03). Increased CRS severity as compared to the grade 0-1 was also predictive of higher risks of NRM (HR = 1.6, 95% CI: 0.95-2.79 for grade 2 and HR = 6.6, 95% CI: 3.12-13.78 for grade 3-4; p We conclude that CRS is a common complication after PB haplo-HCT/PTCy. CRS severity is associated with post-HCT outcomes with grade 3-4 CRS associated with the highest risk of NRM and overall mortality after HCT. Infused CD34 or CD3 cell doses effect on CRS is unclear. RIC and higher degree of HLA-mismatch are predictive of higher-grade CRS. Identification of modifiable risk factors can help to mitigate the risk for serious CRS and subsequent mortality after PB haplo-HCT/PTCy. Figure 1 Disclosures Nishihori: Karyopharm: Other: Research support to institution; Novartis: Other: Research support to institution. Pidala:CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Johnson and Johnson: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding; BMS: Research Funding; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees. Nakamura:Merck: Other: advisory board meeting; Alexion: Other: Support on a meeting presentation; Kyowa-Kirin: Other: Support on a meeting presentation; Celgene: Other: Support on seminar; Magenta Therapeutics: Other: Advisory board meeting; Viracor: Consultancy; Kadmon Corporation: Other: Advisory board meeting; NapaJen Pharma: Consultancy. Al Malki:Rigel Pharma: Consultancy; Jazz Pharmacuticals, Inc: Consultancy; Neximmune: Consultancy. Bejanyan:Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees.

// Alexa Montoya 1, 2, * , Clarissa N. Amaya 1, * , Andres Belmont 3, * , Nabih Diab 3 , Richard Trevino 3 , Geri Villanueva 3 , Steven Rains 1 , Luis A. Sanchez 4 , Nabeel Badri 4 , Salman Otoukesh 4 , Ali Khammanivong 5 , Danielle Liss 4 , Sarah T. Baca 6 , Renato J. Aguilera 6 , Erin B. Dickerson 5, 7 , Alireza Torabi 3, 8 , Alok K. Dwivedi 1, 3, 9 , Aamer Abbas 3, 4 , Karinn Chambers 3, 10 , Brad A. Bryan 1, 3 , Zeina Nahleh 3, 4 1 Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, Texas, USA 2 Department of Biology, University of Texas, El Paso, Texas, USA 3 Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, USA 4 Department of Hematology/Oncology, Loma Linda University Health Sciences Center, Loma Linda, California, USA 5 Department of Veterinary Clinical Sciences, University of Minnesota, Saint Paul, Minnesota, USA 6 Border Biomedical Research Center, University of Texas, El Paso, Texas, USA 7 Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA 8 Department of Pathology, Texas Tech University Health Sciences Center, El Paso, Texas, USA 9 Division of Biostatistics and Epidemiology, Texas Tech University Health Sciences Center, El Paso, Texas, USA 10 Department of Surgery, Texas Tech University Health Sciences Center, El Paso, Texas, USA * These authors contributed equally to this work Correspondence to: Zeina Nahleh, email: zeina.nahleh@ttuhsc.edu Brad A. Bryan, email: brad.bryan@ttuhsc.edu Keywords: beta blocker, propranolol, breast cancer, proliferation, Ki-67 Received: September 07, 2016 Accepted: December 13, 2016 Published: December 23, 2016 ABSTRACT Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% ( p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction ( p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

Recurrence or metastasis remains the major cause of poor prognosis and mortality in Osteosarcoma patients. Therefore, development of more effective therapeutic approaches is required. We showed that indomethacin, significantly induces apoptosis in MNNG/HOS cell line, which was confirmed by morphological changes, increased Annexin-V + cells and nuclear fragmentation. Apoptosis was accompanied by increased cleavage of caspase-3 and PARP, suggesting activation of caspase-dependent cell death. Indomethacin significantly decreased the expression of β-catenin, a key player in tumor metastasis. These results indicate that indomethacin may have the potential to be used as neoadjuvant or adjuvant treatment; however, additional studies are required.

Anaplastic lymphoma kinase–positive (ALK+) non-small cell lung cancer (NSCLC) is diagnosed in up to 126,000 patients worldwide annually. Ceritinib is a next-generation ALK-targeted tyrosine kinase inhibitor that is approved for the treatment of patients with metastatic ALK+ NSCLC. In December 2017, the US Food and Drug Administration–approved dose of ceritinib was changed from 750 mg/day under fasting conditions to 450 mg/day taken with food for the treatment of patients with ALK+ NSCLC. This change was implemented on the basis of data from studies designed to investigate ways to reduce the frequency of gastrointestinal adverse events noted in patients enrolled in several ASCEND clinical trials that evaluated a ceritinib 750-mg fasted dose as either first- or second/third-line treatment. This review highlights and discusses published findings from the ASCEND-8 food-effect trial and includes commentary from physicians regarding their own clinical cases of patients who were enrolled in the trial and treated with either the 750-mg fasted or 450-mg fed dose of ceritinib. The review also discusses the implications of using the recently approved ceritinib 450-mg dose in the clinical setting.

Background: Video assisted thoracoscopic surgery (VATS) has become the recommended approach for treatment of resectable lung cancer. However, no large randomized clinical trial has been conducted formally comparing surgical resections completed by VATS to those done by open thoracotomy (OT) in low volume centers. The current study sought to assess differences in recurrence-free survival (RFS), overall survival (OS), positive margins and postoperative length of stay (LOS) between VATS and OT lobectomies in our center. Method: A single institution retrospective chart review from May 2005 through May 2015 was conducted. All patients diagnosed with stage I through III lung cancer who underwent surgical resection were selected. Patient and tumor characteristics recorded included age at diagnosis, sex, tobacco use, tumor location (side and lobe), stage, size and receipt of chemotherapy or radiotherapy. Chis-square and Wilcoxon-Mann-Whitney tests were used to compare demographics, tumor characteristics and LOS. Multiple logistic and Cox regression analyses were used to compute relative risk (RR) for positive margins and mortality hazard ratios along with 95 percent confidence intervals (95%CI), respectively. Results: Of the 235 patients, 101 subjects had VATS while OT was performed in 134 patients. Age at diagnosis, sex, tobacco use, tumor location, and size were comparable for VATS and OT. No significant difference was observed in the relative risk of positive margins for VATS versus OT, RR = 0.56 (95%CI = 0.26, 1.05). However, VATS had shorter median LOS compared to OT (4 vs. 6 days, respectively), p = 0.002. A comparison of VATS versus OT showed no significant difference in the risk of recurrence, HR = 1.21 (95%CI = 0.74, 2.00), or death, HR = 1.34 (95%CI = 0.88, 2.06), in the intent-to-treat population. Similarly, no significant differences in recurrence or mortality risk were observed between VATS versus OT for analyses conducted separately for each cancer stage group or those limited to patients with negative margins. Conclusion: Our study indicates that compared to OT, VATS leads to shorter LOS while achieving comparable margins status, recurrence-free and overall survival regardless of tumor stage at diagnosis.

BACKGROUND Breast cancer is the leading cause of cancer death in Hispanic/Latina women nationwide. Limited cancer research has been conducted in this population. El Paso, Texas is a large border city with a population of around 900,000, of which 85% are Latinos and would provide a suitable setting for this study. The aim of this study is to evaluate ethnic differences and cancer characteristics in Hispanic/latina women with breast cancer. METHODS After IRB approval, we retrospectively analyzed the variables of patients with breast cancer treated consecutively at a large tertiary medical center in El Paso, TX between 2005-2015. Descriptive statistics, bivariate, and multivariable analyses were conducted. RESULTS 1,252 patients were identified. Mean age at diagnosis was 57 years. 1074 were Hispanics/Latinas (86%). When comparing Hispanics versus non-Hispanics, 31% of Hispanics compared to 24% Non-Hispanics were diagnosed at age

Background There is a paucity of research on the profile of cancers among displaced populations, specifically Afghan refugees in Iran. This study illustrates the pattern of cancers in this population, and highlights the challenges of cancer care in displaced people with the intent that this data will facilitate appropriate allocation of resources to improve care in this population. Material and methods This was a retrospective cross-sectional study, in which we collected the demographics and profile of cancers among Afghan refugees from 2005 to 2010 from referrals to the United Nations High Commissioner for Refugees (UNHCR) offices in Iran. Accrued evidence by other studies published between January 1993 and July 2014 pertaining to cancer diagnoses in refugees from Afghanistan, Tibet, Syria, Jordan, and Iraq was reviewed. Results Cancer diagnoses accounted for 3083 of 23 152 total referrals, with 49% female and 51% male cases; 23.3% were 0-17 years of age, 61.2% were 18-59, and 15.5% were above 60. The most common health referral for females and males (0-17) was malignant neoplasms of lymphatic and hematopoietic tissue, accounting for 34.2%. In the age groups 18-59 and above 60 for both male and females it was malignant neoplasm of the digestive system, occurring in 26.3% and 48.7%, respectively. Conclusions In the setting of humanitarian crises especially war, cancer diagnoses among refugees is a major health burden both on the host countries and the international community with serious implications considering the recent growing trend in the Middle Eastern countries. The prevalence of certain cancer diagnoses among refugees, like gastrointestinal, respiratory, breast, and genitourinary cancers necessitates a multidirectional approach, primarily aimed at prevention and early detection. International partnerships are essential for improvement in cancer surveillance service availability, and delivery of the standard of care, in an overall effort to reduce the human cost, monetary, and resource associated burdens of cancer. Recommendations to implement effective prevention and management goals as well as improved record keeping in the refugee setting and the acquisition of secure and sustainable funding sources should be implemented in collaboration with global humanitarian agencies like UNHCR.

Breast cancer (BC) is the leading cause of cancer death in Hispanic/Latino women nationwide. Hispanic women are more likely to be presented with advanced disease and adverse prognosis subtypes. The aim of this study is to describe the clinico‐ pathological characteristics and disparities in breast cancer in this group at two tertiary care University‐based medical centers. After IRB approval, Cancer registry was used to analyze the variables of 3441 patients with breast cancer diagnosed and treated consecutively at two large tertiary University based medical and cancer center database centers in El Paso, TX and Loma Linda, CA between 2005 and 2015. Association between race/ethnicity and cancer type, stage, hormone receptor status and treatment option were investigated. Overall 45.5% of the patients were Hispanic (n: 1566) and those were more likely to be diagnosed at a younger age (57 years) similar to African Americans, more likely to have invasive ductal carcinoma type (82.7%) & triple negative disease (17.1%, 95%CI: 15% to 19%). 58.8% of Hispanics (95%CI: 56% to 61%) have hormone receptor (HR)+ & HER2− as opposed to 71% in non‐Hispanic White people. In addition, Hispanic individuals presented with advanced stages of BC (25.3%, 95% CI: 23% to 28%) similar to African American (25.4%), and had a lower proportion of lumpectomy (50%) similar to African American (50%). When compared to African American patients, Hispanic patients had a higher prevalence of triple negative BC (17.11% in Hispanics Versus 13.86% in African American). Conclusion: Hispanics had significantly higher relative risk of advanced stages at presentation (Relative Risk Ratio (RRR) = 2.05, P

Patient: Female, 55 Final Diagnosis: Metastatic malignant pheochromocytoma Symptoms: Chest pain • tachycardia • tachypnea Medication: — Clinical Procedure: — Specialty: Oncology Objective: Rare disease Background: Malignant pheochromocytoma is defined as the occurrence of the tumor in an area that is normally devoid of chromaffin tissue, direct tumor invasion, and/or metastasis. Metastatic malignant pheochromocytoma is very rare. Malignant pheochromocytoma carries a poor prognosis with a 5-year survival rate of 44%. The majority of pheochromocytoma cases are sporadic, but a small portion (10%) can be associated with hereditary syndromes such as neurofibromatosis type 1 (NF1). Case Report: A 55-year-old Hispanic woman presented to our care with chest pain. Her past medical problems included hypertension, neurofibromatosis type 1 (NF1), and pheochromocytoma status after right laparoscopic adrenalectomy, which was converted to open procedure about 19 months ago. Initial vital signs were significant for tachycardia, tachypnea, and hypertension. Computed tomography (CT) angiography of the chest was performed to rule out a pulmonary embolism, but instead revealed multiple bilateral lung nodules measuring up to 8 mm, consistent with metastasis. CT of the abdomen and pelvis revealed a lytic lesion in the posterior aspect of the left pedicle and transverse process of L4, and the neck/greater trochanter of the left femur. MIBG scan revealed widespread metastatic disease. She received an outpatient chemotherapy regimen of cyclophosphamide, dacarbazine, and vincristine. Conclusions: Metaiodobenzylguanidine (MIBG) is an alkyl-guanidine derivative similar to noradrenaline, which accumulates in tissue derived from neural crest cells. Current medical literature suggests that therapeutic 131I MIBG has a response rate of 50–75%. Combination chemotherapy using cyclophosphamide, vincristine, and dacarbazine has been the most widely used regimen for malignant pheochromocytoma. This combination of chemotherapy has been shown to have a high response rate and symptomatic improvement. Numerous therapeutic regimens exist for metastatic malignant pheochromocytoma; however, no regimen has been shown to have a benefit significantly superior to the others.

Post-transplant cyclophosphamide (PTCy) in combination with tacrolimus and mycophenolate mofetil (MMF) has been used increasingly in recent years to prevent graft-versus-host disease (GvHD) in patients undergoing hematopoietic cell transplantation (HCT), and has been proven safe and effective regardless of HLA matching criteria. Historically, the therapeutic dose level recommended for tacrolimus has ranged from 10 to 15 ng/mL, when combined with methotrexate, and between 5-10 ng/mL when combined with sirolimus. However, data on the optimal starting dose and serum level of tacrolimus when combined with PTCy does not exist. Given tacrolimus's broad inhibition on T-cells activation and the PTCy's selective inhibition on alloreactive T-cells, we hypothesized that lower serum levels of tacrolimus could suffice to achieve optimal transplant outcomes. We retrospectively identified a consecutive case series of 219 patients who received HCT with PTCy (50 mg/kg on days +3 and +4) in combination with tacrolimus and MMF (day +5) as GvHD prophylaxis at City of Hope from January 2011 to June 2018. Tacrolimus was delivered with continuous intravenous infusion until engraftment, then switched to equivalent oral dose. Tacrolimus dosing was weight-based (WBD) in 80 patients and fixed dose (FD) of 1 mg in 139 patients. We captured Tacrolimus levels at two different time points: 1. the initial steady state (ISS) and 2. at engraftment level (EL) to identify which time point will correlate with better HCT outcomes. At each time point, transplant outcomes were compared between patients with serum levels ≥10 ng/mL and Patients received HCT either from a haploidentical (n=175), matched (n=6), or mismatched donor (n= 38). Tacrolimus levels at the ISS (median: day +9 of HCT, range 8-16) was At ISS, 18 months OS, PFS, relapse rate were 64%, 58% and 19%, respectively, in patients with tacrolimus level In conclusion, tacrolimus dosing at a FD was more likely resulting in ISS of 4-10 ng/mL (86% of patients in Figure 1 Disclosures Salhotra: Celgene: Other: Research Support; Kadmon Corporation: Other: Non paid consultant. Aldoss:Helocyte: Consultancy, Honoraria, Other: travel/accommodation/expenses; Jazz Pharmaceuticals: Honoraria, Other: travel/accommodation/expenses, Speakers Bureau; Agios: Consultancy, Honoraria; AUTO1: Consultancy. Stein:Amgen: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Stemline: Speakers Bureau. Nakamura:Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: support for an academic seminar in a university in Japan; Kirin Kyowa: Other: support for an academic seminar in a university in Japan.

e13130Background: Age at diagnosis is an important prognostic factor for breast cancer in general however its specific significance in triple negative breast cancer (TNBC) is unclear. Few existing ...

e19012Retrospective analysis of AML patients identifies a higher risk of anthracycline associated cardiac toxicity in Hispanic patients. Background: Acute Myeloid Leukemia (AML) is the most common ...

9100Background: Tyrosine Kinase inhibitors (TKI) have changed the treatment paradigm in patients with stage IV adenocarcinoma of the lung (AdenoCa) harboring epidermal growth factor receptor (EGFR)...

In this report, we present a case of isolated liver tuberculosis (TB) as a cause of non-cirrhotic portal hypertension leading to bleeding esophageal varices. Although TB has been known to cause portal hypertension in a variety of ways, this case was notable for the presence of periportal inflammation and granulomas, also seen in hepatic schistosomiasis. Herein, we discuss isolated liver TB and the differential diagnosis of non-cirrhotic portal hypertension. In endemic areas, TB should be considered in the differential diagnosis of non-cirrhotic portal hypertension.

Background Due to a paucity of research on the profile of kidney diseases among refugee populations, specifically Afghan refugees in Iran, this study aimed to illustrate the pattern of kidney disease among Afghan refugees in Iran and create a database for evaluating the performance of future health services. Material/Methods This was a retrospective cross sectional study, in which we collected the demographics and profile of kidney diseases among Afghan refugees between 2005 and 2010 from referrals to the United Nations High Commissioner for Refugees (UNHCR) offices in Iran. Results The total number of referrals in this group of diseases was 3193 out of 23 152 with 41.5% female and 58.5% male. Regarding age distribution, 10.5% were 0–14 years of age, 78% were 15–59, and 11.5% were ≥60. The most common health referral for females and males (0–14) was end-stage renal disease (ESRD), accounting for 34.6%. This was also the main reason of referrals for females and males aged 15–59, accounting for 73.5% and 66.6%, respectively, and in both sexes in the ≥60 age range it was 63.1%. Conclusions The pattern of our renal clinic referrals may gradually change to ESRD, which is associated with a huge economic burden. The need to provide health insurance to everyone or reform the health care system to provide coverage for more of the population can be justified and would improve cost effectiveness.

Castleman’s disease is a group of rare lymphoproliferative disorders. The plasmablastic multicentric Castleman’s disease is frequently discovered in HIV-infected individuals in association with Kaposi sarcoma (HHV-8). Thirty-five year old male presented to our care with the main compliant of severe back pain for one week. His past medical problems include acquired immune deficiency syndrome diagnosed 12 years prior and Kaposi sarcoma, currently on highly active antiretroviral therapy (HAART). Radiographic imaging revealed hepatomegaly and diffuse lymphadenopathy. The HIV viral load was pneumocystis carinii. Multicentric Castleman’s disease has become more relevant in recent years due to its association with HIV and HHV-8 (Kaposi sarcoma) and its potential to progress into plasmablastic B-cell lymphoma. The progression of MCD to B-cell lymphoma is a concern, especially in patients with HIV infection because it precludes the worst outcome and a high mortality, despite treatment. The most intriguing part of this case is that MCD occurred in a HIV-positive on HAART. This case signals a warning that a high suspicion for MCD can be justified even in those HIV-positive patients on HAART because the possibly of progression to plasmablastic B-cell lymphoma.

Rumination syndrome is a behavioral disorder resulting in effortless regurgitation of undigested food within minutes of meal intake that is subsequently either re-swallowed or ejected. It is commonly misdiagnosed, patients often undergo extensive testing and multiple therapies, many of which are directed at suspected gastroparesis. A 25-year-old Caucasian female initially presented to our care 1 year ago with a 4-year history of nausea and vomiting occurring in the immediate postprandial period, specifically within 15 minutes from oral intake. She had an extensive history of multiple diagnostic, therapeutic and surgical procedures over the previous 4 years which included cholecystectomy, botulin toxin injection into the pyloric sphincter, pyloroplasty, placement of a gastric stimulator and jejunal feeding tube with no sustained results. On a previous admission we determined the functional status of the stomach by obtaining full thickness gastric biopsies during a diagnostic laparoscopy. This revealed an adequate population number of cells of Cajal and myenteric neurons as well as normal stomach muscle. After 1 year of attempting “breathing relaxation techniques”, while being nutritionally maintained by nocturnal jejunostomy feedings, the patient presented again to our care with refractory nausea and vomiting and unable to work or function. Her weight was 90 lbs. She underwent a subtotal gastrectomy (80%) with Roux-en-Y reconstruction and continuation of jejunostomy feeding. The refractory nausea and vomiting significantly improved over the 4 weeks after discharge and breathing exercises were continued. On subsequent follow-up visits over a 6-month course, the refractory nausea and vomiting had resolved by more than 85% with and improvement in her BMI and quality of life.The recommended treatment of rumination syndrome is focused on breathing exercises and relaxation techniques to “distract” while eating. We believe our case is the first reported where a subtotal gastrectomy has been used to help overcome refractory rumination along with the usual therapy. This surgery is a “last resort” consideration to improve quality of life, returning the patient to employment and functional social status.

Introduction For nearly three decades, the two neighboring countries of Iran and Pakistan hosted millions of Afghans. Today, Afghans still represent the largest group of refugees in the world. This feature has greatly influenced provision of health care for this population. Due to a paucity of research on the health status of Afghan refugees in Iran, this study aim to make a vista on the pattern of different common diseases among Afghan refugees in Iran and use it as an index for performance evaluation of future health services to them. Methods This is a retrospective cross sectional study, in which we collected the demographic and medical data between 2005 and 2010 from referrals to the United Nations High Commissioner for Refugees (UNHCR) offices in Iran. We also considered a comparative review of the burden of disease estimates by the World Health Organization (WHO) for Afghanistan and Iran. Results Total numbers of referrals were 23,152 with 52.6% Female and 47.66% male. 29% were 0–14 years of age, 54% were 15–59, and 17% were 60+. The most common health referral for females and males (0–14) was perinatal diseases (15.16%, 15.2%, respectively). In the females (15–59) it was ophthalmic diseases (13.65%), and for males it was nephropathies (21.4%), and in both sexes (60+) age range it was ophthalmic diseases (21.3%, 19.9%, respectively). The largest ethnic group of afghan refugees in this study was Hazara (55%) followed by Tajik (14%), Fars (12%), Sadat (9%), and 10% others. Ophthalmic diseases were the major cause of referrals by Hazara, Tajik, Fars, and Sadat groups with 26%, 20%, 26%, and 27% respectively. Referrals by pashtun group were mostly for neoplasms (17%), among Uzbek group it was nephropathies (26%), and in Baluch group Hematopoietic disorders (25%). Conclusion These data indicate higher referral rate for women 15–59 years of old and people in 60+ with ophthalmic diseases, neoplasms, and nephropathies. Even given certain intrinsic limitations of such a study, we believe these unique findings are worth further explanation. This implies the need for public health researchers to pursue prospective studies in these areas.

e12051Background: Low level of Vitamin D(VD) has been linked with a higher risk of cancers in multiple epidemiological studies. Some studies have suggested that VD deficiency is associated with inc...

e12064 Background: Socioeconomic and ethnic disparities still exist that preclude patients from receiving breast-conserving therapy. We sought to determine the rate of mastectomy versus breast-cons...

e11510 Background: The RS (Oncotype DX) is widely used in the U.S. to better define risk and help clinical decision-making in breast cancer (BC). However, it is an expensive tool for underinsured p...

The authors would like to make the following corrections. In Abstract section, the sentence “On subsequent follow-up visits over a 6-month course, the refractory nausea and vomiting had resolved by more than 85% with and improvement in her BMI and quality of life.” should read “On subsequent follow-up visits over a 4-month course, the refractory nausea and vomiting had resolved by more than 70% with and improvement in her nutritional status and quality of life.” In the last paragraph of Case Report section, the sentence “On subsequent follow-up visits over a 6-month course, the refractory nausea and vomiting had resolved by more than 85% with and improvement in her BMI and quality of life.” should read “On subsequent follow-up visits over a 4-month course, the refractory nausea and vomiting had resolved by more than 70% with and improvement in her nutritional status and quality of life.”