23 results on '"Salman Otoukesh"'
Search Results
2. Treatment of allosensitized patients receiving allogeneic transplantation
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Stefan O. Ciurea, Piyanuch Kongtim, Gabriela Rondon, Salman Otoukesh, Stephen J. Forman, Richard E. Champlin, Julianne Chen, Auayporn Nademanee, Michiko Taniguchi, Kai Cao, Ketevan Gendzekhadze, Fleur M. Aung, Jun Zou, and Monzr M. Al Malki
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Male ,medicine.medical_specialty ,Allogeneic transplantation ,Buffy coat ,Gastroenterology ,Desensitization (telecommunications) ,HLA Antigens ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,In patient ,biology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Gamma globulin ,Hematology ,Middle Aged ,Tissue Donors ,Transplantation ,biology.protein ,Female ,Rituximab ,Antibody ,business ,medicine.drug - Abstract
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.
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- 2021
3. Cytokine Release Syndrome Following Peripheral Blood Stem Cell Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide
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Stephen J. Forman, Shukaib Arslan, Hany Elmariah, Taiga Nishihori, Guido Marcucci, Dongyun Yang, Krishnakar Mogili, Mary C. Clark, Haris Ali, Joseph Pidala, Salman Otoukesh, Ryotaro Nakamura, Madiha Siraj, Nelli Bejanyan, Claudio Anasetti, and Monzr M. Al Malki
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Oncology ,medicine.medical_specialty ,Cyclophosphamide ,CD34 ,Graft vs Host Disease ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Immunology and Allergy ,Humans ,Transplantation ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,medicine.disease ,Cytokine release syndrome ,medicine.anatomical_structure ,Peripheral Blood Stem Cells ,Molecular Medicine ,Bone marrow ,Stem cell ,Neoplasm Recurrence, Local ,business ,Complication ,Cytokine Release Syndrome ,medicine.drug - Abstract
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.
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- 2021
4. Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia
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Brian Ball, Haris Ali, Vinod Pullarkat, Karamjeet S. Sandhu, Salman Otoukesh, Anthony S. Stein, Ibrahim Aldoss, Ryotaro Nakamura, Amandeep Salhotra, Stephen J. Forman, Ahmed Aribi, Paul Koller, Sally Mokhtari, Andrew S. Artz, Dat Ngo, Jianying Zhang, Forrest Stewart, Mona Mojtahedzadeh, Guido Marcucci, Peter T. Curtin, Monzr M. Al Malki, and Shukaib Arslan
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Oncology ,Cancer Research ,medicine.medical_specialty ,Treatment response ,Allogeneic transplantation ,business.industry ,Lymphoblastic Leukemia ,Disease ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Pathophysiology ,Extramedullary disease ,Refractory ,Recurrence ,Internal medicine ,Antibodies, Bispecific ,medicine ,Disease Progression ,Humans ,Blinatumomab ,business ,medicine.drug ,Retrospective Studies - Abstract
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.
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- 2021
5. Hemolytic Anemia of Malignancy: A Case Study Involving Signet Ring Cell Metastatic Breast Cancer with Severe Microangiopathic Hemolytic Anemia
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Salman Otoukesh, Gayathri Nagaraj, Eric H. Lee, and Amir Abdi Pour
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0301 basic medicine ,Hemolytic anemia ,medicine.medical_specialty ,Thrombotic microangiopathy ,Case Report ,Malignancy ,lcsh:RC254-282 ,Gastroenterology ,Hemolysis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Plasma exchange ,Paraneoplastic ,Signet ring cell ,business.industry ,Microangiopathic hemolytic anemia ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Metastatic breast cancer ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,business - Abstract
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.
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- 2019
6. Refractory primary autoimmune myelofibrosis treated with ruxolitinib
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Salman Otoukesh, Guido Marcucci, Sally Mokhtari, Haris Ali, Vinod Pullarkat, Joo Y. Song, and Mona Mojtahedzadeh
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Oncology ,medicine.medical_specialty ,Ruxolitinib ,Refractory ,business.industry ,Internal medicine ,medicine ,Hematology ,business ,Myelofibrosis ,medicine.disease ,medicine.drug - Published
- 2021
7. Updates on Acute Myeloid Leukemia Management in older patients
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Julio Alvarenga Thiebaud, Guido Marcucci, Monzr M. Al Malki, and Salman Otoukesh
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Oncology ,medicine.medical_specialty ,Older patients ,business.industry ,Internal medicine ,medicine ,Myeloid leukemia ,business - Published
- 2021
8. Current and Emerging Therapies for Acute Myeloid Leukemia
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Anthony S. Stein, Matthew Mei, Salman Otoukesh, and Brian Ball
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Oncology ,medicine.medical_specialty ,IDH1 ,medicine.drug_class ,Venetoclax ,business.industry ,Myeloid leukemia ,Disease ,medicine.disease ,Monoclonal antibody ,Transplantation ,Leukemia ,chemistry.chemical_compound ,Older patients ,chemistry ,hemic and lymphatic diseases ,Internal medicine ,medicine ,business - Abstract
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.
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- 2021
9. The efficacy of venetoclax and hypomethylating agents in acute myeloid leukemia with extramedullary involvement
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Ibrahim Aldoss, Salman Otoukesh, Jianying Zhang, Vinod Pullarkat, Stephen J. Forman, Ryotaro Nakamura, Anthony S. Stein, and Guido Marcucci
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Oncology ,Cancer Research ,medicine.medical_specialty ,Disease ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Extramedullary Involvement ,Medicine ,Humans ,Sulfonamides ,business.industry ,Venetoclax ,fungi ,food and beverages ,Myeloid leukemia ,Hematology ,Bridged Bicyclo Compounds, Heterocyclic ,Leukemia, Myeloid, Acute ,chemistry ,030220 oncology & carcinogenesis ,business ,030215 immunology - Abstract
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...
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- 2020
10. Outcomes of Venetoclax and Hypomethylating Agents (HMA) in Adult Patients with KMT2A-Rearranged Leukemias
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Salman Otoukesh, Paul Koller, Ryotaro Nakamura, Monzr M. Al Malki, Brian Ball, Guido Marcucci, Vinod Pullarkat, Eileen P. Smith, Ahmed Aribi, Shukaib Arslan, Ibrahim Aldoss, Forrest Stewart, I. Amanam, Karl Gaal, Michelle Afkhami, Haris Ali, Amandeep Salhotra, Joyce Murata-Collins, and Raju Pillai
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Oncology ,medicine.medical_specialty ,biology ,Adult patients ,Venetoclax ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,chemistry.chemical_compound ,KMT2A ,chemistry ,Internal medicine ,medicine ,biology.protein ,business - Abstract
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.
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- 2021
11. Prevalence of Low Vitamin D in Patients with Breast Cancer in a Predominantly Hispanic Population at the American-Mexican Border
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Safa Farrag, Salman Otoukesh, Luis A. Sanchez, Alok Dwivedi, Zeina Nahleh, and Nabeel Badri
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Adult ,Cancer Research ,medicine.medical_specialty ,Population ,Medicine (miscellaneous) ,Breast Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Mexican Americans ,Prevalence ,Vitamin D and neurology ,Humans ,Medicine ,In patient ,Hispanic population ,030212 general & internal medicine ,education ,Aged ,Retrospective Studies ,Gynecology ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,Medical record ,Cancer ,Retrospective cohort study ,Middle Aged ,Vitamin D Deficiency ,medicine.disease ,Texas ,Oncology ,030220 oncology & carcinogenesis ,Female ,business - Abstract
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.
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- 2017
12. Clinical Impact of Cytokine Release Syndrome on Outcomes of Peripheral Blood Stem Cell Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide
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Claudio Anasetti, Haris Ali, Salman Otoukesh, Stephen J. Forman, Monzr M. Al Malki, Hany Elmariah, Dongyun Yang, Krishnakar Mogili, Shukaib Arslan, Nelli Bejanyan, Taiga Nishihori, Madiha Siraj, Joseph Pidala, Sally Mokhtari, Ryotaro Nakamura, and Chatchada Karanes
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Acute leukemia ,medicine.medical_specialty ,Neutrophil Engraftment ,Cyclophosphamide ,business.industry ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Lower risk ,Biochemistry ,Transplantation ,Cytokine release syndrome ,Internal medicine ,Cohort ,medicine ,Complication ,business ,medicine.drug - Abstract
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.
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- 2020
13. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer
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Steven Rains, Andres Belmont, Geri Villanueva, Aamer Abbas, Karinn Chambers, Clarissa N. Amaya, Ali Khammanivong, Alireza Torabi, Nabeel Badri, Sarah T. Baca, Renato J. Aguilera, Erin B. Dickerson, Salman Otoukesh, Luis A. Sanchez, Brad A. Bryan, Zeina Nahleh, Danielle Liss, Nabih Diab, Richard Trevino, Alexa Montoya, and Alok Dwivedi
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0301 basic medicine ,Oncology ,Time Factors ,Metastasis ,0302 clinical medicine ,Epidemiology ,Medicine ,Phosphorylation ,Cyclic AMP Response Element-Binding Protein ,Hematology ,biology ,Middle Aged ,3. Good health ,Treatment Outcome ,030220 oncology & carcinogenesis ,Ki-67 ,Female ,Mitogen-Activated Protein Kinases ,Research Paper ,Signal Transduction ,Adult ,medicine.medical_specialty ,Proliferative index ,Cell Survival ,proliferation ,Adrenergic beta-Antagonists ,Breast Neoplasms ,03 medical and health sciences ,breast cancer ,Breast cancer ,Cell Line, Tumor ,Internal medicine ,Humans ,propranolol ,Aged ,Cell Proliferation ,Neoplasm Staging ,Retrospective Studies ,Dose-Response Relationship, Drug ,business.industry ,Cancer ,medicine.disease ,beta blocker ,Cross-Sectional Studies ,Ki-67 Antigen ,030104 developmental biology ,Receptors, Adrenergic, beta-3 ,Immunology ,biology.protein ,Receptors, Adrenergic, beta-1 ,Apoptosis Regulatory Proteins ,business ,Biomedical sciences - Abstract
// 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.
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- 2016
14. ASCEND-8 pharmacokinetic, safety, and efficacy data for ceritinib 450 mg with food in patients with anaplastic lymphoma kinase-positive non-small cell lung Cancer: A clinical perspective
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Desiree Wallace, Tiffany Sanchez, Salman Otoukesh, Hamid R. Mirshahidi, and Saied Mirshahidi
- Subjects
Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Anaplastic Lymphoma ,medicine.drug_class ,Administration, Oral ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Anaplastic lymphoma kinase ,Humans ,Anaplastic Lymphoma Kinase ,030212 general & internal medicine ,Sulfones ,Adverse effect ,Lung cancer ,Protein Kinase Inhibitors ,Aged ,Neoplasm Staging ,Ceritinib ,business.industry ,Middle Aged ,medicine.disease ,Clinical trial ,Pyrimidines ,Treatment Outcome ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,business ,medicine.drug - Abstract
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.
- Published
- 2019
15. Disparities in breast cancer: a multi-institutional comparative analysis focusing on American Hispanics
- Author
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Salman Otoukesh, Anthony L. Nguyen, Nabeel Badri, Luis A. Sanchez, Alok Dwivedi, Gayathri Nagaraj, Gehan Botrus, Hamid R. Mirshahidi, Zeina Nahleh, Andres Alvarado, and Nabih Diab
- Subjects
Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Hispanic ,Hormone Receptor ,Breast Neoplasms ,Disparities ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Breast Cancer ,Ethnic differences ,medicine ,Biomarkers, Tumor ,Ethnicity ,Humans ,Radiology, Nuclear Medicine and imaging ,030212 general & internal medicine ,Healthcare Disparities ,African American ,Triple-negative breast cancer ,Aged ,Neoplasm Staging ,Original Research ,Triple Negative ,business.industry ,Lumpectomy ,Cancer ,Disease Management ,Hispanic or Latino ,Middle Aged ,medicine.disease ,Prognosis ,Health equity ,Cancer registry ,Black or African American ,Oncology ,030220 oncology & carcinogenesis ,Relative risk ,Female ,business ,Cancer Prevention - Abstract
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
- Published
- 2017
16. Graves’ Disease and Pancytopenia: An Unusual Presentation
- Author
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Salman Otoukesh, Juan Arenas, Tamis Bright, Maryna Popp, Zeina Nahleh, Claudia S. Didia, Osvaldo Padilla, and Mona Mojtahedzadeh
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,Graves' disease ,Medicine ,Presentation (obstetrics) ,business ,medicine.disease ,Pancytopenia ,Dermatology - Published
- 2014
17. 166P Evidence-based conclusions and indinations of pemetrexed, taxane and bevacizumab in advanced lung cancer
- Author
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Liang Ji, Shagufta Shaheen, Salman Otoukesh, John Morgan, and Hamid R. Mirshahidi
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Evidence-based practice ,Taxane ,Bevacizumab ,business.industry ,medicine.disease ,Pemetrexed ,Internal medicine ,medicine ,business ,Lung cancer ,medicine.drug - Published
- 2018
18. Optimization of Tacrolimus Serum Levels When Combined with Post-Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis after Hematopoietic Cell Transplantation: Outcome Data Analysis
- Author
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Janny M. Yao, Shukaib Arslan, Haris Ali, David S. Snyder, Monzr M. Al Malki, Karamjeet S. Sandhu, Saloomeh Mokhtari, Dongyun Yang, Amandeep Salhotra, Ibrahim Aldoss, Ryotaro Nakamura, Vinod Pullarkat, Salman Otoukesh, Stephen J. Forman, Anthony S. Stein, and Guido Marcucci
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Cyclophosphamide ,medicine.medical_treatment ,Immunology ,Hematopoietic stem cell transplantation ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Dosing ,business.industry ,Cell Biology ,Hematology ,Consecutive case series ,medicine.disease ,Tacrolimus ,Transplantation ,surgical procedures, operative ,030104 developmental biology ,Graft-versus-host disease ,Sirolimus ,business ,030215 immunology ,medicine.drug - Abstract
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.
- Published
- 2019
19. The feasibility of venetoclax and decitabine in therapy-related acute myeloid leukemia with concurrent advanced non-hematological malignancies
- Author
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Salman Otoukesh, Stephen J. Forman, Ibrahim Aldoss, Vinod Pullarkat, Guido Marcucci, and Amandeep Salhotra
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Decitabine ,Therapy-Related Acute Myeloid Leukemia ,chemistry.chemical_compound ,Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Sulfonamides ,Therapy related ,business.industry ,Venetoclax ,Neoplasms, Second Primary ,Hematology ,Bridged Bicyclo Compounds, Heterocyclic ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Hypomethylating agent ,chemistry ,business ,medicine.drug - Published
- 2019
20. Prognostic impact of age at diagnosis in triple negative breast cancer: Analysis of 204 patients from single institution registry
- Author
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Alok Dwivedi, Andres Alvarado, Anthony L. Nguyen, Salman Otoukesh, and Gayathri Nagaraj
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Prognostic factor ,business.industry ,Age at diagnosis ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Single institution ,skin and connective tissue diseases ,business ,Triple-negative breast cancer - Abstract
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 ...
- Published
- 2018
21. Retrospective analysis of AML patients to identifiy a higher risk of anthracycline-associated cardiac toxicity in Hispanic patients
- Author
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Kiwon Park, Geoffrey Patrick Shouse, Seema Mukadam, Aldane Hoilett, Lawrence Liu, Muhammad Omair Kamal, and Salman Otoukesh
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Anthracycline ,business.industry ,Myeloid leukemia ,hemic and lymphatic diseases ,Internal medicine ,Cardiac toxicity ,Retrospective analysis ,Medicine ,business ,neoplasms - Abstract
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 ...
- Published
- 2018
22. Prevalence of low vitamin D in patients with breast cancer in a predominantly Hispanic population at the American Mexican border
- Author
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Salman Otoukesh, Nabeel Badri, Alok Dwivedi, Zeina Nahleh, Safa Farrag, and Luis A. Sanchez
- Subjects
Gerontology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.disease ,Breast cancer ,Oncology ,Internal medicine ,Epidemiology ,medicine ,Vitamin D and neurology ,Hispanic population ,In patient ,business - Abstract
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...
- Published
- 2016
23. Concordance of Ki-67 with 21-gene expression profile (RS) in early-stage breast cancer
- Author
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Osvaldo Padilla, Salman Otoukesh, Luis A. Sanchez, Juan Arenas, Alok Dwivedi, Azadeh Nasrazadani, Zeina Nahleh, and Andres Alvarado
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,biology ,medicine.diagnostic_test ,business.industry ,Concordance ,Bioinformatics ,medicine.disease ,Underinsured ,Breast cancer ,Ki-67 ,Internal medicine ,Gene expression ,biology.protein ,medicine ,Stage (cooking) ,Oncotype DX ,business - Abstract
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...
- Published
- 2014
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