Ishmael Jaiyesimi

Beaumont Health System, Detroit, Michigan, United States

Are you Ishmael Jaiyesimi?

Claim your profile

Publications (45)169.29 Total impact

  • Ogunleye Foluso · Alexandra Glick · Michael Stender · Ishmael Jaiyesimi
    [Show abstract] [Hide abstract]
    ABSTRACT: The recent discovery of the role of the B-cell antigen receptor (BCR) signaling pathway in the propagation and maintenance of both normal B-cell function and in B-cell malignancies has highlighted the importance of many protein kinases involved in BCR signal propagation. Considerable research attention has focused on the Bruton tyrosine kinase (BTK) as a potential therapeutic target in B-cell malignancies. Treatment paradigms including ibrutinib, a potent inhibitor of the BTK recently approved by the US Food and Drug Administration, have significantly improved disease outcome among high-risk and relapsed/refractory cases of chronic lymphocytic leukemia. This has provided additional treatment options, especially among the elderly, where improved disease response has been accompanied by more manageable treatment-associated toxicity than commonly found with chemoimmunotherapy. In this review, we provide a synopsis of the current data on the efficacy and clinical utilization of ibrutinib and management of its resistance in the treatment of chronic lymphocytic leukemia.
    No preview · Article · Nov 2015 · Clinical lymphoma, myeloma & leukemia

  • No preview · Article · Sep 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: CD20 antigen, expressed on greater than 90% of B-cell ly mphomas, is an established target for antibody therapy with monoclonal antibodies like Rituximab, which can selectiv ely deplete CD20-expressing cells in peripheral blood and ly mphoid tissues. Understanding properties and interactions of CD20 antigens is quintessential for dev eloping better targeted agents and ov ercoming resistance. It has not been clearly established y et whether CD20 antigen density corresponds with response to Rituximab. Flow cy tometry is still the most widely used technique to detect CD20 lev el in human serum which is expensiv e, time consuming and does not rev eal any details of interaction between the molecules. We hav e dev eloped a new innov ativ e biosensor based nov el technique to study real time interaction of CD20 antigens with Rituximab using QCM Piezo-immunosensor. This quantitativ e label free peptide based assay can be used to characterize cell surface antigen, to study antigen- antibody interactions and obtain understanding of mechanisms of resistance to therapy . Met hod: The immobilization of Raji cells on the QCM gold electrode surface using RGD tripeptide was electrochemically confirmed (Figure 1). The real-time processes of attachment of Raji cells on the gold electrode and the subsequent binding of Rituximab to the cells were studied using QCM biosensor. The interaction between Rituximab and Raji cells led to the increased resonant frequency shifts (df0) in the studied antibody concentration range from 5 to 250 μg mL-1 following the Langmuir adsorption model (Figure 2). From these observ ations, the apparent binding constant between a single-lay er of Rituximab and Raji cells was calculated to be 1.6×106 M-1 (Figure 3). Control experiments using other therapeutic antibodies (i.e., Trastuzumab and Bev acizumab) and different cells (i.e., T cells and endothelial cells) prov ed v ery specific interaction between Rituximab and CD20 antigens on B cells. Calcium and Manganese ions were added to the cell culture and corresponding responses by QCM were monitored. Result s: CD20 binding with Rituximab was v ery specific. This binding decreased the electrochemical activ ity and stability of the cells, supporting the cell ly sis mechanisms of action of Rituximab. We hav e shown a sy stematic approach for using QCM technique to quantify the apparent binding constant between Raji cells and Rituximab which can rev eal CD20 antigen density . Moreov er, increased QCM responses were found in the presence of Ca2+ ions and high concentration Mn2+ ions, supporting the function of CD20 as a calcium ion channel. Microscopic inspection prov ed that increased Ca2+ ions could promote the Rituximab binding and cell ly sis induced by Rituximab, which was not seen with Manganese. Conclusion: CD20 antigen density and interactions of CD20 antigens with respectiv e monoclonal antibodies will help phy sicians to determine the clinical efficacy and resistance mechanisms to targeted antibodies like Rituximab and Ofatumumab. For the first time, we hav e established a low cost, highly sensitiv e, fast, sy nthetic, QCM assay which could be used as a basis for dev eloping a new generation of affinity -based Immunosensor assay s. This real time capability of QCM and its simplicity of operation are highly suitable for multipurpose studies on liv ing cells including cell immobilization, cy totoxicity of drugs, and the cell action mechanisms.
    Full-text · Conference Paper · Dec 2014

  • No preview · Article · Nov 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Asymptomatic (smoldering) multiple myeloma is a heterogeneous plasma cell proliferative disorder with variable rate of progression to active multiple myeloma or related disorders. Hypercalcemia, renal insufficiency, anemia, bone lesions or recurrent bacterial infections characterize active multiple myeloma. Some of the patients with asymptomatic myeloma develop active disease rapidly and others can stay asymptomatic for many years. Those who are likely to progress within the first two years of diagnosis have been categorized as high-risk. The availability of novel agents in the treatment of active multiple myeloma and our better understanding of the heterogeneity of asymptomatic multiple myeloma have spurred the interest in early treatment of these patients. We have reviewed the current proposed definitions of high-risk asymptomatic multiple myeloma, the concerns about future therapy in view of the transient nature, remissions and toxicities of the therapies, and the eventual relapses that characterize this incurable disease.
    No preview · Article · Feb 2014 · Leukemia & lymphoma
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A man in his early 40s with a history of ulcerative colitis, treated with infliximab, was diagnosed with plasmablastic multiple myeloma. He was treated with chemotherapy and stem cell transplant but developed recurrence and ultimately died from metastatic disease. Could inflammatory bowel disease or infliximab therapy have any role in development of myeloma in this young patient? The role of inflammatory bowel disease and infliximab therapy in the development of multiple myeloma is controversial but interesting and worth considering.
    Full-text · Article · Oct 2013 · Case Reports
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A 46-year-old man with a long-standing history of Crohn's disease who was treated with multiple therapies over a period of 9 years presented with oral lesions which on biopsy demonstrated peripheral T-cell lymphoma. Initially, the development of T-cell lymphoma was presumed to be secondary to prolonged immunosuppression but it did not respond to withholding immunosuppressive therapy. On treatment with CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) chemotherapy, complete remission was achieved. Although development of malignancies in the immune-suppressed patient with Crohn's disease has been previously described but we present a rare case of T-cell lymphoma in a similar patient, which has not been reported before.
    Full-text · Article · Oct 2013 · Case Reports
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Worldwide ethnic variations in the distribution of BRCA1 and BRCA2 mutations of breast cancer patients have been recently recognized. This has led to investigations of the epidemiology, genetics and clinical characteristics of BRCA positive individuals within specific populations. This study aims to describe the findings of BRCA genetic testing in a cohort of Arab American women. Methods: A total of 73 women of Arab ancestry were evaluated in the Beaumont Cancer Genetics Program from Jan 2008 to Jan 2013. Criteria for genetic testing included a personal or family history suggestive of Hereditary Breast and Ovarian Cancer Syndrome (HBOC). Patients underwent comprehensive genetic counseling, followed by full sequence analysis for germline mutations in BRCA1 and BRCA2. Results: 63 women of Arab ancestry underwent genetic testing for BRCA1 and BRCA2. 13 (21%) patients were found to be mutation carriers, of whom 10 (16%) of the 63 had deleterious mutations (7 in BRCA2, and 3 in BRCA1), and 3 (5%) had variants of undetermined significance (VUS) in BRCA2. Of the 10 patients with deleterious mutations, 4 (40%) unrelated individuals had the same mutation, 5804del4, in exon 11 of BRCA2. The remaining patients had deleterious mutations in exon 2, exon 20, and exon 13 of BRCA2; one patient had a BRCA1 and BRCA2 mutation (exon 18). 7 of 10 patients with deleterious mutations had a cancer diagnosis, of which 5 had breast cancer, 1 had ovarian cancer, 1 had pancreatic cancer, and 3 were unaffected. Conclusions: This study demonstrates that BRCA mutations
    Full-text · Conference Paper · Jun 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: During induction treatment, acute myeloid leukemia patients may develop pulmonary infiltrates due to infectious or noninfectious etiologies. The risk association and the clinical outcome of such pulmonary infiltrates are poorly characterized in the literature. Methods: We retrospectively reviewed 363 cases of acute myeloid leukemia patients who received induction therapy as inpatients over a period of 11 years at William Beaumont Health System. Of these 363 patients, 120 developed pulmonary infiltrates during induction therapy, those patients were divided into 2 groups based on distribution of the infiltrate presenting as localized or diffuse in nature. Data on patients characteristics, leukemia subtype, cytogenetic risk, microorganism type, white blood cell count at diagnosis, neutrophil count at the time the infiltrate was reported, response to antibiotic and/or antifungal therapy, using respiratory support, and mortality rate were retrieved through chart review. Results: Thirty-three percent of patients developed pulmonary infiltrates during their induction therapy. Sixty-three patients (52.5%) had a localized infiltrates and 57 patients (47.5%) had diffuse infiltrates. Of the 120 patients with pulmonary infiltrates, 48 (40%) had at least 1 pathogenic microorganism identified, and 58 (48.7%) required intubation and ventilatory support. Patients with localized pulmonary infiltrates were more likely to have positive pathogenic microorganisms (68.3% vs. 8.8%, P<0.001), to be neutropenic (96.8% vs. 21%, P<0.001), and tended to have potentially reversible infiltrates after treatment (87.3% vs. 21%, P<0.001). Whereas patients with diffuse infiltrates were more like to require intubation (78.9% vs. 21%, P<0.001), to have leukocytosis (white blood cell >100 billions/L) at diagnosis (54.4% vs. 0%, P<0.001), and had a higher mortality rate (70.2% vs. 9.5%, P<0.001). Conclusions: The radiologic patterns of pulmonary infiltrates showed specific etiological and prognostic associations. Diffuse infiltrates are an unfavorable characteristic with overall dismal outcome.
    Full-text · Article · Jan 2013 · American journal of clinical oncology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: CBs are highly variable at diagnosis and during the course of IT in AML patients. Assessing response to IT carries a huge implication on the prognosis of individual patient with AML. Our study investigates whether late clearance of CBs during IT using standard cytarabine + anthracycline regimen is associated with refractory phenotype. Methods: We retrospectively reviewed the chart of 83 AML patients (43 males, 40 females, mean age 61.7) who received standard cytarabine and anthracycline regimen during induction between January, 2000-January, 2011 at William Beaumont Health System. Data collected include complete blood count with blast count during course of induction, and bone marrow response. AML is considered refractory if morphological evaluation, flow cytometry or cytogenetic study was positive in the first bone marrow post induction. Response to IT was assessed according to Cancer and Leukemia Group B (CALGB) criteria as complete remission versus residual leukemia or treatment failure (failing to achieve complete remission). Results: We noted that 57 of 83 patients (68.7%) showed CBs at the time of diagnosis. During the IT, CBs clearance occurred within 7 days (early clearance) in 38 of these 57 patients. The remaining 19 patients had CBs persistent more than 7 days (delayed clearance). The frequency of bone marrow residual disease at count recovery post IT was significant higher in patients with late clearance and those with early clearance (84% vs 42%, p=0.0015). Further analysis of data showed the frequency of bone marrow residual disease was not significantly different between patients with no CBs at the diagnosis and those with early clearance of CBs (38% vs 42%, p=0.8). Conclusion: Adult AML patients with persistent CBs >7 days during IT with standard induction cytarabine and anthracycline regimen are more likely to have induction failure. CBs clearance can be used as an early assessment of response to the IT. Disclosures: No relevant conflicts of interest to declare. Footnotes * Asterisk with author names denotes non-ASH members.
    Full-text · Conference Paper · Dec 2012
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 5098 Introduction: Follicular Lymphoma (FL) comprises of 20–30% of Non-Hodgkin's Lymphomas. It is the most common lymphoma with varied clinical aggressiveness, depending on morphological grading on histology. The prognosis of FL is heterogeneous. Therefore therapeutic options for FL are increasingly becoming more risk-adopted. Pathologically, FL has been graded into grade 1–2 (FL1–2) and grade 3 (FL3) by visual counting or estimating the absolute number of centroblasts in neoplastic follicles. Recent studies found that the average tumor cell size of FL is highly variable, but is consistently reproducible, achieved by an objective measurement using flow cytometry. A significant variation in metabolic activity has also been observed in FL studied by PET scan. The purpose of this study was to investigate a new risk stratification method for FL using a combined criterion of Flow cytometry based cell size of FL cells and metabolic activity based on FDG PET scan to further evaluate their prognostic values. Materials and Methods: Retrospective study of 64 patients (25 males and 39 females with median age of 61 years), diagnosed with FL between 2006 –2010 in Beaumont Health System with proper HIC approval was performed. 44 cases were graded morphologically into low risk (FL 1–2) and 20 into high risk (FL 3), based on current WHO classification. The average tumor cell size was measured based flow cytometric analysis of the relative forward scatters (FSC) of tumor cells relative to that of internal T-cells in the lymphoma tissue. The metabolic activity was measured as in maximal standardized uptake value (SUV max) of the involved lymph node by PET scan based F-18 FDG uptake. The SUV was normalized to a glucose level of 100 using the formula: SUV100={[100 mg/dl]/[glc]}g where g= [-0. 5] from our prior publication and [Glc] was the glucose level of the patient recorded at the time of PET scan. The difference of average lymphoma cell size between grade 1–2 (FL 1–2, indolent) and grade 3 (FL 3, aggressive) was compared with Student t test. The difference of size distribution between FL with low SUV100 and FL with high SUV100 were compared with Chi square and Kappa tests. A two-tail p-value less than 0. 05 was considered significant in all tests. FSC and Metabolic activity were cross tabbed and correlated using cut off values determined by discriminant analysis. Results: The FSC of B-cells were significantly lower in low grade FL than that in high grade FL (p=0. 00002). In contrast, FSC of residual T-cells in low grade FL and high grade FL were about the same (p=0. 2). Average lymphoma cell size of the low risk group (relative FSC of –15, range of –83 to 153) was significantly smaller than that of high risk group(relative FSC of 92, range of –32 to 243), (P<0. 0005)(figure 1). Using a cut off value FSC= –18 from discriminant analysis, and group them into aggressive and indolent FL, there was significant difference in metabolic activity (SUV 100) between the lymphoma with small and large tumor cell sizes (p=0. 021, by Chi-Square test)(figure 2). Combining these two objective independent measurements could accurately place low risk FL into observation with 95% confidence. Conclusion: The significance of average lymphoma cell size identified by FSC in this study between FL grade 3 and grade 1–2 validate potential utility of flow cytometry in grading FL in refining the grading because the measurement of average lymphoma cell size by flow cytometry it is more reproducible, objective, and easy to use than manual counting centroblasts microscopically. Since increased metabolic activity is often associated with more aggressive clinical behavior, combining tumor cell size by flow cytometry and metabolic activity by FDG PET imaging can potentially serve as an independent criterion in risk stratification and better grading of FL. Further clinical correlation is in progress.
    Full-text · Conference Paper · Dec 2012

  • No preview · Article · Nov 2012 · International Journal of Radiation OncologyBiologyPhysics

  • No preview · Article · Nov 2012 · International Journal of Radiation OncologyBiologyPhysics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 5/12/13 Detection of trastuzumab (T) level in human serum using quartz crystal microbalance (QCM) piezo-immunosensors by immobilization of a HER2 mimotope-… Detection of trastuzumab (T) level in human serum using quartz crystal microbalance (QCM) piezo-immunosensors by immobilization of a HER2 mimotope-derived synthetic peptide and its potential application in breast cancer. Abstract Disclosures Abstract 628
    Full-text · Conference Paper · Jun 2012
  • Source

    Full-text · Article · Jan 2012 · Annals of Hematology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: VTEs are common complications in association with IT which may cause additional morbidity and mortality in AML patients. However, treating patients with AML is challenging because of the cytopenias due to chemotherapy and the high risk for bleeding during IT. This study investigates frequency, risk factors, and safety of using anticoagulation (AC) therapy for VTEs during IT.
    Full-text · Conference Paper · Dec 2011
  • [Show abstract] [Hide abstract]
    ABSTRACT: To compare outcomes after accelerated partial breast irradiation (APBI) between node-negative and node-positive patients. A total of 534 patients with early-stage breast cancer received APBI including 39 node-positive (N+) cases. Clinical, pathologic, and treatment-related factors were compared between node-negative (N-) and N+ cohorts. Local recurrence (LR), regional recurrence (RR), axillary failure (AF), distant metastases (DM), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. N+ patients were younger (p = 0.04), had larger tumors (p < 0.001), and were more likely to receive chemotherapy (p < 0.001). Mean follow-up was 7.8 years for N+ patients and 6.3 years for N- patients (p = 0.06). No differences were seen in 5-year actuarial rates of LR (2.2% vs. 2.6%, p = 0.86), AF (0% vs. 0%, p = 0.69), DFS (90.0% vs. 88.0%, p = 0.79), or OS (91.0 vs. 84.0%, p = 0.65) between the two groups, whereas higher rates of RR (0% vs. 6.1%, p < 0.001) and DM (2.2% vs. 8.9%, p = 0.005) were noted in N+ patients. A trend for improved CSS (p = 0.06), was seen in N- patients. Age, tumor size, receptor status, T-stage, chemotherapy, APBI technique, and nodal status (p = 0.86) were not associated with LR, while a trend for an association with LR was noted with close/positive margins, (p = 0.07), and failure to receive adjuvant hormonal therapy (p = 0.06). No differences were seen in the rates of LR or AF between N- and N+ patients after APBI. These results support the continued enrollment of node-positive patients in Phase III trials evaluating the efficacy of APBI including the National Surgical Adjuvant Breast and Bowel Project-B39/Radiation Therapy Oncology Group 0413.
    No preview · Article · Sep 2011 · International journal of radiation oncology, biology, physics
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: We analyzed differences in disease presentation, outcomes, and toxicities between African American (AA) and White (W) men treated with definitive radiation therapy for their prostate cancer. METHODS: Three thousand one hundred eighty cases of prostate cancer treated with various radiation modalities at a single institution were reviewed. The cohort consisted of 92% W patients and 8% AA patients. Clinical and pathologic characteristics at presentation, treatment outcomes, and related toxicities were analyzed between the 2 groups. The median follow-up was 6.6 years (0.6 to 22.4 y). RESULTS: At presentation, AA men were younger (P<0.001) and more likely to have a Gleason score of ≥7 (47.9% vs. 39.2%, P=0.006). No difference in the 5 or 10-year rates of biochemical failure, disease-free survival, or distant metastases were noted. Although there was a trend for improved 10-year overall survival for AA men (65.3% vs. 57.4%, P=0.06), cause-specific survival was significantly improved at 10 years (98.6% vs. 90.6%, P=0.002). Similar findings were seen when controlling for radiation therapy dose, the use of hormonal therapy, and modality of radiation therapy used. Overall, genitourinary/gastrointestinal toxicities were similar regardless of the modality used. CONCLUSIONS: Despite differences in presenting characteristics, AA men did not have inferior clinical outcomes but rather improved cause-specific survival when treated with standard of care radiation therapy. Regardless of the treatment modality used, toxicities between AA and W men were comparable.
    No preview · Article · Jun 2011 · American journal of clinical oncology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute promyelocytic leukemia (APL) with the unique t(15;17) translocation has a high complete remission and disease-free survival rates following chemotherapy with all-trans-retinoic acid. Chemotherapy complications including secondary malignancies are rare. In this report we present therapy-related T-lymphoblastic lymphoma following APL treatment. The bone marrow analysis showed MLL and MAML2 genes rearrangement that can explain the molecular basis for the lymphoma development.
    Full-text · Article · Jun 2011
  • [Show abstract] [Hide abstract]
    ABSTRACT: We studied the feasibility of implementing a community-based participatory process (CBPP) that addressed cancer education, prevention, and screening in 2 ethnic minority populations by evaluating the improvement in rates of cancer screening compared with historical benchmarks. From 2003 to 2009, 2281 community members participated in CBPPs conducted by the Beaumont Cancer Institute in cooperation with the Arab American and Chaldean (AAC) Council, the National Cancer Institute, and the American Cancer Society. The study population consisted of 1067 individuals who completed a postcancer forum survey: 642 from the African American (AA) and 425 from the AAC forums. Data were collected on participants' screening history and participation in subsequent screening tests after the previous year's CBPP. Following attendance of at least one cancer forum the previous year, 329 (30.8%) of the 1067 participant respondents underwent some type of cancer screening, 32% in the AA forums and 28.9% in the AAC forums. Compared with published controls, the CBPPs led to a 38.6% increase in mammographic screening and a 28.7% increase in prostate-specific antigen screening; the AA cohort had 39.7% and 28.4% increases whereas the AAC cohort had 36.3% and 28.9% increases in mammographic and prostate-specific antigen screening, respectively. The results of this study suggest that implementing CBPPs are feasible in underscreened ethnic minority populations. Further studies need to be performed to determine the absolute benefit of CBPPs compared with baseline levels of screening within these ethnic minority populations.
    No preview · Article · May 2011 · American journal of clinical oncology

Publication Stats

794 Citations
169.29 Total Impact Points

Institutions

  • 2014
    • Beaumont Health System
      Detroit, Michigan, United States
  • 2011-2013
    • Oakland University
      Рочестер, Michigan, United States
  • 2000-2013
    • William Beaumont Army Medical Center
      El Paso, Texas, United States
  • 1993-1994
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States