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Experimental Hematology & Oncology

Jeffrey Ahn, Justin Moyers, John Wong, Chung-Tsen Hsueh
Background: Thyroid dysfunction has not been previously reported in clinical trials of selective fibroblast growth factor receptor (FGFR) inhibitors including AZD4547. Herein, we report a case of worsening hypothyroidism in a patient with advanced urothelial cancer treated with AZD4547. Case presentation: An 80-year-old Caucasian female with metastatic urothelial carcinoma failed first-line chemotherapy with gemcitabine and carboplatin and second-line treatment with atezolizumab, an inhibitor of programmed cell death ligand 1...
2019: Experimental Hematology & Oncology
Vaibhav Verma, Geeti Sharma, Abhijai Singh
Small cell lung cancer which constitutes about 15% of lung cancers is pathobiologically and clinically distinct from non small cell cancer. Histologically it is characterized by small cells with scant cytoplasm, absent or inconspicuous nucleoli, extensive necrosis, and expresses neuroendocrine markers. It is on a spectrum of neuroendocrine cancer that extend from typical carcinoids to large cell to small cell cancer. Clinically it behaves in a more malignant fashion with a rapid doubling time, early metastasis...
2019: Experimental Hematology & Oncology
N O'Connor-Byrne, S Glavey, R Tudor, P Murphy, C J Thompson, J Quinn
The development of hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is well recognised in multiple myeloma (MM). SIADH, due to either MM or Bortezomib can be hazardous as severe hyponatremia may develop if large volumes of hypotonic intravenous fluid are used as an adjunct to chemotherapy. We report a case of Bortezomib-induced SIADH, in whom the use of tolvaptan, a vasopressin receptor-2 antagonist, permitted the continuation of triple combination anti-MM therapy with lenalidomide, Bortezomib and dexamethasone (RVD) in a female with aggressive disease, without the development of hyponatremia...
2019: Experimental Hematology & Oncology
Abdullah Ladha, Jianzhi Zhao, Elliot M Epner, Jeffrey J Pu
Mantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5-6% non-Hodgkin's lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experimental oncology and clinical oncology. Overexpression of cyclin D1 and chromosome t(11,14) translocation are the known molecular biomarkers of this disease. Mantle cell international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation are emerging as the prognostic biomarkers...
2019: Experimental Hematology & Oncology
Pimjai Niparuck, Nittaya Limsuwanachot, Sulada Pukiat, Pichika Chantrathammachart, Budsaba Rerkamnuaychoke, Sutada Magmuang, Sithakom Phusanti, Kochawan Boonyawat, Teeraya Puavilai, Pantep Angchaisuksiri, Artit Ungkanont, Suporn Chuncharunee
Background: Cytogenetic abnormalities and mutated genes indicate the role of consolidation therapy with hematopoietic stem cell transplantation (HSCT) or chemotherapy in acute myeloid leukemia (AML). In this study, we conducted a retrospective study in adult AML patients with newly diagnosed with de novo AML who did not undergo HSCT, to study long term relapse free survival (RFS) and overall survival (OS) after consolidation chemotherapy. Methods: We recruited 141 consecutive AML patients during January 2010-June 2017, the patients received induction chemotherapy with standard dose Ara-C and Idarubicin (7 + 3 or 5 + 2 regimen) followed by intermediate (IDAC) or high dose Ara-c (HiDAC) consolidation therapy...
2019: Experimental Hematology & Oncology
Yun Fan, Andrew S Artz, Koen van Besien, Wendy Stock, Richard A Larson, Olatoyosi Odenike, Lucy A Godley, Justin Kline, John M Cunningham, James L LaBelle, Michael R Bishop, Hongtao Liu
Background: Second allogeneic hematopoietic stem cell transplant (HCT) remains as an option for disease relapse after initial HCT. Methods: We analyzed retrospectively the outcomes of 65 consecutive patients who underwent a second HCT for disease relapse at the University of Chicago. Univariate and multivariate analysis were conducted, and a scoring system was generated to select the patients who would benefit second HCT. Results: All except four patients received T cell depleted (TCD) first HCT...
2019: Experimental Hematology & Oncology
Stephen Capone, Anthony R Colombo, Benjamin K Johnson, Tim J Triche, Giridharan Ramsingh
Senescence, a state of permanent cell cycle arrest, can be induced by DNA damage. This process, which was initially described in fibroblasts, is now recognized to occur in stem cells. It has been well characterized in cell lines, but there is currently very limited data available on human senescence in vivo. We recently reported that the expression of transposable elements (TE), including endogenous retroviruses, was up-regulated along with inflammatory genes in human senescent hematopoietic stem and progenitor cells (HSPCs) in vivo...
2018: Experimental Hematology & Oncology
Yee Yee Yap, Kian Boon Law, Jameela Sathar, Ngee Siang Lau, Ai Sim Goh, Teng Keat Chew, Soo Min Lim, Padmini Menon, Yong Khee Guan, Azlan Bin Husin, Lily Lee Lee Wong, Lee Ping Chew, Sinari Salleh, Kim Yen Goh, Kin Wah Leong, Sen Mui Tan, Tee Chuan Ong, Su Hong Lim, See Guan Toh, Xavier Sim Yoon Han, Syed Carlo Edmund, Jenq Tzong Tan, Kian Meng Chang
Background: The evolution of molecular studies in myeloproliferative neoplasms (MPN) has enlightened us the understanding of this complex disease consisting of polycythaemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The epidemiology is well described in the western world but not in Asian countries like Malaysia. Materials and methods: This retrospective national registry of MPN was conducted from year 2009 to 2015 in Malaysia. Results: A total of 1010 patients were registered over a period of 5 years...
2018: Experimental Hematology & Oncology
Hanxiao Xu, Ying Jiao, Shuang Qin, Weiheng Zhao, Qian Chu, Kongming Wu
Organoid technology bridges the gap between conventional two-dimensional cell line culture and in vivo models. The near-physiological technology can virtually recapitulates organ development and human diseases, such as infectious diseases, genetic abnormality and even cancers. In addition, organoids can more accurately predict drug responses, and serve as an excellent platform for drug development, including efficacy evaluation, toxicity testing and pharmacokinetics analysis. Furthermore, organoids can also be exploited to explore the possible optimized treatment strategies for each individual patient...
2018: Experimental Hematology & Oncology
Wasil Jastaniah, Naglla Elimam, Khalid Abdalla, Aeshah A AlAzmi, Aml M Elgaml, Ahmad Alkassar, Mustafa Daghistani, Sami Felimban
Background: Refinement of risk-based treatment stratification by minimal residual disease (MRD) at different time points has improved outcomes of childhood acute lymphoblastic leukemia (ALL). In this prospective study we evaluated effects of such stratification, including intensification of therapy based on response assessment at day-15 and MRD at day-29 of induction to test if treatment intensification would improve outcomes. Methods: 241 patients, 1-14 years old, newly diagnosed with ALL, were recruited and stratified by risk and MRD response into three treatment Arms (A, B, or C)...
2018: Experimental Hematology & Oncology
Ming Yi, Shuang Qin, Weiheng Zhao, Shengnan Yu, Qian Chu, Kongming Wu
Immune checkpoint inhibitor induces tumor rejection by activated host immune system. The anti-tumor immune response consists of capture, presentation, recognition of neoantigen, as well as subsequent killing of tumor cell. Due to the interdependence among this series of stepwise events, neoantigen profoundly influences the efficacy of anti-immune checkpoint therapy. Moreover, the neoantigen-specific T cell reactivity is the cornerstone of multiple immunotherapies. In fact, several strategies targeting neoantigen have been attempted for synergetic effect with immune checkpoint inhibitor...
2018: Experimental Hematology & Oncology
Xun Ma, Sandy W Wong, Ping Zhou, Chakra P Chaulagain, Parul Doshi, Andreas K Klein, Kellie Sprague, Adin Kugelmass, Denis Toskic, Melissa Warner, Kenneth B Miller, Lisa Lee, Cindy Varga, Raymond L Comenzo
Background: The monoclonal antibody daratumumab, approved for treating myeloma, targets CD38, a protein on myeloma and also on CD34+ hematopoietic progenitor cells. Because mobilized CD34+ cells are critical for stem cell transplant, we investigated the in vitro activity of daratumumab on mobilized CD34+ cells from myeloma patients with no prior exposure to daratumumab. Methods: We determined the number of CD38 molecules per CD34+ cell, and whether daratumumab bound to CD34+ cells, whether C1q bound to daratumumab-coated CD34+ cells and whether daratumumab-related complement-dependent cytotoxicity (CDC) occurred...
2018: Experimental Hematology & Oncology
Kamal Chamoun, Sanam Loghavi, Naveen Pemmaraju, Marina Konopleva, Michael Kroll, Madeleine Nguyen-Cao, Marisa Hornbaker, Courtney D DiNardo, Tapan Kadia, Jeffrey Jorgensen, Michael Andreeff, Shimin Hu, Christopher B Benton
Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy characterized by neoplastic cells that are positive for CD123, CD4, BDCA2, and TCL1 and aberrant expression of CD56. Historically, patients with BPDCN have an unfavorable prognosis and the optimal treatment is not established due to lack of prospective data. Case report: In this report we describe a patient with Felty's syndrome and myelodysplastic syndrome (MDS) in whom a population of aberrant plasmacytoid dendritic cells emerged while on treatment with decitabine...
2018: Experimental Hematology & Oncology
Alejandro Pando, John L Reagan, Martha Nevola, Loren D Fast
Background: Immunotherapeutic protocols have focused on identification of stimuli that induce effective anti-leukemic immune responses. One potent immune stimulus is the encounter with allogeneic cells. Our group previously showed that the infusion of haploidentical donor white blood cells (1-2 × 108 CD3+ cells/kg) into patients with refractory hematological malignancies induced responses of varying magnitude in over half of the patients. Because donor cells were eliminated within 2 weeks in these patients, it is presumed that the responses of recipient lymphocytes were critically important in achieving prolonged anti-leukemic responses...
2018: Experimental Hematology & Oncology
Hui Hua, Hongying Zhang, Qingbin Kong, Yangfu Jiang
Estrogen is a steroid hormone that has critical roles in reproductive development, bone homeostasis, cardiovascular remodeling and brain functions. However, estrogen also promotes mammary, ovarian and endometrial tumorigenesis. Estrogen antagonists and drugs that reduce estrogen biosynthesis have become highly successful therapeutic agents for breast cancer patients. The effects of estrogen are largely mediated by estrogen receptor (ER) α and ERβ, which are members of the nuclear receptor superfamily of transcription factors...
2018: Experimental Hematology & Oncology
Satish Maharaj, Simone Chang, Karan Seegobin, James Morales, Agnes Aysola, Fauzia Rana, Marwan Shaikh
Background: Heparin-induced antibodies (HIA) are responsible for causing heparin-induced thrombocytopenia and thrombosis. Research has shown that the temporality of heparin-induced antibodies does not follow the classic immunologic response. The immunobiology of HIA generation remains unclear with varying in vitro and in vivo data. Outpatients undergoing hemodialysis (HD) are exposed to heparin chronically. The HIA immune response can therefore be investigated in vivo in this population...
2018: Experimental Hematology & Oncology
Kalpna Desai, Priya Misra, Sanyukta Kher, Nirmesh Shah
Background: Chemotherapy-induced neutropenia is a common result of myelosuppressive chemotherapy treatment. Infections such as febrile neutropenia (FN) are sensitive to the duration of neutropenia as well as the depth of absolute neutrophil count (ANC) at nadir. Filgrastim, a granulocyte colony stimulating factor (G-CSF), can stimulate the function of mature neutrophils. Pegfilgrastim, a long-acting form of filgrastim, has been shown to reduce FN to a greater extent compared to filgrastim...
2018: Experimental Hematology & Oncology
Elena V Poddubskaya, Madina P Baranova, Daria O Allina, Philipp Y Smirnov, Eugene A Albert, Alexey P Kirilchev, Alexey A Aleshin, Marina I Sekacheva, Maria V Suntsova
Background: Cholangiocarcinoma is an aggressive tumor with poor prognosis. Most of the cases are not available for surgery at the stage of the diagnosis and the best clinical practice chemotherapy results in about 12-month median survival. Several tyrosine kinase inhibitors (TKIs) are currently under investigation as an alternative treatment option for cholangiocarcinoma. Thus, the report of personalized selection of effective inhibitor and case outcome are of clinical interest. Case presentation: Here we report a case of aggressive metastatic cholangiocarcinoma (MCC) in 72-year-old man, sequentially treated with two targeted chemotherapies...
2018: Experimental Hematology & Oncology
John D Strickley, Aaron C Spalding, M Tye Haeberle, Timothy Brown, Don A Stevens, Jae Jung
Background: Lapatinib is a tyrosine kinase inhibitor that blocks the HER2 receptor and is typically used in the setting of metastatic breast cancer. Both ERBB2 (HER2) and ERBB3 (HER3) belong to the same family of receptor tyrosine kinases. Dimerization of these receptors leads to activation of cell proliferation and survival pathways, granting oncogenic potential to dysregulated ERBB/HER receptors. Next generation sequencing (NGS) of tumors has ushered in a new era of personalized oncology therapy and has the ability to detect mutations in ERBB receptors...
2018: Experimental Hematology & Oncology
Xiaojing Wang, Gang An, Jiying Wang, Yan Zhang, Qinghua Li, Hui Wei, Lugui Qiu, Kun Ru
Background: The positive association of multiple myeloma (MM) risk with HLA-C loci C*07:02 g and C*02:02 g, and the negative association of that with C*05:01 g were statistically significant in Whites have recently been reported. However, no association between HLA-C alleles and MM risk was found in Asians/Pacific Islanders. Here we identified 316 Chinese patients with MM, and reported the results of our investigation of HLA-C in MM in Chinese population. Methods: We identified 316 Chinese patients with MM diagnosed in our hospital, and typed for HLA-C by using Sanger sequence-based typing...
2018: Experimental Hematology & Oncology
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