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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
Henrik Gregersen, Trung Do, Ida Bruun Kristensen, Ulf Christian Frølund, Niels Frost Andersen, Lene Kongsgaard Nielsen, Christen Lykkegaard Andersen, Tobias Wirenfeldt Klausen, Annette Juul Vangsted, Niels Abildgaard
Background: The objective of this randomized placebo-controlled study was to investigate the efficacy and safety of clarithromycin in combination with bortezomib-cyclophosphamide-dexamethasone (VCD) in patients with newly diagnosed multiple myeloma eligible for high-dose therapy. Methods: Patients were randomized to receive tablet clarithromycin 500 mg or matching placebo tablet twice daily during the first 3 cycles of VCD induction therapy. Primary endpoint was to compare the rate of very good partial response (VGPR) or better response after three cycles of VCD combined with clarithromycin or placebo...
2018: Experimental Hematology & Oncology
Sowmini Medavaram, Yue Zhang
Background: Prognosis is very poor for advanced HCC patients partially due to lack of effective systemic treatment. Sorafenib was the only approved agent for advanced HCC since 2007 until recent breakthroughs. In this article, we will review the newer approved and promising agents in the treatment of advanced HCC in the first line setting and beyond progression. Main body: The Food and Drug Administration approved sorafenib as it demonstrated 3 months overall survival benefit compared to placebo in the first line setting over 10 years ago...
2018: Experimental Hematology & Oncology
Dilan Paranagama, Philomena Colucci, Kristin A Evans, Machaon Bonafede, Shreekant Parasuraman
Background: Patients with polycythemia vera (PV) have a higher mortality risk compared with the general population, primarily driven by cardiovascular disease, thrombotic events (TEs), and hematologic transformations. The goal of risk-adapted therapy in PV is prevention of TEs. Current treatment recommendations indicate that high-risk patients (aged ≥ 60 years and/or with history of TEs) should be managed with cytoreductive medications, phlebotomy, and low-dose aspirin. This noninterventional study was conducted to describe real-world cytoreductive medication treatment in adult patients with PV, stratified by risk, in the United States...
2018: Experimental Hematology & Oncology
Armand Russo, Susanna Curtis, Raisa Balbuena-Merle, Roxanne Wadia, Ellice Wong, Herta H Chao
Bullous hemorrhagic dermatosis (BHD) is a systemic side-effect of low molecular weight heparin, characterized by multiple intra-epidermal hemorrhages distant from the site of injection. There have been several small case series and literature reviews on BHD, but none have captured a complete set of reported patients. We sought to describe a case of BHD with late diagnosis and completely summarize the existing English and Spanish literature with searches of Pubmed, Scopus, Ovid Embase and Ovid Medline. After narrowing to 33 relevant reports, we describe 90 reported cases worldwide from 2004 to 2017, in addition to a new case from our institution as a means of comparison...
2018: Experimental Hematology & Oncology
Eric Wirtschafter, Christine VanBeek, Yuliya Linhares
Background: Bone marrow transplant-associated thrombotic microangiopathy (TA-TMA) is a relatively frequent but under-recognized and under-treated hematopoietic stem cell transplant (HSCT) complication that leads to significant post-transplant morbidity and mortality. Classic TMA-defining laboratory abnormalities appear at different times in the course of TA-TMA development, with schistocytes often appearing later in the disease course. In some severe TMA cases, schistocytes may be absent due to increased endothelial permeability...
2018: Experimental Hematology & Oncology
Kwasi M Connor, Young Hsu, Pardeep Kumar Aggarwal, Stephen Capone, Anthony R Colombo, Giridharan Ramsingh
Background: Aging is associated with complex molecular alterations at the cellular level. Bone marrow exhibits distinct phenotypic, genetic and epigenetic alterations with aging. Metabolic changes in the bone marrow related to aging have not been studied. Methods: In this study, we characterized the metabolome and transcriptome of aging murine bone marrow and compared it with bone marrow from young healthy mice and chemotherapy treated mice; chemotherapy treatment is known to induce age-related changes in hematopoiesis...
2018: Experimental Hematology & Oncology
Patrick B Johnston, Lauren C Pinter-Brown, Ghulam Warsi, Kristen White, Radhakrishnan Ramchandren
Background: The current standard of care for classical Hodgkin lymphoma (HL) is multiagent chemotherapy with or without radiation. In patients who relapse or fail to respond, additional high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) can improve progression-free survival (PFS). Novel therapies are required for patients refractory to chemotherapy and AHSCT. The mammalian target of rapamycin inhibitor everolimus has shown preliminary activity in preclinical models of HL and promising efficacy in patients with relapsed or refractory HL...
2018: Experimental Hematology & Oncology
Shagufta Shaheen, Hamid Mirshahidi, Gayathri Nagaraj, Chung-Tsen Hsueh
Background: Nivolumab is an immune checkpoint inhibitor targeting programmed death-1 protein and has been approved for the treatment of multiple advanced malignancies. Adverse effects of immune checkpoint inhibitors are distinct from conventional cytotoxic chemotherapy and can be life-threatening if left unrecognized. Here, we present a case of nivolumab-induced pericardial effusion successfully managed with high-dose corticosteroids. Case presentation: A 70-year-old Caucasian female with a history of 50-pack-year cigarette smoking was diagnosed of recurrent adenocarcinoma of lung after initial surgery...
2018: Experimental Hematology & Oncology
Rafael Sebastián Fort, Cecilia Mathó, Carolina Oliveira-Rizzo, Beatriz Garat, José Roberto Sotelo-Silveira, María Ana Duhagon
Prostate cancer is a major health problem worldwide due to its high incidence morbidity and mortality. There is currently a need of improved biomarkers, capable to distinguish mild versus aggressive forms of the disease, and thus guide therapeutic decisions. Although miRNAs deregulated in cancer represent exciting candidates as biomarkers, its scientific literature is frequently fragmented in dispersed studies. This problem is aggravated for miRNAs belonging to miRNA gene clusters with shared target genes. The miRNA cluster composed by hsa-mir-130b and hsa-mir-301b precursors was recently involved in prostate cancer pathogenesis, yet different studies assigned it opposite effects on the disease...
2018: Experimental Hematology & Oncology
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