Therapy-Related Myeloid Neoplasms In Lymphoma Survivors: Reducing Risks

Publication date: Available online 16 February 2019Source: Best Practice &Research Clinical HaematologyAuthor(s): Taha Al-Juhaishi, Arushi Khurana, Danielle ShaferAbstract:Treatment for Hodgkin (HL) and non-Hodgkin’s lymphoma (NHL) has changed dramatically in the last fifty years. While there are increasing numbers of long-term survivors, there has been increasing recognition of the long-term toxicities of treatments, particularly therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML). The survival for t-MDS/AML is extremely poor. Multiple heterogeneous retrospective studies have reported risk factors for the development of t-MDS/AML. Chemotherapy and radiation therapy have been most closely examined as possible t-MDS/AML risk factors. In this paper, we will review the risks of t-MDS/AML for HL and NHL patients as reported in the literature and assess for any changes over time. In HL patients, the incidence of t-MDS/AML has decreased with a reduction in alkylating agents. In indolent NHL patients, we anticipate decreased incidence of t-MDS/AML as targeted therapies begin to replace cytotoxic chemotherapy.
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research

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The objective of this study was to develop a population-pharmacokinetic model of durvalumab in patients with various hematologic malignancies and to investigate the effects of demographic and disease factors on the pharmacokinetics in this population.MethodsA total of 1812 concentrations from 267 patients with myelodysplastic syndromes, acute myeloid leukemia, multiple myeloma, non-Hodgkin lymphoma, or Hodgkin lymphoma were included in the analysis.ResultsThe pharmacokinetics of durvalumab was adequately described by a two-compartment model with first-order elimination. A decrease in durvalumab clearance over time was main...
Source: Clinical Pharmacokinetics - Category: Drugs & Pharmacology Source Type: research
The objective of this study was to develop a population-pharmacokinetic model of durvalumab in patients with various hematologic malignancies and to investigate the effects of demographic and disease factors on the pharmacokinetics in this population. METHODS: A total of 1812 concentrations from 267 patients with myelodysplastic syndromes, acute myeloid leukemia, multiple myeloma, non-Hodgkin lymphoma, or Hodgkin lymphoma were included in the analysis. RESULTS: The pharmacokinetics of durvalumab was adequately described by a two-compartment model with first-order elimination. A decrease in durvalumab clearance ov...
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: Clin Pharmacokinet Source Type: research
This study aimed to investigate the transcript dynamics of PLK1 and determine its role in the pathophysiology of MDS. Methods: PLK1 mRNA obtained from the bone marrow samples of 67 patients with MDS, 16 patients with secondary acute myeloid leukemia (sAML), and 10 healthy controls were analyzed using quantitative real-time PCR and compared according to various clinical parameters. Results: The median PLK1 expression levels differed slightly, but not significantly, between MDS and sAML patients [661.21 (range, 29.38-8,987.31) vs. 1,462.05 (32.22-5,734.09), respectively], but were significantly higher (P
Source: Blood Research - Category: Hematology Tags: Blood Res Source Type: research
Conclusions The discovery of JAK2V617F mutation in BCR-ABL1-negative MPNs by four different international cooperative groups in 2005 (2–5) led to significant insights on the pathogenesis of these disorders. In fact, this mutation results in a gain-of-function with activation of cytokine and growth factor receptors, and thus of the downstream JAK-STAT pathway (79, 95–98). The JAK2 point mutation in exon 12, present in a small percentage of patients with PV, is able to induce the MPN phenotype through the same pathogenic mechanism (6, 7). In 2006 the MPLW515L/K was reported in ET and PMF patients (44, 45) and d...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, we showed hypermethylation of CpGs as a novel mechanism of action for DNMTi agents and identified 638 hypermethylated molecular targets (CpGs) common to decitabine and azacytidine therapy. These novel results suggest that hypermethylation of CpGs should be considered when predicting the DNMTi responses and side effects in cancer patients. Introduction DNA methyltransferase inhibitors (DNMTi) are widely used as chemical tools for hypomethylating the genome, with an aim to understand the role of DNA methylation in multiple processes (e.g., X-chromosome inactivation and DNA imprinting) and as an anti-ca...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study proposed a pilot study of a new tool for a reliable and accurate stratification of patients with acute leukemia based on an integrative model of leukemia behavior, cell characterization, and clinical features, in addition, to an evaluation of intra-tumor and inter-tumor heterogeneity. Together our approach allows us to introduce an integrative quantitative approach to use zebrafish and tumor characterization as a prediction tool for the behavior of acute leukemia in young adults. Materials and Methods Animal Care and Handling Zebrafish wild-type (A/B and TAB5) adults were raised and maintained according to st...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionHistory of CLL did not independently affect OS in t-MDS patients beyond IPSS-R score.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Publication date: Available online 23 January 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Krzysztof Mądry, Karol Lis, Przemysław Biecek, Magda Młynarczyk, Jagoda Rytel, Michał Górka, Piotr Kacprzyk, Magdalena Dutka, Marek Rodzaj, Łukasz Bołkun, Dorota Krochmalczyk, Ewa Łątka, Joanna Drozd-Sokołowska, Anna Waszczuk-Gajda, Wanda Knopińska-Posłuszny, Anna Kopińska, Edyta Subocz, Anna Masternak, Renata Guzicka-Kazimierczak, Lidia GilAbstractBackgroundMyelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) patients, including those treated wit...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Authors: Yuan T, Zhang F, Zhou X, Li Y, Zhang Y, Xu Y, Wang X Abstract Proteasome inhibitors represent a novel class of drugs that have clinical efficacy against hematological and solid cancer types, including acute myeloid leukaemia, myelodysplastic syndrome an non-small cell lung cancer. It has been demonstrated that the anti-apoptotic protein B-cell lymphoma-2-associated athanogene 3 (BAG3) is induced by proteasome inhibitors in various cancer cells and serves an important role in chemotherapy resistance. The phosphatidylinositol 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT) pathway is consti...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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