Article
Oncology
Siyu Gu, Jingya Xia, Yulu Tian, Jie Zi, Zheng Ge
Summary: A novel risk scoring system MIPSS-R was developed by integrating IPSS-R and mutation scores, effectively separating patients into different risk levels and providing more accurate prognosis and treatment guidance for MDS patients.
Article
Oncology
Zaker Schwabkey, Najla Al Ali, Onyee Chan, David A. Sallman, Eric Padron, Andrew T. Kuykendall, Chetasi Talati, Kendra Sweet, Jeffrey E. Lancet, Rami S. Komrokji
Summary: The yield of detecting cytogenetic abnormalities in patients with normal karyotype by using a myelodysplastic syndromes fluorescence in situ hybridization (FISH) panel is low, but it significantly impacts risk stratification.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2021)
Article
Cell Biology
Ziqi Wan, Bing Han
Summary: The study found that for LR-MDS patients, azacytidine at a specific dose had better treatment outcomes, while decitabine, compared to azacytidine, may lead to higher rates of anemia and lower rates of diarrhea/constipation.
Review
Oncology
Giulio Cassanello, Raffaella Pasquale, Wilma Barcellini, Bruno Fattizzo
Summary: This review article discusses the development of novel therapies for patients with myelodysplastic syndromes (MDS), including drugs aimed at improving hematopoiesis and differentiation, hypomethylating agents, compounds targeting intracellular pathways, and immunotherapies. The current management of MDS relies on risk stratification and has limited options for patients with treatment failure. Recent advances in genetic mutations and intracellular pathways are improving disease risk stratification and highlighting therapeutic targets. Several drugs are under evaluation for MDS patients, which differ in mechanism of action, efficacy, and development phase.
Review
Oncology
Giulia Ciotti, Giovanni Marconi, Giovanni Martinelli
Summary: Allogeneic stem cell transplantation is a preferred treatment for acute myeloid leukemia, but relapse rates are high. Hypomethylating agents (HMAs) show promise as a backbone for combination therapies, particularly in combination with donor lymphocyte infusion (DLI). Other combination strategies with lenalidomide and tyrosine kinase inhibitors have shown competitive response rates. However, gemtuzumab ozogamicin and immune checkpoint inhibitors have shown less promising results. Furthermore, investigation into histone deacetylase inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors as combination strategies is needed.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Ilaria Scarpelli, Valerie Beyer Stalder, Gerasimos Tsilimidos, Katrin Rapakko, Mariangela Costanza, Sabine Blum, Jacqueline Schoumans
Summary: Genetic testing is crucial in the diagnosis, prognosis, and treatment decisions for myelodysplastic neoplasms (MDS). This study compared chromosome banding analysis (CBA) with single nucleotide polymorphism (SNP) array testing in a large MDS cohort and found that SNP array provided a more refined cytogenetic IPSS-R score. This confirms the effectiveness of SNP array in MDS risk stratification and highlights the importance of assessing overall genomic complexity.
GENES CHROMOSOMES & CANCER
(2023)
Article
Immunology
Abdulla Watad, Mark Kacar, Nicola Luigi Bragazzi, Qiao Zhou, Miriam Jassam, Jan Taylor, Eve Roman, Alexandra Smith, Richard A. Jones, Howard Amital, Catherine Cargo, Dennis McGonagle, Sinisa Savic
Summary: Research on MDS patients shows that autoinflammatory complications are common, with somatic mutations and abnormal karyotypes being associated with these complications. Autoinflammatory diseases may lead to malignant transformation and poorer prognosis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Bert Heyrman
Summary: This paper argues for the importance of paying attention to health-related quality of life as a study endpoint in lower-risk MDS patients. Currently, there are limited therapeutic options available for this population, with new treatments mainly being studied in clinical trials. However, data on health-related quality of life during phase III studies are not commonly published, undermining its significance as a treatment goal. The paper suggests that health-related quality of life should be the main treatment goal in this population.
JOURNAL OF CLINICAL MEDICINE
(2022)
Editorial Material
Medicine, General & Internal
John T. Wilkins, Donald M. Lloyd-Jones
Summary: This article reviews different lipid-lowering therapies including traditional statins and ezetimibe, as well as new therapies like PCSK-9 inhibitors, bempedoic acid, icosapent ethyl, and inclisiran, prescribed to reduce cardiovascular risk.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2021)
Article
Multidisciplinary Sciences
Jun Yin, Yu Du, Rui Qin, Shihao Shen, Sumithra Mandrekar
Summary: Traditional dose-finding designs are inefficient for targeted agents and cancer immunotherapies due to lack of efficacy signals and late toxicities. A new R package, phase1RMD, has been developed to implement novel phase I designs with repeated toxicity measures and early efficacy, offering a more accurate estimation of toxicity trends and appropriate patient allocation.
Article
Oncology
Tobias Silzle, Sabine Blum, Annika Kasprzak, Kathrin Nachtkamp, Martina Rudelius, Barbara Hildebrandt, Katharina S. Goetze, Norbert Gattermann, Michael Lauseker, Ulrich Germing
Summary: The absolute monocyte count (AMC) at the time of diagnosis in myelodysplastic syndromes (MDS) has a prognostic impact independent of the revised international prognostic scoring system (IPSS-R). Patients with a low AMC (<0.2 x 10(9)/L) have a higher risk of transformation to acute myeloid leukemia. Considering the AMC might help identify MDS patients who could benefit from more intense treatment strategies.
Review
Medicine, General & Internal
Richard T. Amison, Clive P. Page
Summary: Asthma is a chronic inflammatory disease that requires the development of new anti-inflammatory therapies. Different pharmacological approaches are being studied.
Review
Medicine, General & Internal
Jia Chen, Kefei Wang, Zhijian Xiao, Zefeng Xu
Summary: Combination therapy with hypomethylating agents (HMAs) and venetoclax/ruxolitinib showed better outcomes than HMA monotherapy in patients with Philadelphia chromosome-negative accelerated or blast phase myeloproliferative neoplasms (MPN-AP/BP).
ANNALS OF MEDICINE
(2023)
Review
Oncology
Julia Stomper, John Charles Rotondo, Gabriele Greve, Michael Luebbert
Summary: Aberrant DNA methylation is crucial in tumor development and progression. DNA hypomethylating agents can reverse DNA methylation and re-program tumor cells, but long-term use leads to resistance. First-generation HMAs are now standard for treating acute myeloid leukemia and myelodysplastic syndromes, but resistance is a growing concern.
Review
Pharmacology & Pharmacy
Aira Sarkar, Srushti Jayesh Sodha, Vijayabhaskarreddy Junnuthula, Praveen Kolimi, Sathish Dyawanapelly
Summary: This review highlights the current progress and future perspectives of novel and investigational therapeutic strategies for age-related macular degeneration (AMD). For wet AMD, biologics with dual functionalities and combined therapies with long-acting capabilities are expected to lead the drug pipeline, while significant breakthroughs are yet to be made for dry AMD.
DRUG DISCOVERY TODAY
(2022)
Article
Oncology
Rami Komrokji, Megan Melody, Najla Al Ali, Onyee Chan, Virginia Klimek, Brian J. Ball, Mikkael A. Sekeres, George Lucas, Jaroslaw P. Maciejewski, David A. Sallman, Eric Padron, Andrew Kuykendall, Terra Lasho, Aref Al-Kali, Kiran Naqvi, David P. Steensma, Guillermo Garcia-Manero, Mrinal M. Patnaik
Summary: In patients with MDS/MPN-RS-T, those treated with lenalidomide or erythropoiesis-stimulating agents showed higher rates of hematological improvement compared to those treated with hypomethylating agents.
LEUKEMIA & LYMPHOMA
(2022)
Article
Hematology
Andrew T. Kuykendall, Libo Sun, John Mascarenhas, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Julia Wang, Qi Xia, Eugene Zhu, Faye Feller, Aleksandra Rizo, Jacqueline Bussolari, Ying Wan, Rami Komrokji
Summary: Treatment with imetelstat resulted in longer overall survival compared to BAT in closely matched patients with MF after JAK inhibitor failure, with a significantly lower risk of death. Further evaluation of imetelstat in this poor-prognosis patient population is warranted based on these promising results.
ANNALS OF HEMATOLOGY
(2022)
Article
Oncology
Onyee Chan, Najla Al Ali, David Sallman, Eric Padron, Jeffrey Lancet, Rami Komrokji
Summary: This study retrospectively reviewed 132 del(5q) MDS patients and described the treatment outcomes and prognostic impact of gene mutations. The study found that lenalidomide was an effective treatment for del(5q) MDS patients, but hypomethylating agents after lenalidomide failure did not provide survival advantage. There was no significant difference in overall survival between patients with or without TP53 mutations, but patients with SF3B1 mutations had inferior survivals.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Letter
Oncology
Connor Walsh, Anthony Hunter, Terra Lasho, Christy Finke, Rhett Ketterling, Rami Komrokji, Ayalew Tefferi, Abhishek Mangaonkar, Matthew Howard, Naseema Gangat, Aref Al-Kali, Najla Al Ali, Eric Padron, Mrinal M. Patnaik
Letter
Oncology
Rami S. Komrokji, Uwe Platzbecker, Pierre Fenaux, Amer M. Zeidan, Guillermo Garcia-Manero, Ghulam J. Mufti, Valeria Santini, Maria Diez-Campelo, Carlo Finelli, Joseph G. Jurcic, Peter L. Greenberg, Mikkael A. Sekeres, Amy E. DeZern, Michael R. Savona, Jeevan K. Shetty, Rodrigo Ito, George Zhang, Xianwei Ha, Jay T. Backstrom, Amit Verma
Review
Medical Laboratory Technology
Akriti G. Jain, Ling Zhang, John M. Bennett, Rami Komrokji
Summary: In this review, the available literature on the presentation and prognosis of patients with MDS and concurrent BMF is discussed, highlighting the importance of considering BMF in treatment decisions. The prognostic impact of BMF should be taken into account when deciding on transplantation, especially for intermediate-risk patients.
ANNALS OF LABORATORY MEDICINE
(2022)
Article
Hematology
Virginia O. Volpe, Najla Al Ali, Onyee Chan, Eric Padron, David A. Sallman, Andrew Kuykendall, Kendra Sweet, Jeffrey E. Lancet, Rami S. Komrokji
Summary: SF3B1 mutation in the context of therapy-related MDS may have an impact on prognosis, with significant differences observed among different subtypes.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Rami Komrokji, Luis E. Aguirre, Najla Al Ali, Mohamad Hussaini, David Sallman, Dana Rollison, Eric Padron
Summary: Hemolysis is a significant clinical feature in some patients with myelodysplastic syndromes (MDS). It is often caused by ineffective erythropoiesis or acquired defects in red blood cell (RBC) membrane. This study found that 10% of MDS patients had hemolysis, which was mostly nonimmune. Patients with hemolysis had lower survival rates, decreased response to erythropoiesis-stimulating agents, and higher response to hypomethylating agents. They also had higher prevalence of U2AF1 and EZH2 hotspot mutations, suggesting a role of splicing factor mutations in the development of hemolysis in MDS.
Editorial Material
Hematology
Naseema Gangat, Rami S. Komrokji, Ayalew Tefferi
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Review
Oncology
Virginia O. Volpe, Guillermo Garcia-Manero, Rami S. Komrokji
Summary: MDS is a stem cell neoplasm with varying risk levels, and most patients suffer from complications related to cytopenia. Anemia is a hallmark of the disease and commonly requires treatment. Different approaches, such as erythroid stimulating agents and targeted drugs, can effectively improve cytopenias in specific MDS patient populations. However, refractory cytopenias remain a challenge, and more treatment options are needed.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Review
Hematology
Julian A. Waksal, Claudia Bruedigam, Rami S. Komrokji, Catriona H. M. Jamieson, John O. Mascarenhas
Summary: Human telomeres are repetitive sequences at the ends of chromosomes, playing important roles in preserving genomic integrity and preventing loss of genetic information. Telomerase, an enzyme involved in maintaining telomere length, is upregulated in malignant cells, making it a potential target for cancer therapy. This review focuses on the biology of telomeres and telomerase, and discusses the development of telomerase-targeted therapeutic candidates, particularly imetelstat, which has shown promising results in myeloid malignancies.
Article
Hematology
Gregory A. Abel, Donnie Hebert, Cecilia Lee, Dana Rollison, Nancy Gillis, Rami Komrokji, James M. Foran, Jane Jijun Liu, Tareq Al Baghdadi, Joachim Deeg, Steven Gore, Wael Saber, Steffanie Wilson, Michael Otterstatter, Jason Thompson, Christine Borchert, Eric Padron, Amy DeZern, David Cella, Mikkael A. Sekeres
Summary: This study investigates the impact of myelodysplastic syndromes (MDS) and other cytopenic states on health-related quality of life (HRQoL) and vulnerability. The findings show that patients with cytopenias undergoing MDS evaluation have similar HRQoL, regardless of the eventual diagnosis, but vulnerable individuals have worse HRQoL. Among MDS patients, lower-risk disease is associated with better HRQoL, except in vulnerable individuals.
Article
Hematology
Rami S. Komrokji, Luis E. Aguirre, Najla H. Al Ali, Onyee Chan, Zhuoer Xie, Andrew Kuykendall, Kendra Sweet, Jeffrey E. Lancet, Eric Padron, David A. Sallman
Letter
Oncology
Uwe Platzbecker, Valeria Santini, Rami S. Komrokji, Amer M. Zeidan, Guillermo Garcia-Manero, Rena Buckstein, Dimana Miteva, Karen Keeperman, Natalia Holot, Jose Alberto Nadal, Yinzhi Lai, Sadanand Vodala, Barbara Rosettani, Ana Carolina Giuseppi, Aylin Yucel, Pierre Fenaux