Review
Infectious Diseases
Su Ann Ho, Monica Slavin, Jason A. Roberts, Michelle Yong
Summary: Ganciclovir therapeutic drug monitoring is crucial for optimizing efficacy in selected patient groups, but there is currently no defined pharmacokinetic exposures that correlate with treatment efficacy and toxicity. Prospective clinical studies are needed to clarify this issue.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2021)
Article
Immunology
Alicja Sadowska-Klasa, Wendy M. Leisenring, Ajit P. Limaye, Michael Boeckh
Summary: A systematic review of randomized and observational studies from 2013-2023 indicated that antiviral preemptive therapy initiated at cytomegalovirus viral load thresholds between 2 and 3 log10 IU/mL had comparable cytomegalovirus disease rates. Thus, viral thresholds within this range appeared to effectively safeguard patients who did not receive prophylaxis.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Monica Rika Nakamura, Lucio R. Requiao-Moura, Roberto Mayer Gallo, Camila Botelho, Julia Taddeo, Laila Almeida Viana, Claudia Rosso Felipe, Jose Medina-Pestana, Helio Tedesco-Silva
Summary: The study compares the effectiveness of preemptive treatment for cytomegalovirus (CMV) infection after kidney transplant using antigenemia and RT-PCR testing. It finds that both methods yield similar results in preventing CMV disease and related events. Acute rejection and glomerular filtration rate are identified as risk factors for CMV disease.
SCIENTIFIC REPORTS
(2022)
Review
Infectious Diseases
Raymund R. Razonable
Summary: This review examines the treatment of cytomegalovirus (CMV) disease in transplant recipients, particularly the use of oral antiviral drugs. Intravenous and oral valganciclovir are the standard first-line treatments. Oral maribavir has shown superior efficacy and safety for refractory or resistant CMV infection.
CLINICAL MICROBIOLOGY AND INFECTION
(2023)
Article
Ophthalmology
Anastasia Tasiopoulou, Cristhian A. Urzua, Susan Lightman
Summary: This study retrospectively analyzed seven cases of patients with systemic lymphoma and CMV retinitis who received treatment from oncologists. The combination of oral and intravitreal antiviral agents resulted in effective disease control.
Article
Infectious Diseases
Jessica Leung, Scott D. Grosse, Bryan Yockey, Tatiana M. Lanzieri
Summary: The study investigated the use of antiviral treatment in 342 US infants with congenital cytomegalovirus. Among them, 33% received ganciclovir (with or without valganciclovir) and 67% received valganciclovir only. The duration of treatment and the timing of initiation differed for the two drugs, with neutropenia being a common side effect.
JOURNAL OF THE PEDIATRIC INFECTIOUS DISEASES SOCIETY
(2022)
Article
Immunology
Moritz B. Immohr, Payam Akhyari, Charlotte Bottger, Arash Mehdiani, Hannan Dalyanoglu, Ralf Westenfeld, Daniel Oehler, Igor Tudorache, Hug Aubin, Artur Lichtenberg, Udo Boeken
Summary: CMV infections are associated with complications following heart transplantation. The impact of serologic mismatch and the necessity of prophylactic virostatic medication remain concerns. Different serologic CMV matching did not significantly affect postoperative morbidity, but seropositive recipients had a higher risk for CMV-DNAemia.
IMMUNITY INFLAMMATION AND DISEASE
(2021)
Article
Immunology
Shu-Li Yang, Ting-Wei Lin, Hsin-Chieh Lin, Hsin-Yao Wang, Pi-Yueh Chang, Po-Nan Wang, Shuan Yang, Jang-Jih Lu
Summary: This study in Taiwan identified various mutations in the UL54 and UL97 regions of CMV in patients with CMV infections. A subset of patients displayed antiviral resistance mutations in UL54 and UL97, emphasizing the need to determine genetic profiles of UL54 and UL97 in immunocompromised populations with refractory CMV infections.
JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION
(2021)
Article
Hematology
Kotaro Miyao, Seitaro Terakura, Yukiyasu Ozawa, Masashi Sawa, Akio Kohno, Senji Kasahara, Hiroatsu Iida, Kazuko Ino, Shigeru Kusumoto, Masanobu Kasai, Akiyoshi Takami, Shingo Kurahashi, Tomohiro Kajiguchi, Takanobu Morishita, Tetsuya Nishida, Makoto Murata
Summary: In allogeneic hematopoietic stem cell transplantation recipients, the choice between FCN and GCV as first-line preemptive anti-CMV therapy does not impact overall survival, relapse, or nonrelapse mortality. However, the selection may influence the clinical course related to cGVHD.
TRANSPLANTATION AND CELLULAR THERAPY
(2021)
Article
Immunology
Kjersti B. Blom, Grete K. Birkeland, Karsten Midtvedt, Trond G. Jenssen, Anna V. Reisaeter, Halvor Rollag, Anders Hartmann, Solbjorg Sagedal, Ivar Sjaastad, Garth Tylden, Gro Njolstad, Einar Nilsen, Andreas Christensen, Anders Asberg, Jon A. Birkeland
Summary: This study compares the long-term outcomes of prophylactic and preemptive CMV preventive strategies in kidney transplant recipients. The study found that there were no significant differences in long-term outcomes such as patient death and graft loss between the two strategies in D+/R- kidney transplant recipients.
Article
Hematology
Po-Hsien Li, Cheng-Hsien Lin, Yu-Hui Lin, Tsung-Chih Chen, Chiann-Yi Hsu, Chieh-Lin Jerry Teng
Summary: The study suggests that low-dose valganciclovir prophylaxis may be an effective strategy to prevent CMV infection in patients undergoing allo-HSCT, particularly in resource-limited countries.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jocelyne Piret, Nathalie Goyette, Guy Boivin
Summary: Letermovir (LTV) exhibits similar susceptibility against clinical HCMV isolates and recombinant viruses with similar drug susceptibility phenotypes to currently-approved DNA polymerase inhibitors or maribavir.
ANTIVIRAL RESEARCH
(2022)
Article
Immunology
Vera Portillo, Stavroula Masouridi-Levrat, Lena Royston, Sabine Yerly, Manuel Schibler, Maria Mappoura, Sarah Morin, Federica Giannotti, Anne-Claire Mamez, Christian van Delden, Yves Chalandon, Dionysios Neofytos
Summary: Positive CMV serology in allogeneic hematopoietic cell transplant recipients (allo-HCTRs) may be false-positive due to transfusion-associated passive immunity. Reclassifying CMV status can help accurately assess the risk of CMV infection in these patients.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Alicia Galar, Maricela Valerio, Pilar Catalan, Xandra Garcia-Gonzalez, Almudena Burillo, Ana Fernandez-Cruz, Eduardo Zatarain, Iago Sousa-Casasnovas, Fernando Anaya, Maria Luisa Rodriguez-Ferrero, Patricia Munoz, Emilio Bouza
Summary: This prospective study aimed to evaluate the adequacy of valganciclovir/ganciclovir doses, assess interpatient variability in ganciclovir serum levels, identify predictive factors for this variability, and evaluate the clinical impact. The study found challenges in achieving adequate dosing of valganciclovir/ganciclovir and significant inter-individual variability in serum levels. Further research is needed to confirm these results and determine if therapeutic drug monitoring could improve outcomes in specific clinical situations.
Review
Medicine, Research & Experimental
Elise De Cuyper, Frederic Acke, Annelies Keymeulen, Ingeborg Dhooge
Summary: This systematic review found evidence supporting the treatment of symptomatic children with congenital cytomegalovirus (cCMV) and hearing loss with (val)ganciclovir. However, there is still insufficient evidence for the potential beneficial role of (val)ganciclovir in children with isolated hearing loss, late-onset hearing loss, and asymptomatic cCMV. Future prospective, randomized clinical trials are urgently needed to provide more conclusive evidence.
Review
Immunology
Amit D. Raval, Kristin D. Kistler, Yuexin Tang, Yoshihiko Murata, David R. Snydman
Summary: Kidney transplant recipients are at increased risk for CMV infection due to necessary immunosuppression, with prophylaxis and preemptive therapy being common management approaches. Despite prevention measures, a significant percentage of patients still develop CMV infection, with age and D+/R- serostatus being consistent risk factors. CMV infection is associated with increased mortality and graft loss. New strategies may be necessary to optimize CMV management.
TRANSPLANT INFECTIOUS DISEASE
(2021)
Article
Oncology
Phaedon D. Zavras, Aditi Shastri, Mendel Goldfinger, Amit K. Verma, Yogen Saunthararajah
Summary: The success of hypomethylating agents in myelodysplastic syndromes and acute myelogenous leukemias lies in their ability to selectively target DNA methyltransferase 1 (DNMT1) during the S-phase. Lessons learned from clinical trials suggest that dose and schedule selection are crucial for maintaining clinical response while avoiding detrimental effects on bone marrow reserves. Combination therapy with investigational agents should focus on enhancing HMA activity through manipulations of pyrimidine metabolism and inhibition of epigenetic enzymes, while adhering to principles of therapeutic index and molecular targeting.
CLINICAL CANCER RESEARCH
(2021)
Article
Hematology
Phaedon D. Zavras, Vikas Mehta, Sanjay Goel, Henny H. Billett
Summary: The study revealed that cancer patients with COVID-19 have a high incidence of thromboembolism, particularly arterial events, which are associated with worse survival outcomes.
ACTA HAEMATOLOGICA
(2022)
Article
Immunology
Yiqi Su, Anat Stern, Eleni Karantoni, Tamara Nawar, Gyuri Han, Phaedon Zavras, Henry Dumke, Christina Cho, Roni Tamari, Brian Shaffer, Sergio Giralt, Ann Jakubowski, Miguel-Angel Perales, Genovefa Papanicolaou
Summary: The study found that letermovir prophylaxis (LET) can reduce the mortality disparity between cytomegalovirus-negative and positive hematopoietic cell transplant (HCT) recipients at 1 year after transplantation. Among all cytomegalovirus-positive recipients, LET is associated with decreased mortality, especially in T-cell depleted HCT.
CLINICAL INFECTIOUS DISEASES
(2022)
Review
Pharmacology & Pharmacy
Nitasha Gupta, Tzu-Ting Huang, Sachi Horibata, Jung-Min Lee
Summary: Poly (ADP-ribose) polymerase (PARP) inhibitors have become a mainstay of therapy in ovarian cancer and other malignancies. However, an increasing number of patients develop resistance to PARP inhibitors, necessitating a deeper understanding of the mechanisms of resistance and the development of effective treatment strategies.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Immunology
Joyce J. Johnsrud, Isabelle T. Nguyen, Walter Domingo, Amit D. Raval, Yuexin Tang, Balasubramanian Narasimhan, Bradley Efron, Janice (Wes) Brown
Summary: This study retrospectively analyzed the impact of cytomegalovirus (CMV) in 1065 patients who underwent allogeneic hematopoietic cell transplantation (alloHCT). The results showed that 51% of patients developed clinically significant CMV infection and 6.5% had CMV disease. The use of certain therapy was associated with the development of CMV infection. Patients with CMV infection had longer hospital stays and higher rates of rehospitalization compared to those without CMV infection.
TRANSPLANT INFECTIOUS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Tzu-Ting Huang, Sandra Sczerba Burkett, Mayank Tandon, Tomomi M. Yamamoto, Nitasha Gupta, Benjamin G. Bitler, Jung-Min Lee, Jayakumar R. Nair
Summary: Resistance to PARP inhibitors in ovarian cancer can be influenced by treatment strategies and is related to the functionality of BRCA2. Different dosing/timing schemes can lead to the development of distinct resistance mechanisms, including rapid restoration of BRCA2 function and promotion of drug efflux activity, as well as activation of alternative signaling pathways to restore DNA repair and fork stabilization.
Review
Immunology
Amit D. D. Raval, Kristin D. D. Kistler, Yuexin Tang, Flavio Vincenti
Summary: This systematic literature review summarizes the incidence, risk factors, and clinical and economic outcomes associated with leukopenia and neutropenia (L/N) after kidney transplantation. The findings indicate that L/N is common post-transplant and is associated with the need for immunosuppressive agent modifications, the use of granulocyte colony-stimulating factor (G-CSF), and increased risks of acute rejection and opportunistic infections.
TRANSPLANT INFECTIOUS DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Phaedon D. D. Zavras, Ilias Sinanidis, Panagiotis Tsakiroglou, Theodoros Karantanos
Summary: Myelodysplastic syndrome (MDS) is a blood cancer characterized by bone marrow dysplasia and failure of hematopoiesis. Recent studies have shown that specific molecular abnormalities at earlier stages of MDS can predict progression to acute myeloid leukemia (AML). Different chromosomal abnormalities and somatic mutations present in MDS and AML-MRC have important prognostic implications. Changes in the classification of these neoplasms reflect the advances in understanding their biology. Novel therapeutic approaches, including adding venetoclax to hypomethylating agents and targeting specific mutations, have emerged for high-risk MDS and AML-MRC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Surgery
Amit D. D. Raval, Michael L. L. Ganz, Kathy Fraeman, Andrea L. L. Lorden, Shanmugapriya Saravanan, Yuexin Tang, Carlos A. Q. Santos
Summary: Limited data exist on CMV antiviral treatment patterns among kidney transplant recipients. This study used registry data and claims to examine CMV antiviral use in KTRs. The findings suggest suboptimal adherence to recommended duration of CMV prophylaxis for high and intermediate-risk patients and overuse of CMV prophylaxis in low-risk patients.
TRANSPLANT INTERNATIONAL
(2022)
Review
Hematology
Ivan Gur, Amir Giladi, Yonathan Nachum Isenberg, Ami Neuberger, Anat Stern
Summary: Patients with hematologic malignancies (HM) are at increased risk of severe and prolonged COVID-19 due to impaired immune function and cytokine release syndrome, highlighting the importance of understanding immunopathology and exploring new treatments for this population.
ACTA HAEMATOLOGICA
(2022)
Article
Hematology
Eleni Karantoni, Phaedon D. Zavras, Yiqi Su, Jiaqi Fang, Roni Tamari, Christina Cho, Miguel-Angel Perales, Anat Stern, Genovefa A. Papanicolaou
Summary: Refractory CMV infection is associated with increased mortality and healthcare resource utilization after hematopoietic cell transplantation. Improved therapies have the potential to improve outcomes and reduce resource utilization.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Hematology
Haneen Daoud-Asfour, Israel Henig, Itai Ghersin, Stav Rakedzon, Anat Stern, Milena Pitashny, Tsila Zuckerman, Haggai Bar-Yoseph
Summary: The impact of omitting prophylactic ciprofloxacin during allo-HSCT on lower GI GVHD rate, microbiome composition, and other clinical outcomes was assessed. The study found that omitting prophylactic ciprofloxacin did not significantly affect the outcomes, suggesting further evaluation of the use of prophylactic antibiotics in this setting.
TRANSPLANTATION AND CELLULAR THERAPY
(2022)
Article
Infectious Diseases
Anat Stern, Carolyn D. Alonso, Carolina Garcia-Vidal, Celia Cardozo, Monica Slavin, Michelle K. Yong, Su Ann Ho, Seema Mehta Steinke, Robin K. Avery, Philipp Koehler, Christof Scheid, Oliver A. Cornely, Johan Maertens, Yasmine Abi Aad, David J. Epstein, Genovefa A. Papanicolaou, Dionysios Neofytos
Summary: This study evaluated the safety and efficacy of cidofovir in treating double-stranded DNA viral infections following allogeneic haematopoietic cell transplant. One-fourth of patients developed reversible nephrotoxicity during treatment. Careful patient selection and close monitoring of renal function can help minimize toxicity.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)