Cytovene (ganciclovir) / Roche - LARVOL DELTA

GRAIL^3: Ganciclovir to Prevent Reactivation of Cytomegalovirus in Patients With Acute Respiratory Failure and Sepsis (clinicaltrials.gov) - P3 | N=205 | Terminated | Sponsor: Fred Hutchinson Cancer Center | N=500 ➔ 205 | Trial completion date: Aug 2027 ➔ Apr 2025 | Active, not recruiting ➔ Terminated; due to increased mortality and futility analyses

Enrollment change • Trial completion date • Trial termination • Cytomegalovirus Infection • Infectious Disease • Respiratory Diseases • Septic Shock

Epidemiology, risk factors, and outcomes of cytomegalovirus (CMV) reactivation in allogeneic hematopoietic stem cell transplantation: A retrospective observational single-centre study from western India (ASH 2025) - "While pre-emptive therapy has reduced CMV disease, reactivation remains common, particularly in alternate donor transplants and resource-limited settings where access to newer antivirals like letermovir is limited...Serotherapy type did not impact overall reactivation, but early reactivation was significantly higher with Grafalon vs. Thymoglobulin (90% vs. 33.6%, p<0.001)...Adverse effects included neutropenia (ganciclovir/valganciclovir) and nephrotoxicity (foscarnet/cidofovir)... This single-centre study demonstrates a high CMV reactivation rate (89.7%) in a high-seroprevalence Indian cohort, especially in alternate donor and PTCy-treated patients. While CMV disease was rare due to effective surveillance and pre-emptive therapy, recurrence and antiviral toxicity were common. The type of serotherapy influenced early reactivation risk."

Retrospective data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Cytomegalovirus Infection • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Immunology • Neutropenia • Transplantation

Persistent hyponatremia as a distinctive feature of HHV-6B encephalitis in pediatric hematopoietic stem cell transplant recipients: A case series (ASH 2025) - "All five patients were administered antiviral therapy comprising ganciclovir, foscarnet, and intravenous immunoglobulin. Persistent hyponatremia may act as a distinctive clinical indicator of HHV-6B encephalitis in pediatric patients undergoing HSCT. The underlying mechanisms require further investigation."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Cardiovascular • Chronic Myelomonocytic Leukemia • CNS Disorders • Dermatology • Endocrine Disorders • Epilepsy • Heart Failure • Hematological Malignancies • Infectious Disease • Juvenile Myelomonocytic Leukemia • Leukemia • Movement Disorders • Myelodysplastic Syndrome • Nephrology • Pediatrics • Pruritus • Rare Diseases • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation • CD7

Novel use of low-dose cidofovir (2.5 mg/kg Weekly) as CMV prophylaxis in the pre-engraftment Phase of stem cell transplantation: A viable alternative when ganciclovir is contraindicated and letermovir is not available (ASH 2025) - "These include CMV-seropositive recipients (R+) with seronegative donors (D-) who are deemed to be at highest risk of CMV infection due to latent virus reactivation, those with previous CMV infections and in haploidentical BMT cases where Post Transplant Cyclophosphamide (PTCy) was used as GVHD prophylaxis. Low-dose weekly cidofovir represents a novel, cost-effective, and practical approach for CMV prophylaxis and treatment in the pre-engraftment phase of HSCT, particularly in settings where letermovir is unavailable. This strategy may reduce CMV-related graft loss while avoiding the myelotoxicity of ganciclovir. Further prospective studies are warranted to validate its role in global transplant protocols."

Beta-Thalassemia • Bone Marrow Transplantation • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Graft versus Host Disease • Immunology • Infectious Disease • Transplantation

GMP-compliant generation, expansion, and a preliminary safety evaluation of CMV-specific t cells using a closed system for post-transplant viral control (ASH 2025) - "His prior treatments included ABVD, DHAP, ICE, GVD, brentuximab vedotin (BV), autologous hematopoietic stem cell transplantation, and pembrolizumab, which led to complete remission...The post-transplant course was complicated by chronic graft-versus-host disease (overlap subtype), presenting with grade 3 skin and grade 2 oral involvement, which was managed with prednisone and tacrolimus. In early 2025, the patient developed CMV reactivation with a high viral load (>200,000 copies/mL) that proved refractory to ganciclovir, which was discontinued due to hematologic toxicity and the detection of viral resistance associated with an M460V mutation...These findings support further investigation of CMV-specific T cell therapy as a valuable adjunct in managing opportunistic infections in immunocompromised hosts. Funding: Ministry of Health of Brazil, SIPAR (NUP) 25000.156425/2023-06"

Clinical • Post-transplantation • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Classical Hodgkin Lymphoma • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Infectious Disease • Lymphoma • Transplantation • IFNG • IL2 • IL7

Concurrent culprits: Deciphering CMV co-infection in persistent COVID-19 scenarios. (PubMed, Przegl Epidemiol) - "This case series highlights the complex relationship between SARS-CoV-2 and CMV, emphasizing the need for a comprehensive virological evaluation of persistent COVID-19 cases. As the global medical landscape has grappled with the evolving challenges of the pandemic, incorporating such multifaceted clinical insights remains paramount."

Journal • Cytomegalovirus Infection • Immunology • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Efficacy of iptacopan in treatment of transplant-associated thrombotic microangiopathy (TA-TMA) post-allogeneic hematopoietic stem cell transplantation: A case series analysis (ASH 2025) - "Case III (28M, MDS-LB) . Baseline Characteristics Diagnosis Severe Aplastic Anemia (SAA) Myelodysplastic Syndrome with Excess Blasts-2 (MDS-EB-2) Myelodysplastic Syndrome-Low Blast (MDS-LB) Pre-Treatment Labs - WBC: ↓ (2.13×10⁹/L) - HGB: 65g/L↓ - PLT: 4×10⁹/L↓↓ - ALT/AST: ↑ (44.56/50.96 U/L) - WBC: ↓ (3.73×10⁹/L) - HGB: 44g/L↓↓ - PLT: 19×10⁹/L↓ - PT/INR: ↑ (24.8s/2.17) - WBC: ↑ (15.42×10⁹/L) - HGB: 105g/L↓ - ALT/AST: ↑ (35.49/47.32 U/L) - D-dimer: 3.56 mg/L↑ Complications CMV viremia, TA-TMA, intestinal GVHD, heart failure EBV infection, TA-TMA, intestinal GVHD EBV viremia, liver GVHD, intestinal GVHD, TA-TMA New Drugs Used Iptacopan, Vedolizumab Iptacopan Iptacopan, Vedolizumab, Ruxolitinib Post-Treatment Trends Blood Routine - WBC/HGB/PLT: Continued fluctuations (no stabilization) - PLT: ↑ (improvement) - WBC/HGB: Partial stabilization - WBC: Stabilized - HGB/PLT: Gradual improvement Liver Function - ALT/AST: Persistent fluctuations..."

Clinical • Aplastic Anemia • Bone Marrow Transplantation • Cardiovascular • Congestive Heart Failure • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Heart Failure • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Myelodysplastic Syndrome • Transplantation

Single-center retrospective analysis of maribavir in the treatment of refractory and drug-intolerant cytomegalovirus viremia and cytomegalovirus disease after allogeneic hematopoietic stem cell transplantation (ASH 2025) - P3 | "Maribavir, a novel anti-CMV agent, exhibits multimodal anti-CMV activity without cross-resistance to ganciclovir or foscarnet...Fifty patients received letermovir for CMV prophylaxis...The 1-year overall survival rate was 86.5% (95% CI: 74.7%–98.4%). Conclusion Maribavir demonstrated high efficacy and a favorable safety profile in treating refractory or drug-intolerant CMV viremia and CMV disease post- allo HSCT, characterized by rapid viral clearance (shortmedian time to response) and minimal adverse effects."

Retrospective data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Cutaneous T-cell Lymphoma • Cytomegalovirus Infection • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Lymphoblastic Lymphoma • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Nephrology • Pneumonia • Respiratory Diseases • Septic Shock • T Cell Non-Hodgkin Lymphoma • Transplantation

Clinical characteristics of human herpesvirus 7 (HHV-7) reactivation following umbilical cord blood transplantation: A retrospective study (ASH 2025) - "HHV-7 was detected during ganciclovir (GCV)or valganciclovir (VGCV) treatment in 9 blood samples (47.4%) and 3 BAL samples (30.0%). A total of 1,625 CBT was performed during the study period. Among them, 1,325 patients (81.5%)underwent at least one multiplex PCR test, with a median of 4 tests per patient (range, 1–43), totaling6,744 samples (blood n=5,328; CSF n=1,069; BAL n=140; ascites n=114; pleural effusion n=91; lymph noden=2). HHV-7 DNA was detected in 33 of 1,325 patients (2.5%) who underwent post-transplant viralsurveillance."

Retrospective data • Bone Marrow Transplantation • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Graft versus Host Disease • Herpes Simplex • Herpes Zoster • Immunology • Infectious Disease • Respiratory Diseases • Transplantation • Varicella Zoster

Assessment of EBV DNA methlyation to guide antiviral use in EBV-associated lymphoma (ASH 2025) - "The antiviral ganciclovir (GCV) iseffective specifically against lytic EBV due to viral BGLF4 expression...Inclusion criteria for GCV response assessment was a negative 0.5log(10) change in viralload, lack of recent or current chemotherapy, rituximab, reduction in immunosuppression (RIS), and un-interrupted GCV use. Our cohort consisted of n=23 NK/T cell lymphoma, n=15 Hodgkin lymphoma, n=39 PTLD, n=25diffuse large B cell lymphoma (DLBCL), n=21 EBV viremia, and n=39 "other" samples, which were excludedfrom analysis... We identified site specific BGLF4 methylation loss to be widespread in EBV+lymphoma,challenging the current dogma of EBV latency in lymphoma. Our BGLF4 demethylation assay is highthroughput, inexpensive, and proves clinically superior to viral load alone, serving as a potentialbiomarker to successfully guide GCV administration in EBV-driven lymphomas."

B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • T Cell Non-Hodgkin Lymphoma

Development of synthetic introns for selective elimination of U2AF1 mutant MDS (ASH 2025) - "HSV-TK is inert in cells until the prodrug ganciclovir is provided which leads to cytotoxicmetabolite production...Moreover, the syntheticintrons responsive to U2AF1 mutations created here enable future mechanistic studies to identify cis andtrans factors required for mutant U2AF1 function. Finally, we investigate means for in vivo delivery ofplasmid DNAs to myeloid cells which could have broader applications in gene therapy for myeloidneoplasms."

Acute Myelogenous Leukemia • Gene Therapies • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • SF3B1 • SRSF2 • STING • U2AF1

Intracellular Ganciclovir Tri-Phosphate Concentrations in Children with Congenital Cytomegalovirus Infection. (PubMed, J Infect Dis) - "These findings underscore the need to define the kinetics of GCV-TP in cell matrices relevant to its activity to determine appropriate VGCV dosing strategies in this population and establish safe and define effective therapeutic concentration targets."

Clinical • Journal • Cytomegalovirus Infection • Hematological Disorders • Infectious Disease • Neutropenia • Otorhinolaryngology • Pediatrics

Low-Dose Valganciclovir for Primary Cytomegalovirus Prophylaxis After Heart Transplant: A 10-Year Experience. (PubMed, Clin Transplant) - "This is the largest report of LD VGCV use in HTR. Despite reduced VGCV exposure, HTR remain at high risk for cytopenias. Regardless of potential risk factors, including a high prevalence of overweight BMI and adequate renal function, LD VGCV was associated with expected rates of BT CMV and CMV resistance, suggesting LD VGCV could be considered in HTR. Identification of CMV end-organ disease and GCV resistance suggests that LD VGCV could be considered cautiously in CMV D+/R- HTR."

Journal • Retrospective data • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Hematological Disorders • Immunology • Leukopenia • Neutropenia • Obesity • Ocular Inflammation • Ophthalmology • Retinal Disorders • Transplantation

Peritoneal Dialysis-Associated Peritonitis Caused by Lautropia Mirabilis and Concurrent Viral Infection: A Case Report. (PubMed, Case Rep Nephrol Dial) - "Therapy with intravenous moxifloxacin, intraperitoneal gentamicin, and oral ganciclovir led to rapid WBC decline and clinical improvement within 48 h. After 1 week of inpatient monitoring, the patient was discharged with a 2-week course of oral moxifloxacin. Culture-negative PDAP often necessitates empirical antibiotic therapy, carrying a high risk of failure and increased healthcare costs. This case suggests that tNGS could be used as a complementary diagnostic tool in selected cases of refractory, culture-negative PDAP, potentially aiding the identification of pathogens and guiding therapy."

Journal • Chronic Kidney Disease • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Genetic Disorders • Infectious Disease • Nephrology • Polycystic Kidney Disease • Renal Disease

A Matched Case-Control Study to Evaluate Predicted Drug Exposures and Neutropenia during Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients. (PubMed, Transpl Infect Dis) - "Predicted GCV exposures were similar among pSOT recipients with and without neutropenia, suggesting that differences in dosing and pharmacokinetics covariates did not drive toxicity in our population. Measurement of GCV concentrations may discern whether toxicity relates to exposures/concentrations or intrinsic factors (i.e., genetics) in the pSOT population."

Journal • Cytomegalovirus Infection • Hematological Disorders • Infectious Disease • Neutropenia • Pediatrics • Solid Organ Transplantation • Transplantation

Cytomegalovirus and Crohn's disease as competing causes of small bowel inflammation after double-lung transplantation. (PubMed, Eur Clin Respir J) - "CMV infection was identified in intestinal biopsies and initially managed with two courses of valganciclovir. Due to persistent symptoms, genotypic analysis was performed, revealing UL97 mutations conferring ganciclovir resistance. Sequential therapy with foscarnet, maribavir, and letermovir achieved virological clearance, but diarrhea persisted...The patient was commenced on standard biological therapy for Crohn's disease, resulting in marked clinical improvement and recovery. This case illustrates the diagnostic challenge of distinguishing CMV enteritis from de novo Crohn's disease and determining the primary driver of the clinical presentation."

Journal • Crohn's disease • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Mucositis • Respiratory Diseases • Solid Organ Transplantation • Transplantation

Neuropsychiatric Symptoms After HHV-6 Encephalitis in an Immunocompetent Child: A Case Report. (PubMed, Am J Case Rep) - "The patient received ganciclovir and lorazepam, resulting in substantial improvement. Neuropsychiatric manifestations, including catatonia, may occur even in the absence of classical signs of encephalitis. Awareness of this rare presentation may facilitate timely diagnosis and treatment."

Journal • CNS Disorders • Epilepsy • Epstein-Barr Virus Infections • Immunology • Infectious Disease • Insomnia • Mood Disorders • Pediatrics • Psychiatry • Sleep Disorder

Exploration of molecular diagnosis for HHV-6 encephalitis in immunocompetent individuals: A study combining mNGS and PCR. (PubMed, Diagn Microbiol Infect Dis) - "mNGS enables rapid detection of the rare but treatable HHV-6 meningitis in immunocompetent adults that conventional tests miss, prompting early antiviral therapy and better outcomes."

Journal • CNS Disorders • Cognitive Disorders • Epilepsy • Epstein-Barr Virus Infections • Infectious Disease • Pain

Cytomegalovirus Pneumonia—An Uncommon Entity in Immunocompetent Individuals (APSR 2025) - "Treatment with Ganciclovir caused remarkable improvement for 6 patients...Remaining 5 patients died. Conclusion : Cytomegalovirus infection in immunocompetent individuals, though mortality rate is high, early detection and aggressive management is rewarding sometimes, so possibility should be kept in mind always."

Clinical • Cardiovascular • Cough • Cytomegalovirus Infection • Hypertension • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

Does treatment with antiviral medication affect mortality among immunocompetent individuals with cytomegalovirus reactivation? A systematic review and meta-analysis. (PubMed, BMC Infect Dis) - No abstract available

Journal • Retrospective data • Review • Cytomegalovirus Infection

Targeting SOX9-positive therapy-resistant medulloblastoma with a novel suicide gene therapy (SNO 2025) - "We further show that S9RE-minP can be used in an adeno-associated virus (AAV) to drive herpes simplex virus thymidine kinase in a suicide gene therapy where ganciclovir can be converted to cytotoxically target mitotic SOX9-positive cancer cells. This AAV gene therapy could be safely combined with fractionated radiation and worked efficiently together with standard therapy to eradicate SOX9-positive medulloblastoma cells in vitro and in vivo. We suggest this treatment as an attractive approach to target therapy-resistant malignant pediatric brain tumors."

Gene therapy • Brain Cancer • Gene Therapies • Herpes Simplex • Medulloblastoma • Solid Tumor • COL2A1 • SOX9

Reversion of Val(Ganciclovir)-Resistance-Associated Mutations in Two SOT Patients with Mismatched Serostatus for CMV (D+/R-). (PubMed, Viruses) - "Following CMV DNA suppression, secondary prophylaxis with letermovir and val(ganciclovir) was initiated...Therapy was then switched to foscarnet, which was suspended due to renal failure, and then to maribavir...Detecting gene mutations that confer drug resistance is crucial for managing antiviral therapy when virological response is lacking. In our cases, the reversion of (va)ganciclovir-resistance mutations occurred after drug withdrawal, a previously unreported finding."

Journal • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Immunology • Renal Disease • Solid Organ Transplantation • Transplantation

Arginine Metabolism Supports De Novo Pyrimidine Biosynthesis to Block DNA Damage and Maintain Epstein-Barr Virus Latency. (PubMed, bioRxiv) - "Despite current interest in EBV lytic antigen induction therapy, in which viral lytic reactivation sensitizes tumors to the highly cytotoxic effects of the antiviral ganciclovir, there has been no systemic study of extracellular amino acid that controls EBV latency. Disruption of arginine metabolism or de novo pyrimidine synthesis caused DNA damage. As arginine restriction was also found to cause Burkitt DNA hypermethylation, we provide evidence that the combination of arginine restriction and DNA hypomethylation by decitabine or by CRISPR approaches together induced EBV reactivation more highly than either alone, suggesting a therapeutic approach."

Journal • Burkitt Lymphoma • Epstein-Barr Virus Infections • Gastric Cancer • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

Therapeutic Potential of SHED-Derived Suicide Gene Therapy for Brain Tumors Using HSV-TK/Ganciclovir System (SNO 2025) - "SHED-TK cells demonstrated robust tumor-tropic migration and potent antitumor efficacy via the HSV-TK/GCV system. These findings support SHED-TK as a promising delivery platform for suicide gene therapy in primary and metastatic brain tumors. Ongoing studies aim to enhance therapeutic outcomes through combination strategies with oncolytic virotherapy."

Gene therapy • Brain Cancer • Gene Therapies • Glioma • Herpes Simplex • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Disseminated CMV in immunocompetent patient post-first anal intimacy: A captivating case report. (PubMed, Diagn Microbiol Infect Dis) - "Treatment with intravenous ganciclovir led to clinical improvement and resolution of symptoms. This case underscores the importance of considering CMV infection in Immunocompetent patients with refractory rectal symptoms post-STI treatment, highlighting the need for thorough diagnostic assessment and timely initiation of antiviral therapy for effective management."

Journal • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Pain