valacyclovir and Graft-vs-Host-Disease

We examined the incidence of herpes varicella-zoster virus (VZV) infection in 151 patients undergoing allogeneic BMT between August 1990 and September 1997 and who survived at least 3 months. Median follow-up was 17 (range 3.3-80.7) months. Herpes simplex virus antibody positive (HSV+) patients received aciclovir 1200 mg p.o. daily or 750 mg i.v. daily, in divided doses from day 0 to engraftment. Ganciclovir (5 mg/kg i.v. three times per week) was given in CMV+ patients (or if the donor was CMV+) from engraftment to day 84. Ganciclovir was continued or recommenced if a dose of greater than 20 mg of prednisone was used for the treatment of GVHD otherwise aciclovir was recommenced. In HSV+ patients not receiving ganciclovir, aciclovir 600 mg p.o. daily in divided doses was given until at least 6 months after BMT. Thirty-two patients developed VZV infection from 4.1 to 28 months after transplant. The estimated cumulative incidence of VZV was 13% (95% confidence interval 6-19%) at 12 months, 32% (22-42%) at 24 months and 38% (27-50%) at 28 months, with no further cases beyond that time. No patient developed VZV whilst receiving aciclovir or ganciclovir (P < 0.0001). However, there was a rapid onset of VZV following cessation of antiviral therapy (33% (20-46%) at 1 year post cessation). The presence of GVHD and the prior duration of antiviral prophylaxis were significant and independent risk factors for the development of VZV. Age, underlying disease, conditioning therapy or donor type were not. We conclude that 3-6 months of low-dose aciclovir and ganciclovir are effective at delaying the onset of VZV after allogeneic BMT, but may not affect the overall incidence of infection. Prolonged prophylaxis may be warranted in patients at high risk of infection, for example those patients with GVHD.

Topics: 2-Aminopurine; Acyclovir; Adolescent; Adult; Age of Onset; Aged; Analysis of Variance; Antiviral Agents; Bone Marrow Transplantation; Chickenpox; Dose-Response Relationship, Drug; Enzyme Activation; Famciclovir; Female; Ganciclovir; Graft vs Host Disease; Herpes Zoster; Herpesvirus 3, Human; Humans; Incidence; Male; Middle Aged; Prodrugs; Retrospective Studies; Risk Factors; Skin Diseases; Transplantation, Homologous; Valacyclovir; Valine

Patients undergoing haploidentical or mismatched unrelated donor (haplo/MMUD) allogeneic hematopoietic cell transplantation (alloHCT) receiving post-transplant cyclophosphamide (PTCy) are at high risk of cytomegalovirus (CMV) infection. Experience with letermovir (LET) in this population is limited. This single center retrospective cohort study compared CMV and transplant outcomes between LET and a historical control with high-dose valacyclovir (HDV) prophylaxis in adults undergoing haplo/MMUD alloHCT. Thirty-eight CMV seropositive patients were included, 19 in each arm. LET reduced the incidence of CMV infection (5% vs. 53%, RR 0.01, 95% CI 0.014-0.71,

Topics: Acetates; Adult; Cyclophosphamide; Cytomegalovirus; Cytomegalovirus Infections; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Quinazolines; Retrospective Studies; Unrelated Donors; Valacyclovir

We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortality is >80%. Early suspicion and immediate therapy are the keys to improve patient survival.

Topics: Acyclovir; Adrenal Cortex Hormones; Antiviral Agents; Bone Marrow Transplantation; Drug Resistance, Viral; Fatal Outcome; Foscarnet; Graft vs Host Disease; Hepatitis, Viral, Human; Humans; Liver; Liver Failure, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Patient Comfort; Polymerase Chain Reaction; Simplexvirus; Transaminases; Transplantation, Homologous; Valacyclovir; Valine

Brincidofovir (BCV) is a broad-spectrum antiviral agent active in vitro against double-stranded DNA viruses including herpesviruses, adenoviruses, polyomaviruses, and poxviruses. We report successful BCV use in management of disseminated acyclovir- and cidofovir-resistant varicella zoster virus in an immunocompromised hematopoietic stem cell transplant patient with chronic graft-versus-host disease who was intolerant to foscarnet.

Topics: Acyclovir; Adult; Antibiotic Prophylaxis; Antineoplastic Agents; Antiviral Agents; Cytosine; Drug Resistance, Viral; Drugs, Investigational; Female; Foscarnet; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Investigational New Drug Application; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Organophosphonates; Transplantation, Homologous; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Epstein-Barr Virus Infections; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Middle Aged; Tongue Diseases; Treatment Outcome; Valacyclovir; Valine

Over an eight-month period from October 1997 to May 1998, four patients who had received bone marrow transplant (BMT) from unrelated donor presented with severe mucosal cutaneous infections involving acyclovir resistant herpes simplex virus 1 (HSV-1). The four isolates were acyclovir (ACV) resistant, three of which were also foscarnet resistant as determined by the dye uptake method. The sequencing of the thymidine kinase (TK) gene did not permit to establish a relation between mutations and resistance to ACV. Three patients were considered as clinically cured of their HSV infection by replacement of ACV or foscarnet with either valacyclovir (one case) or cidofovir (two cases) but eventually two of them died of graft vs host disease. One patient died of extensive HSV infection despite administration of cidofovir. This study emphasizes the importance of monitoring the herpes virus resistance to antiviral drugs in bone marrow transplant recipients and the usefulness of the evaluation of novel antiviral drug for treatment of infections due to strains of HSV resistant to ACV and foscarnet that occur in about 5% of immunocompromised patients.

Topics: Acute Disease; Acyclovir; Adolescent; Amino Acid Substitution; Antiviral Agents; Bone Marrow Transplantation; Child; Cidofovir; Codon; Cytosine; DNA Mutational Analysis; Drug Resistance, Viral; Female; Foscarnet; Graft vs Host Disease; Herpes Simplex; Humans; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Mutation, Missense; Organophosphonates; Organophosphorus Compounds; Point Mutation; Salvage Therapy; Simplexvirus; Thymidine Kinase; Transplantation, Homologous; Valacyclovir; Valine; Viral Proteins; Virus Activation