acyclovir and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

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

Granulocytic sarcomas, or chloromas, are extramedullary collections of immature granulocytes. Central nervous system involvement is rare and of those cases described, most are complications of acute myelogenous leukemia.. A 40-year-old man with chronic myelogenous leukemia presented with seizure and encephalopathy. Magnetic resonance imaging of the brain revealed temporal T2 hyperintensities with gyriform cortical enhancement. Cerebrospinal fluid showed mild pleocytosis and elevated protein. Electroencephalography demonstrated periodic lateralized epileptiform discharges. Acyclovir was initiated for herpes simplex encephalitis, however, follow-up MRI showed extension of the lesion. MR spectroscopy suggested tumor, confirmed by brain biopsy. Postradiation MRI showed a significant decrease in lesion size.. Granulocytic sarcoma can present as intraparenchymal cerebral lesions in patients with chronic myelogenous leukemia and may mimic herpes simplex encephalitis.

Topics: Acyclovir; Adult; Antiviral Agents; Biopsy; Brain; Brain Neoplasms; Diagnosis, Differential; Electroencephalography; Encephalitis, Herpes Simplex; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Magnetic Resonance Imaging; Male; Sarcoma, Myeloid

Topics: Action Potentials; Acyclovir; Antiviral Agents; Electrodiagnosis; Electromyography; Female; Glucocorticoids; Herpes Zoster; Humans; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Magnetic Resonance Imaging; Median Nerve; Middle Aged; Neural Conduction; Peripheral Nervous System Diseases; Prednisolone; Radial Nerve

Topics: Acyclovir; Female; Hematopoietic Stem Cell Mobilization; Herpes Zoster; Herpesvirus 3, Human; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Stem Cell Transplantation; Tissue Donors; Transplantation, Homologous

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

A 45-year-old matched unrelated BMT recipient had sequential mucocutaneous herpes simplex virus (HSV) type 2 infections. Five months after BMT, a penile lesion occurred and was cured using acyclovir, as expected from in vitro susceptibility results. The same lesion recurred 1 month later but worsened with acyclovir. The HSV isolate was resistant to acyclovir (IC(50) = 105 microM), and a nucleotide (G) was added to the thymidine kinase gene leading to a premature stop codon. The lesion improved markedly with foscarnet. During this treatment a second HSV infection occurred on the buttocks 2 weeks after the first one and healed completely with acyclovir. This course correlated with in vitro results of the buttock HSV isolate which was foscarnet-resistant (IC(50) = 300 microg/ml) and acyclovir-sensitive. Surprisingly, no mutation gene of the foscarnet-resistant isolate was detected in the DNA polymerase gene. This case shows that an HSV acyclovir-resistant infection may be followed by an acyclovir-sensitive one. Determination of antiviral susceptibility is needed to monitor the treatment of various HSV infections in immunocompromised BMT recipients.

Topics: Acyclovir; Antineoplastic Agents, Alkylating; Antiviral Agents; Bone Marrow Transplantation; Cidofovir; Combined Modality Therapy; Cyclosporine; Cytarabine; Cytomegalovirus Infections; Cytosine; Drug Resistance, Viral; Fatal Outcome; Foscarnet; Graft vs Host Disease; Herpes Genitalis; Herpes Simplex; Humans; Hydroxyurea; Immunocompromised Host; Immunosuppressive Agents; Interferons; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Methotrexate; Middle Aged; Organophosphonates; Organophosphorus Compounds; Simplexvirus; Transplantation Conditioning; Whole-Body Irradiation

Topics: Acyclovir; Adult; Age of Onset; Antiviral Agents; Bone Marrow Transplantation; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lung Diseases, Interstitial; Male; Pneumonia, Viral

This case report shows reversible brain MRI changes probably associated with acyclovir toxicity. So far, neuroimaging in acyclovir toxicity had been negative or uninformative. A 12-year-old girl developed focal secondary generalizing epileptic fits following 4 weeks of prophylactic administration of acyclovir (3 x 10 mg/kg body weight/day i.v.) on day +22 after allogeneic peripheral blood stem cell transplantation for CML. Infective causes were excluded. Brain MRI demonstrated multiple gadolinium-enhancing areas with impairment of the blood-brain barrier in cortical and subcortical regions. Clinical symptoms and neuroimaging pathology resolved completely within 9 days of acyclovir withdrawal.

Topics: Acyclovir; Antiviral Agents; Blood-Brain Barrier; Brain; Child; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Magnetic Resonance Imaging

This is a report on 60 consecutive patients with chronic myeloid leukemia (CML) who received an allogeneic bone marrow transplant (BMT) in this Unit. Donors were HLA-identical siblings (SIB) (n = 36) or unrelated donors (MUD) (n = 24) matched by serology for HLA A and B and by molecular biology for HLA DR. All patients were prepared with cyclophosphamide 120 mg/kg and fractionated total body irradiation 10-12 Gy. GVHD prophylaxis consisted of cyclosporin A (CsA) starting on day -7 and short-course methotrexate. Bone marrow was unmanipulated in all cases. Cytomegalovirus prophylaxis consisted of acyclovir for SIBs and foscarnet for MUDs. When compared to SIB transplants, MUD patients were younger (29 vs 36 years; P = 0.002), had younger donors (31 vs 39; P = 0.001), had a longer interval between diagnosis and BMT (1459 vs 263 days; P < 0.001) and received a smaller number of nucleated cells at transplant (3.3 vs 4.4 x 10(8)/kg; P = 0.003). More MUDs had advanced disease (50 vs 17%, P = 0.005). The median day to 0.5 x 10(9)/l neutrophils was similar in both groups (18 days for SIBs vs 17 days for MUDs; P = 0.06); the median platelet count on days +30, +50, +100 was significantly (P < 0.01) higher in SIB than in MUD patients (122 vs 38, 113 vs 50 and 97 vs 45 x 10(9)/l, respectively). Acute GVHD was scored as absent-mild, moderate, or severe, in 36, 58 and 6% of SIBs vs 25, 42 and 33% in MUD patients (P = 0.01). Chronic GVHD was comparable (P = 0.1). The actuarial risk of CMV antigenemia at 1 year was 60% in both groups. There were six deaths in SIB patients (two leukemia, two infections, one GVHD, one pneumonitis) and four deaths in MUD patients (three acute GVHD and one infection). Fifty patients survive with a median follow-up of 656 days for SIBs and 485 for MUDs. The actuarial 3-year transplant-related mortality is 12% in SIBs and 17% in MUDs (P = 0.5); the actuarial relapse is 18% in SIBs vs 6% in MUDs (P = 0.4) and 3-year survival 78% in SIBs vs 82% in MUDs (P = 0.7). This study suggests that survival of CML patients after marrow transplantation from unrelated or sibling donors is currently similar, provided the former are well matched. The increased incidence of GVHD in MUD patients is possibly compensated by a lower risk of relapse.

Topics: Acyclovir; Adolescent; Adult; Antigens, Viral; Antiviral Agents; Bone Marrow Transplantation; Cause of Death; Cytomegalovirus; Cytomegalovirus Infections; Disease-Free Survival; Female; Foscarnet; Graft vs Host Disease; Histocompatibility Testing; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukocyte Count; Life Tables; Male; Middle Aged; Neutrophils; Nuclear Family; Premedication; Prospective Studies; Recurrence; Risk; Tissue Donors; Transplantation, Homologous; Viremia

Acyclovir (ACV), a nucleoside analog, has been demonstrated previously to suppress selectively the proliferation of NIH3T3 fibroblastic cells transformed by either v-abl or bcr-abl gene transfection. From a viewpoint of clinical application of ACV, we investigated whether ACV inhibited the growth of leukemia cells expressing either p210 BCR-ABL or p185BCR-ABL. Acyclovir exerted an inhibitory effect on OM9;22 cells, p185BCR-ABL expressing cells, in a dose-dependent manner. Despite no down-modulation of a BCR-ABL tyrosine kinase activity or its expression was observed after treatment with ACV, cell cycle analysis demonstrated synchronization of OM9;22 cells at the G0/G1 phase. This suggests that, although ACV does not directly act on BCR-ABL tyrosine kinase, ACV may exert its inhibitory effect on some leukemia cell lines via alterations of the cell cycle. Although selective inhibition of Philadelphia chromosome-positive leukemia cell growth was not apparent, our data provides a therapeutic possibility for ACV in the treatment for leukemia.

Topics: Acyclovir; Antimetabolites, Antineoplastic; Cell Division; Evaluation Studies as Topic; Fusion Proteins, bcr-abl; G1 Phase; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Resting Phase, Cell Cycle; Thymidine Kinase; Tumor Cells, Cultured

A 30-year-female with chronic myelogenous leukemia received allogeneic bone marrow transplantation (BMT). On day 104, low-grade fever, cough, and general malaise developed, resulting in hospitalization 10 days later. Chest X ray revealed diffuse infitrates, suggesting cytomegalovirus interstitial pneumonia. Ganciclovir (DHPG) was given daily and all symptoms disappeared three days later. However, a very few vesicular lesions appeared on her trunk and her two children had chickenpox at that time. Chest CT was taken and disclosed diffuse nodular shadows. Clinical course and chest CT suggested varicella pneumonia. DHPG administration was stopped and acyclovir PO started to be given. She was discharged in excellent condition. In this report, we show a rare case of varicella pneumonia after allogeneic BMT and efficacy of DHPG for the treatment of varicella pneumonia.

Topics: Acyclovir; Adult; Antiviral Agents; Bone Marrow Transplantation; Chickenpox; Female; Ganciclovir; Humans; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Opportunistic Infections; Pneumonia, Viral; Tomography, X-Ray Computed; Transplantation, Homologous

The acyclic nucleoside phosphonate (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was used topically for the treatment of persistent mucocutaneous infections in two cases. One patient with AIDS suffered from a perineal lesion due to infection with herpes simplex virus type 2 (HSV-2) and did not respond to acyclovir and was intolerant of foscarnet. A bone marrow transplant recipient developed orofacial lesions due to infection with herpes simplex virus type 1 (HSV-1) that failed to respond to therapy with both acyclovir and foscarnet. After topical application of HPMPC, the HSV-2 lesions completely resolved. However, the lesions recurred 3 weeks later, and, upon subsequent treatment with HPMPC, regressed. On recurrence, the virus was found to be sensitive to acyclovir, which the patient was given. Again HSV-2, which was resistant to acyclovir, emerged; similar observations were made after another cycle of HPMPC therapy. The HSV-1 isolates were resistant to acyclovir and foscarnet. Following local HPMPC treatment, the lesions regressed, but after 1 week, a second course of topical HPMPC therapy had to be instituted for recurrent infection. The lesions again regressed, and as the recurrent virus was sensitive to acyclovir, the patient was successfully treated with the drug. The results of this study point to the potential usefulness of topical HPMPC in the treatment of immunocompromised patients with HSV-related mucocutaneous infections that are refractory to therapy with acyclovir and/or foscarnet.

Topics: Acyclovir; Administration, Topical; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytosine; DNA Restriction Enzymes; DNA, Viral; Drug Resistance, Microbial; Foscarnet; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Opportunistic Infections; Organophosphonates; Organophosphorus Compounds; Skin Diseases, Viral; Thymidine Kinase

Primary varicella-zoster virus infection in children with haematological malignancy is a life threatening disease. In one year, there were 10 cases of varicella and 2 cases of zoster among these children as well as 5 mothers who were accompanying their children who developed varicella in the oncology ward. Two children died of fulminating disease despite aggressive antiviral and supportive treatment. Acyclovir can be used in treatment and prophylaxis in exposed susceptible children. Varicella -zoster immune globulin is not available in this country. Vaccination with live virus has been shown to be protective in immunocompromised children and needs consideration.

Topics: Acute Disease; Acyclovir; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; Cross Infection; Disease Outbreaks; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Infection Control; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Severity of Illness Index; Survival Rate; Treatment Outcome; Vaccines, Attenuated; Viral Vaccines

Abdominal and back pain has until now been reported as a first sign of severe varicella in immunocompromised children only. We report two adult leukemia patients in whom these symptoms preceded visceral dissemination of varicella infection. Recognizing that this syndrome may occur in adult patients is of clinical importance, since it allows early diagnosis and treatment of the infection.

Topics: Abdominal Pain; Acyclovir; Adult; Back Pain; Chickenpox; Humans; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma

A series of herpes simplex virus isolates were recovered from a bone marrow transplant patient who received prolonged acyclovir therapy for indolent herpes simplex mouth and throat ulceration. Of 14 isolates received 10 were resistant to acyclovir and partially resistant to phosphonoacetic acid. Biochemical characterization revealed that resistance was due to an alteration in the virus DNA polymerase. DNA sequence analysis of the polymerase gene of a plaque-purified resistant virus isolate revealed a single nucleotide change when compared with the sequence of the gene of a plaque-purified sensitive isolate. This single base change resulted in a predicted amino acid substitution of Gly to Ser at residue number 841, a putative functional region of the polymerase.

Topics: Acyclovir; Adult; Base Sequence; Bone Marrow; Bone Marrow Transplantation; DNA-Directed DNA Polymerase; Drug Resistance, Microbial; Female; Genes, Viral; Humans; Immunologic Deficiency Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mutation; Simplexvirus; Stomatitis, Herpetic