gw-257406x and Hematologic-Neoplasms

Cytomegalovirus is one of the most important infections to occur after allogeneic haematopoietic stem cell transplantation (HSCT), and an increasing number of reports indicate that cytomegalovirus is also a potentially important pathogen in patients treated with recently introduced drugs for hematological malignancies. Expert recommendations have been produced by the 2017 European Conference on Infections in Leukaemia (ECIL 7) after a review of the literature on the diagnosis and management of cytomegalovirus in patients after HSCT and in patients receiving other types of therapy for haematological malignancies. These recommendations cover diagnosis, preventive strategies such as prophylaxis and pre-emptive therapy, and management of cytomegalovirus disease. Antiviral drugs including maribavir and letermovir are in development and prospective clinical trials have recently been completed. However, management of patients with resistant or refractory cytomegalovirus infection or cytomegalovirus disease is a challenge. In this Review we summarise the reviewed literature and the recommendations of the ECIL 7 for management of cytomegalovirus in patients with haematological malignancies.

Topics: Antiviral Agents; Benzimidazoles; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Practice Guidelines as Topic; Ribonucleosides

Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality in immunocompromised patients, particularly following allogeneic haematopoietic transplantation. One of the principal factors leading to this increased risk is the loss of T-cell immunity.. In a recent review, we assessed the treatment strategies for prophylaxis and pre-emptive treatment of CMV, particularly where relevant to the high-risk patient populations following allogeneic haematopoietic transplantation. This review is a focused update to our previous article and presents a more detailed analysis of the developments in drugs, vaccines and adoptive T-cell therapies since that time. Relevant studies were selected from PubMed and clinicaltrials.gov. The search terms include allogeneic transplant, cytomegalovirus, multidrug-resistant virus and adoptive T-cell therapy.. The current randomised controlled studies evaluating pharmacological agents for CMV should inform as to whether these provide significant clinical benefits. Adoptive cell therapy provides a more physiological approach to the problem of lack of CMV-specific immunity. Recent reports add to the evidence that culture-based techniques can create cellular products that are safe and efficacious, although without Phase III data to definitively support their routine application and the difficulty of satisfying GMP standards.

Topics: Acetates; Antiviral Agents; Benzimidazoles; Cytomegalovirus; Cytomegalovirus Infections; Cytosine; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Organophosphonates; Quinazolines; Ribonucleosides; T-Lymphocytes; Transplant Recipients; Transplantation, Homologous

Antiviral prophylaxis is commonly prescribed to haematological cancer patients. We conducted a systematic review and meta-analysis to quantify its overall benefit in specific clinical scenarios.. Randomised controlled trials assessing antiviral prophylaxis versus placebo, no treatment, pre-emptive treatment or another antiviral drug were included. Patients undergoing haematopoietic stem cell transplantation (HSCT) or intensive chemotherapy for acute leukaemia or high-grade lymphoma were included. No restrictions on language, year or publication status were applied. Overall mortality, herpes simplex virus (HSV) and cytomegalovirus (CMV) diseases were assessed as primary outcomes. Pooled relative risks (RRs) and numbers needed to treat (NNT) with 95% confidence intervals (CI) are reported.. HSCT was the condition assessed in 22 trials and intensive chemotherapy in 5 trials. In the pre-engraftment setting of autologous or allogeneic HSCT, antiviral prophylaxis (mainly acyclovir for HSV seropositive recipients) significantly reduced HSV (NNT 2, 2-2, control event rate (CER) 61.9%) and CMV disease, with no effect on overall mortality. In the allogeneic post-engraftment setting (mainly CMV-seropositive recipients/donors), antiviral prophylaxis resulted in a significant reduction in overall mortality, RR 0.79 (0.65-0.95), NNT 12 (7-50, CER 39.4%) and all viral-related outcomes. In this setting, acyclovir significantly reduced overall mortality (RR 0.71, 0.53-0.96, 4 trials) and ganciclovir/maribavir significantly reduced CMV disease (RR 0.26, 0.14-0.48, 5 trials). During chemotherapy, acyclovir significantly decreased HSV disease (NNT 3, 2-4, CER 37.4%) and infection rates, with no effect on mortality.. Antiviral prophylaxis reduced mortality with a small NNT in the post-engraftment setting of allogeneic HSCT. In the pre-engraftment phase and during chemotherapy only viral-related morbidity was reduced.

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Benzimidazoles; Cytomegalovirus Infections; Ganciclovir; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Herpes Simplex; Humans; Oral Ulcer; Randomized Controlled Trials as Topic; Ribonucleosides; Treatment Outcome

Management of pan-resistant cytomegalovirus infection (CMVi) requires a multifaceted approach, including host defence optimization by reducing immunosuppression, and standard or experimental antiviral therapy.. A 36-year-old man with anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma, who underwent allogeneic haematopoietic stem cell transplant (alloHCT) with resultant graft-versus-host disease treated with immunosuppressive therapy, developed pan-resistant CMVi. He was successfully treated with combination therapy of maribavir and letermovir.. Combination therapy, used for other infections to prevent cross-resistant, may apply for CMVi.

Topics: Acetates; Adult; Antiviral Agents; Benzimidazoles; Cytomegalovirus; Cytomegalovirus Infections; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Quinazolines; Ribonucleosides