scholarly journals VaccHemInf project: protocol for a prospective cohort study of efficacy, safety and characterisation of immune functional response to vaccinations in haematopoietic stem cell transplant recipients

BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e026093 ◽  
Author(s):  
Anne Conrad ◽  
Mathilde Boccard ◽  
Florent Valour ◽  
Vincent Alcazer ◽  
Aydee-Tamara Tovar Sanchez ◽  
...  
Keyword(s):  
Cohort Study ◽  
Stem Cell ◽  
Immune Function ◽  
Immune Status ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Serological Response ◽  
Vaccine Response ◽  
Functional Assays ◽  
Prospective Longitudinal

IntroductionImmune reconstitution after haematopoietic stem cell transplantation (HSCT) is a complex and dynamic process, varying from a state of nearly complete immunosuppression to an expected full immune recovery. Specific vaccination guidelines recommend reimmunisation after HSCT but data regarding vaccine efficacy in this unique population are scarce. New immune functional assays could enable prediction of vaccine response in the setting of HSCT.Methods and analysisA prospective, longitudinal single-centre cohort study of autologous and allogeneic HSCT recipients was designed in order to determine the vaccine response to five vaccine targets (pneumococcus, hepatitis B virus,Haemophilus Influenzaetype b, tetanus and diphtheria) and to correlate it to immune function parameters. A workflow was set up to study serological response to vaccines and to describe the functional immune status of 100 HSCT recipients (50 autologous and 50 allogeneic) before and 3, 12 and 24 months after primary immunisation. At each time point, ‘basic’ immune status recording (serology, immunophenotyping of lymphocyte subsets by flow cytometry) will be assessed. The immune response will furthermore be evaluated before and 3 months after primary vaccination by two ex vivo immune functional assays assessing: (1) tumour necrosis factor alpha, interferon gamma production and host messenger RNA expression on whole-blood stimulation by lipopolysaccharide orStaphylococcus aureusenterotoxin B and (2) T-lymphocyte proliferation in response to a standard mitogen (phytohaemagglutinin) or to selected recall antigens. Reference intervals will be determined from a cohort of 30 healthy volunteers. This translational study will provide data describing vaccine response, immune functionality of HSCT recipients over time and will allow mapping HSCT recipients with regard to their immune function.Ethics and disseminationEthical approval has been obtained from the institutional review board (no 69HCL17_0769). Results will be communicated at scientific meetings and submitted for publication in peer-reviewed journals.Trial registration numberNCT03659773; Pre-results.

scholarly journals Assessing the impact on intestinal microbiome and clinical outcomes of antibiotherapy optimisation strategies in haematopoietic stem cell transplant recipients: study protocol for the prospective multicentre OptimBioma study

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e034570
Author(s):  
Silvia Jiménez-Jorge ◽  
Gema Labrador-Herrera ◽  
Clara M Rosso-Fernández ◽  
Nancy Rodríguez-Torres ◽  
María Eugenia Pachón-Ibáñez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Outcomes ◽  
Intestinal Microbiota ◽  
Acute Gvhd ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Microbiota Composition ◽  
Prospective Longitudinal ◽  
The Impact ◽  
Microbiota Diversity

IntroductionHaematopoietic stem cell transplantation (HSCT) is a life-saving treatment for a number of haematological diseases. Graft versus host disease (GVHD) is its main complication and hampers survival. There is strong evidence that intestinal microbiota diversity of the recipient may increase the risk of GVHD worsening survival. Antibiotic regimens used during the early phase of the transplant may influence clinical outcomes by reducing intestinal microbiota diversity. Present guidelines of European Conference on Infections in Leukaemia exhort to optimising antibiotic use in haematological patients including HSCT recipients. The present study aims to investigate if, in HSCT recipients, the optimisation of antibacterial use may preserve intestinal microbiota composition reducing the incidence and severity of acute GVHD and improving relevant clinical outcomes.Methods and analysisThis is a prospective longitudinal observational study of two cohorts of HSCT recipients: (1) the intervention cohort includes patients treated in centres in which a predefined strategy of antibiotherapy optimisation is implemented, with the objective of optimising and reducing antibiotic administration according to clinical criteria and (2) the control cohort includes patients treated in centres in which a classic permissive strategy of antibiotic prophylaxis and treatment is used. Adult patient receiving a first HSCT as a treatment for any haematological condition are included. Clinical variables are prospectively recorded and up to five faecal samples are collected for microbiota characterisation at prestablished peritransplant time points. Patients are followed since the preconditioning phase throughout 1-year post-transplant and four follow-up visits are scheduled. Faecal microbiota composition and diversity will be compared between both cohorts along with acute GVHD incidence and severity, severe infections rate, mortality and overall and disease-free survival.Ethics and disseminationThe study was approved between 2017 and 2018 by the Ethical Committees of participant centres. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences.Trial registration numberNCT03727113

scholarly journals Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients

2021 ◽  
Vol 8 ◽  
pp. 204993612199137
Author(s):  
Aditya Jandial ◽  
Kundan Mishra ◽  
Rajeev Sandal ◽  
Kamal Kant Sahu
Keyword(s):  
Stem Cell ◽  
Platelet Rich Plasma ◽  
Severe Disease ◽  
Unmet Need ◽  
Bk Virus ◽  
Haematopoietic Stem Cell ◽  
Cellular Immunotherapy ◽  
Cell Transplant ◽  
Clotting Factors ◽  
Haemorrhagic Cystitis

BK virus (BKV)-related haemorrhagic cystitis (HC) is an important cause of morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). The various risk factors include high-level BKV viruria and/or viremia, myeloablative conditioning, acute graft versus host disease (GVHD), cytomegalovirus viremia, and unrelated or HLA-mismatched donor. The presence of high plasma BK viral load and cytopenias have been implicated as important predictors for protracted disease course. These patients frequently require hospitalisation which may extend for several weeks. Supportive measures in the form of analgesics, intravenous hydration, bladder irrigation, and transfusion support remain the mainstay of management. Various drugs have been used with limited success in this setting. These include antiviral drugs, fluoroquinolones, leflunomide, growth factors, clotting factors, estrogens, and prostaglandins. The role of adoptive cellular immunotherapy has also been explored but lacks clinical validation. The strategies aimed at expediting urothelial repair like hyperbaric oxygen therapy (HBOT), intravesical fibrin glue and platelet-rich plasma (PRP) are emerging. Some patients with severe disease do require surgical intervention to relieve urinary obstruction. The frequent co-occurrence of acute GVHD and CMV disease further complicates the management in such patients. There is an unmet need for effective and evidence-based options for the prevention and management of this disease. Due to lack of robust data supported by randomised trials, the acceptability of the available guidelines to simplify the treatment is expected to be low. Despite the availability of various treatment options, the management of BKV-related HC in day-to-day practice continues to be a challenge. The aim of this article is to put forward an up-to-date review of the preventive and therapeutic strategies for BKV-related HC.

Carbapenem-resistant Klebsiella pneumoniae colonization and infection is associated with lower overall survival in a cohort of haematopoietic stem-cell transplantation patients: mechanism of resistance and virulence by whole-genome sequencing

2021 ◽  
Vol 70 (10) ◽  
Author(s):  
Hermes Ryoiti Higashino ◽  
Ana Paula Marchi ◽  
Roberta Cristina Ruedas Martins ◽  
Laina Bubach Carvalho ◽  
Lauro Vieira Perdigão Neto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Klebsiella Pneumoniae ◽  
Genome Sequencing ◽  
Stem Cell Transplant ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Whole Genome ◽  
Carbapenem Resistant ◽  
Overall Mortality

Carbapenem-resistant Klebsiella pneumoniae (CRK) infections are a growing concern in immunocompromised patients. The aim of the present study was to evaluate the impact of CRK colonization and infection in overall mortality for haematopoietic stem-cell transplant (HSCT) patients. We also aimed to investigate resistance and virulence profiles of CRK isolates and assess their epidemiological and genetic relatedness. Patients in the HSCT unit were screened for colonization with CRK with weekly rectal swab or stool cultures and placed under contact precautions. We defined CRK colonization as positive culture from a swab or stool sample grown in MacConkey agar with meropenem at 1 µg ml−1. Demographic and clinical data were retrieved from the patients’ charts and electronic records. According to resistance mechanisms and pulsed field gel electrophoresis profile, isolates were selected based on whole-genome sequencing (WGS) using MiSeq Illumina. Outcomes were defined as overall mortality (death up to D+100), and infection-related death (within 14 days of infection). We report a retrospective cohort of 569 haematopoietic stem-cell transplant patients with 105 (18.4 %) CRK colonizations and 30 (5.3 %) infections. blaKPC was the most frequent carbapenemase in our cohort with three isolates co-harbouring blaKPC and blaNDM. We found no difference in virulence profiles from the CRK isolates. There were also no significant differences in virulence profiles among colonization and infection isolates regarding genes encoding for type 1 and 3 fimbriae, siderophores, lipopolysaccharide and colibactin. In clonality analysis by PFGE and WGS, isolates were polyclonal and ST340 was the most prevalent. Overall survival at D+100 was 75.4 % in in CRK-colonized (P=0.02) and 35.7 % in infected patients and significantly lower than non-colonized patients (85.8 %; P<0.001). We found a higher overall mortality associated with colonization and infection; KPC was the main resistance mechanism for carbapenems. The polyclonal distribution of isolates and findings of CRK infection in patients not previously colonized suggest the need to reinforce antibiotic stewardship.

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