Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell ...transplantation. To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.
The aim of this survey was to summarize the current antimicrobial practice in febrile neutropenia and the presence of key aspects of antimicrobial stewardship. A questionnaire was sent to 567 ...centers, and complete responses were obtained from 194 (34.2%). Fluoroquinolone and co-trimoxazole prophylaxis are used in 57.1% and 89.1%, respectively. In 66.4%, the first-line empirical therapy is piperacillin/tazobactam, whereas 10.9% use carbapenems. Empirical combination therapy is used in stable patients without history of resistant pathogens in 37.4%. De-escalation to monotherapy is performed within 3 days in 35.3% and after 10 days in 19.1%. Empirical addition of a glycopeptide is performed when fever persists more than 2-3 days in 60.8%. Empirical escalation to a broader spectrum agent is performed when fever persists more than 3-5 days in 71.4%. In case of positive blood cultures with a susceptible pathogen and uncomplicated presentation, 76.7% of centers de-escalate and 36.6% discontinue before neutrophil recovery. In fever of unknown origin with uncomplicated presentation, 54.1% of centers de-escalate and 49.5% discontinue before neutrophil recovery. Recommendations put forward in the ECIL guidelines are not widely implemented in clinical practice. Specific problems include overuse of carbapenems and combination therapy and unjustified addition of glycopeptides without further de-escalation or discontinuation.
Abstract
This study reports on 382 COVID-19 patients having undergone allogeneic (
n
= 236) or autologous (
n
= 146) hematopoietic cell transplantation (HCT) reported to the European Society for ...Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (
p
= 0.02), need for ICU (
p
< 0.0001) and moderate/high immunodeficiency index (
p
= 0.04) increased the risk while better performance status (
p
= 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.
The new coronavirus SARS-CoV-2 has rapidly spread over the world causing the disease by WHO called COVID-19. This pandemic poses unprecedented stress on the health care system including programs ...performing allogeneic and autologous hematopoietic cell transplantation (HCT) and cellular therapy such as with CAR T cells. Risk factors for severe disease include age and predisposing conditions such as cancer. The true impact on stem cell transplant and CAR T-cell recipients in unknown. The European Society for Blood and Marrow Transplantation (EBMT) has therefore developed recommendations for transplant programs and physicians caring for these patients. These guidelines were developed by experts from the Infectious Diseases Working Party and have been endorsed by EBMT's scientific council and board. This work intends to provide guidelines for transplant centers, management of transplant candidates and recipients, and donor issues until the COVID-19 pandemic has passed.
Background. The use of a cytomegalovirus (CMV)–seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance ...of donor serostatus in CMV-seropositive patients is controversial. Methods. A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. Results. Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio HR, 1.13; 95% confidence interval CI, 1.06–1.21; P < .0001) compared with seronegative donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86–.98; P < .01) compared with seronegative donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. Conclusions. We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen.
Hematopoietic-cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants performed in Europe and associated countries continues ...to rise with 47,468 HCT in 42,901 patients 19,630 allogeneic (41%) and 27,838 autologous (59%) reported by 701 centers in 50 countries in 2018. Main indications were myeloid malignancies 10,679 (25%; 97% allogeneic), lymphoid malignancies 27,318 (64%; 20% allogeneic), solid tumors 1625 (4%; 2.9% allogeneic), and nonmalignant disorders 3063 (7%; 81% allogeneic). This year's analysis focuses on cellular therapies with the marked growth in CAR T-cell therapies from 151 in 2017 to 301 patients reported in 2018. Other cellular therapy numbers show less significant changes. Important trends in HCT include a 49% increase in allogeneic HCT for chronic phase CML (although transplant numbers remain low) and a 24% increase in aplastic anemia. In autologous HCT, there is an ongoing increase in autoimmune diseases (by 19%), predominantly due to activity in multiple sclerosis. This annual report reflects current activity and highlights important trends, useful for health care planning.
Summary Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell ...transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript.
Hematopoietic cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants done in Europe and associated countries continues to ...rise with 45,418 HCT in 41,100 patients (17,155 allogeneic (42%) and 23,945 autologous (58%) reported by 683 centers in 50 countries in 2017. Main indications were myeloid malignancies 10,147 (25%; 96% allogeneic), lymphoid malignancies 26,488 (64%; 19% allogeneic), solid tumors 1,607 (3.9%; 2% allogeneic), and nonmalignant disorders 2,667 (7%; 81% allogeneic). Trends in donor choice seen before continue, with growing numbers of haploidentical HCT and decreasing use of cord blood. Of interest is that after many years of continued growth, the number of patients receiving an allogeneic HCT for marrow failure is decreasing slightly (p < 0.001). Such a change may be explained by the use of thrombopoietin analogs in aplastic anemia patients. Other nonmalignant indications, however continue to grow, most importantly HCT for hemoglobinopathies by 36%, equally for thalassemias and sickle cell disease. Non-HCT cell therapies have increased by 28% since 2015 and genetically modified T cells is type of cell therapy with the fastest growth. These annual reports reflect current activity and trends and are useful for health-care planning.
Cytomegalovirus (CMV) is an agent of global infection, and its acquisition in a population is characterized by an age-dependent rise in seropositivity. After primary infection, CMV remains in the ...host cells in latent form, and it can reactivate in the case of immune suppression. The risk of CMV recurrence is dependent on the level of incompetency of the immune system, manifested as an impairment of T-cell immunity, including the presence and function of CMV-specific cytotoxic T lymphocytes. This article presents data on the incidence of CMV recurrence in groups of immunocompromised patients, including allogeneic hematopoietic stem cell transplantation (HSCT) patients and other groups of patients, based on a summary of reported data. The median rate of CMV recurrence in HSCT recipients was estimated as 37% after allogeneic transplant and 12% after autologous transplant, 5% in patients with nontransplant hematological malignancies, 14% in recipients of anti-CD52 therapy, 30% in solid organ transplant recipients, 21% in patients with primary immunodeficiencies, 20% during active replication in HIV-positive patients and 3.3% during antiretroviral therapy, 7% in patients with chronic kidney disease, 0.6% in patients with congenital infection, and 0.6% in neonates with primary infection. The highest risk of CMV recurrence and CMV disease is reported for HSCT CMV-seropositive recipients, regardless of donor serostatus. The odds ratio (OR) for CMV recurrence is higher for recipient-positive versus recipient-negative CMV serostatus transplants (OR 8.0), donor-negative/recipient-positive versus donor-positive/recipient-positive CMV serostatus transplants (OR 1.2), unrelated/mismatched versus matched-family donor transplants (OR 1.6), and acute graft-versus-host-disease versus other diseases (OR 3.2). Other risk factors have minor significance.
PDF
