Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although ...SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.
Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a ...significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.
The clinical picture of coronavirus disease 2019 (COVID-19) in various target organs has been extensively studied and described. However, relatively little is known about the characteristics of oral ...cavity involvement. This is surprising, considering that oral mucosal and salivary gland cells are known targets for the direct replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and that the presence of the virus in saliva is a source of transmission of the infection. The aim of our study was to investigate the presence and prevalence of oral manifestations in COVID-19 survivors. We profiled the oral involvement in 122 COVID-19 survivors that were hospitalized and followed up at a single-referral university hospital in Milan, Italy, between July 23, 2020 and September 7, 2020, after a median (interquartile range) time from hospital discharge of 104 (95 to 132) d. We found that oral manifestations, specifically salivary gland ectasia, were unexpectedly common, with oral manifestations being detected in 83.9% while salivary gland ectasia in 43% of COVID-19 survivors. Salivary gland ectasia reflected the hyperinflammatory response to SARS-CoV-2, as demonstrated by the significant relationship with C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels at hospital admission, and with the use of antibiotics during acute disease. Both LDH levels and antibiotic administration survived as independent predictors of salivary gland ectasia at multivariable analysis. Temporomandibular joint abnormalities, facial pain, and masticatory muscle weakness were also common. Overall, this retrospective and prospective cohort study of COVID-19 survivors revealed that residual damage of the oral cavity persists in the vast majority of patients far beyond clinical recovery, and suggests that the oral cavity represents a preferential target for SARS-CoV-2 infection. Further studies are needed to clarify the connection between SARS-CoV-2 infection and oral disorders.
•Prenatal stress and inflammatory markers were associated with outcomes at birth.•Maternal interleukine-6 levels were negatively associated with head circumference.•Maternal alpha amylase levels were ...positively associated with birthweight.•Maternal diurnal cortisol was associated with newborn’s stress reactivity.•Future research should explore mechanisms underlying these associations.
Accumulating evidence suggests that antenatal maternal stress is associated with altered behavioral and physiological outcomes in the offspring, however, whether this association is causal and the underlying biological mechanisms remain largely unknown. While the most studied mediator of maternal stress influences on the fetus has generally been cortisol, alternative novel markers of stress or inflammation warrant further consideration. The current investigation explored the influence of variations in self-reported symptoms of distress, stress hormones and inflammatory markers on infant birth outcomes and early stress regulation. The sample consisted of 104 pregnant women (mean gestational age = 34.76; SD = 1.12) and their healthy newborns. Maternal self-reported symptoms of depression and anxiety were evaluated through the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory and levels of serum Interleukine-6 (IL-6), C-Reactive Protein (CRP), salivary cortisol and alpha amylase (sAA) were measured in late pregnancy. Newborns’ cortisol and behavioral response to the heel-stick was assessed 48–72 hours after birth. The associations between maternal stress measures and infant birth outcomes and stress reactivity, adjusted for potential confounders, were examined through hierarchical linear regressions and hierarchical linear models. Higher maternal IL-6 levels were associated with smaller head circumference at birth, while diurnal sAA levels were positively associated with birthweight. Maternal diurnal cortisol was related to newborn’s stress reactivity: a flatter infant cortisol response to the heel-stick was associated with greater maternal cortisol increases after awakening during pregnancy, while greater infant behavioural reactivity was related to a flatter maternal diurnal cortisol profile. The observational nature of these data does not allow for causal inferences but the current findings illustrate that antenatal factors related to alterations in maternal stress and immune response systems are associated with fetal growth and neonatal stress reactivity. This may have implications for later health and psychological outcomes.
Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the ...European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children.
Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, ...high-grade B-cell lymphoma and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future.
The European Society for Blood and Marrow Transplantation (EBMT)-Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association collaborated to draft best practice recommendations based on the current literature to support health care professionals in delivering consistent, high-quality care in this rapidly moving field.
Thirty-six CAR-T experts (medical, nursing, pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post-authorisation safety surveillance and regulatory issues.
We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for haematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.
•Antenatal depressive symptoms were associated with diurnal cortisol variations.•Antenatal depressive symptoms were associated with heightened IL-6 levels.•A disruption of stress-immune circuits ...might be involved in perinatal depression.
Well-established evidence exists of an association between depressive symptoms and alterations in the stress and inflammatory response systems; however, the picture is far less coherent during the perinatal period. This study combines the assessment of multiple stress and inflammatory biomarkers in late pregnancy and after delivery in order to investigate cross-sectional and prospective associations with perinatal depressive symptoms.
One-hundred-ten healthy women were assessed in late pregnancy (mean gestational age=34.76; SD=1.12) and 89 were re-evaluated after delivery (mean hours after delivery=52.36; SD=19.70) for depressive and anxiety symptoms through the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory. Serum Interleukin-6 (IL-6), C-Reactive Protein (CRP) and diurnal salivary cortisol levels were measured on both occasions, while diurnal salivary alpha amylase (sAA) levels were assessed in late pregnancy.
Using Hierarchical Linear Models, higher depressive symptoms were found to be associated with higher IL-6 levels, lower morning cortisol levels and a flatter cortisol diurnal slope during pregnancy, while adjusting for potential confounders. No significant associations were found after delivery or with change in biomarker levels from pre- to post-partum. Furthermore, preliminary evidence of a positive association between inflammation and stress markers in women with higher antenatal depressive symptoms was found.
The sample was relatively small and highly selected, thus limiting generalizability of the findings.
Results emphasize the need for an integrated multi-systems approach to the understanding of the biological underpinnings of perinatal depression and suggest that the stress-immune interactions represent a promising avenue for future endeavor.
Systemic Lupus Erythematosus (SLE) is a progressive disease leading to immune-mediated tissue damage, associated with an alteration of lymphoid organs. Therapeutic strategies involving regulatory T ...(Treg) lymphocytes, which physiologically quench autoimmunity and support long-term immune tolerance, are considered, as conventional treatment often fails. We describe here a therapeutic strategy based on Tregs overexpressing FoxP3 and harboring anti-CD19 CAR (Fox19CAR-Tregs). Fox19CAR-Tregs efficiently suppress proliferation and activity of B cells in vitro, which are relevant for SLE pathogenesis. In an humanized mouse model of SLE, a single infusion of Fox19CAR-Tregs restricts autoantibody generation, delay lymphopenia (a key feature of SLE) and restore the human immune system composition in lymphoid organs, without detectable toxicity. Although a short survival, SLE target organs appear to be protected. In summary, Fox19CAR-Tregs can break the vicious cycle leading to autoimmunity and persistent tissue damage, representing an efficacious and safe strategy allowing restoration of homeostasis in SLE.
Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat ...patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT and Haplo in adults with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Median follow-up was 24 months. Analysis was performed separately for patients with AML, n=918 (Haplo=360, UCBT=558) and ALL, n=528 (Haplo=158 and UCBT=370). UCBT was associated with delayed engraftment and higher graft failure in both AML and ALL recipients. In multivariate analysis, UCBT was associated with lower incidence of chronic graft-vs-host disease both in the AML group (hazard ratio (HR)=0.63, P=0.008) and in the ALL group (HR=0.58, P=0.01). Not statistically significant differences were observed between Haplo and UCBT for relapse incidence (HR=0.95, P=0.76 for AML and HR=0.82, P=0.31 for ALL), non-relapse mortality (HR=1.16, P=0.47 for AML and HR=1.23, P=0.23 for ALL) and leukemia-free survival (HR 0.78, P=0.78 for AML and HR=1.00, P=0.84 for ALL). There were no statistically differences on main outcomes after unmanipulated Haplo and UCBT, and both approaches are valid for acute leukemia patients lacking a HLA matched donor. Both strategies expand the donor pool for patients in need.
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