The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease ...(SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate >80%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation.
Thoracolumbar myelopathies in pug dogs Wachowiak, Ian J.; Patterson, Jon S.; Winger, Kathryn M. ...
Journal of veterinary internal medicine,
March/April 2023, Letnik:
37, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Background
Constrictive myelopathy (CM) involving a fibrous band around the spinal cord is a newly recognized disease in pug dogs.
Objectives
To identify the frequency of CM based on diagnostic ...imaging supplemented with necropsy; to determine whether a relationship exists between the sites of CM and other described T3‐L3 myelopathies; and to determine the frequency of caudal articular process dysplasia (CAPD).
Animals
Thirty‐two client‐owned pug dogs diagnosed with a chronic, progressive T3‐L3 myelopathy based on neurological examination performed by a board‐certified neurologist.
Methods
This is a prospective study. All dogs underwent computed tomography (CT) and magnetic resonance imaging (MRI) reviewed by a board‐certified radiologist. Magnetic resonance imaging abnormalities were categorized into diseases; CM only, CM plus other non‐CM condition(s), or non‐CM condition. Sites of CAPD were reported on CT. Nineteen dogs underwent necropsy.
Results
Magnetic resonance imaging revealed 3 dogs with CM only, 17 with CM plus at least 1 other myelopathy, 11 dogs with non‐CM myelopathies only, and 1 with no MRI abnormalities. Nineteen of 32 dogs had >1 myelopathy diagnosis on MRI whereas 15/32 had >1 site of spinal cord compression. All dogs had CAPD at >1 site in the T3‐L3 vertebral column on CT.
Conclusions and Clinical Importance
Constrictive myelopathy affected more than half of pug dogs presenting with chronic thoracolumbar myelopathies. Most had multilevel disease, concurrent myelopathies, or both. There was no apparent relationship between anatomic locations of CAPD and most severe myelopathy or myelopathy type.
Allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential to cure patients with an inherited bone marrow failure syndrome (IBMFS). However, the procedure involves the risk of ...treatment-related mortality and may be associated with significant early and late morbidity. For these reasons, the benefits should be carefully weighed against the risks. IBMFS are rare, whereas case reports and small series in the literature illustrate highly heterogeneous practices in terms of indications for HSCT, timing, stem cell source and conditioning regimens. A consensus meeting was therefore held in Vienna in September 2012 on behalf of the European Group for Blood and Marrow Transplantation to discuss HSCT in the setting of IBMFS. This report summarizes the recommendations from this expert panel, including indications for HSCT, timing, stem cell source and conditioning regimen.
After allogeneic hematopoietic stem cell transplantation (allo-HSCT), especially from an unrelated donor, infectious complications are frequent and severe, sometimes with fatal outcomes. Despite ...using highly sensitive molecular techniques for close monitoring in the early post-transplant period for early diagnosis, not every viral infection or reactivation can be detected adequately early, even with highly sensitive methods. Particularly after toxic and deeply immunosuppressive treatment, multiple infections or reactivations, uncommon infections, or infections in unusual locations can occur. Here, we present a case of multiple viral infections or reactivations and cerebral toxoplasmosis in a 17-year-old youth with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) treated with allo-HSCT who suffered multiple viral infections followed by cerebral toxoplasmosis.
Fertility preservation is an urgent challenge in the transplant setting. A panel of transplanters and fertility specialists within the Pediatric Diseases Working Party of the European Society for ...Blood and Marrow Transplantation (EBMT) and the International BFM Study Group provides specific guidelines. Patients and families should be informed of possible gender- and age-specific cryopreservation strategies that should be tailored according to the underlying disease, clinical condition and previous exposure to chemotherapy. Semen collection should be routinely offered to all postpubertal boys at the diagnosis of any disease requiring therapy that could potentially impair fertility. Testicular tissue collection might be offered to postpubertal boys; nevertheless, its use has been unsuccessful to date. Oocyte collection after hormonal hyperstimulation should be offered to postpubertal girls facing gonadotoxic therapies that could be delayed for the 2 weeks required for the procedure. Ovarian tissue collection could be offered to pre-/post-pubertal girls. Pregnancies have been reported after postpubertal ovarian tissue reimplantation; however, to date, no pregnancy has been reported after the reimplantation of prepubertal ovarian tissue or in vitro maturation of pre-/post-pubertal ovarian tissue. Possible future advances in reproductive medicine could change this scenario. Health authorities should prioritize fertility preservation projects in pediatric transplantation to improve patient care and quality of life.
Nowadays, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure and often the only cure for many patients with malignant and non-malignant ...diseases. Decrease in short-term complications has substantially contributed to increased survival. Therefore long-term sequelae are reaching the focus of patient care. One of the most important risks of stem cell transplant survivors is infertility. As well as in the field of allo-HSCT also the field of reproductive medicine has achieved substantial advances to offer potential options for fertility preservation in both boys and girls. Access to these procedures as well as their financing differs significantly throughout Europe. As all European children and adolescents should have the same possibility, the Paediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation organised an expert meeting in September 2015. This manuscript describes the recommendations for the diagnosis and pre-emptive procedures that should be offered to all children and adolescents in Europe who have to undergo an allo-HSCT.
Aims
Multidrug‐resistant (MDR) bacteria are an emerging cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT). The aim of the study was to analyse the incidence, ...clinical characteristics and survival from bacterial infections (BI) caused by MDR pathogens in paediatric HSCT recipients.
Methods and Results
Among 971 transplanted patients, BI were found in 416 children between the years 2012 and 2017. Overall, there were 883 bacterial episodes, which includes 85·8% after allo‐HSCT and 14·2% after auto‐HSCT. MDR strains were responsible for half of the total number of bacterial episodes. Over 50% of MDR pathogens were Enterobacteriaceae causing mainly gut infections or urinary tract infections.
Conclusions
Regarding HSCT type, we did not find differences in the profile of MDR BI between allo‐ and auto‐HSCT recipients. However, survival in MDR and non‐MDR infections was comparable.
Significance and Impact of the Study
The large sample size enables unique analysis and makes our data more applicable to other paediatric HSCT centres. In the absence of local epidemiological data, presented clinical characteristics of MDR‐caused infections may be used to optimize the prophylactic strategies, early identification of infectious complications of MDR aetiology and thus promptly initiate adequate antibiotic therapy and further improve patients’ outcome.
This retrospective analysis evaluated 51 children (0.7-17 years; median eight) with high-risk or advanced hematological malignancies, including 18 (35%) patients undergoing second/third hematopoietic ...SCT (allo-HSCT), not eligible for standard myeloablative regimens and transplanted from matched sibling (MSD) (n=24) or matched unrelated (MUD) (n=27) donors. Preparative regimens were based on treosulfan (TREO) i.v., a structural analog of BU, given at total dose of 30 g/m(2) (n=21) or 36-42 g/m(2) (n=30) in combination with, fludarabine, cyclophosphamide, melphalan and/or VP-16 according to diagnosis, and risk factors. Deaths due to early regimen-related toxicity (RRT) did not occur. Nonrelapse mortality was 8% at 1 year and 16% after 4 years. Myeloid engraftment was achieved in 94%, complete donor chimerism in 90% of patients. A 4-year incidence of relapse was 24%, and was significantly lower after MUD-HSCT (8%) than after MSD-HSCT (39%), but similar in children undergoing first (28%) or second/third HSCT (17%). A 4-year disease-free survival was 61%, but it was significantly better in myeloid (73%), than in lymphoid malignancies (41%). Thus, children with high-risk and advanced hematological malignancies and high-risk of life-threatening RRT can be transplanted effectively and safely using TREO-based regimens. Particularly favorable results were achieved in myeloid malignancies and in children undergoing second HSCT.
Pharmacokinetic studies of high-dose treosulfan were carried out in seven paediatric patients (age range: 2-15 years) undergoing treosulfan-based conditioning regimen prior to allogeneic ...haematopoietic SCT. Treosulfan was administered intravenously in a daily dose of 10, 12 or 14 g/m(2) within 2 h. Five out of seven patients received 12 g/m(2). The plasma concentrations of treosulfan and its quantity eliminated with urine were determined using a validated HPLC method with refractometric detection. Pharmacokinetic parameters were evaluated following first dose using a two-compartment disposition model. These studies demonstrated a dose-dependent increase of area under the concentration (AUC) and maximum concentrationplasma (C(max)), but there was variability of these parameters. Rapid clearance of tresoulfan was observed, especially in 10 and 12 g/m(2) doses. Terminal half-life (t(0.5)) of treosulfan was in the range of 1.71-2.15 h, but the mean percent of parent drug eliminated with urine was 30%, range 16.3-45.4% of the total dose eliminated during the first 12 h after administration. The results of this study confirmed the linear pharmacokinetics of treosulfan, as used in children. However, variability of pharmacokinetic results observed in children studied demonstrates the need for pharmacokinetic evaluation in each paediatric patient undergoing the treosulfan-based preparative regimen, including those using different doses. This approach could enable further reduction of the risk of early and late organ toxicity related to high-dose treosulfan in paediatric patients.
We analyzed incidence and profile of infections in children with acute lymphoblastic leukemia (ALL) treated with hematopoietic stem cell transplantation (HSCT) in Polish pediatric HSCT departments, ...over a 2-year period.
Hospital records of 67 patients, who underwent allogeneic HSCT for ALL, were analyzed retrospectively for microbiologically documented infection: bacterial infection (BI), viral infection (VI), and fungal infection (FI). The majority of patients (40/67; 59.7%) underwent HSCT from matched unrelated donors (MUD).
In total, 84 BI in 31 patients, 93 VI in 50 patients, and 27 FI in 22 patients were diagnosed. No differences were found in the frequency of occurrence of BI according to the type of transplant (P = .16); the occurrence of VI was statistically more frequent in MUD transplant recipients as compared with matched sibling donors (MSD) and mismatched related donors (MMFD; P = .001) and there was a trend in MUD patients for the higher occurrence of FI in comparison with MSD and MMFD transplants (P = .08). Regarding disease status, the occurrence of BI, VI, and FI was statistically more frequent in children who underwent transplantation in their first complete remission (CR1), rather than those who underwent transplantation in ≥CR2 (P < .05). In conclusion, infectious complications are an important cause of morbidity in children with ALL treated with allogeneic HSCT and the incidence of infections is high in this group of patients.
•We analyzed the incidence and profile of infections in children with ALL following HSCT.•No differences were found between the occurrence of BI and donor type.•Statistically there was a higher occurrence of VI in unrelated donor transplants.•There was a trend of higher occurrence of FI in unrelated donor transplants.•There was a more frequent occurrence of infectious complications in children who underwent transplantation in CR1.
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