The main aim of the Leucémies de l'Enfant et l'Adolescent (LEA) project (Childhood and Adolescent Leukaemia) is to study the determinants (medical, socioeconomic, behavioural and environmental) of ...medium- and long-term outcomes of patients treated for childhood acute leukaemia (AL). The LEA study began in 2004 and is based on a French multicentric prospective cohort. Included are children treated for AL since January 1980 (incident and prevalent cases), surviving at month 24 for myeloblastic AL and lymphoblastic AL grafted in first complete remission or at month 48 for lymphoblastic AL not grafted in first complete remission. Information is collected during specific medical visits and notably includes the following data: socioeconomic data, AL history, physical late effects (such as fertility, cardiac function and metabolic syndrome) and quality of life. Data are collected every 2 years until the patient is 20 years old and has had a 10-year follow-up duration from diagnosis or last relapse. Thereafter, assessments are planned every 4 years. In active centres in 2013, eligible patients number more than 3000. The cohort has already included 2385 survivors, with rate of exhaustiveness of almost 80%. Data access can be requested from principal coordinators and must be approved by the steering committee.
Corticosteroid can induce osteonecrosis in children with leukemia. Few studies have been designed to assess the influence of a wide range of cumulative steroid dose on this side effect. Prevalence, ...risk factors of symptomatic osteonecrosis and its impact on adults' Quality of Life were assessed in 943 patients enrolled in the French "Leucémies de l'Enfant et de l'Adolescent" (LEA) cohort of childhood leukemia survivors. During each medical visit, data on previous osteonecrosis diagnosis were retrospectively collected. Patients without a history but with suggestive symptoms were investigated with magnetic resonance imaging. The total steroid dose in equivalent of prednisone was calculated for each patient and its effect on osteonecrosis occurrence was studied in multivariate models. Cumulative incidence was 1.4% after chemotherapy alone versus 6.8% after transplantation (P<0.001). A higher cumulative steroid dose, age over ten years at diagnosis, and treatment with transplantation significantly increased the risk of osteonecrosis. A higher post-transplant steroid dose and age over ten years at time of transplantation were significant factors in the transplanted group. With patients grouped according to steroid dose quartile, cumulative incidence of osteonecrosis reached 3.8% in the chemotherapy group for a dose beyond 5835 mg/m(2) and 23.8% after transplantation for a post-transplant dose higher than 2055 mg/m(2). Mean physical composite score of Quality of Life was 44.3 in patients with osteonecrosis versus 54.8% in patients without (P<0.001). We conclude that total and post-transplant cumulative steroid dose may predict the risk of osteonecrosis, a rare late effect with a strong negative impact on physical domains of Quality of Life.
Background
Apheresis is a major challenge in peripheral stem cell collection from low‐weight children with cancer. Comparisons between the new apheresis device Optia (TerumoBCT) and the earlier COBE ...Spectra (CaridianBCT) have been performed in adults but not in low‐weight children. The objective was to compare the performance of these two devices in small children.
Study Design and Methods
In this retrospective study, all patients were reviewed weighing less than 15 kg undergoing stem cell collection using the Optia device between April 2011 and April 2012. They were paired on weight in a 3:1 ratio with patients whose cells had been collected with the COBE Spectra since 2006.
Results
Six patients were treated with the Optia and were matched with 18 patients treated with the Spectra. No side effects occurred. Collection efficiency (CE) was similar between the two groups (50% vs. 47%), but CD34 cell blood clearance was lower with the Optia (0.4 mL/min/kg vs. 0.6 mL/min/kg, p < 0.01). Platelet (PLT) loss and hemoglobin (Hb) loss were significantly reduced with the Optia (respectively, 32% vs. 54%, p < 0.01; and 1.4 g/dL vs. 2.9 g/dL, p < 0.01). Apheresis duration was increased with the Optia (159 min vs. 134 min, p < 0.05). The cell product harvested with the Optia had a lower volume and lower hematocrit, but similar white blood cell and PLT content.
Conclusion
Compared with the Spectra, the Optia allows similar CE with a reduced PLT and Hb loss but with a longer duration.
The prognosis of patients with relapses of ETV6/RUNX1-positive acute lymphoblastic leukemia remains to be evaluated, particularly with regards to the frequency of late relapses. We performed a ...long-term, follow-up retrospective study to address the outcome of patients with ETV6/RUNX1-positive leukemia relapses.
Among the 713 children tested for ETV6/RUNX1 enrolled into the FRALLE 93 protocol, 43 ETV6/RUNX1-positive patients relapsed (19.4%). Most were initially stratified in the low or intermediate risk groups. The median follow-up after relapse was 54.2 months. All but three received second-line salvage therapy and 16 underwent allogeneic transplantation.
ETV6/RUNX1 had a strong effect on overall survival after relapse (3-year survival= 64.7% for positive cases versus 46.5% for negative cases) (P=0.007). The 5-year cumulative incidence of relapse was 19.4% and testes were more frequently involved in ETV6/RUNX1-positive relapses (P=0.04). In 81.4% of cases the relapses were late, early combined or isolated extramedullary relapses. The 5-year survival rate of patients with ETV6-RUNX1-positive acute lymphoblastic leukemia relapses reached 80.8% when the relapse occurred after 36 months (versus 31.2% when the relapse occurred earlier). In univariate analysis, female gender was associated with a poor survival, whereas site of relapse, age at diagnosis, leukocytosis and consolidation strategy had no effect. In multivariate analysis, only the duration of first remission remained associated with outcome.
We found an excellent outcome for patients with ETV6/RUNX1-positive leukemia relapses that occurred more than 36 months after diagnosis. The duration of first complete remission may, therefore, be a guide to define the treatment strategy for patients with relapsed ETV6/RUNX1- positive leukemia.
Enteroviruses (EVs) are a major cause of aseptic meningitis, and RNA detection using molecular assay is the gold standard diagnostic test. The aim of this study was to assess the impact of an EV ...positive diagnosis on the clinical management of patients admitted for meningitis over the course of two observational study periods (2005 and 2008-09) in the same clinical departments. We further investigated in multivariate analysis various factors possibly associated with hospital length of stay (LOS) in all age groups (infants, children, and adults). The results showed an overall improvement in the management of patients (n = 142) between the study periods, resulting in a significantly shorter hospital LOS for adults and children, and a shorter duration of antibiotic use for adults and infants. In multivariate analysis, we observed that the time from molecular test results to discharge of patients and the median duration of antibiotic treatment were associated with an increase in LOS in all age groups. In addition, among adults, the turnaround time of the molecular assay was significantly correlated with LOS. The use of CT scan in children and hospital admission outside the peak of EV prevalence in infants tended to increase LOS. In conclusion, the shorter length of stay of patients with meningitis in this study was due to various factors including the rapidity of the EV molecular test (particularly in adults), greater physician responsiveness after a positive result (in adults and children), and greater experience on the part of physicians in handling EV meningitis, as evidenced by the shorter duration of antibiotic use in adults and infants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Graft versus host disease (GvHD) is the main complication after hematopoietic stem-cell transplantation.Extracorporeal photochemotherapy (ECP) is a cell therapy currently used for the treatment of ...T-cell–mediated diseases and seems as a valuable second-line therapy for patients suffering from steroid-refractory acute or chronic GvHD. ECP induces the apoptosis of treated cells and is believed to elicit a specific immune regulation of alloreactive T cells through repeated apoptotic T-cell infusions. However, its mechanisms of action have not yet been elucidated. In GvHD,alloreactive but not non alloreactive T cells are continuously activated by their environment. We hypothesized that ECP has a differential apoptotic effect on activated compared with resting T cells.
The ECP-induced apoptosis of resting and activated T cells from patients with chronic GvHD was assessed.The kinetic of apoptosis was also evaluated using several triggers of T-cell activation such as mitogenic or antigen specific activation. The influence of survival cytokines (interleukin-2, -7, and -15) was also evaluated.
Activated T cells from patients with chronic GvHD underwent apoptosis faster than resting T cells. This phenomenon was confirmed using mitogenic and antigen-specific activated T cells from healthy donors and cannot be delayed by protective cytokines.
ECP induces a faster apoptosis of alloreactive activated T cells than of non alloreactive resting T cells in GvHD and more generally of activated T cells than of resting T cells. These novel findings provide new insights about the ECP-induced specific control of pathogenic T cells in GvHD.
Better understanding of the antitumor effect of allogeneic transplant and the need to reduce the toxicity of the procedure, particularly in elderly patients have spurred the development of ...reduced-intensity conditioning regimens (RIC). These regimens allow fast engraftment with very low chemotherapy-induced toxicity. They are widely used in adults and there are numerous studies to demonstrate their feasibility and efficiency, but in pediatrics, the place of RIC remains to be determined. They can be proposed in two pediatric populations. First, solid tumors or hematological malignancies remaining unresponsive to the reference strategies according to best practices in pediatrics. Second, in children presenting malignancies for which allografting is the only recognized curative indication but is contraindicated with myeloablative conditioning regimens. More than 100 pediatrics cases have been reported in various pathologies, including blood diseases, acute leukemia, Hodgkin's lymphoma and solid tumors, and promising results published recently underline how RIC warrants further investigation in prospective comparative multicentric trials. The use of new post-graft treatment modalities is expected to pave the way to the development of RIC in pediatric patients.
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