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Background: To investigate the educational outcomes of siblings of childhood leukemia survivors, explore determinants of school difficulties, and compare the rates of repeating grades between siblings and the general population. Methods: A cross‐sectional study of childhood leukemia survivors' siblings recruited through the Leucémies de l'Enfant et de l'Adolescent cohort, a French long‐term follow‐up program, was conducted, and education‐related data were obtained via self‐report questionnaires. Adjusted logistic regression models were used to identify variables associated with school difficulties and time since diagnosis. Rates of repeating a grade in middle school were compared between siblings and the general population of the same generation. Results: A total of 564 siblings with a mean time from diagnosis of 14.1 ± 6.4 years were included, among whom 139 (24.6%) repeated a grade, at an average of 6.4 ± 4.5 years after diagnosis. In multivariate analysis, the risk factors for repeating a grade were older siblings (odds ratio [OR] 2.3, p = 0.006), family financial difficulties (OR 2.8, p = 0.008), and history of repetition in survivors (OR, 2.5, p = 0.001). Sibling hematopoietic stem cell donors were at greater risk of repeating a grade long‐term after diagnosis (p = 0.018). Overall, siblings did not have a higher risk of educational delays at the end of middle school than the general population. Conclusion: Although the results are reassuring, socioeconomic and cancer‐related factors may have an impact on siblings' schooling long after diagnosis. Paying attention to siblings contributes to identifying the most vulnerable families, allowing more attention and appropriate resources to avoid long‐term repercussions. Additionally, supportive and targeted interventions can be developed to improve the organization of education and the health care system. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer confront the whole family with a traumatic event. Because brothers and sisters may encounter emotional problems that can remain for a long time and that only few studies have assessed their long‐term outcome, our present objectives were to describe the long‐term quality of life (QoL) of childhood leukemia survivors' siblings and to explore its determinant. Methods: Brothers and sisters (from 8‐year‐old) of survivors included in the French LEA Cohort completed a QoL questionnaire (according to their age). Scores were compared with those reported by age‐ and gender‐matched French general population and by survivors. Using a clustering method, siblings were categorized into 3 groups depending on their level of QoL's scores and factors likely to be linked with these clusters were explored with multivariate analyses. Results: We included 689 brothers and sisters (313 minors, 376 adults) and the mean time from diagnosis was 13.2 ± 6.6 years. Minor siblings reported higher QoL scores than general population (p < 0.001), but a lower score for relationship with family than survivors (p < 0.001). In adult siblings, Mental Component Summary score was lower than general population (p < 0.001). Level of siblings' QoL was linked with female gender, but no association was found with cancer‐related factors. Conclusion: Brothers and sisters expressed a divergent perception of their long‐term QoL depending on their age. To minimize the impact from childhood to adulthood, long‐term attention should also be paid to siblings, often referred as "forgotten children". [ABSTRACT FROM AUTHOR]

Summary: Childhood chronic immune thrombocytopenic purpura (cITP) is a rare disease. In severe cases, there is no evidence for the optimal therapeutic strategy. Our aim was to describe the real‐life management of non‐selected children with cITP at diagnosis. Since 2004, patients less than 18 years old with cITP have been enrolled in the national prospective cohort, OBS'CEREVANCE. From 1990 to 2014, in 29 centres, 392 children were diagnosed with cITP. With a median follow‐up of six years (2·0–25), 45% did not need second‐line therapy, and 55% (n = 217) received one or more second lines, mainly splenectomy (n = 108), hydroxychloroquine (n = 61), rituximab (n = 61) or azathioprine (n = 40). The overall five‐year further second‐line treatment‐free survival was 56% [95% CI 49·5–64.1]. The use of splenectomy significantly decreased over time. Hydroxychloroquine was administered to children with positive antinuclear antibodies, more frequently older and girls, and reached 55% efficacy. None of the patients died. Ten years after the initial diagnosis, 55% of the 56 followed children had achieved complete remission. Children with cITP do not need second‐line treatments in 45% of cases. Basing the treatment decision on the pathophysiological pathways is challenging, as illustrated by ITP patients with positive antinuclear antibodies treated with hydroxychloroquine. [ABSTRACT FROM AUTHOR]

Background: Efforts to improve the quality of end-of-life (EOL) care depend on better knowledge of the care that children, adolescents, and young adults with cancer receive, including high-intensity EOL (HI-EOL) care. The objective was to assess the rates of HI-EOL care in this population and to determine patient- and hospital-related predictors of HI-EOL from the French national hospital database.Methods: This was a population-based, retrospective study of a cohort of patients aged 0 to 25 years at the time of death who died at hospital as a result of cancer in France between 2014 and 2016. The primary outcome was HI-EOL care, defined as the occurrence of ≥1 chemotherapy session <14 days from death, receiving care in an intensive care unit ≥1 time, >1 emergency room admission, and >1 hospitalization in an acute care unit in the last 30 days of life.Results: The study included 1899 individuals from 345 hospitals; 61.4% experienced HI-EOL care. HI-EOL was increased with social disadvantage (adjusted odds ratio [AOR], 1.30; 95% confidence interval [CI], 1.03-1.65; P = .028), hematological malignancies (AOR, 2.09; 95% CI, 1.57-2.77; P < .001), complex chronic conditions (AOR, 1.60; 95% CI, 1.23-2.09; P = .001) and care delivered in a specialty center (AOR, 1.70; 95% CI, 1.22-2.36; P = .001). HI-EOL was reduced in cases of palliative care (AOR, 0.31; 95% CI, 0.24-0.41; P < .001).Conclusion: A majority of children, adolescents, and young adults experience HI-EOL care. Several features (eg, social disadvantage, cancer diagnosis, complex chronic conditions, and specialty center care) were associated with HI-EOL care. These findings should now be discussed with patients, families, and professionals to define the optimal EOL. [ABSTRACT FROM AUTHOR]

Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML) and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a diagnostic challenge because this distinction has a major incidence on the management of patients. Here, we report an uncommon pediatric case of ALL with cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement on blood neutrophils, which was positive consistent with the diagnosis of lymphoid blast crisis of CML. This case illustrates the major interest of interphase FISH for BCR-ABL1 rearrangement on blood neutrophils as a decisive method to discriminate a lymphoid blast crisis of CML from a de novo BCR-ABL1 positive ALL. [ABSTRACT FROM AUTHOR]

ETV6 is a target of recurrent aberrations in sporadic and familial acute lymphoblastic leukemia ( ALL). Here, we report on a new pedigree with a germline ETV6 mutation in which the index patient and his father developed high hyperdiploid (HeH) ALL and polycythemia vera at age 13 and 51, respectively. The index patient achieved durable complete remission without transplantation but had persistent moderate thrombocytopenia without bleeding tendency. To determine the prevalence of ETV6 alterations in HeH- ALL, we screened 81 unrelated subjects with HeH- ALL by single nucleotide polymorphism array and high-throughput sequencing for the ETV6 gene. Overall, ETV6 microdeletions and mutations were identified in 9% of cases, all of which were somatic and considered as secondary events. Apart from the index patient, no germline ETV6 aberration was identified. Finally, we reviewed the literature for ETV6 germline aberrations and predispositions to ALL. [ABSTRACT FROM AUTHOR]

The early persistence of minimal residual disease (MRD) is considered a poor prognostic factor indicative of chemoresistance in acute lymphoblastic leukemia. In French children, chemosensitivity is assessed at day 21 post-induction by cytomorphology. Here, it was investigated whether a more precise evaluation could be obtained at this time point with multiparameter flow cytometry (MFC). This study enrolled 123 children with de novo acute lymphoblastic leukemia. MRD0 was investigated at day 21 in MFC with a combination of antibodies based on the immunophenotype of diagnosis. It was also evaluated at day 35 by immunoglobulin/T-cell receptor quantitative real-time polymerase chain reaction (MRD1). Three risk groups could be delineated based on MRD0. Patients with MFC/MRD0 levels >10-2 (n = 25) were considered high risk, those with levels between 10-2 and 10-4 (n = 46) intermediate risk, and those <10-4 (n = 50) low risk. Overall survival (p = 0.048) and event-free survival (EFS, p = 0.00017) were significantly different between these three groups. EFS of the 14 corticoresistant patients strongly depended on their MRD0 level (p = 0.004). Similarly, both EFS (p = 0.0004) and overall survival (p = 0.02) were significantly different in the 109 chemosensitive patients, according to MRD0 levels. MRD0 and MRD1 levels, compared with 112 patients, were consistent (-/- or +/+) in 57.2% of the cases. Both MRD0+/MRD1+ and MRD0+/MRD1- patients had a significantly worse EFS (p = 0.0001) than those with undetectable MRD at both MRD0 and MRD1. This study confirms the usefulness and superiority of an early point of MRD detection by MFC. In addition, MRD0 in MFC identifies a subgroup of patients with poorer prognosis (MRD0+/MRD1-). Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Patients with Langerhans cell histiocytosis ( LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarabine; the other approach is allogeneic haematopoietic stem cell transplantation ( HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990 and 2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning ( MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality ( TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning ( RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, P = 0·02), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain. [ABSTRACT FROM AUTHOR]

Objective The objectives of this study are to assess the quality of life (QoL) of siblings of childhood leukemia survivors in comparison with population controls and to identify determinants of sibling's QoL. Methods The nearest-aged siblings (8-17 years) of minor CLS participating in the French LEA cohort (Childhood and Adolescent Leukemia), at the Marseilles center, were included. Siblings' QoL was self-reported using the 'Vécu et Santé Perçue de l'Adolescent et l'enfant' questionnaire. Results were compared with those obtained for age-matched and sex-matched French controls subjects. Characteristics likely to be associated with siblings' QoL (sibling's and survivor's sociodemographic and health-related and cancer-related characteristics) were explored through multivariate analysis. Results Fifty-one siblings participated (mean age 12.7 ± 2.8 years, mean follow-up duration from diagnosis to evaluation 8.8 ± 2.5 years). They reported a significantly higher perception of QoL compared with the general population regarding psychological domains, while reporting a lower perception regarding social domains. In multivariate analysis, older age at diagnosis for both siblings and survivors was risk factor for impaired psychological QoL. An elevated leukemia burden index was linked with lower scores in self-esteem dimension, whereas having at least one sequelae for the survivor was linked with better scores in psychological well-being dimension. Low or middle affluence and older sibling's age at diagnosis were risk factors for impaired social QoL. Maximal R2 was 30%. Conclusions Minor siblings of CLS reported a relatively good QoL, particularly in psychological domains. Given the low proportion of QoL variability explained, other contributing factors (e.g., family functioning) must be explored. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia ( ALL). Here, we report the findings of a prospective national study designed to investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease ( MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days −30, 30, 90 and 150 post-transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions ( DLI) were programmed for patients with a pre- or post-transplant MRD status ≥10−3. Only nine patients received DLI. Pre- and post-transplant MRD status, and the duration of ciclosporin were independently associated with 5-year overall survival ( OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre-transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment ( P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post-transplantation was a valuable prognostic tool to guide therapeutic intervention. [ABSTRACT FROM AUTHOR]

Cataract was prospectively assessed by serial slip lamp tests in 271 patients included in the Leucémie Enfants Adolescents ( LEA) programme, the French cohort of childhood leukaemia survivors. All had received haematopoietic stem cell transplantation ( HSCT) after total body irradiation ( TBI, n = 201) or busulfan-based ( n = 70) myeloablative conditioning regimen. TBI was fractionated in all but six patients. The mean duration of follow-up from HSCT was 10·3 years. Cataract was observed in 113/271 patients (41·7%); 9/113 (8·1%) needed surgery. Cumulative incidence after TBI increased over time from 30% at 5 years to 70·8% and 78% at 15 and 20 years, respectively, without any plateau thereafter. The 15-year cumulative incidence was 12·5% in the Busulfan group. A higher cumulative steroid dose appeared to be a cofactor of TBI for cataract risk, in both univariate and multivariate Cox analysis. In the multivariate analysis, cataract had an impact in two quality of life domains: 'the role limitation due to physical problems' and 'the role limitation due to emotional problems'. These data suggest that with increasing follow-up, nearly all patients who receive TBI, even when fractionated, will suffer from cataract that can impact on their quality of life and that high cumulative steroid dose is a cofactor. [ABSTRACT FROM AUTHOR]

This study aimed to describe kinetics of complete donor chimerism occurrence ( cDC, >99·9% donor) after unrelated cord blood transplantation ( UCBT), to identify its predictive factors and its impact on post-transplant outcome. Ninety-four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post-transplant dates, using a real-time polymerase chain reaction method with 0·1% sensitivity. Cumulative incidence of cDC at 1 year post-transplantation was 61·8%. Three predictive factors were identified in multivariate analysis: history of malignant disease ( P = 0·03), older age (above 2·16 years, the first quartile of age, P = 0·0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5-6/6, P < 0·001) increased the probability of post-transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99·9% donor chimerism on days 15-30 post-transplant) appeared useful to predict engraftment ( P = 0·003) as well as acute and chronic graft-versus-host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ≤99·9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT. [ABSTRACT FROM AUTHOR]

Minimal residual disease ( MRD) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia ( ALL). Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse. Between 2005 and 2008, we conducted a prospective study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non- ex vivo T depleted myeloablative transplantation. Immunoglobulin (Ig)H/T-cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high-risk paediatric ALL enrolled. There were no significant demographic differences except remission status (first or second complete remission) between the 95 children with MRD <10−3 and the 27 with MRD ≥10−3. Multivariate analysis identified sex match and MRD as being significantly associated with 5-year survival. MRD ≥10−3 compromised the 5-year cumulative incidence of relapse (43·6 vs. 16·7%). Complete remission status and stem cell source did not modify the relationship between MRD and prognosis. Thus, pre-transplant MRD is still a major predictor of outcome for ALL. The MRD-guided strategy resulted in survival for 72·3% of patients with MRD<10−3 and 40·4% of those with MRD ≥10−3. [ABSTRACT FROM AUTHOR]

Corticosteroid and central nervous system ( CNS) irradiation can induce cataract in childhood lymphoblastic leukaemia survivors. Few prospective studies with systematic ophthalmological evaluation have been published. Cataract was prospectively assessed by serial slip lamp tests in 517 patients. All had acute lymphoblastic leukaemia, all had been treated by chemotherapy with or without CNS irradiation, and none had received haematopoietic stem cell transplantation. Median ages at last evaluation and follow-up duration from leukaemia diagnosis were 16·8 and 10·9 years, respectively. Cataract was observed in 21/517 patients (4·1%). Cumulative incidence was 4·5 ± 1·2% at 15 years and reached 26 ± 8·1% at 25 years. CNS irradiation was the only risk factor: prevalence was 11·1% in patients who had received irradiation and 2·8% in those who did not. We did not detect any steroid dose effect: cumulative dose was 5133 and 5190 mg/m2 in patients with and without cataract, respectively. Cataract occurrence did not significantly impact quality of life. We conclude that, in the range of steroid dose reported here, the cataract risk proves very low 15 years after treatment without CNS irradiation but an even more prolonged follow-up is required because of potential very late occurrence. [ABSTRACT FROM AUTHOR]

There is little data available regarding children and adolescents with Hodgkin lymphoma (HL) who relapse after combined-modality treatment, even though they have a substantial chance of cure. The purpose of this national retrospective study was to evaluate the outcome of patients with recurrent/refractory HL and determine adverse prognostic factors. From 1990 to 2006, 70 patients (median age 13·9 years) with refractory ( n = 31) or first relapse ( n = 39) HL were identified. Median time from end of treatment to relapse was 6 months (3-56). Relapses occurred in irradiated areas in 43/70 patients. Salvage therapy consisted of chemotherapy and 50 patients received high-dose chemotherapy with autologous stem cell transplantation. Radiotherapy was performed in 29 cases, tandem autologous transplantation in five and allograft in three. With a median follow-up of 40 months (2-140), significant prognostic factors were time to progression/relapse and response to therapy before autograft. Event-free survival and overall survival in patients with refractory disease, early relapse and late relapse were 35 ± 9%, 67 ± 11%, 76 ± 10% and 48 ± 11%, 89 ± 7% and 80 ± 10%, respectively. As progression <3 months was a major adverse prognostic factor, novel therapeutic approaches are needed for this group of patients. By contrast, patients have substantial chance of long term second remission in case of relapse >3 months. [ABSTRACT FROM AUTHOR]

Since several years, the use of intravenous immunoglobulins (IVIg) has increased. This growth has encouraged some countries to publish guidelines. In parallel, some countries have conducted audits to know how IVIg are used in clinical practice in the light of the available guidelines. The objective of this study was to assess IVIg use in three French university hospitals in 2006. All IVIg administrations were evaluated during 6 months (12 September 2005-12 March 2006) in French university hospitals of Marseille. Different data were recorded for each administration: patient characteristics, indication, formulation and quantity. During the study period, 2802 administrations of IVIg (corresponding to a total quantity of 76 780 g) have been recorded. Four hundred and thirty-five patients received at least one of these administrations. The five most reported indications were multifocal motor neuropathy (11.0% of total quantity), chronic inflammatory demyelinating polyradiculoneuropathy (10.2%), corticoresistant dermatomyositis (10.2%), immune thrombocytopaenia (9.9%) and primary immune deficiency (9.1%). According to available French recommendations, 70% of the IVIg use was for 'acknowledged indications', 9% for 'indications to be assessed' and 18% for 'unwarranted indications'. The 10 most reported indications were 'acknowledged indications' according to available recommendations of the French expert group. Nevertheless, the two most reported indications were not approved by the French Health Products Agency (AFSSAPS) at the time of the study and were approved since. [ABSTRACT FROM AUTHOR]

The study investigated the role of factors considered related to the early stimulation of the immune system in the aetiology of childhood lymphoma. The national registry-based case-control study, Escale, was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. Data from 128 cases of Hodgkin's lymphoma (HL) aged 5-14 years, 164 cases of non-Hodgkin's lymphoma (NHL) aged 2-14 years and 1,312 controls were analyzed. Negative associations were observed between HL and day care attendance [OR = 0.5 (0.2-1.2)] and between HL and repeated early common infections among non-breastfed children [OR = 0.3 (.2-0.7), p = 0.003] [OR for breastfed children: 1.0 (.5-2.1)], but not for the other factors investigated. Negative associations were observed between NHL and birth order 3 or more [OR = 0.7 (0.4-1.1)], prolonged breastfeeding [OR = 0.5 (0.3-1.0)], regular contact with farm animals [OR = 0.5 (0.3-1.0)], frequent farm visits in early life [OR = 0.6 (0.4-1.1)] and history of asthma [OR = 0.6 (0.3-1.1)]. In conclusion, the results partly support the hypothesis that an abnormal maturation of the immune system may play a role in childhood HL or NHL, and call for further investigations. [ABSTRACT FROM AUTHOR]

We report the post-transplant lymphocyte subset recovery of 226 children treated with Unrelated Cord Blood transplant (UCBT) ( n = 112) or Unrelated Bone Marrow Transplant (UBMT) ( n = 114) for malignant or non-malignant diseases. Absolute numbers of natural killer (NK), B and T cells were monitored by flow cytometry up to 5 years post-transplant. Immunological endpoints were: time to achieve a CD3 cell count >0·5 and 1·5 × 10/l, CD4 > 0·2 and 0·5 × 10/l, CD8 > 0·25 × 10/l, CD19 > 0·2 × 10/l, NK > 0·1 × 10/l. These endpoints were analysed through the use of cumulative incidence curves in the context of competing risks. CD8 T cell recovery was delayed after UCBT with a median time to reach CD8 T cells > 0·25 × 10/l of 7·7 months whereas it was 2·8 months in UBMT ( P < 0·001). B cell recovery was better in UCBT, with a median time to reach CD19 cells > 0·2 × 10/l of 3·2 months in UCBT and 6·4 months in UBMT ( P = 0·03). Median time for CD4 T cell and NK cell recovery was similar in UCBT and UBMT. CD4 T cells recovery was negatively correlated to age (better reconstitution in younger patients, P = 0·002). CD8 T cells recovery was shorter in recipients with a positive cytomegalovirus serology ( P = 0·001). [ABSTRACT FROM AUTHOR]

Summary Gram-negative bacteria have evolved several types of secretion mechanisms to release proteins into the extracellular medium. One such mechanism, the type II secretory system, is a widely conserved two-step process. The first step is the translocation of signal peptide-bearing exoproteins across the inner membrane. The second step, the translocation across the outer membrane, involves the type II secretory apparatus or secreton. The secretons are made up of 12–15 proteins (Gsp) depending on the organism. Even though the systems are conserved, hetero-logous secretion is mostly species restricted. Moreover, components of the secreton are not systematically exchangeable, especially with distantly related microorganisms. In closely related species, two components, the GspC and GspD (secretin) family members, confer specificity for substrate recognition and/or secreton assembly. We used Pseudomonas aeruginosa as a model organism to determine which domains of XcpP (GspC member) are involved in specificity. By constructing hybrids between XcpP and OutC, the Erwinia chrysanthemi homologue, we identified a region of 35 residues that was not exchangeable. We showed that this region might influence the stability of the XcpYZ secreton subcomplex. Remarkably, XcpP and OutC have domains, coiled-coil and PDZ, respectively, which exhibit the same function but that are structurally different. Those two domains are exchangeable and we provided evidence that they are involved in the formation of homomultimeric complexes of XcpP. [ABSTRACT FROM AUTHOR]

The xcp gene products in Pseudomonas aeruginosa are required for the secretion of proteins across the outer membrane. Four of the Xcp proteins, XcpT, U, V and W, present sequence homology to the subunits of type IV pili at their N-termini, and they were therefore designated pseudopilins. In this study, we characterized the xcpX gene product, a bitopic cytoplasmic membrane protein. Remarkably, amino acid sequence comparisons also suggested that the XcpX protein resembles the pilins and pseudopilins at the N-terminus. We show that XcpX could be processed by the prepilin peptidase, PilD/XcpA, and that the highly conserved glycine residue preceding the hydrophobic segment could not be mutated without loss of the XcpX function. We, therefore, classified XcpX (GspK) as the fifth pseudopilin of the system. [ABSTRACT FROM AUTHOR]

We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subsequent complete remission (CR) underwent allogeneic bone marrow transplantation from HLA-identical siblings after a preparative regimen comprising total body irradiation (TBI), high-dose cytosine arabinoside and melphalan (TAM regimen). The Kaplan-Meier product-limit estimate (mean ± SE) of disease-free survival (DFS) at 7 years was 59.5 ± 9% (95% confidence interval). The estimated chance of relapse was 22.5 ± 15% with a median follow-up of 88.5 months (range 51–132). 26 patients (22.4%) died with no evidence of recurrent leukaemia, mainly from interstitial pneumonitis, veno-occlusive disease or acute graft-versus-host disease (GVHD). Three factors significantly affected DFS: acute GVHD, site of relapse and, for children in second remission after a marrow relapse, the disease status at the time of transplantation. The DFS were 59.02 ± 12.6%, 37.5 ± 19.8% and 77.4 ± 15% among patients in CR2 after a marrow relapse, in CR3 or in untreated partial marrow relapse, and in CR2 after an isolated CNS relapse, respectively. The lowest DFS was seen in children with acute GVHD grades 3–4. Two significant factors were associated with relapse: the marrow status at the time of transplantation and chronic GVHD. The relapse rate was lower among children in CR2 or with chronic GVHD. We conclude that transplantation after the TAM regimen is an effective therapy for this population with acceptable toxicity, particularly for children in second remission after a very early marrow relapse, or those with early isolated CNS involvement. [ABSTRACT FROM AUTHOR]

The article focuses on a 16-month-old male, born to consanguineous Algerian parents, who were presented with pallor, asthenia, anorexia, mild diarrhoea and vomiting.

The article discusses a medical case of a 6-week-old infant girl with early morphological diagnosis of Farber disease or Farber lipogranulomatosis, an inherited metabolic disorder. Topics discussed include the medical history of the patient and diagnosis to be considered when associated with inappropriate activation of macrophages.