Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes.

Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M- group). The M+ group displayed more severe disease than the M- group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.

Access of non-residents to transplantation of deceased donor organs: practices and strategies in the European setting.

The access of non-resident patients to the deceased donor waiting list (DDWL) poses different challenges. The European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) has studied this phenomenon in the European setting. A questionnaire was circulated among the Council of Europe member states to inquire about the criteria applied for non-residents to access their DDWL. Information was compiled from 28 countries. Less than 1% of recipients of deceased donor organs were non-residents. Two countries never allow non-residents to access the DDWL, four allow access without restrictions and 22 only under specific conditions. Of those, most give access to non-resident patients already in their jurisdictions who are in a situation of vulnerability (urgent life-threatening conditions). In addition, patients may be given access: (i) after assessment by a specific committee (four countries); (ii) within the framework of official cooperation agreements (15 countries); and (iii) after patients have officially lived in the country for a minimum length of time (eight countries). The ethical and legal implications of these policies are discussed. Countries should collect accurate information about residency status of waitlisted patients. Transparent criteria for the access of non-residents to DDWL should be clearly defined at national level.

Neurological Involvement in Childhood Evans Syndrome.

PURPOSE: Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are associated in the definition of Evans syndrome (ES). The occurrence of neurological involvement in this population is poorly described and suggests an underlying primary immunodeficiency (PID). We aimed to describe the clinical manifestations, evolution, and PID profiles of these patients. METHODS: OBS'CEREVANCE is a French, nationwide prospective cohort that includes children with chronic ITP, AIHA, and ES. Patients with a neurological involvement were described. Centralized radiological and pathological reviews and genetic analyses were performed. RESULTS: On October 2016, eight patients (7/181 ES, 1/371 AIHA, and 0/615 ITP) were identified, all male, with a median age (range) at cytopenia onset of 11.5 years (1.6-15.8). Neurological symptoms appeared with a median delay of 6 years (2.5-18) after cytopenia and were polymorphic: seizures (n = 4), cranial nerve palsy (n = 2), Brown-Sequard syndrome (n = 2), intracranial pressure (n = 2), vertigo (n = 1), and/or sensory neuropathy (n = 1). Magnetic resonance imaging (MRI) showed inflammatory lesions, confirmed by pathology for five patients with macrophagic or lymphoplasmocytic infiltrates. All patients had other relevant immunopathological manifestations: pulmonary nodules (n = 6), lymphoproliferation (n = 4), abnormal immunophenotype (n = 8), and hypogammaglobulinemia (n = 7). Treatment consisted of steroids that improved symptomatology and MRI. Five patients relapsed and three had an asymptomatic radiological progression. A PID was identified in 3/8 patients: 22q11.2 microdeletion (n = 1) and CTLA deficiency (n = 2). CONCLUSION: Neurological involvement is a rare and severe late event in the course of childhood ES, which can reveal an underlying PID. Imaging and pathology examination highlight a causative immune dysregulation that may guide targeted therapeutic strategies.

Benefits of rituximab as a second-line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study.

Childhood autoimmune haemolytic anaemia (AIHA) requires second-line immunosuppressive therapy in 30-50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES). Sixty-one children were given rituximab between 2000 and 2014. The median interval from diagnosis to rituximab was 9·9 [interquartile range (IQR) 1·6-28·5] months. Forty-six patients responded (75%) and the 6-year relapse-free survival (RFS) was 48%. Twenty patients relapsed at a median interval of 10·8 (IQR 3·9-18·7) months, rituximab allowed steroid withdrawal in 44/61 (72%) of children. In isolated AIHA, complete response and 6-year RFS were significantly higher than in ES (P < 0·05). Ten out of 61 patients were infants, seven of who responded with a 6-year RFS of 71%. Among patients without immunoglobulin substitution before rituximab, 4 are still receiving substitutions. Five patients died, including one potentially attributable to rituximab. This large observational series of childhood AIHA established the rituximab benefit-risk ratio, allowing steroid withdrawal, with 37% of long-term responders, mainly in isolated AIHA. All subgroups of patients drew benefit. Our long-term results indicate the baseline to be challenged by new treatment approaches.

Non syndromic childhood onset congenital sideroblastic anemia: A report of 13 patients identified with an ALAS2 or SLC25A38 mutation.

The most frequent germline mutations responsible for non syndromic congenital sideroblastic anemia are identified in ALAS2 and SLC25A38 genes. Iron overload is a key issue and optimal chelation therapy should be used to limit its adverse effects on the development of children. Our multicentre retrospective descriptive study compared the strategies for diagnosis and management of congenital sideroblastic anemia during the follow-up of six patients with an ALAS2 mutation and seven patients with an SLC25A38 mutation. We described in depth the clinical, biological and radiological phenotype of these patients at diagnosis and during follow-up and highlighted our results with a review of available evidence and data on the management strategies for congenital sideroblastic anemia. This report confirms the considerable variability in manifestations among patients with ALAS2 or SLC25A38 mutations and draws attention to differences in the assessment and the monitoring of iron overload and its complications. The use of an international registry would certainly help defining recommendations for the management of these rare disorders to improve patient outcome.

Impact of shared care program in follow-up of childhood cancer survivors: An intervention study.

BACKGROUND: With the growing rate of childhood cancer cure and the risks of sequelae, long-term follow-up (FU) of survivors is a central issue. Several models have been proven far from satisfactory. Shared care FU is the result of collaboration between general practitioners (GPs) and cancer centers. We sought to demonstrate the feasibility of setting up a shared care program based on the patient-centered education of GPs and to evaluate the impact of this model in an intervention study. METHODS: We compared the FU care achievement in two childhood cancer survivor cohorts in the same pediatric oncology center, (i) control group (n = 134) and (ii) intervention study cohort (n = 137), after setting up the program. RESULTS: The rate of survivors answering the survey and the rate of patients involved in FU by their GPs were higher in intervention study cohort than in baseline one (132/137 vs. 72/134 and 110/132 vs. 13/72; P ≤ 0.0001). The lack of any FU was definitely lower (10/132 vs. 18/72; P = 0.001) in the intervention study cohort. CONCLUSION: In this shared care program, survivors overcame distrust in their GP's knowledge and entered the FU program after their GPs had been involved in patient-centered education. Personalized and incentive-based guidance was very useful in helping survivors to adhere to FU. Support of a dedicated long-term FU team was very useful. A nationwide organization, consideration of special needs in subgroups of survivors and sustained funding are needed to adjust the program in the very long term.

Childhood immune thrombocytopenia: A nationwide cohort study on condition management and outcomes.

OBJECTIVES: Nationwide prospective cohort study exploring (i) the factors associated with treatment initiation (vs. watchful waiting) in children with primary immune thrombocytopenia (ITP) followed in routine clinical practice and (ii) the predictors of chronicity at 12 months. PROCEDURE: Between 2008 and 2013, 23 centers throughout France consecutively included 257 children aged 6 months-18 years and diagnosed with primary ITP over a 5-year period. Data on ITP clinical features along with medical management were collected at baseline and 12 months. Multivariate logistic regressions were used to determine (i) and (ii) as defined above, providing odds ratio (OR) with 95% confidence interval (95% CI). RESULTS: One hundred thirty-seven (53%) children were males, median age was 4.6 years, median platelet count was 7 × 109/l, and 214 (81%) patients initiated medication. Factors independently associated with treatment initiation included platelet counts <10 × 109/l (P < 0.0001) and mucocutaneous bleeding symptoms at baseline (P < 0.001). At 12 months, data were available for 211 (82%) children, of whom 160 (74%) had recovered. Predictors of chronicity included female gender (OR = 2.2; 95% CI = 1.0-4.8), age ≥10 years (OR = 2.6; 95% CI = 1.1-6.0), and platelet counts ≥10 × 109 /l (OR = 3.2; 95% CI = 1.5-6.9). CONCLUSIONS: In routine clinical practice, the decision to apply a watchful waiting strategy seems to be driven by platelet counts even in the absence of bleeding symptoms, resulting in treatment being initiated in more than 80% of the children surveyed. Overall, younger children with ITP showed good prognosis, with lower platelet counts and, to a lesser extent, male gender predicting more favorable outcomes.

Reliable assessment of the incidence of childhood autoimmune hemolytic anemia.

BACKGROUND: Childhood autoimmune hemolytic anemia (AIHA) is a rare and severe disease characterized by hemolysis and positive direct antiglobulin test (DAT). Few epidemiologic indicators are available for the pediatric population. The objective of our study was to reliably estimate the number of AIHA cases in the French Aquitaine region and the incidence of AIHA in patients under 18 years old. PROCEDURE: In this retrospective study, the capture-recapture method and log-linear model were used for the period 2000-2008 in the Aquitaine region from the following three data sources for the diagnosis of AIHA: the OBS'CEREVANCE database cohort, positive DAT collected from the regional blood bank database, and the French medico-economic information system. RESULTS: A list of 281 different patients was obtained after cross-matching the three databases; 44 AIHA cases were identified in the period 2000-2008; and the total number of cases was estimated to be 48 (95% confidence interval [CI]: 45-55). The calculated incidence of the disease was 0.81/100,000 children under 18 years old per year (95% CI 0.76-0.92). CONCLUSION: Accurate methods are required for estimating the incidence of AIHA in children. Capture-recapture analysis corrects underreporting and provides optimal completeness. This study highlights a possible under diagnosis of this potentially severe disease in various pediatric settings. AIHA incidence may now be compared with the incidences of other hematological diseases and used for clinical or research purposes.

Paediatric anaplastic large cell lymphoma with leukaemic presentation in children: a report of nine French cases.

This study aimed to describe the clinical features and outcome of anaplastic large cell lymphoma (ALCL) with leukaemic presentation in children. Among 267 patients included in the French paediatric ALCL database between 1989 and 2012, nine (3%) were described as having cytologically detectable circulating tumour cells. Clinical features combined fever (8/9), nodal and extra-nodal disease (9/9), including hepato-splenic (9/9) and lung involvement (7/9). The level of hyperleucocytosis ranged from 30 to 120 × 10(9) /l, with 12-90% of tumour cells. Diagnosis relied on a lymph node biopsy, with a positive ALK+ antibody immunostain in all nine cases, a T-cell immunophenotype in 7/9 cases and CD3 positivity in 5/9 cases. A small cell component was present in 6/9 cases. Only four patients achieved a complete remission with first-line therapy and 3/4 relapsed. Four patients are alive with a median follow-up of 31 months, two of them after allogeneic haematopoietic stem cell transplantation (HSCT), and five patients died, two of them of disease. In conclusion, ALCL with leukaemic presentation is very unusual and should be considered as high-risk lymphoma requiring new therapeutic strategies. The respective role of new agents and allogeneic HSCT in first complete remission still has to be assessed.

Outcome of children and adolescents with recurrent/refractory classical Hodgkin lymphoma, a study from the Société Française de Lutte contre le Cancer des Enfants et des Adolescents (SFCE).

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.

Excellent prognosis of late relapses of ETV6/RUNX1-positive childhood acute lymphoblastic leukemia: lessons from the FRALLE 93 protocol.

BACKGROUND: 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. DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A dose-intensive approach (NB96) for induction therapy utilizing sequential high-dose chemotherapy and stem cell rescue in high-risk neuroblastoma in children over 1 year of age.

BACKGROUND: To improve outcome and overall survival (OS) in high-risk neuroblastoma, NB96 induction therapy was intensified using sequential high-dose chemotherapy and autologous stem cell rescue. PROCEDURE: Twenty children were included in this pilot study undertaken at seven reference centers in France, between May 1995 and October 1996. Induction began with one cycle of conventional chemotherapy followed by six sequential cycles of high-dose chemotherapy comprising two cycles of etoposide 800 mg/m(2)/day over 3 days, two cycles of cyclophosphamide 2,000 mg/m(2)/day over 3 days, and two cycles of carboplatin 400 mg/m(2)/day over 5 days, followed by stem cell rescue. RESULTS: Thirteen patients (13/20) received this induction with acceptable toxicity and adequate stem cell harvest. Of these, nine (9/13) underwent surgery according to the protocol, while one patient was given a consolidation regimen prior to surgery. No toxic death was recorded. At the end of induction, complete remission was achieved in 10 cases (50%), with six still alive in July 2009. The 5-year event-free survival and OS were 35 ± 11% and 40 ± 11%, respectively. CONCLUSION: NB96 therapy is feasible and tolerated without lethal toxicity. Nevertheless, given the small sample size and absence of randomization in our study, the effectiveness of this strategy based on metastasis complete response rates and long-term outcome was not superior to other intensive chemotherapy regimens.

Myeloid leukaemia in children with Down syndrome: report of the registry-based French experience between 1990 and 2003.

AIM: To determine the epidemiology of myeloid leukaemia (ML) in children with Down syndrome (DS) and the efficacy of two approaches, low-dose cytarabine-based regimen (LDC) and standard-dose intensive chemotherapy (SD). PROCEDURE: All children with Down syndrome aged from 2 months to 15 years with ML/myelodysplasia registered in the French registry between January 1990 and December 2003 were included. RESULTS: Forty-four patients were included. The median age was 1.75 years. The French-America-British subtypes were as follows: M7: 24, M0: 6, M2: 5, M6: 2. Forty-three patients were treated with curative prospect, 20 patients with LDC regimen and 22 according to SD protocols, 1 was given the LDC regimen plus autologous stem-cell transplantation. The event-free survival (EFS) and overall survival (OS) at 5 years were 64.4% and 76.8%. At 5 years, OS in LDC and SD groups were 65% and 85.9% (P = 0.08). EFS were 45% and 80.3% respectively (P < 0.01). CONCLUSION: Children with DS can adequately tolerate SD chemotherapy with a significant superiority of EFS relative to LDC. We suggest that higher levels of cure can be obtained in DS-ML with SD chemotherapy including cytarabine and anthracyclines.

The French paediatric cohort of Castleman disease: a retrospective report of 23 patients.

BACKGROUND: Castleman disease (CD) is a rare non-malignant lymphoproliferation of undetermined origin. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis confirmation is based on histopathological findings in a lymph node. We attempted to survey all cases of paediatric CD identified to date in France to set up a national registry aiming to improve CD early recognition, treatment and follow-up, within the context of a new national reference center (http://www.castleman.fr). METHODS: In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the paediatric rheumatology society and the Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory. RESULTS: We identified 23 patients (12 girls) with a diagnosis of UCD (n = 17) and MCD (n = 6) between 1994 and 2018. The mean age at first symptoms was 11.47 ± 4.23 years for UCD and 8.3 ± 3.4 years for MCD. The mean diagnosis delay was 8.16 ± 10.32 months for UCD and 5.16 ± 5.81 years for MCD. In UCD, the initial symptoms were isolated lymph nodes (n = 10) or lymph node associated with other symptoms (n = 7); fever was present in 3 patients. Five patients with MCD presented fever. No patients had HIV or human herpesvirus 8 infection. Autoinflammatory gene mutations were investigated in five patients. One patient with MCD carried a K695R heterozygous mutation in MEFV, another patient with MCD and Duchenne myopathy carried two variants in TNFRSF1A and one patient with UCD and fever episodes carried two heterozygous mutations, in IL10RA and IL36RN, respectively. Treatment of UCD was mainly surgical resection, steroids, and radiotherapy. Treatment of MCD included tocilizumab, rituximab, anakinra, steroids, chemotherapy, and splenectomy. Overall survival after a mean of 6.1 ± 6.4 years of follow-up, was 100% for both forms. CONCLUSION: Paediatric CD still seems underdiagnosed, with a significant diagnosis delay, especially for MCD, but new international criteria will help in the future. Unlike adult CD, which is strongly associated with HIV and human herpesvirus 8 infection, paediatric CD could be favored by primary activation of innate immunity and may affect life expectancy less.

Impact of age, leukocyte count and day 21-bone marrow response to chemotherapy on the long-term outcome of children with philadelphia chromosome-positive acute lymphoblastic leukemia in the pre-imatinib era: results of the FRALLE 93 study.

BACKGROUND: We explored the heterogeneity of philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL) in a study of the effect of early features on prognosis in children. Here we report the long-term results of the FRALLE 93 study conducted in the era before the use of tyrosine kinase inhibitors. METHODS: Between 1993 and 1999, 36 children with Ph1-ALL were enrolled into the FRALLE 93 protocol. After conventional four-drug induction, children were stratified by availability of an HLA-matched sibling. RESULTS: Complete remission (CR) was observed in 26 children (72%), of which 13 underwent allogeneic bone marrow transplantation (BMT). Thirty-one children were good responders to prednisone, defined on day 8, and 21 were good responders to chemotherapy, defined by day-21 bone marrow (M1). Overall five-year disease-free survival (DFS) was 42 +/- 9.7%. Based on multivariate analysis, two groups showed marked differences in five-year outcome: children with age<10, leukocyte count <100,000/mm3 and day-21 M1 marrow had a more favorable prognosis (14 pts: 100% CR, event free survival [EFS]: 57%, overall survival [OS]: 79%), than the high-risk group (22 patients: 55% CR, EFS: 18%, OS: 27%) (p < 0.005). We also observed a non statistically significant difference (p = 0.14) in outcome between these groups for transplanted patients (5-year DFS: 83 +/- 14% and 33 +/- 15%, respectively). CONCLUSION: Age, leukocyte count and early response to treatment defined by the D21 bone marrow response provide an accurate model for outcome prediction. The combination of available tools such as minimal residual disease assessment with determination of these simple factors could be useful for refining indications for BMT in the current era of tyrosine-kinase inhibitor-based therapy.

Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome.

BACKGROUND: The prognostic value of the ectopic activation of TLX3 gene expression, a major oncogenetic event associated with pediatric T-cell acute lymphoblastic leukemia, is controversial. Likewise, the frequency and the prognostic significance in pediatric T-cell acute lymphoblastic leukemia of the newly characterized NUP214-ABL1 fusion transcript is not yet clear. DESIGN AND METHODS: Two hundred children with T-cell acute lymphoblastic leukemia were treated in the French FRALLE-93 study from 1993 to 1999. The expression of TLX3, TLX1 and SILTAL1 genes was analyzed in samples from 92 patients by real-time quantitative reverse transcriptase polymerase chain reaction. Most of these samples were further studied for NUP214-ABL1 and CALM-AF10 fusion transcripts. RESULTS: The median follow-up was 7.9 years. At 5 years the overall survival (+/- standard deviation, %) was 62 (+/-3%) and leukemia-free survival was 58 (+/-3%). Patients with T-cell acute lymphoblastic leukemia positive for TLX3 had a poorer survival compared to those with T-ALL negative for TLX3 (overall survival: 45+/-11% vs. 57+/-5%, p=0.049). In multivariate analysis, TLX3 expression was an independent adverse risk factor predicting relapse with a hazard ratio of 2.44 (p=0.017) and an overall survival with a hazard ratio of 3.7 (p=0.001). NUP214-ABL1 was expressed in 16.6% of patients with TLX3-positive T-ALL (3 of 18); all of the patients with this association died before completion of the treatment. SILTAL expression did not significantly affect the prognosis of patients with T-cell acute lymphoblastic leukemia. Only three of 92 patients expressed the TLX1 gene and all three are alive. CONCLUSIONS: TLX3 gene expression is an independent risk factor predicting poor survival in childhood T-cell acute lymphoblastic leukemia. When co-expressed with TLX3, NUP214-ABL1 transcripts may increase the risk of poor survival.

Vaccination and the risk of childhood acute leukaemia: the ESCALE study (SFCE).

BACKGROUND: In 2002, a poster alerted the French health authorities to the possibility that the risk of childhood leukaemia might be increased by hepatitis B vaccination. Elucidating the role of vaccination in the aetiology of childhood acute leukaemia (AL) was therefore included in the objectives of an ongoing national study. METHODS: The ESCALE study was a French national population-based case-control study conducted in France in 2003 and 2004 in order to investigate the role of infectious, environmental and genetic factors in four childhood neoplastic diseases (leukaemia, lymphoma, neuroblastoma and brain tumour). The controls were randomly selected from the French population and age and gender frequency matched with the cases. A total of 776 cases of AL (91% of the eligible cases) and 1681 controls (71% of the eligible controls) were included. In a specific standardized telephone interview, which was the same for both the cases and controls, each mother was asked to read out her child's complete vaccination record. RESULTS: No association between vaccination and the risk of childhood AL: acute lymphoblastic leukaemia or acute myeloblastic leukaemia was observed. No relationship between the risk of leukaemia and the type of vaccine, number of doses of each vaccine, total number of injections, total number of vaccine doses or number of early vaccinations was evidenced. No confounding factor was observed. CONCLUSION: The study did not show any evidence of a role of vaccination in the aetiology of childhood leukaemia.

Rituximab therapy for childhood Evans syndrome.

The safety and efficacy of rituximab have been retrospectively assessed in 17 children with Evans syndrome. Patients received 4 or 3 weekly doses of rituximab (375 mg/m(2) per dose) associated with prednisone, alone (14 patients) or associated with other immunosuppressive drugs. Complete or partial remission of at least one cytopenia was achieved in 13 out of the 17 patients (76%), and lasted in 11 of them with a mean follow-up of 2.4 years (range 0.5-7 years). Steroid therapy was stopped or tapered at 50-100% of the baseline dosage in all long-term responders. Moderate side effects and infection occurred only in 4 and 1 children respectively.