Red blood cell exchange in children and adolescents with sickle cell disease.

Automatic red blood cell exchange i.e. using devices (RBCX) has become a standard therapy to remove abnormal red blood cells (RBC) in adults and children affected by sickle cell disease (SCD). This treatment is performed both in emergency to treat acute complications and through a regular program of RBCX to prevent the recurrence of complications. However, small children, i.e. those with a low body weight, height and total blood volume, are at risk of relative hypovolemia and metabolic complications during the procedure. Moreover, the peripheral venous access is limited among young children, which requires alternative short- or long-term venous access. These two main limiting factors necessitate adaptations of the procedures and subsequent monitoring during and after the sessions. However, performing RBCX in children requires other adaptations and cautions that must be considered. Our review summarizes the limits, safety precautions and the adaptations of the techniques to ensure RBCX in children.

A French retrospective study on clinical outcome in 102 choroid plexus tumors in children.

The aim of this study was to review and describe therapeutic approaches in children with choroid plexus tumor (CPT) based on a nationwide series. The World Health Organization classification subdivides these rare tumors into three histological subtypes corresponding to three grades of malignancy: low grade (grade I) choroid plexus papilloma (CPP), intermediate grade (grade II) atypical choroid plexus papilloma (aCPP) and high grade (grade III) choroid plexus carcinoma (CPC). This retrospective study included 102 French children younger than 18 years, treated from 2000 to 2012: 54 CPP, 26 aCPP and 22 CPC. The 5 year overall survival was 100% in CPP, 96.2% in aCPP and 64.7% in CPC. In patients with localized disease, complete surgical resection was achieved in 48/52 CPP, 20/26 aCPP and 7/14 CPC. In this group, patients with complete surgical resection had better event free survival than patients with partial resection (88.9 vs. 41.6%). 28 patients (1 CPP, 6 aCPP and 22 CPC) had adjuvant chemotherapy. 2 aCPP and 9 CPC had radiotherapy. We underlined the need for a central histological review to accurately analyze clinical data; we reported a much higher overall survival for CPC than in most previous CPT series probably including atypical teratoid rhabdoid tumors. In our series, the 5 years overall survival in CPC (64.7%) was higher than event free survival (25.2%) and could be interpreted as a clue for the efficiency of adjuvant/salvage therapy even if the heterogeneity of applied treatments in this retrospective series does not allow for meaningful statistical comparisons.

Molecular assessment of minimal residual disease in PBSC harvests provides prognostic information in neuroblastoma.

As almost all patients with high-risk neuroblastomas have autograft, we aimed to determine if minimal residual disease (MRD) quantified by RT-PCR for tyrosine hydroxylase in PBSC is prognostic in neuroblastomas. PBSC harvests from 38 children were analyzed. Seven had harvests positive for TH-mRNA. Patients with a positive MRD had a lower 2-year-overall-survival compared to those with negative MRD (P = 0.04) regardless of whether or not PBSC were re-infused. Patients in CR/VGPR group with positive MRD have hazard ratio of death at 7.3 [1.3-40.5]. In conclusion, molecular MRD status in PBSC of good response group may be of interest as a survival prognostic factor in high-risk neuroblastomas.

Non-invasive biological quantification of acute gastrointestinal graft-versus-host disease in children by plasma citrulline.

Clinical grading of GI involvement during acute GVHD remains a challenging issue, especially in children. Plasma citrulline, a non-protein amino acid selectively produced and released by enterocytes, is a suitable surrogate endpoint for small intestinal epithelial cell mass, irrespective of the underlying cause of cell loss. Children referred for allogeneic bone marrow transplantation who were free from chronic malabsorption or constitutional disease involving the GI tract were consecutively included in this prospective study. Plasma citrulline and albumin concentration was measured every week between day 7 and day 28 of BMT until resolution of the aGVHD or occurrence of chronic GVHD. In total, 31 children were included between 2008 and 2011. After a CR, citrulline levels fell to a minimum level on day 7 and then increased to reach the initial value on day 28. After day 28, plasma citrulline but not albumin was strongly linked to the occurrence of GI GVHD, the threshold being set at 10 µmol/L. The correlation with clinical grade of GI-aGVHD now needs to be assessed in larger populations. In pediatric patients, citrulline is valuable as a suitable non-invasive marker of GI involvement in acute GVHD.

Long-term red blood cell exchange in children with sickle cell disease: manual or automatic?

Little information is available on erythrocytapheresis in children with sickle cell disease, and no comparison has ever been made with manual exchanges in a long-term blood exchange program. We matched a historical cohort of five patients who received 60 erythrocytapheresis procedures with five who received 124 manual exchanges. Long-term erythrocytapheresis was feasible and well-tolerated even in children of low weight. In a long-term approach, automated exchanges were more efficient in maintaining a low HbS level, and exchanges could be spaced out. This approach appears especially useful in the cases where the HbS level must be maintained below 30%.

Evidence of a clinical response at one yr after reduced-intensity allogeneic hematopoietic stem cell transplantation in heavily pretreated adolescents with aggressive refractory Hodgkin's lymphoma.

We report results of RIC AHSCT in four adolescents with aggressive refractory HL. They all received three or four lines of therapy prior to RIC-AHSCT including autografts. At the time of RIC, they were in partial response except for one patient who had progressive chemoresistant disease. The conditioning regimen consisted of fludarabin, busulfan and ATG. They all had a matched related donor. The median follow-up was 12-16-month post-allograft. All patient transplants engrafted rapidly. The median time of hospitalization was 35 days. The median time to neutrophil recovery (>or=500/muL) was 19 days. All the patients were in complete donor chimerism at day 60. Four patients developed skin (grade

Four successful pregnancies in a patient with mucopolysaccharidosis type I treated by allogeneic bone marrow transplantation.

To date, little is known about the fertility of women suffering from mucopolysaccharidosis type I (MPS I). We report on a female patient with MPS I treated by allogeneic bone marrow transplantation (BMT) at the age of 4 years (after a conditioning regimen containing busulfan 16 mg/kg and cyclophosphamide 100 mg/kg) who had four successful pregnancies without any reproductive assistance. Clinical and biological examinations of the children were normal. On the basis of this case, we discuss the fertility counselling of female MPS I patients at the time of BMT.

[Implementation of quality assurance program ISO 9001 in a department of paediatric oncology]. / Mise en place d'un système d'assurance qualité ISO 9001 en cancérologie pédiatrique.

OBJECTIVE: Our objective was to improve the organization and management of care facilities for children suffering from cancer or leukaemia and to be aligned with the legislation in force in France. METHODS: Our report is on the successive steps for the implementation of a quality assurance system, methods used, motivations, cost, difficulties encountered as well as the advantages obtained. In the Regional Centre for Paediatric Oncology (CRCP) at the CHU in Clermont-Ferrand, we launched a quality programme based on ISO9001/2000 standards. The implementation of the quality assurance system was conducted as a research project and an established medical project with the support of the Management Team. The mission was divided into several "processes", an approach consisting of considering the clinical service in terms of flow and successions of transformations (reception, care, support, accompaniment, etc.) which produce added-value (services and products adapted to the needs of the "customers": children, families, correspondents). RESULTS: We singled out ten physical processes or "job specializations" such as "diagnosis", "care" or "project for the child". The cartography which is the systematic representation of the processes and the interactions between them made it possible to draw up a global vision of the CRCP "care" activity. CONCLUSION: The ISO9001/2000 standard is a tool designed to help organization and management. The benefit obtained in implementing it in a clinic was perceived in organisational terms and lead to a true team spirit, a standardization of the professional practices and the enhancement of the role of each person. The advantages appear at three levels: the child and his/her family, the medical and paramedical teams, and the administrative supervisory bodies.

[Photopheresis: an alternative therapeutic approach in corticoresistant erosive oral lichen planus]. / La photophérèse: une alternative thérapeutique aux corticoïdes pour le lichen érosif muqueux corticorésistant.

BACKGROUND: The immunomodulatory effect of extracorporeal photochemotherapy (photopheresis) coupled with its efficacy in lymphocytic skin diseases provides a rationale for its use for erosive lichen planus. We report two cases of chronic oral erosive and corticoresistant lichen planus successfully treated with photopheresis. PATIENTS AND METHODS: Case 1. A 61-years-old man had erosive oral lichen planus for four years. Oral steroids were contra-indicated due to iatrogenic pancreatitis. After nine photopheresis sessions, subjective improvement occurred and the oral lesions were stabilized. Case 2. A 17-years-old woman presented corticodependent oral and genital erosive lichen planus and cutaneous lesions. After seven sessions of photopheresis, the patient was able to eat again and the pain decreased. After 20 sessions, the cutaneous lichen planus disappeared and complete remission of the mucous lesions was obtained without corticotherapy. DISCUSSION: These two cases, together with 23 other cases reported elsewhere, strongly suggested the value of photopheresis in the treatment of erosive lichen planus. However, relapses after treatment withdrawal appear extremely frequent.

Pseudomonas aeruginosa and Pseudomonas putida outbreak associated with contaminated water outlets in an oncohaematology paediatric unit.

This paper describes an outbreak of Pseudomonas aeruginosa and Pseudomonas putida that occurred in an oncohaematology paediatric unit between January and April 2005. Eight children had nosocomial infections due to P. aeruginosa (N=5) or P. putida (N=3), which were recovered from central venous catheter blood cultures (N=4), the catheter exit site alone (N=2), or the catheter exit site and the catheter tip (N=2). Subsequent investigation showed that contaminated water outlets represented the possible source of spread. Studies of nursing and environmental cleaning practices revealed two modes of catheter contamination. A reduction in the size of the catheter dressing at the exit site gave less protective cover during showers, and a detergent-disinfectant diluted with tap water had contaminated perfusion bottles. Repetitive intergenic consensus polymerase chain reaction indicated two discrete patterns for P. aeruginosa and one for P. putida. The water network was chlorinated, and disposable seven-day filters were fitted on all taps and showers. Due to the deleterious effects of chlorination on the water network and the cost of the weekly filter change, a water loop producing microbiologically controlled water was installed. In addition, the concentration of the detergent-disinfectant was increased and refillable sprayers were replaced with ready-to-use detergent-disinfectant solution for high-risk areas. Following these measures, no Pseudomonas spp. have since been isolated in clinical or environmental samples from the ward.

Prevalence and risk factors of iron overload after hematopoietic stem cell transplantation for childhood acute leukemia: a LEA study.

Data on post-transplant iron overload (IO) are scarce in pediatrics. We conducted a prospective multicenter cohort study (Leucémie de l'Enfant et de l'Adolescent cohort) to determine the prevalence and risk factors of IO in 384 acute leukemia survivors transplanted during childhood. Prevalence of IO (ferritin level ⩾350 ng/mL) was 42.2% (95%CI 37.2-47.2%). Factors significantly associated with IO were: 1) in univariate analysis: older age at transplant (P<0.001), allogeneic versus autologous transplantation (P<0.001), radiation-based preparative regimen (P=0.035) and recent period of transplantation (P<0.001); 2) in multivariate analysis: older age at transplant in quartiles (Odds Ratio (OR)=7.64, 95% CI: 3.73-15.64 for age >12.7 years and OR=5.36, 95% CI: 2.63-10.95 for age from 8.2 to 12.7 years compared to age < 4.7 years), acute myeloid leukemia (OR=3.23, 95% CI: 1.47-7.13), allogeneic graft (OR=4.34, 95% CI: 2.07-9.12 for alternative donors and OR=2.53, 95% CI: 1.2-5.33 for siblings, compared to autologous graft) and radiation-based conditioning regimen (OR=2.45, 95% CI: 1.09-5.53). Graft-versus-host disease was an additional risk factor for allogeneic graft recipients. In conclusion, IO is a frequent complication in pediatric long-term survivors after transplantation for acute leukemia, more frequently observed in older children, those transplanted from alternative donors or with graft-versus-host disease.

Cytogenetics and outcome of allogeneic transplantation in first remission of acute myeloid leukemia: the French pediatric experience.

We analyzed the impact of cytogenetics on 193 children enrolled in two successive French trials (LAME89/91 and ELAM02), who received hematopoietic stem cell transplantation during CR1. Detailed karyotype was available for 66/74 (89%) in LAME89/91 and 118/119 (99%) in ELAM02. Several karyotype and transplant characteristics differed according to therapeutic protocol: unfavorable karyotypes were more frequent in ELAM02 (36% vs 18%), pretransplant chemotherapy included high-dose cytarabine in ELAM02 and not in LAME89/91, IV replaced oral busulfan in the conditioning regimen, methotrexate was removed from post-transplant immunosuppression, and matched unrelated donor and cord blood transplantation were introduced. Five-year overall survival (OS) was 78.2% in LAME89 and 81.4% in ELAM02. OS was significantly lower for the unfavorable cytogenetic risk group in LAME89/91 when compared with intermediate and favorable groups (50% vs 90.6 and 86.4%, P=0.001). This difference was no longer apparent in ELAM02 (80.9% vs 71.3% and 5/5, respectively). Survival improvement for children with unfavorable karyotype was statistically significant (P=0.026) and was due to decrease in relapse risk. Five-year transplantation-related mortality was 6.75% in LAME89/91. In ELAM02, it was 3.2% for patients with a sibling donor and 10.9% with an unrelated donor or cord blood. We conclude that the outcome of children with unfavorable karyotype transplanted in CR1 has improved.

[Pedagogic focus-group in pediatrics]. / Initiation à la pédagogie narrative en pédiatrie : le focus-groupe pédagogique.

AIM: To assess a new behavioral teaching technique called "focus group pedagogy" (FGP), which consists in a three-step meeting between sick children's parents and medical students (first with students alone, then with parents and students together, then with students alone). METHODS: This qualitative research ran two sessions (each totaling four to six parents and six students) in which parents were questioned on four main themes: their knowledge of the medical hierarchy, their ability to identify the people in the hospital, their communication with medical staff, and the overall care delivered to their children. A thematic analysis of the verbatim transcript was performed. RESULTS: In the FGP sessions, medical students voiced opinions on their degree of insertion in the medical and paramedical staff, and reported their presence as ambiguous, between care and learning. Parents voiced their experience of their child's hospital stay but also their wider conception of the parent/patient-physician relationship based on their parent-of-patient/parent-as-patient experiences. The meeting of parents and students highlighted divergent narratives on relationships with caregivers, communication, attitudes, knowledge, and competencies. This approach made it possible to hear and learn the point of view "from the other side," which proved beneficial for students, session leaders, and the care unit organization alike. CONCLUSION: FGP is a novel and easy way to discover diverse narratives and the technique is feasible and beneficial in pediatric settings.

Update on extracorporeal photochemotherapy for graft-versus-host disease treatment.

Pediatric experience with extracorporeal photochemotherapy (ECP) for graft-versus-host disease (GvHD) has mainly been reported by Italian and French groups. Data concerning 41 children with acute GvHD and 63 children affected by chronic GvHD are available. In 73 and 63% of them, respectively, improvement was observed, with addition of ECP to their immunosuppressive regimen. Treatment with ECP was associated with minimal side effects, even in the smallest of patients. In all responded pediatric patients, both with acute and chronic GvHD, ECP allowed progressive reduction or discontinuation of the concomitant pharmacological immunosuppressive therapy without an increase in GvHD activity. These data show that ECP is a useful therapy for children affected by GvHD resistant to conventional treatment and can be safely used.

Incidence and survival of childhood central nervous system tumors: A report of the regional registry of childhood cancers in Auvergne-Limousin.

INTRODUCTION: Central nervous system tumors (CNST) are the most lethal of solid tumors in childhood cancer. PATIENTS AND METHODS: We report incidence and survival data for all CNST (International Classification of Diseases for Oncology third edition, category III or Xa) recorded in children under 15 years of age by the Auvergne-Limousin cancer registry for the period 1986-2009. RESULTS: Annual incidence of all CNST was 3.27 per 100,000 and the male to female ratio was 0.95. Over 45.0% of CNST were glial. Astrocytomas (36.2%) showed the highest incidence for each age group except between 1 and 4 years where embryonal tumors were more common. For all CNST, no significant variation in incidence over time was observed for the evaluated period of 23 years (annual percent change: -0.4%, 95% CI, [-2.8-2.1]). Globally, 5 years overall survival was 67% [59-73] and had increased by more than 16% between 1986-1999 and 2000-2009, mainly due to better survival for astrocytomas, other gliomas, ependymomas and choroid plexus tumors (P=0.01). CONCLUSION: We report that the incidence of CNST in Auvergne-Limousin is similar to that in the literature and did not increase between 1986 and 2009. In addition, 5 years overall survival increased after 1999, especially for surgically treatable tumors.

Hematopoietic stem cell transplantation in relapsed ALK+ anaplastic large cell lymphoma in children and adolescents: a study on behalf of the SFCE and SFGM-TC.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a treatment option for relapsed anaplastic large cell lymphoma (ALCL) in children, but reports on its efficacy in this disease are still limited. We analyzed data concerning 34 patients under 18 years of age prospectively registered in the French SFGM-TC database, who had undergone an allo-SCT for the treatment of ALK+ ALCL between 1993 and 2011. At transplant, 28 patients (82.4%) were in CR, whereas 6 exhibited detectable disease. Conditioning regimens were mostly myelo-ablative (n=31). With a median follow-up of 6 years, 5-year overall and event-free survival rates were 70% (SE=8%) and 58% (SE=9%), respectively. The 5-year cumulative incidence of relapse and treatment-related mortality was 18% (SE=7%) and 24% (SE=8%), respectively. Six patients had relapsed (median time, 141 days (35-235)). A durable CR had been obtained in 4/6 patients after injection of donor lymphocytes (n=1) or vinblastine-corticosteroid therapy (n=3). Ten patients had died, eight due to transplant toxicity and two due to progressive disease. Allo-SCT is an efficient treatment for pediatric patients with high-risk relapsed ALK+ ALCL. However, the overall morbidity of allo-SCT raises questions about its place, given the efficacy of targeted agents currently under development in this disease.

Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study.

We evaluated prospectively the incidence and risk factors of the metabolic syndrome (MS) and its components in 170 adult patients (mean age at evaluation: 24.8±5.4 years) who received an hematopoietic stem cell transplantation for childhood ALL, n=119, or AML, n=51. TBI was carried out in 124 cases; a busulfan-based conditioning was done in 30 patients. Twenty-nine patients developed a MS (17.1%, 95% confidence intervals: 11.7-23.6). The cumulative incidence was 13.4% at 25 years of age and 35.5% at 35 years of age. A higher body mass index (BMI) before transplantation and a growth hormone deficiency were associated with increased MS risk (P=0.002 and 0.01, respectively). MS risk was similar for patients who received TBI or busulfan-based conditioning. The TBI use increased the hyperglycemia risk (odds ratio (OR): 4.7, P=0.02). Women were at the risk of developing increased waist circumference (OR: 7.18, P=0.003) and low levels of high-density lipoprotein cholesterol (OR: 2.72, P=0.007). The steroid dose was not a risk factor. The MS occurs frequently among transplanted survivors of childhood leukemia. Its incidence increases with age. Both intrinsic (BMI, gender) and extrinsic factors (TBI, alkylating agents) contribute to its etiopathogenesis.

Non-metastatic Ewing's sarcoma of the ribs: the French Society of Pediatric Oncology Experience.

From 1984 to 1997, 57 consecutive patients with non-metastatic Ewing's sarcoma of the ribs were treated according to multimodal French Society of Pediatric Oncology (SFOP) protocols EW 84, EW 88 and EW 93. The results of treatment were reviewed and analysed. Median age was 12 years. 34 patients had large tumours (greatest tumour dimension > or = 8 cm); pleural effusion was noted in 26. A tumour-positive margin after surgery was noted in 15 patients. Histological response after chemotherapy was assessed in 34 patients. 34 patients received radiation therapy. With a median follow-up of 5 years, the projected overall and relapse-free survival rates were 69 and 62%, respectively. The major site of relapse was local. None of the following was significant in predicting relapse: tumour size, gender, age at diagnosis, existence of pleural effusion, level of rib tumour, rib component, type of local control, surgical margin (positive or negative). Response to chemotherapy was the sole significant prognostic factor (P=0.004). Patients with pleural effusion had a higher percentage of relapse if they were treated without local radiation therapy. Our study confirms the prognostic significance of response to initial chemotherapy. Radiation therapy may be withheld in selected cases, but seems necessary in patients with pleural effusion.

Using peripheral blood progenitor cells (PBPC) for transplantation in pediatric patients: a state-of-the-art review.

This paper presents a state-of-the-art review of using mobilized-peripheral blood progenitor cells (PBPC) for transplantation in children. Our own data and those from Medline searches and meeting reports, are analyzed and presented for the different sections that involve transplantation. Recommendations concerning the choice of mobilization regimens, venous access, priming of separator extracorporeal line, anticoagulation, and number of CD34+ cells to infuse for rapid engraftment are proposed. In the allogeneic setting, we analyze ethical and safety aspects of pediatric donor mobilization and collection. Data from the literature suggest that the use of cytokine-mobilized PBPC for allogeneic transplantation appears to be safe both for pediatric donors and patients leading a rapid hematopoietic engraftment with a similar incidence of acute graft-versus-host disease (GVHD). The high incidence of chronic GVHD and its management emerge as the most concerning aspect in allogeneic PBPC transplantation.

Evaluation of erythropoietic/hematopoietic reconstitution after BMT by highly fluorescent reticulocyte counts compares favorably with traditional peripheral blood cell counting.

Highly fluorescent reticulocyte (HFR) counts and reticulocyte counts were analyzed daily using a Sysmex R-1000 automated reticulocyte counter after 42 BMT in children (median age 7 years, range 10 month-18.5 years). White blood cell levels were also analyzed daily using either traditional counting methods or, when levels were very low, cytocentrifuge preparations. Twenty-eight patients received autologous and 14 allogeneic BMT. After myeloablative therapy, HFR counts fell to zero and rose to 2% of the reticulocyte total after a median time of 10 days (range 6-23 days) post-autoBMT and 14 days (range 9-29 days) post-alloBMT. The appearance of HFR (at least 2% in two successive counts) preceded the attainment of 20 x 10(9)/l reticulocytes in 23 of 26 autoBMT by a median time of 3 days, and in 13 of 13 alloBMT with a median time of 4 days (p < 0.001). Two per cent HFR preceded the attainment of 0.5 x 10(9)/l neutrophils in the majority of BMT by a median time > 6 days (p < 0.001). The attainment of 0.05 x 10(9)/l monocytes was preceded by a rise in HFR in 12 of 26 autoBMT and in 7 of 13 alloBMT. Median times between 2% HFR and monocyte levels of 0.05 x 10(9)/l were respectively 2 (range 0- > 24) and 3 (range: 0- > 19) days after auto and alloBMT. These results show that the evaluation of erythropoiesis following BMT by means of HFR counting provides an early measure of hematopoietic reconstitution which is as precise and considerably more practical than monitoring the monocyte level.