Extended induction chemotherapy does not improve the outcome for high-risk neuroblastoma patients: results of the randomized open-label GPOH trial NB2004-HR.

BACKGROUND: Long-term survival of high-risk neuroblastoma patients is still below 50% despite intensive multimodal treatment. This trial aimed to address whether the addition of two topotecan-containing chemotherapy courses compared to standard induction therapy improves event-free survival (EFS) of these patients. PATIENTS AND METHODS: An open-label, multicenter, prospective randomized controlled trial was carried out at 58 hospitals in Germany and Switzerland. Patients aged 1-21 years with stage 4 neuroblastoma and patients aged 6 months to 21 years with MYCN-amplified tumors were eligible. The primary endpoint was EFS. Patients were randomly assigned to standard induction therapy with six chemotherapy courses or to experimental induction chemotherapy starting with two additional courses of topotecan, cyclophosphamide, and etoposide followed by standard induction chemotherapy (eight courses in total). After induction chemotherapy, all patients received high-dose chemotherapy with autologous hematopoietic stem cell rescue and isotretinoin for consolidation. Radiotherapy was applied to patients with active tumors at the end of induction chemotherapy. RESULTS: Of 536 patients enrolled in the trial, 422 were randomly assigned to the control arm (n = 211) and the experimental arm (n = 211); the median follow-up time was 3.32 years (interquartile range 1.65-5.92). At data lock, the 3-year EFS of experimental and control patients was 34% and 32% [95% confidence Interval (CI) 28% to 40% and 26% to 38%; P = 0.258], respectively. Similarly, the 3-year overall survival of the patients did not differ [54% and 48% (95% CI 46% to 62% and 40% to 56%), respectively; P = 0.558]. The response to induction chemotherapy was not different between the arms. The median number of non-fatal toxicities per patient was higher in the experimental group while the median number of toxicities per chemotherapy course was not different. CONCLUSION: While the burden for the patients was increased by prolonging the induction chemotherapy and the toxicity, the addition of two topotecan-containing chemotherapy courses did not improve the EFS of high-risk neuroblastoma patients and thus cannot be recommended. CLINICAL TRIALS. GOV NUMBER: NCT number 03042429.

[Home Enteral Nutrition (NED) in children and adolescents. Recommendations of the Nutrition Branch of the Chilean Society of Pediatrics]. / Nutrición Enteral Domiciliaria (NED) en niños y adolescentes. Recomendaciones de la Rama de Nutrición de la Sociedad Chilena de Pediatría.

The use of home enteral or parenteral nutrition has been a necessary step in the optimization of nu tritional support in patients who, due to several diseases, fail to meet their nutritional requirements by oral feeding. This article presents the recommendations of the Chilean Pediatric Society Nutritio nal Branch, aimed at health teams that treat pediatric patients who require enteral feeding for a long time. The general objective is to provide guidelines for the proper management of these patients. It describes the ideal conformation of the health team for the care and follow-up of those patients, the program admission criteria, and its evaluation method over time. In addition, it describes general characteristics of enteral feeding, routes of administration, available enteral formulas, complications, and patient follow-up.

High pressure induced spin state crossover in Sr2CaYCo4O10.5.

The layered cobaltite Sr(2)CaYCo(4)O(10.5) with formal average cobalt oxidation state close to 3+ has been studied as functions of both temperature and pressure up to 4 GPa by neutron powder diffraction (NPD). The crystal structure is shown to have tetragonal symmetry (space group I4/mmm; 2a(p) × 2a(p) × 4a(p) superstructure), and the magnetic structure at ambient pressure is found to be G-type antiferromagnetic with TN close to 310 K. The magnetic moments within the CoO(6) octahedral layers and anion-deficient CoO(4.5) layers are 1.2µ(B) and 2.8µ(B), respectively. At 25 K, and applied pressure of 3.5 GPa is sufficient to completely suppress a long-range magnetic order. This result is interpreted in terms of a pressure-induced high-to-low spin state crossover of the Co(3+) ions.

Neuroblastoma mass screening: the arguments for and against.

Neuroblastoma is the second commonest malignancy in childhood. The prognosis of the disease is largely dependent on the extension of the tumour at diagnosis. For disseminated disease the survival rate is very low. The question as to whether mass screening in infants can improve the prognosis of the disease was first addressed in Japan more than 20 years ago. Since then, more than 7 million children have been screened in Japan and over 650 cases of neuroblastoma have been detected. However, the available data are compromised by an inadequate cancer registry and conclude that screening at 6 months of age seems to double the incidence of neuroblastoma. This result has been verified by a Canadian study conducted from 1989 to 1994 in the province of Quebec. The incidence of neuroblastoma appeared to have tripled, and there was no decrease in the rate of advanced disease. Mass screening pilot studies have also been conducted in the U.K., France, Austria, Australia, U.S.A., Italy, Norway and Germany. Analysis of the results shows that neuroblastoma screening before the age of 6 months is feasible, but no significant reduction in mortality could be shown until now. Moreover, most of the cases diagnosed by screening have favourable biological markers. Only a few with unfavourable parameters, such as amplification of proto-oncogene MYCN, diploidy and/or del 1p36 could be detected. A screening programme that includes 1.25-2 million screened and unscreened children at 1 year of age monitored by an almost complete national cancer registry should show whether mass screening for early detection of neuroblastoma is worthwhile.

Coexpression of mRNA for the full-length neurotrophin receptor trk-C and trk-A in favourable neuroblastoma.

Neuroblastoma, a childhood tumour of the sympathetic nervous system, may sometimes regress spontaneously in infants, or progress to a poor clinical outcome despite intensive therapy. Neuroblastomas express neurotrophin receptors and high levels of mRNA for trk-A correlates with favourable outcome, whereas trk-B mRNA is expressed by more unfavourable tumours. Using a sensitive RNase protection assay, mRNA expression for the neurotrophin receptor trk-C was investigated in 50 tumour samples from 45 children at different stages including metastatic and relapsing tumour tissue, out of which 22 were also investigated for trk-A mRNA. Thirty-seven of 43 primary tumours (86%) showed trk-C mRNA with more than 300-fold difference between the highest and the lowest values. A higher trk-C index (trk-C mRNA/GAPDH mRNA) was associated with favourable features such as younger age (P = 0.009-0.003), favourable tumour stage (1, 2 or 4S; P < 0.001) and favourable prognosis (P = 0.044). Better survival probability was shown in children with intermediate or high trk-C index compared with patients with low or undetectable levels (P = 0.031). All localised tumours co-expressed mRNA for trk-A and trk-C receptors. RT-PCR analysis detected mRNA encoding the cytoplasmic trk-C tyrosine kinase region only in favourable neuroblastomas. We conclude that favourable neuroblastoma may express the full-length trk-C receptor while unfavourable tumours, especially those with MYCN amplification, seem to either express no trk-C or truncated trk-C receptors with unknown biological function. Trk-C and possibly its preferred ligand NT-3 may be involved in the biology of favourable neuroblastomas showing apoptosis or differentiation.

Somatostatin in neuroblastoma and ganglioneuroma.

Neuroblastoma, a childhood tumour of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. Somatostatin may inhibit neuroblastoma growth and induce apoptosis in vitro and was therefore investigated. Using a radioimmunoassay, we found that all ganglioneuromas contained high somatostatin concentrations (> 16 pmol/g), significantly higher than neuroblastomas (n = 117, median 2.8 pmol/g), healthy adrenals, Wilms' tumours, phaeochromocytomas and other neuroendocrine tumours (P < 0.001). Neuroblastomas contained more somatostatin than control tumours (P < 0.001-0.05). Neuroblastomas amplified for the MYCN oncogene contained less somatostatin than non-amplified tumours (1.2 pmol/g versus 4.0 pmol/g, respectively; P = 0.026). In a clinically unfavourable neuroblastoma subset (age > 12 months, stage 3 or 4) 16 children with high concentrations of somatostatin in primary tumours had a better prognosis than 23 with low somatostatin (46.7% versus 0% survival at 5 years, P < 0.005). Scintigraphy using 111In-pentetreotide identified tumours expressing high-affinity somatostatin receptors in vivo. However, no significant correlation was found between somatostatin receptor expression and peptide content in 15 tumours. Similarly, human SH-SY5Y neuroblastoma xenografts grown in nude rats showed low somatostatin concentrations, but were positive for somatostatin receptor scintigraphy. Treatment of these rats with the somatostatin analogue octreotide seemed to upregulate in vivo receptor expression of somatostatin and vasoactive intestinal peptide more effectively than 13-cis retinoic acid. In conclusion, somatostatin in neuroblastoma is associated with differentiation to benign ganglioneuromas in vivo and favourable outcome in advanced tumours. Furthermore, somatostatin receptor scintigraphy may identify tumours with high-affinity receptors in children that might benefit from targeted therapy using synthetic somatostatin analogues.

10 years' neuroblastoma screening in Europe: preliminary results of a clinical and biological review from the Study Group for Evaluation of Neuroblastoma Screening in Europe (SENSE).

Between January 1986 and May 1996, 870,313 children were tested in European neuroblastoma (NB) screening programmes. Among these children, 82 cases of NB (age range 4-24 months, median 11 months) were detected by screening. 83% of the patients had localised NB and 17% were diagnosed with generalised NB (stage 4, 10%; stage 4s, 7%). Unfavourable biological markers (MYCN amplification, loss of heterozygosity (LOH) 1p36, DNA di/tetraploidy) were observed in 14% of 76 biologically examined cases. The median follow-up time of all the patients was 21.5 months (range 1-101 months). To date, 69 patients are in complete remission (CR) and 2 patients have died due to therapy (stage 4, 1 patient; stage 3, 1 patient with unfavourable markers). Apart from screened patients, 16 other patients with NB were found who had previously had a normal screening test, i.e. 'false negative' patients (age range 10-41 months, median 31.5 months). The median interval between screening and diagnosis was 24.5 months (range 6-35 months). 11 of the 'false negative' patients suffered from generalised NB (stage 4) and 5 had localised NB at diagnosis. Unfavourable biological markers were observed in 7/12 patients. 5 patients have died, 2 achieved partial remission and 9 CR. 9 of the 11 patients with unfavourable biological markers diagnosed due to NB screening are currently in CR. It is very likely that, among the patients without unfavourable biological markers, we detected tumours which may have regressed spontaneously. These children may have undergone 'unnecessary,' but unavoidable, diagnostic procedures and therapy. To reduce the number of 'false negative' patients, a later screening could be helpful and should be evaluated.

Long-term results and risk profiles of patients in five consecutive trials (1979-1997) with stage 4 neuroblastoma over 1 year of age.

During the last two decades new diagnostic and therapeutic tools have been utilized to improve the poor survival chances of children with stage 4 neuroblastoma. This study reviews the risk profiles and the long-term outcome of patients from five consecutive German neuroblastoma trials. A total of 96% of all German patients registered at the German childhood cancer registry with neuroblastoma stage 4 over 1 year of age at diagnosis entered one of the trials during 1979-2001. Eight hundred and twenty-eight consecutive children were analyzed retrospectively. In spite of having significantly improved diagnostic tools like bone marrow superstaging and mIBG scintigraphy the stage 4 incidence did not increase after reaching completeness of the registry (5.4 cases/100,000 children at 1-14 years of age; P=0.52). The distribution of the primary tumors and of metastases was constant over the periods. The amount of bone marrow infiltration did not change with time. The risk factors lactate dehydrogenase, ferritin and MYCN, and the clinical risk groups 4A, 4B, 4C also remained constant over the trials with a few exceptions for NB97. The 5-year event free survival increased from 0.01+/-0.01 (NB79) to 0.14+/-0.03 (NB85), 0.16+/-0.04 (NB82), 0.27+/-0.02 (NB90), and 0.33+/-0.04 (NB97). The overall survival rates improved similarly from 0.04 (NB79) to 0.44 (NB97). In conclusion, the improved survival was associated with better treatment and not caused by lower risk profiles in stage 4 neuroblastoma patients.

Expression analysis of multidrug resistance associated genes in neuroblastomas.

In a series of 40 neuroblastomas we analyzed the relative mRNA levels of the MDR associated genes encoding MDR1/P-glycoprotein (MDR1), multidrug resistance associated protein (MRP), lung cancer resistance related protein (LRP) and topoisomerase IIalpha (TOPO IIalpha) by cDNA-PCR. Cyclin A (CYCA) was included to examine cellular proliferation activity. MYCN gene expression was analyzed as it was recently shown to be associated with enhanced MRP gene expression in neuroblastomas. We found that tumors with MYCN gene amplification exhibit significantly increased MYCN and MRP gene expression levels. Tumors with an allelic loss of the chromosomal 1p region showed significant (P<0.05) lower MDR1 gene expression (MDR1: 50+/-29, n=4) than tumors without (MDR1: 117+/-81, P<0.05, n=36). Moreover, significant positive correlations were found for MYCN/TOPO IIalpha (P<0.0001), MYCN/CYCA (P<0.05), TOPO IIalpha/CYCA (P<0.01), MRP/CYCA (P<0.0001) and MRP/LRP (P<0.05). Our results give evidence that MDR in neuroblastomas might be caused by multiple resistance factors and that a higher proliferation rate of neuroblastoma cells possibly based on altered MYCN gene expression is associated with enhanced MRP, CYCA and TOPO IIalpha gene expression.

[Chronic recurrent multifocal osteomyelitis (CRMO)]. / Die chronisch rekurrierende multifokale Osteomyelitis (CRMO).

Chronic recurrent multifocal osteomyelitis (CRMO) is an unusual clinical entity. More than 200 cases are described in the literature and it is presented here with special reference to its radiological aspects. It is an acquired disease of the skeleton which occurs predominantly during childhood and adolescence. About ten per cent of cases begin in early or, rarely, in later adult life. This variant is described here for the first time and is discussed as "adult CRMO". The underlying pathology is a bland, predominantly lympho-plasma cellular osteomyelitis which is self-limiting and leads to bone sclerosis (Garrè). It probably involves an abnormal immune process which follows an infection but remains clinically latent and remains aseptic and sterile. In a quarter of cases there is an association with pustulosis palmo-plantaris and its relationship with psoriatic arthropathy is discussed. The clinical, histopathological and imaging features (radiological and particularly MRT) and the bone changes are described. This provides a spectrum of symptoms; the radiological differential diagnosis and the relationship with hyperostotic spondyloarthroses during adult life are discussed. The relationship between CRMO, the SAPHO syndrome and acquired hyperostosis syndrome are analysed.

[Spondarthritis hyperostotica pustulo-psoriatica: nosologic study with clinical and radiologic presentation in relation to the SAPHO syndrome]. / Die Spondarthritis hyperostotica pustulo-psoriatica: Nosologische Studie mit klinischer und radiologischer Darstellung innerhalb des SAPHO-Syndroms.

Spondarthritis hyperostotica pustulo-psoriatica (Spond.hyp.pp-Schilling), corresponding nosologically to pustulotic arthroosteitis, is a dermato-skeletal "double system" disease of adults. It consists of the triad (a) palmo-plantar pustulosis (Ppp) or, alternatively, Königsbeck-Barber-type psoriasis, (b) sternocostoclavicular hyperostosis (SCCH), and (c) truncal-skeletal changes with syndesmophite-like, hyperostotic and/or parasyndesmophite-like ossifications of layers of the anterior vertebral ligament taken together in the sense of a desmophytal hyperostosis. There is also a potential for sclerosing inflammatory arthritis of the sacro-iliac joints and "dry" inflammatory arthritis of peripheral joints. Thus, the pustulo-psoriatic terrain seems to have a decisive influence on osseous pathology. A total of 38 cases from a study during the years 1982 to 1992 is analysed with regard to morphological characteristics. Rare cases with diaphyseal and pelvic hyperostotic lesions subsequent to bland sclerosing osteomyelitis constitute an overlapping region to chronic recurrent multifocal osteomyelitis (CRMO) and illustrate the relationship between hyperostotic spondarthritis and CRMO. The syndromes of "acquired hyperostosis" and "SAPHO", the former more radiologically oriented and the latter more clinically oriented, together with mainly CRMO and hyperostotic spondarthritis and its forms, constitute the "Spond.hyp.pp.". Although hyperostosis is a guidepost for the radiologist and SAPHO symptoms are one for the clinician, the syndrome does not represent a diagnosis by itself and requires further differentiation. In this report the entity "Spond.hyp. pp." is considered and required contributions from rheumatologically and osteologically oriented radiologist.

[Vertebral manifestation of chronic recurrent multifocal osteomyelitis (CRMO)]. / Wirbelsäulenmanifestationen der chronischen rekurrierenden multifokalen Osteomyelitis (CRMO).

Chronic recurrent multifocal osteomyelitis (CRMO) is a systemic osteo-articular disease that is characterized by a sterile, primarily chronic osteomyelitis with various distribution patterns of the individual lesions. In this article, we describe the "axial type" with predominant involvement of the spine, which represents 13 of our 41 CRMO cases of different age groups. The important element of its diagnosis is the typical lympho-plasmacellular spondylitis that can be detected and staged by scintigraphy, MRI and conventional radiography. Potentially affected are all vertebrae from the mid-cervical spine to the sacrum. One or several segments can be involved, sometimes as transient inflammatory edema, sometimes as "migratory spondylitis" or "saltatory spondylitis", but also as chronic sclerosing type with early radiographically detectable manifestation. Vertebral deformity due to compression and total collapse (vertebra plana) are rare. A complicated course with patulous perivertebral edema can lead to concomitant symptomatic inflammatory changes in adjacent regions and organs. In the course of CRMO, spondylodiscitis only develops as secondary destruction following the spondylitis. This can help to differentiate spondyloarthropathies from CRMO that is initially detected as primary lesion in the spine. While CRMO generally has a good prognosis, its radiological differentiation from rheumatologic conditions plays an important role.

A meta-model of chemotherapy planning in the multi-hospital/multi-trial-center-environment of pediatric oncology.

OBJECTIVE: Chemotherapy planning in pediatric oncology is complex and time-consuming. The correctness of the calculation according to state-of-the-art research is crucial for curing the child. Computer-assistance can be of great value. The objective of our research was to work out a meta-model of chemotherapy planning based on the Unified Modeling Language (UML). The meta-model is used for the development of an application system which serves as a knowledge-acquisition tool for chemotherapy protocols in pediatric oncology as well as for providing protocol-based care. METHODS: We applied evolutionary prototyping, software reengineering techniques and grounded theory, a qualitative method in social research. We repeated the following steps several times over the years: Based on a requirements analysis (i) a meta-model was developed or adapted, respectively (ii). The meta-model served as a basis for implementing evolutionary prototypes (iii). Further requirements were identified (i) from clinical use of the systems. RESULTS: We developed a comprehensive UML-based meta-model for chemotherapy planning in pediatric oncology (chemoMM). We implemented it and introduced evolutionary prototypes (CATIPO and DOSPO) in several medical centers. Systematic validation of the prototypes enabled us to derive a final meta-model which covers the requirements that have turned out to be necessary in clinical routine. CONCLUSIONS: We have developed an application system that fits well into clinical routine of pediatric oncology in Germany. Validation results have shown that the implementation of the meta-model chemoMM can adequately support the knowledge acquisition process for protocol-based care.

Integrating specialized application systems into hospital information systems--obstacles and factors for success.

Hospital information systems are often huge and heterogeneous systems. To support physicians with their daily clinical work, application systems are developed which are dedicated to particular medical fields or tasks and which have to be integrated into the hospital information system. The integration process is quite complicated, because it makes the information system's infrastructure even more heterogeneous. We developed an application system for documentation and therapy planning in pediatric oncology (DOSPO) and we started to introduce it into the Department of Pediatric Oncology of Heidelberg University Hospital. The fact that DOSPO is developed as a universal system for nationwide use made the integration process more difficult. In any case, the introduction of specialized application systems has to be planned systematically in advance, regarding the prevailing information system's infrastructure, available resources and established processes. To simplify the integration process comprehensive electronic patient records for the future should be designed in a way that they can be enhanced easily by new clinical functions.

Computer-aided documentation and therapy planning in pediatric oncology.

In the past 20 years considerable progress was made in pediatric oncology concerning the results of therapy in Germany. Nationwide multicentre trials provide protocols for the therapy of the children. The calculation of the chemotherapy according to the protocols is rather complex and the documentation efforts for the pediatricians are enormous. Thus, we developed as a first step an application system for Computer Aided Therapy Planning In Pediatric Oncology (CATIPO), that is in routine use in about 20 pediatric clinics in Germany. In order to support the physician comprehensively with the documentation that is necessary for the trials we currently develop a Documentation System for Pediatric Oncology (DOSPO) that comprises the functionality of chemotherapy planning according to the protocols released by the trial centres. Besides supporting the physician in clinical routine the major objective is to improve the quality of the documented data. To reach this aims DOSPO combines research aspects of decision support and clinical documentation: formal representation of general protocols, calculating of a particular therapy for a patient, data acquisition, communication interfaces for transferring the data to the trial centres. In order to support trial centres an authoring system and a central data dictionary will be developed. This will enable the trial centres to develop new modules for trial-specific data acquisition in the clinics.

Requirements and design aspects of a data model for a data dictionary in paediatric oncology.

German children suffering from cancer are mostly treated within the framework of multicentre clinical trials. An important task of conducting these trials is an extensive information and knowledge exchange, which has to be based on a standardised documentation. To support this effort, it is the aim of a nationwide project to define a standardised terminology that should be used by clinical trials for therapy documentation. In order to support terminology maintenance we are currently developing a data dictionary. In this paper we describe requirements and design aspects of the data model used for the data dictionary as first results of our research. We compare it with other terminology systems.

Object-oriented business process analysis of the cooperative soft tissue sarcoma trial of the german society for paediatric oncology and haematology (GPOH).

The German Society for Paediatric Oncology and Haematology (GPOH) runs nation-wide multicentre clinical trials to improve the treatment of children suffering from malignant diseases. We want to provide methods and tools to support the centres of these trials in developing trial specific modules for the computer-based DOcumentation System for Paediatric Oncology (DOSPO). For this we carried out an object-oriented business process analysis for the Cooperative Soft Tissue Sarcoma Trial at the Olgahospital Stuttgart for Child and Adolescent Medicine. The result is a comprehensive business process model consisting of UML-diagrams and use case specifications. We recommend the object-oriented business process analysis as a method for the definition of requirements in information processing projects in the field of clinical trials in general. For this our model can serve as basis because it slightly can be adjusted to each type of clinical trial.

Nutrición Enteral Domiciliaria (NED) en niños y adolescentes: recomendaciones de la Rama de Nutrición de la Sociedad Chilena de Pediatría / Home Enteral Nutrition (NED) in children and adolescents: recommendations of the Nutrition Branch of the Chilean Society of Pediatrics

Resumen: El uso de apoyo nutricional ambulatorio, enteral o parenteral, ha sido un paso necesario en la opti mización del soporte nutricional en pacientes, que, por diversas patologías, no logran cumplir con sus requerimientos por vía oral (VO). En el presente artículo se presentan las recomendaciones de la Rama de Nutrición, dirigidas a los equipos de salud que atienden pacientes pediátricos, que requieran alimentación enteral por un tiempo prolongado. Su objetivo general es entregar pautas para un co rrecto manejo en estos pacientes. Se describe la conformación ideal del equipo de salud para atención y seguimiento de dichos pacientes, los criterios de ingreso al programa y su forma de evaluación en el tiempo. Además, se describen características generales de la alimentación enteral, vías de admi nistración, fórmulas enterales disponibles, complicaciones de este soporte nutricional y por último monitorización y seguimiento del paciente.

Abstract The use of home enteral or parenteral nutrition has been a necessary step in the optimization of nu tritional support in patients who, due to several diseases, fail to meet their nutritional requirements by oral feeding. This article presents the recommendations of the Chilean Pediatric Society Nutritio nal Branch, aimed at health teams that treat pediatric patients who require enteral feeding for a long time. The general objective is to provide guidelines for the proper management of these patients. It describes the ideal conformation of the health team for the care and follow-up of those patients, the program admission criteria, and its evaluation method over time. In addition, it describes general characteristics of enteral feeding, routes of administration, available enteral formulas, complications, and patient follow-up.

[Therapy of inherited diseases of platelet function. Interdisciplinary S2K guideline of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.)]. / Therapie hereditärer Thrombozytopathien. Interdisziplinäre S2K-Leitlinie der Ständigen Kommission Pädiatrie der Gesellschaft für Thrombose- und Hämostaseforschung e. V.

Inherited disorders of platelet function are a heterogeneous group. For optimal prevention and management of bleeding, classification and diagnosis of the underlying defect are highly recommended. An interdisciplinary guideline for a diagnostic approach has been published (AWMF # 086-003 S2K; Hämostaseologie 2014; 34: 201-212). Underlying platelet disorder, platelet count, age and clinical situation modify treatment. Exclusive transfusion of platelet concentrates may be inappropriate as potentially adverse effects can outweigh its benefit. A stepwise and individually adjusted approach for restitution and maintenance of haemostasis is recommended. Administration of antifibrinolytics is generally endorsed, but is of particular use in Quebec disease. Restricted to older children, desmopressin is favourable in storage pool disease and unclassified platelet disorders. Although licensed only for patients with Glanzmann thrombasthenia and alloantibodies, in clinical practice rFVIIa is widely used in inherited platelet disorders with severe bleeding tendency. This guideline aims at presenting the best available advice for the management of patients with inherited platelet function disorders.