Paediatric Diseases

The EBMT Paediatric Diseases Working Party: Current Concepts and Future Aims

In 1995, during the annual meeting of the EBMT, the issues related to the differences underlying treatment approaches towards adult and paediatric patients were discussed in-depth. An outcome of this exchange was the creation by some EBMT Members of the Paediatric Diseases Working Party (PDWP), whose overriding mission was to design specific transplantation programmes for children and adolescents. Professor Dietrich Niethammer chaired the WP till 2002. Professor Giorgio Dini was the chairman from 2002-2008. In 2008, the EBMT PDWP constituted a new board chaired by Christina Peters and co-chaired by Ruth Ladenstein. Leading experts from different European countries are actively involved in all fields of allogeneic and autologous stem cell transplantation for children and adolescents.

The specific needs of children and adolescents undergoing haematopoietic stem cell transplantation (HSCT):

According to the definition of the International Conference of Harmonization children are defined as individuals under the age of 18 years. Approximately 20% of patients meet this criterion. Children and adolescents have different diseases and different indication for HSCT: e.g. acute leukaemias are only treated by HSCT in the high risk population, in contrast paediatric myelodysplastic syndromes are only curable by allogeneic HSCT.

The patterns of acute and especially late effects are different and demand special attention in the vulnerable organism of a growing child. Mental development, growth and hormonal disorders, fertility and risk for secondary cancer (particularly after total body irradiation) are of special interest. Moreover, adequate reporting on the outcome of clinical trials in children and adolescents must be a prerequisite for paediatric HSCT centres. Children and adolescents need age appropriate information, education, treatment and supportive care requirements before, during and after HSCT.

Since the first successful allogeneic HSCT more than 40.000 paediatric patients have undergone this procedure in Europe. However, their access to well designed prospective clinical trials on HSCT is still low and many of these studies have not yet been published.

Aims of the PDWP:

• To support research and education to improve the availability, safety, and efficacy of hematopoietic stem cell transplantation and other cellular therapeutics for children and adolescents
• To engage and promote active co-operation with all EBMT working parties treating children and adolescents, particularly with the Inborn Errors WP, Aplastic Anaemia, Infectious Diseases, Late Effects and Immunobiology, in an effort to meet the total needs of the full spectrum of paediatric HSCT patients.
• To initiate prospective, collaborative, GCP-conformed studies for malignant and non malignant paediatric diseases. This has become a time and cost intensive task because the new EU regulations and funding remains a difficult and controversial issue but nevertheless critical.
• To develop further the close collaboration with experts from the Leukaemia/Chemotherapy national frontline studies in order to define the optimal timing of HSCT and incorporate transplant recommendations into the disease specific protocols.
• To implement the new regulations on paediatric medicines from the European Medicines Agency (EMEA), which aim to ensure that drugs used to treat children are properly tested and the availability is expanded.
• To offer physicians and nursing staff from small or new centres practical training and fellowships in experienced transplantation units through a European Collaborative Paediatric HSCT network.
• To further develop established Paediatric Standards within the Accreditation Process through JACIE to guarantee and maintain a high quality of patient care and experience.

Current activities:

One primary objective of 2008 was to engage and promote active co-operation with the Inborn Errors WP, Aplastic Anaemia, Infectious Diseases, Late Effects and Immunobiology, in an effort to meet the total needs of the full spectrum of paediatric HSCT patients.

Another important achievement of 2008 was the constitution of the paediatric nurses group which held their first workshops during the 6th PDWP meeting in June 2008 in Poznan. A Bone Marrow Transplantation-supplement covered the current achievements and novel treatment strategies which were presented during the meeting.

In 2009, the next joint meeting was the second training course for paediatricians and paediatric nurses on HSCT in children and adolescents and took place in Genova in June (4th to 6th of June 2009). The aim was to promote and facilitate access to state–of-the-art and cutting-edge knowledge in blood and marrow transplantation at the European level. Beside this, two autumn meetings are planned (St. Petersburg, September 17th-19th and in Barcelona, October 15th-17th, 2009) to realise specific study proposals dealing with prophylaxis and therapy of acute and chronic GVHD in children and adolescents. The prospective randomised study on the prophylactic use of defibrotide for prevention of veno-occlusive disease completed the patient recruitment and is currently under statistical evaluation.

The study on outcome after allogeneic SCT in adolescents is also undergoing final analysis. The European Medicines Evaluation Agency (EMEA) actively involved the PDWP in the implementation of the new regulations on paediatric medicines. These regulations will result in prospective clinical trials which warrant accurate and non-competing collaboration within all European centres that are involved in paediatric stem cell transplantation.

Future Plans:

Although in general the risk of transplant-related mortality (TRM) has been reduced during the last years the burden of acute and chronic GVHD in children and adolescents is still one of the crucial points after allogeneic HSCT. It is, therefore one major focus of our next retrospective analysis and prospective trials to improve definition, prophylaxis and treatment of GVHD without jeopardising engraftment and graft versus leukaemia effect.

Another scientific emphasis is the control of late effects. In children and adolescents, disorders of growth and the endocrine system have been observed to occur frequently. The assurance of normal growth, puberty, fertility and endocrine function – including the prevention of secondary malignancies – is of utmost importance for the overall success of treatment and the maintenance of a high quality of life. This, however, requires a systematic and structured follow-up programme for patients after SCT. Patients and their families need to be made familiar with this concept early and physicians need to understand that such a system must be implemented as part of a comprehensive care.

Organisation of the PDWP

The PDWP Board

The Board of PDs WP is made up of the representatives of the most active European countries involved in Haematopoietic Stem Cell Transplantation. This group collaborates with the Chairman for the realisation of the programme planned before his election. Today, the Board includes the representatives of Austria, Germany, Italy, Spain, The Netherlands, The UK. Two members represent France (one for autologous one for allogeneic HSCT), whereas Nordic European Countries (Norway,  Denmark, Finland, Sweden) and , Eastern European Countries (Poland, Slovakia, Czech Rep., Romania, Lithuania, Russia, Slovenia) and non- European have one representative per group.

Some members of the Board have specific roles: Dr Isaac Yaniv is the PDs WP representative within the EBMT Definition Committee, and Dr Angelucci is responsible of the EBMT Thalassemia Registry.