Building a National Framework for Adolescent and Young Adult Hematology and Oncology and Transition from Pediatric to Adult Care: Report of the Inaugural Meeting of the “AjET” Working Group of the German Society for Pediatric Oncology and Hematology

Introduction

Adolescents and young adults (AYAs) with hemato-oncological problems constitute a heterogenous group with special characteristics and needs, age-specific clinical and unique psychosocial features. Strong collaboration between the pediatric and the adult hemato-oncology settings is essential if their needs are to be addressed in an appropriate manner. ¹ This is not only true for patients who first become ill during adolescence or young adulthood, but equally so for people who contract hemato-oncological diseases congenitally, as infants, or as younger children and who are now becoming old enough to leave the pediatric age range and have to transit into “adult” medical care. Their number is increasing due to the outstanding improvements in the treatment of childhood cancer as well as of inborn hematologic disorders (IHDs).^2–5

As is the case for the typical AYA cancer patient, the specific needs of this patient group have to be recognized.^6–8 On one hand, their age-specific challenges frequently mirror those of patients who contract cancer as AYAs. On the other hand, they also face rather specific health-related challenges, which often become apparent only during the transition period and which carry a considerable risk of increasing with age.^9,10

The important needs of both of these patient groups have been addressed by many authors earlier.^5–10 Patients in both groups have an incremental risk of chronic health conditions for several reasons: In childhood cancer survivors, not only the treatment of childhood cancer but also age at diagnosis, the cancer diagnosis itself, and host factors such as genetic alterations influencing pharmacologic factors and lifestyle variants are important factors influencing long-term morbidity.^9,10 Patients with inborn hematologic diseases, for example, the hemoglobinopathies or immunodeficiency syndromes, suffer chronic illnesses with the need for continuous medical care. The risks of severe disease or treatment-related complications are increasing with age in these patients.^11,12

Efforts to create environments that fulfil the specific needs of the AYA population affected by hemato-oncological diseases have been initiated in many countries.^9,13–15 Due to international variations between societies in general and between healthcare infrastructures in particular, the challenges posed to creating such environments vary considerably from country to country. Aiming at addressing these on a national basis for Germany, a dedicated Working Group on Adolescents, Young Adults, and Transition (Arbeitsgemeinschaft Adoleszenten, junge Erwachsene, Transition, AjET) was established within the German Society for Pediatric Oncology and Hematology (GPOH). Following the reasoning provided earlier, we chose not to limit ourselves to “AYA oncology,” but to also work on AYA hematology—hematology and oncology are a single specialty in our country—and to include the topic of transition in close cooperation with partners from medical oncology and other “adult” disciplines as well as partners from other national and international AYA networks.

The aim of the first national, interdisciplinary meeting of our AjET group was to bring together the activities of existing projects and to integrate adult care workers and pediatric hematologists and oncologists. Core elements of the presentations and discussions of the meeting are summarized next.

Cancer in AYAs

Cancer in adolescents and young adults (CAYA) is relatively rare. Each year in Germany, ∼10,000 individuals aged 15–29 years are diagnosed with cancer. ¹⁶ The group of patients to consider is heterogeneous; however, patients with mesenchymal tumors such as sarcomas of bone and soft tissue (∼12%) and leukemias (∼8%) are overrepresented in this age group.

Cancer risk and adverse cancer outcome in AYAs are not well recognized in Germany, although it is the second most common cause of death in this age group. In contrast to the general trend observed in young cancer patients, AYA patients have benefited less from recent improvements in prognosis. ¹⁷ In the United States, twice as many AYA patients die from cancer than children up to 15 years. ¹⁸ Whether the international data are transposable into the German situation remains to be evaluated. However, age-related prognostic differences are well described not only for AYA patients with pediatric malignancies such as blastomas, ¹⁹ but also for those cancers with a higher incidence in AYAs such as bone sarcomas ²⁰ and soft tissue sarcomas.^21–23

In cancer of childhood, the successful collaborative endeavors conducted in Germany under the auspices of the GPOH have impressively improved the prognosis. Large-scale, first-line investigator-initiated trials (IITs) under the auspices of the German Society of Hematology and Oncology (DGHO) and the German Cancer Society (DKG) have achieved similar improvements of outcome in adult leukemia and lymphoma, but less so in other entities. Industry-sponsored trials and IITs have, due to the larger number of patients, been focused on the main cancers of adulthood, with major improvements of outcome still being awaited for some of these entities. CAYA, however, has been underrecognized and the increment in prognosis in AYA patients is significantly behind that of younger age groups.

It is well known that long-term side effects of chemotherapy, radiotherapy, and surgery may increase the risk of chronic health problems.^6,7 A sustained follow-up and quality of life (QoL) program must, thus, be an essential component of care in young cancer patients. Although long-term follow-up in pediatric patients is often assured by follow-up visits to the primary treating clinic, the situation is different in AYAs.^24,25 They will move on to adult settings and might no longer be seen by an oncologist. A standardized transfer of information and sustained long-term follow-up programs supported by health insurance carriers are needed to soon enough identify conditions that are better treated at an early stage and to prevent secondary chronic diseases.

Transition of Childhood Cancer Survivors

Transition should start in the teens; an example was demonstrated by the Stuttgart team, which organizes special camps for teenagers and young adult survivors on a regular basis. “Prima Klima” is an initiative that was set up in 1991. The aim is the planning and conducting of an annual 5-day camp for children and adolescents with cancer, in which they are unaccompanied by their parents. The core team of “Prima Klima” consists of psychosocial workers, two nurses, and a doctor. Besides these professionals, volunteer (themselves survivors of childhood or adolescent cancers who are now young adults) are involved in all stages of planning and realization of the initiative. The survivors act as inspiring examples of successful integration into society after life-threatening illnesses. On the other hand, active participation is a way of coping for the survivors themselves.

A website addressing AYAs specific problems: “www.junge-erwachsene-mit-krebs.de” and moreover, a web-based consulting service: and “www.junges-krebsportal.de” were presented as an initiative of the DGHO's Foundation for Young Adults with Cancer (Deutsche Stiftung für junge Erwachsene mit Krebs). The lack of specific information for this age group and the low threshold service are addressed by this website. Contacts with medical specialists and access to their clinics are organized via the portal. The aim is to offer this service in all fields that are relevant for young patients with cancer and long-term survivors.

A “Network Oncological Advisory Service” (Netzwerk Onkologische Fachberatung/NOF) is active within the German Federal State of Lower Saxony and started its work in November 2013. The advisory service and hotline are open to former pediatric cancer patients of all age groups as well as their family members. Next to a telephone hotline, which is operative twice weekly, the NOF Team advises former pediatric cancer patients (“survivors”) by using a case-related approach. The advice comprises medical, psychosocial, and medico-legal issues as well as cancer and treatment-related everyday coping problems. The documentation and scientific evaluation of the work to date shows a significant detriment in QoL for many of the clients. The main concerns reported include long-term medical problems and a lack of availability of expert advisory staff. Further significant issues for former patients include reactions/coping in their social networks to the illnesses and insufficient long-term support within the medical system.

An advisory service focusing on psychosocial issues has also been established in Munich (KONA—Koordinationsstelle psychosoziale Nachsorge für Familien mit an Krebs erkrankten Kindern). This project offers support not only for the patients but also for all family members. In 2006, KONA started their project “Jugend & Zukunft” (youth and future) for AYAs cancer survivors and adolescents with hematologic disorders.

The University Cancer Center in Hamburg (UCCH) has established a program for AYA cancer survivors aged between 15 and 39 years to ensure interdisciplinary and multiprofessional survivorship care in this particularly vulnerable population. Besides improving the transition process by joint pediatrician and medical oncologist patient care, treatment and disease-related physiological and psychological long-term effects are addressed by a multidisciplinary team of physicians, psycho-oncologists, and nutritional and sport counselors. Accompanying research projects include the evaluation of lifestyle-modifying interventions and long-term follow-up of this patient group in a biobank-linked registry.

A multidisciplinary clinic for childhood cancer survivors is also available at the University Hospital Schleswig-Holstein (Luebeck, Germany). Here, adult endocrinologists and pediatric oncologists see former pediatric oncology patients together in an interdisciplinary outpatient clinic. The prerequisite is that patients are at least 16 years old and their cancer diagnosis dates back at least 5 years. In a retrospective questionnaire-based unicenter study, the Luebeck group observed that adults younger than 25 years were the most likely to accept an invitation for consulting a specialized late-effects clinic. Survivors accepting such an invitation showed a poorer overall QoL and more often consulted a general practitioner than those survivors not following the invitation for the late-effects clinic.

Aiming at addressing the specific psychosocial needs of AYA survivors of pediatric cancers, the rehabilitation center Katharinenhoehe has developed special programs for these particular patient cohorts. The therapeutic concept is based on forming small groups of either adolescents or young adults who spend a whole 4-week stay together. Sharing similar age and experiences, the attendees of these peer groups are enabled to bond, form deep mutual understanding, and regain a sense of normality in their lives. This approach activates individual resources and facilitates coping with the disease to an extent that is unattainable in surroundings shared with elder patients. As the repercussions on personal life and development brought about by cancer are fundamentally different in different stages of life, distinct challenges arise. The support between patients of the same age delivers unique advantages for group-based psycho-oncological interventions, fosters active coping, and improves the quality of living.

Transition in the Field of Hematologic Disorders

Advances in medical treatment, as well as in research, have dramatically increased the lifespan and QoL in patients with rare anemias (e.g., thalassemia major, sickle cell disease, or Diamond Blackfan anemia). Especially in patients with sickle cell disease, clinical problems are increasing with age and the rate of acute care encounters in the age group from 18 to 30 years is nearly twice as high as in earlier years. Pediatric teams are frequently not familiar with medical and psychosocial problems associated with adulthood in patients with both of these disease entities. On the other hand, adult hematologists experienced in these “benign” hematological disorders are very sparse. The great need to develop transition programs and specialized care teams to ensure ongoing adequate care for patients with hemoglobinopathies is obvious, but still there are many barriers.

Transition in patients with chronic hematological disorders is a very complex process comprising many different parts, including continuous medical care according to common pediatric and internal medicine standards as well as developmental aspects such as social integration, puberty, professional education, and social integration. Both medical and non-medical aspects strongly interact with each other. Interruption of state-of-the-art treatment carries the risk of life-threatening acute complications as seen in patients with sickle cell disease or of irreversible organ damage leading to long-term complications as found in patients with thalassemia and iron overload.^5,8

In the optimal situation, transition will consider the change of a well-educated patient from an experienced pediatric hematologist to a well-qualified internal hematologist at the place where the patient lives. Alternatively, in the lack of sufficient local experience, the transition process has to be accompanied by a specialized hematologist—either pediatric or internal hematologist—in a center with experience in the care for these rare disorders counseling the local healthcare providers. Apart from continuous medical education of healthcare providers, education of adolescent patients toward an “expert patient” will be one of the most important strategies to ensure continuous adequate care.

The University Medical Center Hamburg-Eppendorf (UKE) is striving to achieve a smooth transition progress by starting the process as early as during puberty. During yearly patient and family workshops, pediatric patients and their parents meet older patients as well as members of the adult care team. The willingness of parents to hand over the responsibility for medical treatment to their affected offspring is of central importance within the transition process. An interdisciplinary team of physicians from different adult care facilities (e.g., emergency room, cardiology, endocrinology, gynecology, radiology) has been formed at the UKE. Thus, similar to the pediatric setting, adolescent and adult patients can be followed and treated within one communicating team. A pediatric hematologist working in both the pediatric and the adult hematology outpatient clinic assumes the central coordinating role in this process.

The more recent wave of migration from areas of the world with a high prevalence of hemoglobin disorders to Germany represents a new and additional challenge within the transition progress. Apart from “informed, well treated migrants” coming from areas with adequate medical and social care, other patients are coming from areas with almost absent care, presenting many complications of their disease, lacking specific medical education on their disease, and often suffering from stronger cultural, religious, and social barriers. These patients actually constitute an enormous challenge for hematologists and related healthcare professionals.

Paucity of knowledge and experience in treating these disorders, a lack of competence in structuring the transition process, and a lack of competence in multicultural care are seen as major reasons for an increased incidence of medical problems within patients with chronic hematologic disorders. These difficulties underline the need to support patient empowerment and participation of patients.

The need of a structured and guided transition process was underlined by the team from Stuttgart for patients with inherited bleeding disorders. The goal of transition is to provide healthcare that is uninterrupted, coordinated, developmentally appropriate, and psychologically sound before and throughout transfer into the adult system. A survey carried out in late 2015 showed that transition in Germany is exclusively based on local conditions, regardless of size and type of treatment centers. Development of checklists and national guidelines are demanding projects for the future.

Taking dyskeratosis congenita (DKC) as an example, the necessity of informed patients and awareness of clinicians of diseases outside of their original field was also emphasized for patients with other rare inborn hematologic diseases such as telomeropathies. These diseases mostly manifest in children, but the awareness of late-onset hereditary telomeropathies that may first become apparent as bone marrow failure syndromes, pulmonary fibrosis, or liver cirrhosis up to the age of 40+ years is increasing. The disease is suspected to be largely underdiagnosed in adults. Telomere length screening is being offered, and cases are being collected at the Telomeropathy Registry of the Department of Hematology and Oncology at the University Hospital of the RWTH Aachen. Due to otherwise irreversible organ dysfunction in patients who are diagnosed too late, early detection and diagnosis is mandatory to optimize treatment response and to prevent avoidable toxicities.

Summary and Conclusion

With the increasing availability of potentially curative therapies for AYAs with cancer and with increasing numbers of cancer survivors and patients with chronic hematologic disorders now reaching adulthood, developing specific guidelines as well as dedicated multidisciplinary teams and multidisciplinary infrastructures that address the specific needs of these patient groups assume ever-increasing importance. Within this context, transition has to be considered and managed as a dynamic process rather than a fixed event.

Aiming at improving the situation in Germany, the AjET working group of the GPOH led by Prof. U.D. intends to strongly enhance the national awareness for AYAs with hemato-oncologic diseases, to strengthen collaboration between pediatric and adult care givers and to initiate, promote, and coordinate collaborative activities in the fields of basic and translational research, clinical care, and long-term follow-up (Table 1). AjET's activities are embedded in European and other international activities. AjET strongly supports the AYA objective of SIOP-Europe's (SIOPE's) Strategic Plan: “to address the specific needs of teenagers and young adults in cooperation with adult oncology,” and one of the co-authors of this article (S.B.) co-chairs the joint “Cancer in AYA” Working Group of the European Societies for Medical (ESMO) and Pediatric (SIOPE) Oncology, created in 2016. AjET members also participate in European Networks dedicated to research on late effects in childhood cancer survivors (PanCare SURFup ²⁶ and Pan Care LIFE ²⁷ ) and the International Guideline Harmonization Group. ²⁸

It was clearly stated by all participants of the kickoff-meeting of the German AjET group that the major objective is an improved outcome in this group of young patients with cancer, survivors of childhood cancer, as well as IHDs. This will be achieved by:

• setting up a nationwide multiprofessional network dedicated to adolescents and young adult AYAs with malignant or chronic hematological disease

This encouragement should be supported by our medical healthcare system and should be adapted to the needs of the patients rather than the patient adapting to the medical health system.