of possible late effects that interfere with health conditions. The setup of an LTFU clinic is part of the LTFU program chosen by the transplant center. There are different models of long‐term transplantation clinics, all of them with their advantages and their drawbacks. However, to provide optimal LTFU care to the long‐term survivors, they must all fulfill some minimal characteristics. A common outpatient HSCT clinic, where acute care and long‐term follow‐up are mixed, allows continuity in the care but faces the risk that the particular needs of long‐term survivors are left behind the daily care of the new post‐transplant patients.
In this chapter, the setup of a long‐term transplant clinic and the essential functions and components of an LTFU care program will be outlined. Different models of survivorship programs and LTFU clinics will be considered, and barriers, as well as the minimal requirements, discussed. There are many similarities between LTFU of cancer and of HSCT recipients. Therefore, in this chapter, studies of cancer survivorship are included; similarities and differences between both are discussed.
Concept of long‐term survivorship
The concept of survivorship in cancer patients was created by the National Coalition for Cancer Survivorship (NCCS) in 1986 [9]. According to the Institute of Medicine, cancer survivorship is the phase of care that follows primary treatment. However, this definition allows a wide range of interpretations, depending on the time of diagnosis, the completion of treatment, and the time interval between the diagnosis and the end of treatment of cancer. The Institute of Medicine and leaders in cancer survivorship have recommended cancer centers to examine and evaluate the setup of services for survivors. In a first step, general recommendations and the development of guidelines have been assessed for pediatric and young adult cancer survivors [10,11]. The Institute of Medicine provided a template for the four essential elements of survivorship care: prevention and detection of late effects, surveillance, interventions to manage side effects, and coordination of care and information [12]. Meanwhile, awareness for needs of HSCT survivorship care has risen, and was addressed in a workshop from the National Academies of Science, Engineering, and Medicine. The participants of the Workshop suggested to include issues on education and training, employment and work‐related concerns, financial toxicity and insurance concerns, as well as research needs [13].
Late effects after HSCT
Late mortality is increased in long‐term survivors of allogeneic HSCT when compared with an age‐ and gender‐matched general population. More than 25 years after transplantation there is still a two‐fold excess in death rate [14]. Life expectancy among 5‐year survivors after HCT is reduced by approximately 30% compared to the general population, regardless of current age or time from transplantation [15]. A variety of pre‐ and posttransplant factors can contribute to the risk of late complications. They include patient‐related factors (e.g. age, gender), lifestyle factors (smoking, physical inactivity, unhealthy diet), pretransplant co‐morbidity (particularly in elderly patients), chemotherapy and radiotherapy applied before transplantation or as conditioning regimen, and posttransplant complications (GVHD and its treatment) [16]. Some of the late complications, such as secondary malignancies and vascular complications are expected very late after HSCT. Even three decades after allogeneic HSCT, the cumulative incidence for secondary solid tumors or vascular complications continues to increase, with no indication of a plateau developing [17,18]. Other late effects appear early after HSCT but have relevant consequences on the long‐term health condition and quality of life. A typical example is bronchiolitis obliterans syndrome often occurring within the first year after allogeneic HSCT, with respiratory consequences in the long‐term. Infertility is also an early consequence of pretransplant treatment and the conditioning regimen used for HSCT. However, this complication worries survivors many years after HSCT, frequently at a time when they have overcome acute toxicity and the phase of early complications. These data demonstrate that individuals undergoing HSCT, even when cured of their primary disease, will mandatorily need a lifelong commitment for posttransplant survivorship care.
Timing and transition to long‐term survivorship care
When does survivorship care start? Most studies on late effects after HSCT include recipients surviving two years or longer after transplantation when they are in remission of their primary disease. However, in daily routine, the precise timing of long‐term survivorship care is not stringent. In cancer patients, it is usually defined by the time the primary treatment ends. In many HSCT centers, the posttransplant survivorship begins when the patient no longer needs regular posttransplant care. At that time, annual survivorship visits are considered as a standard for long‐term follow‐up. With growing numbers of long‐term survivors after HSCT, many centers refer their patients back to the primary care provider or to the referring hemato‐oncology center. However, some long‐term follow‐up may need to be conducted by the transplant center or a specialized LTFU clinic, especially if patients present transplant‐related complications such as chronic GVHD (cGVHD) [16]. The transition to long‐term follow‐up care from the HSCT team to another set of providers, ensuring optimal care of long‐term survivors is a vulnerable period. This transition may result in fragmentation of care and poor communication between the different care providers and for some groups of patients represent a risk being lost in transition. Continuity of care implicates an adapted model of LTFU clinic, but also optimal coordination between the LTHU clinic, the primary care provider and the long‐term survivor, with a clear definition of the responsibilities of each part. An HSCT long‐term survivorship care lasts until the recurrence of the primary disease, development of a subsequent cancer, or death of the patient. In the case of relapse or secondary cancer, survivors become cancer patients again, reentering possibly in the acute phase of cancer treatment [12]. Some of the controversial issues of a survivorship program concern the type and frequency of optimal follow‐up care, the increased expenses caused, as well as the extra time and the physical space needed to run such a program. In many countries, insurances that cover expenses of the HSCT, will not cover the costs of the follow‐up care.
The transition from pediatric to adult long‐term care
Survivors of childhood cancer have a high rate of illness due to the occurrence of chronic health conditions [19]. Despite long‐term late effects and care impact on all age groups, there is a paucity of data on the transition to adult healthcare from young adults transplanted during childhood. There are some specific issues for this subpopulation [20]. Several modes of cancer survivor care are applied, mainly depending on the size of the pediatric HSCT center and the center’s preferences: HSCT center‐based model (I) without a referral, where adult survivors are kept indefinitely at the treating institution; community referral model (II), where survivors are transitioned at adulthood to their primary care professionals; hybrid model (III), where the survivors are transitioned to community healthcare providers who collaborate closely with the treating institution for all questions concerning long‐term survivorship; adult HSCT LTFU model (IV), where the survivors are transitioned definitively to an LTFU‐clinic or HSCT center [21]. Independent of the selected model, there is the need to identify healthcare professionals with experience in childhood and adult HSCT, expertise in long‐term follow‐up and able to coordinate healthcare transition and future planning. During the childhood of the young cancer patient, the parents or other adult family members took the responsibility and the decisions for the child’s healthcare. In the preparation for the transition phase, the young adult survivor has to be motivated to become responsible for his survivorship care. Furthermore, it must be ensured that the healthcare insurance will continue to cover for all HSCT‐related complication through the adulthood [21,22].
Barriers to successful healthcare transition included the survivor’s psychological condition and knowledge about their primary disease, the attitude of pediatric and adult health‐providers, and the health system itself. Unlike their adult counterparts, childhood HSCT survivors have often limited access to information on the diagnosis and treatment of their malignancy, as well as on adverse effects that can occur later in life. They may
