Blood and Marrow Transplantation Long Term Management. Группа авторов
Чтение книги онлайн.
Читать онлайн книгу Blood and Marrow Transplantation Long Term Management - Группа авторов страница 41
![Blood and Marrow Transplantation Long Term Management - Группа авторов Blood and Marrow Transplantation Long Term Management - Группа авторов](/cover_pre922544.jpg)
5 5. Children’s Oncology Group Nursing Discipline, Clinical Practice Subcommittee/Survivorship, Late Effects Committee (2007). Establishing and Enhancing Services for Childhood Cancer Survivors: Long‐Term Follow‐Up Program Resource Guide. Available from: http://www.survivorshipguidelines.org/pdf/LTFUResourceGuide.pdf (accessed 7 September 2020).
6 6. Majhail N, Hashmi S. Long‐term follow‐up program. In: Gluckman E, Niederwieser D, Aljurf M (eds). Establishing a Hematopoietic Stem Cell Transplantation Unit. Cham: Springer, 2018; pp.231–243.
7 7. Rizzo JD, Wingard JR, Tichelli A, et al. Recommended screening and preventive practices for long‐term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT). Bone Marrow Transplant. 2006; 37(3):249–261.
CHAPTER 6 Late effects post‐allogeneic hematopoietic stem cell transplantation
Shahrukh K. Hashmi1 and Yoshihiro Inamoto2
1 Division of Blood and Marrow Transplantation, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA
2 Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
Introduction
Advances in allogeneic hematopoietic cell transplantation (HCT) have increased the curative potential of the procedure and HCT survivors are living longer, however, at a cost of a higher burden of late complications (also known as “late effects”). The late effects have traditionally been defined as the complications arising at least six months after [1], and include both relapse and non‐relapse complications. Though the relapse incidence is highest early after HCT, most recipients remain at risk for relapse beyond one year following HCT [2] and support the use of an intense monitoring program for high‐risk patients with disease‐specific morphologic, radiologic, and/or molecular parameters. Since patients with relapsed disease are treated with intensive therapies, they are conventionally excluded from the general management model of a typical long‐term follow‐up, as discussed in detail elsewhere in this book. The basic concepts of non‐relapse late effects, including the role of chronic graft‐versus‐host disease (cGVHD) in late effects, are discussed in this chapter. The details of management for individual late effects are described later in the book. Details of cGVHD and its management are also described elsewhere.
Most of the late effects can be categorized based on the organ or system‐specific complications and usually arise due to a complex interaction of various factors which may include:
1 Chemotherapy/radiotherapy‐ or immunosuppressive therapy (IST)‐related complications (e.g., increased risk of subsequent cancers or increased risk of diabetes)
2 Direct effect of cGVHD (e.g., dry eye or dry mouth resulting from cGVHD)
3 Pretransplant co‐morbidities (e.g., a high HCT‐CI score)
4 Genetic predisposition to enhanced toxicities. (e.g., the presence of certain polymorphisms can predict late cardiotoxicity).
The complications arising from either of these variables may coalesce to decrease both the survival and the quality of life (QoL), (see Figure 6.1) thus making the biologic plausibility of a particular outcome with causation very difficult. An example of such an interaction in post‐HCT patients is fertility loss, which is a well‐known phenomenon in the survivors of HCT [3] and is associated with total body irradiation (TBI) due to endocrine disruption (central or gonadal) [4,5]. cGVHD may also lead to unsuccessful conception due to anatomic complications, especially when vaginal stenosis or strictures develop [6]. Among the baseline health parameters, smoking has an established relationship with fertility loss [7] (though data are lacking regarding this association within the HCT literature). Thus, various factors combine to cause adverse outcomes in an allogeneic HCT survivor.
Certain late effects of allogeneic HCTs are likely underestimated owing to the long time of occurrence of these effects. Since the probability of being lost to follow‐up is increasing by years after HCT [8], the data for the incidence of very late complications (e.g., subsequent neoplasms and cardiovascular effects) may not be appropriately captured and thus may lead to an underestimation of the true incidence.
The late effects of cGVHD occur in a nonsystematic fashion. Once cGVHD starts to manifest in a particular organ or system, quite frequently other organs/systems may also show signs of involvement with cGVHD, leading to autoimmune‐like systemic syndrome [9]. However, histologic and immunologic studies indicate a wide variety of differences in pathologic manifestations among different organs involved with cGVHD; for example, in liver cGVHD, the biopsies have indicated the presence of lobular hepatitis and a reduction or absence of small bile ducts with cholestasis resembling primary biliary cirrhosis [10], whereas, in cutaneous cGVHD, epidermal atrophy and dense focal dermal fibrosis are apparent without any significant inflammation [11]. Furthermore, specific organ late effects thought to occur only from cGVHD may have other etiologic factors playing a role. In summary, the exact pathogenesis of the late effects manifested as organ‐specific cGVHD are complex and a detailed discussion of this issue is beyond the scope of this chapter.
Figure 6.1 Dynamics of etiology of late effects in allogeneic HCT survivors.
Identification of late effects
Various methods of identifying late effects can be utilized. Unfortunately, since many organs or organ systems can be involved simultaneously, a strict timeline for the preventive landmarks post‐HCT cannot be formulated. Very late effects can be defined as those occurring at least 5 years post‐HCT. A general guidance strategy for psychological and organ‐based aspects of late effects is delineated. The common non‐relapse late effects occurring after HCTs are depicted in Table 6.1 and a brief description of each complication is given in this chapter.
Late effects
Acute and chronic infections
Infections occurring late in allogeneic‐HCT recipients typically have an onset within the first year of transplant, but HCT recipients remain at risk for a long period, especially when being treated with IST for cGVHD. After an allogeneic‐HCT, it may take a few months or up to one year for the immune system to completely reconstitute, thus justifying scheduled re‐vaccinations at regular intervals late after transplant, as indicated per the current immunization guidelines unless treatment for GVHD is ongoing. Owing to both IST and cGVHD, immune recovery can be delayed and a functional immunodeficiency state can persist post‐transplant beyond one year due to impairment of both humoral and cell‐mediated immunity (mainly