1.1 Timelines for post‐HCT late effects.
(Source: Courtesy of Prof. John Barrett.)
Long‐term issues in long‐term survivors
For long‐term survivors (beyond 2 years post‐HSCT), the prospect for long‐term survival is excellent (85% at 10 years after HSCT). Yet, among long‐term survivors, mortality rates are four‐ to nine‐fold higher than observed in an age‐adjusted general population for at least 30 years after HCT, yielding an estimated 20–30% lower life expectancy compared with someone who has not been transplanted [19,20]. The most common causes of excess deaths, other than recurrent malignancy, are chronic GVHD (cGVHD), infections, second malignancies, respiratory diseases, and cardiovascular disease and many other late effects reviewed in this book.
cGVHD is a multisystem chronic alloimmune and autoimmune disorder that occurs later after allo‐HCT. It is characterized by immunosuppression, immune dysregulation, decreased organ function, significant morbidity, and impaired survival. A number of patients require continued immunosuppressive treatment beyond 5 years from the initial diagnosis of cGVHD. Therefore, it is not surprising that corticosteroid and other immunosuppressive therapies are major contributors of late complications after allo‐HCT. If not treated adequately, and in severe cases, cGVHD can result in major disability related to keratoconjunctivitis sicca, pulmonary insufficiency due to bronchiolitis obliterans, or restrictive lung disease related to scleroderma or fasciitis, as well as joint contractures, skin ulcers, esophageal and vaginal stenosis, and many other long‐term complications [4,21].
Several factors impact on recovery from and late effects of HCT, including previous therapy for the underlying disease, pretransplant co‐morbidities and psychosocial status, intensity of the transplant conditioning regimen and, most importantly, duration of cGVHD and immunosuppressive therapy [18,22]. Other complications are related to the prolonged use of glucocorticoids and other immunosuppressive drugs, and many are multifactorial in etiology. Side effects of the treatment of acute complications early after HCT (e.g., the use of corticosteroids) may also contribute to long‐term complications. Nearly all organ systems can be affected by late effects of HCT. However, the burden of late effects can greatly differ among long‐term survivors, primarily depending on patient‐ and transplant‐related risk factors.
Developing resources and a guide for long‐term survivors
Ongoing research is focused on better understanding of late effect issues and prediction of posttransplant long‐term complications, which allows transplant‐eligible patients to incorporate this knowledge into more informative decision making [18,23]. Therefore, significant resources should be focused on the better implementation of how patients and physicians use extensive data regarding posttransplant late complications in clinical care.
With survivorship, a shift in care occurs from large transplant centers to community healthcare providers. As a result, many hematologist/oncologist and primary care physicians are assuming the posttransplant care of long‐term survivors. Preventive measures, as well as early detection and treatments, are important aspects to reducing morbidity and mortality in long‐term survivors after HCT. This book [17] offers the updated practical advice and outlines late effect experts’ personal approaches in managing long‐term survivors after HCT. The management of late HCT effects is important to improve long‐term survival of HCT recipients but should be tailored to the risks specific to the primary disease and transplant type. Future planning should account for the impact of the expected increase in transplant activity and number of survivors on resource utilization.
We also recommend early referral or discussion with a transplant center for enrolment of patients in available late effect studies and for management guidelines. A better understanding of the pathogenesis of late effects will allow for more effective screening to identify patients at risk prior to the HCT procedure, and allow more effective monitoring to detect early evolution of the late effects after HCT. This may, in turn, allow for improved therapeutic decision making while evaluating patients for HCT, and early institution of treatments directed at preventing and treating late effects in patients at risk after HCT. To better inform the needs of the contemporary HCT survivor generation and guide the delivery of late effects services, periodic analysis of new survivor cohorts is needed.
Declaration of commercial interest
None.
References
1 1. D'Souza A, Fretham C, Lee SJ, et al. Current use of and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant, 2020.
2 2. Blume KGT, E. D. Chapter 1: A history of allogeneic and autologous hematopoietic cell transplantation (ed Fifth). Oxford, UK, John Wiley & Sons, Ltd, 2015 pp. 1–11
3 3. Horowitz MM. Chapter 2: Uses and Growth of Hematopoietic Cell Transplantation (ed Fifth). Oxford, UK, John Wiley & Sons, Ltd, 2015 pp. 8–17.
4 4. Savani BM (Editor). Blood and marrow transplantation long‐term management: prevention and complications (ed First). Oxford, UK, John Wiley & Sons, Ltd, 2013.
5 5. Shah NN, Ahn KW, Litovich C, et al. Allogeneic transplantation in elderly patients >/=65 years with non‐Hodgkin lymphoma: a time‐trend analysis. Blood Cancer J 9:97, 2019.
6 6. Cooper JP, Storer BE, Granot N, et al. Allogeneic hematopoietic cell transplantation with non‐myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica, 2020.
7 7. Canaani J, Beohou E, Labopin M, et al. Trends in patient outcome over the past two decades following allogeneic stem cell transplantation for acute myeloid leukaemia: an ALWP/EBMT analysis. J Intern Med 285:407–418, 2019.
8 8. Bakhtiar S, Salzmann‐Manrique E, Hutter M, et al. AlloHSCT in paediatric ALL and AML in complete remission: improvement over time impacted by accreditation? Bone Marrow Transplant 54:737–745, 2019
9 9. Khoury HJ, Wang T, Hemmer MT, et al. Improved survival after acute graft‐versus‐host disease diagnosis in the modern era. Haematologica 102:958–966, 2017.
10 10. Kanate AS, Majhail NS, Savani BN, et al. Indications for Hematopoietic Cell Transplantation and Immune Effector Cell Therapy: guidelines from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant 26:1247–1256, 2020.
11 11. Hashmi S, Carpenter P, Khera N, et al. Lost in transition: the essential need for long‐term follow‐up clinic for blood and marrow transplantation survivors. Biol Blood Marrow Transplant 21:225–232, 2015.
12 12. Hashmi SK, Lee SJ, Savani BN, et al: ASBMT Practice Guidelines Committee Survey on Long‐Term Follow‐Up Clinics for Hematopoietic Cell Transplant Survivors. Biol Blood Marrow Transplant 24:1119–1124, 2018.
13 13. Savani BN, Griffith ML, Jagasia S, et al. How I treat late effects in adults after allogeneic stem cell transplantation. Blood 117:3002–3009, 2011.
14 14. Majhail NS, Rizzo JD, Lee SJ, et al. Recommended screening and preventive practices for long‐term survivors after hematopoietic cell transplantation. Biol Blood Marrow Transplant 18:348–371, 2012.
15 15. Bhatia S, Armenian SH, Landier W. How I monitor long‐term and late effects after blood or marrow transplantation. Blood 130:1302–1314, 2017.
16 16. Inamoto Y,
