Solid tumors may develop during LTFU and a study of >4900 survivors reported 22% CI of SMN at 30 years (8.1% if < age 20) [113]. This corresponds to a standardized incidence ratio (SIR) of 2.8‐fold higher than the rate for an age‐, sex‐, and calendar‐year matched SEER population; SIRs for children were 15‐fold higher at 1–10 years post‐HCT and 5‐fold higher at >30 years, thus lifetime monitoring is needed. It is noteworthy that the risk for SMN is not significantly different for 2–4.5 Gy TBI compared to chemotherapy only but still 2‐fold higher than the general population. Fractionated TBI 6–14 Gy is associated with higher rates of SMN, higher again for TBI 14.4–17.5 Gy, but not as high as for historical unfractionated TBI 6–10 Gy. The highest excess absolute risks per 1000 patient years were for breast cancer (EAR 2.2) and for oral (EAR 1.5) and skin cancers (EAR 1.5).
Certain heritable pediatric conditions have an increased risk for solid tumors independent of HCT that warrant SMN screening beyond the usual and might require relevant organ‐specific subspecialist consultation (see Table 8.1). Examples are DBA, certain phenotypes of FA, and DC. In patients with Li Fraumeni syndrome, HCT does not correct the underlying germline TP53 mutation and post‐HCT SMN risk is extremely high; cancer surveillance protocols are thus intense [114]; through age 18 years, surveillance focuses on “core” cancers: brain tumors, adrenocortical carcinoma, soft‐tissue sarcomas, bone tumors, and early onset breast cancer.
Multiple melanocytic nevi can develop after high‐dose chemotherapy exposures [115] and are best monitored periodically by a dermatologist with mole mapping. Osteochrondromas may appear incidentally on plain X‐rays after an average of 4.6 years in up to one‐quarter of children who received TBI before age 5 years; they rarely become malignant [116].
Survivorship care plans
Compliance with LTFU guidelines is suboptimal with non‐adherence by survivors and healthcare providers [9,10,117]. Young adults are most at risk, often because routine LTFU attenuates over time, possibly more at risk if their HCP perceives that the patient is doing well. Given the latency of late effects, LTFU requires education of survivors, their families, and also their pediatric and future adult HCPs. The Institute of Medicine has recommended that all survivors receive treatment summaries with individualized care plans [118]. Survivorship care plan usage appears to improve quality of life among HCT survivors [119]. There is inability of transplant centers to provide comprehensive survivorship care. More work is needed to assess the impact of models of survivor care [120, 121]. An ASTCT Practice Guidelines Committee survey found that respondents agreed that allogeneic HCT survivors have needs separate from GVHD, that complications could arise during transitions of care from pediatric to adult or from transplant center to PMD, but 55% did not have an LTFU clinic; 84% of individual practitioners prefer to provide their own survivorship care. Other barriers include a lack of expertise in sub‐specialties relevant to LTFU, logistics of the LTFU model of care, and financial issues [120]. Clearly, there is much more work to be done to optimize LTFU particularly for pediatric HCT survivors who are more prone to becoming lost to follow‐up.
References
1 1. Majhail NS, Tao L, Bredeson C, et al. Prevalence of hematopoietic cell transplant survivors in the United States. Biol Blood Marrow Transplant. 2013; 19(10):1498–1501.
2 2. Martin PJ, Counts GW Jr, Appelbaum FR, et al. Life expectancy in patients surviving more than 5 years after hematopoietic cell transplantation. J Clin Oncol. 2010; 28(6):1011–1016.
3 3. Majhail NS, Bajorunaite R, Lazarus HM, et al. Long‐term survival and late relapse in 2‐year survivors of autologous haematopoietic cell transplantation for Hodgkin and non‐Hodgkin lymphoma. Br J Haematol. 2009; 147(1):129–139.
4 4. Bhatia S, Francisco L, Carter A, et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long‐term survivors: report from the Bone Marrow Transplant Survivor Study. Blood. 2007; 110(10):3784–3792.
5 5. Wingard JR, Majhail NS, Brazauskas R, et al. Long‐term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2011; 29(16):2230–2239.
6 6. Sun CL, Francisco L, Kawashima T, et al. Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study. Blood. 2010; 116(17):3129–3139.
7 7. Stewart BL, Storer B, Storek J, et al. Duration of immunosuppressive treatment for chronic graft‐versus‐host disease. Blood. 2004; 104(12):3501–3506.
8 8. Newell LF, Flowers ME, Gooley TA, et al. Characteristics of chronic GVHD after cord blood transplantation. Bone Marrow Transplant. 2013; 48(10):1285–1290.
9 9. Miyamura K, Yamashita T, Atsuta Y, et al. High probability of follow‐up termination among AYA survivors after allogeneic hematopoietic cell transplantation. Blood Adv. 2019; 3(3):397–405.
10 10. Khera N, Chow EJ, Leisenring WM, et al. Factors associated with adherence to preventive care practices among hematopoietic cell transplantation survivors. Biol Blood Marrow Transplant. 2011; 17(7):995–1003.
11 11. Center for International Blood and Marrow Transplant Research (CIBMTR). Post‐transplant guidelines. 2012. Available from: https://www.cibmtr.org/ReferenceCenter/Patient/Guidelines/pages/index.aspx (accessed 24 August 2020).
12 12. Children's Oncology Group: Long‐term follow‐up guidelines for survivors of childhood, adolescent, and young adult cancers. 2018. Available from: http://www.survivorshipguidelines.org/ ().
13 13. Chow EJ, Anderson L, Baker KS, et al. Late effects surveillance recommendations among survivors of childhood hematopoietic cell transplantation: A children's oncology group report. Biol Blood Marrow Transplant. 2016; 22(5):782–795.
14 14. International Guideline Harmonization Group for Late Effects of Childhood Cancer. Available from: https://www.ighg.org/international‐guideline‐harmonization‐group/ (accessed 24 August 2020).
15 15. Shenoy S, Gaziev J, Angelucci E, al. Late effects screening guidelines after hematopoietic cell transplantation (HCT) for hemoglobinopathy: Consensus statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT. Biol Blood Marrow Transplant. 2018; 24(7):1313–1321.
16 16. Heimall J, Buckley RH, Puck J, et al. Recommendations for Screening and Management of Late Effects in Patients with Severe Combined Immunodeficiency after Allogenic Hematopoietic Cell Transplantation: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT. Biol Blood Marrow Transplant. 2017; 23(8):1229–1240.
17 17. Dietz AC, Savage SA, Vlachos A, et al. Late effects screening guidelines after hematopoietic cell transplantation for inherited bone marrow failure syndromes: Consensus statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects After Pediatric HCT. Biol Blood Marrow Transplant. 2017; 23(9):1422–1428.
18 18. Hartz B, Marsh R, Rao K, et al. The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis. Blood. 2016; 127(25):3281–3290.
19 19. Rose C, Ernst O, Hecquet B, et al. Quantification by magnetic resonance imaging and liver consequences of post‐transfusional iron overload alone in long term survivors after allogeneic hematopoietic stem cell transplantation (HSCT). Haematologica. 2007; 92(6):850–853.
20 20. Altes A, Remacha AF,