the incidence of CKD in AHSCT recipients was comparable to that with matched sibling donor allogeneic‐transplant but lower than matched unrelated donor allogeneic‐transplant. Analysis of the entire cohort showed older age at transplant and prophylaxis or treatment of GVHD with cyclosporine +/‐ tacrolimus as independent risk‐factors for subsequent CKD [49]. Another cohort study showed the cumulative incidence of dialysis to be 2.3% posttransplant compared to a pretransplant prevalence of 1.4% in auto‐transplant recipients [3]. Posttransplant dialysis was also a risk‐factor for subsequent cardiovascular disease. In pediatric populations, AHSCT for neuroblastoma is an independent risk‐factor for development of subsequent hypertension, which can further predispose to kidney complications [50]. Monitoring for renal complications after transplant should include measurement of serum creatinine, blood urea nitrogen, urine protein, and blood pressure management [17]. Further investigations, including imaging or kidney biopsy, should be performed as clinically indicated. A small randomized clinical trial demonstrated renal‐protective benefit to initiation of captopril in patients receiving TBI‐based conditioning prior to transplant [51]. Patients in the captopril arm had a lower serum creatinine and higher eGFR at 1 year compared to placebo.
Infectious Complications
Late infectious complications are more common with allogeneic‐transplant compared to AHSCT due to the need for prolonged immunosuppression in allogeneic‐transplant recipients. In the Bone Marrow Transplant Survivor Study, late infections were not a major cause of mortality in AHSCT survivors [8]. However, the median age at transplant in this study was low at 37 years and the cohort did not include patients with MM, which is currently the most common indication for AHSCT. A Finnish study of approximately 1500 adult AHSCT recipients with lymphoma, MM, or breast cancer demonstrated infectious complications as a cause of later (>100 days) non‐relapse mortality in one‐third of patients who had died at latest follow‐up [52]. The most common fatal late infections were sepsis and pneumonia, with the median time from AHSCT to fatal infection being 28 months [52]. A French study on late effects (defined as >30 days) in AHSCT recipients of aggressive NHL showed infections in approximately one‐third of patients with late toxicities though none were fatal [53]. Another Canadian study on long‐term survivors of AHSCT for primary‐refractory or relapsed HL showed unusual infections, including varicella zoster virus (VZV) infection in 34% of patients at a median of 6 months and cutaneous or respiratory infections beyond 5 years posttransplant, including S. aureus and Aspergillus pneumonia, streptococcal necrotizing fasciitis, and bacterial endocarditis [54].
All patients should receive recommended posttransplant vaccinations, starting 3 months after AHSCT [19]. Since efficacy of most vaccinations depend on reconstitution of the adaptive immune system, consensus guidelines recommend deferring vaccinations to 12 months after transplant, if patients have received anti‐CD20 monoclonal antibody less than six months prior [19]. Similar logic can be extended to those who had received monoclonal antibodies directed against plasma cells, including anti‐CD38, anti‐SMAMF7, and anti‐BCMA. Detailed guidelines on posttransplant vaccinations are beyond the scope of this chapter and have been summarized elsewhere [19].
Quality of Life and Psychosocial Effects
Though there are abundant studies on early health‐related quality of life (HRQoL) and psychosocial effects of auto‐transplant, data on long‐term HRQoL are scant in this population [55,56]. Common late psychosocial effects after AHSCT that have been described include distress, anxiety, and depression. In a study on HRQoL and psychosocial health in transplant survivors at a median of 7 years posttransplant, significantly inferior HRQoL was noted compared to healthy controls [57]. Approximately 60% of patients in this cohort were auto‐transplant survivors. HRQoL decrement was noted in several domains, including physical health, physical functioning, social functioning, psychological adjustment, and relationship adjustment [57]. Within the physical functioning domain, transplant survivors reported more sleep and sexual problems, higher fatigue, pain, and cognitive dysfunction. Furthermore, transplant survivors also reported more depressive symptoms, anxiety, poor mental health, and poor spiritual well‐being compared to controls [57]. Another prospective study on long‐term HRQoL after AHSCT showed stabilization of most domains at 3 years, except for role functioning and patient‐reported dyspnea, which had improved compared to baseline [58]. Notably, patients with a primary lymphoma diagnosis had a superior HRQoL at 3 years compared to those with MM [58], which is likely explained by the fact that patients with MM are not cured with transplant, and thus will eventually have progressive disease. Transplant‐related concerns or problems reported by more than one out of four survivors are fatigue, worsening overall condition, lack of sexual interest and satisfaction, changes in appearance, pain, retaining job, being able to work at home, and transplant being unsuccessful [59]. In patients with relapsed MM undergoing salvage auto‐transplant, patient‐reported global health status/QoL is significantly worse at day 100 compared to those undergoing non‐transplant consolidation. However, the QoL decrement in the transplant arm dissipates at 6‐month and beyond [60]. The incidence of depressive symptoms in long‐term transplant survivors ranges from 7–15% [59,61], however, granular data on depression in auto‐transplant survivors are lacking. Auto‐transplant survivors with three or more non‐malignant late effects have worse physical functioning, higher likelihood of moderate to severely limited usual activities, and lower likelihood of returning to full‐time work or study compared to those with two or less late effects [3]. Auto‐transplant survivors are also more likely to have difficulty maintaining a job due to health problems compared to their siblings, with the risk being 2.6‐fold higher in older survivors [8].
Patients should be clinically assessed for distress, anxiety, depression, and HRQoL during the transplant recovery period, at 6 months, 1 year, and annually thereafter, ideally in a dedicated survivorship clinic with dedicated social workers. Referral should be made to a mental health professional if clinically indicated [17]. Transplant survivors should also be queried about sexual functioning periodically and caregivers should be assessed for mental health, psychological, and relationship adjustment. Long‐term financial toxicity due to inability to retain jobs especially in high‐risk patients can be potentially addressed by social work or a financial navigator in the transplant clinic.
Cognitive Dysfunction
Neurocognitive deficit is a well‐recognized late effect in HSCT recipients [7]. Cognitive dysfunction can be measured by subjective patient‐reported instruments (e.g. FACT‐Cog or PROMIS‐Cognitive Function) or objective neuro psychological testing, with the optimal tool depending on the clinical or research question [62]. In patients with breast cancer, receipt of high‐dose chemotherapy followed by autologous hematopoietic progenitor cell infusion was associated with a higher incidence of late cognitive impairment compared to standard dose chemotherapy (32% vs 17%) on neuro psychological testing [63]. Regarding self‐reported cognitive problems, auto‐transplant recipients scored significantly worse on the domains of concentration, memory, and thinking, compared to those who had received standard chemotherapy [63]. Another study on 388 transplant survivors with hematologic malignancies or breast cancer, approximately 80% of whom had received an auto‐transplant, showed significant improvement in objectively measured cognitive abilities at 1 year after transplant [64]. Performance in individual cognitive domains, as well as total neuro psychological performance score, was equal or superior to the population mean at 1 year [64]. Definitive data on comparative effect of auto‐transplant with high‐dose melphalan conditioning on patient‐reported cognitive impairment has been reported in the Myeloma X trial [60]. It was a large RCT comparing salvage second auto‐transplant to non‐transplant consolidation with oral cyclophosphamide in patients with relapsed MM. In auto‐transplant recipients, a clinically significant decrement in cognitive functioning was noted at day 100 compared to the non‐transplant arm. However, at 6‐month, 1‐year, and 2‐year marks, cognitive functioning gradually improved in the transplant arm, with the magnitude of improvement over non‐transplant arm increasing at each time‐point [60]. Cognitive rehabilitation
