Cataracts and Other Neurosensory and Neuromotor Late Effects in Childhood HSCT Survivors.
Authors: Gurney James G. , Ness Kirsten K. , Rosenthal Joseph , Forman Stephen J. , Bhatia Smita , Baker K. Scott 
Published: April 2020

A variety of life threatening childhood conditions are now successfully treated with hematopoietic stem cell transplantation (HSCT), as either a first line or rescue therapy. Improved survival rates have sharpened the need for research focused on adverse medical effects that may emerge or persist many years after treatment. Few studies on late effects related to neurological functioning have been conducted among survivors treated with HSCT as children or adolescents. This analysis from the Bone Marrow Transplant Survivor Study quantified the frequency of neuromotor and neurosensory outcomes, including cataracts, using a self- or parent-reported questionnaire. Eligibility included HSCT survivors of 2-years or longer who were transplanted before age 21 years between 1974 and 1998 at the University of Minnesota or City of Hope Cancer Center. Outcomes on sensory, visual, auditory, or motor impairments among 235 HSCT survivors were compared to 705 siblings of childhood cancer survivors with similar age, sex, and race distributions (1:3 frequency matching). Risk ratios (RR) and confidence intervals were modeled using generalized estimating equations with a Poisson distribution and a log link. Cumulative incidence of cataracts by time since transplant was calculated in a competing risk analysis using the Markov Chain Approach. Wilcoxon signed rank tests were used to test differences in cataract cumulative incidence between allogeneic and autologous transplant, and by those with versus without a history of chronic graft versus host disease (cGVHD) among allogeneic transplant recipients. Of survivors successfully contacted, 60% participated in the study. Non-participants did not differ statistically from participants by transplant type, conditioning regimen, cGVHD (past or present), or age at transplant. Among participants, median age at HSCT was 10 years and 82% received their transplant at least 11 years before interview. Diagnoses included 57% with acute leukemia and 13% with aplastic anemia. Persistent pain was reported by 21% of survivors (RR 2.1, p&lt;.001) and cataracts by 38% (RR 270, p&lt;.001). The cumulative incidence of cataracts was 21% at year 5 post-transplant, 32% at year 10, and 36% at year 15. Although cumulative incidence curves for cataracts were significantly higher in allogeneic versus autologous recipients (p=.009), 86 of the 90 survivors with cataracts received total body irradiation (TBI). When the analysis was limited to those who received TBI, no differences in cataract incidence by transplant type (p=.47) or by cGVHD history (p=.43) were observed. Other than cataracts and persistent pain, motor impairments, including problems with swallowing (7.7%; RR 7.7, p&lt;.001); coordination (6.8%; RR 4.3, p&lt;.001) and muscle weakness (5.5%; RR 5.3, p=.002) constituted the most frequent late effects considered. Overall, with the exception of cataracts, relatively few neuromotor and neurosensory problems were reported by childhood HSCT recipients. However, one-fifth of childhood HCST survivors reported persistent pain, suggesting the need for further investigation to understand the causes. As in adults, cataracts are a frequent adverse effect of childhood HSCT, occurring in nearly 40% of these survivors within 15 years post-transplant. Close follow-up with preservation of vision, particularly among those who received TBI, should be a primary goal in this patient population.