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PURPOSE To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS ( P = .412) and OS ( P = .600). CONCLUSION Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.

Background Cancer survival rates have been steadily improving in the adolescent and young adult (AYA) population, but survivors are at increased risk for cardiovascular disease (CVD). The cardiotoxic effects of anthracycline therapy have been well studied. However, the cardiovascular toxicity associated with newer therapies, such as the vascular endothelial growth factor (VEGF) inhibitors, is less well understood. Objective This retrospective study of AYA cancer survivors sought to gain insight into their burden of cardiovascular toxicities (CT) following anthracycline and/or VEGF inhibitor therapy. Methods Data were extracted from electronic medical records over a fourteen-year period at a single institution. We utilized Cox proportional hazards regression modeling to examine risk factors for CT within each treatment group. Cumulative incidence was calculated with death as a competing risk. Results Of the 1,165 AYA cancer survivors examined, 32%, 22%, and 34% of patients treated with anthracycline, VEGF inhibitor, or both, developed CT. Hypertension was the most common outcome reported. Males were at increased risk for CT following anthracycline therapy (HR: 1.34, 95% CI 1.04–1.73). The cumulative incidence of CT was highest in patients who received both anthracycline and VEGF inhibitor (50% at ten years of follow up). Conclusions CT was common among AYA cancer survivors who received anthracycline and/or VEGF inhibitor therapy. Male sex was an independent risk factor for CT following anthracycline treatment. Further screening and surveillance are warranted to continue understanding the burden of CVD following VEGF inhibitor therapy.

Purpose The purpose of this study was to describe the academic performance of childhood retinoblastoma (RB) survivors. Design Retrospective cohort study. Methods Retrospective chart review of children followed in a survivorship clinic. Results A total of 73 patients with RB (median age at diagnosis: 9.97 months; range: 0.29-65.1) were followed for a median of 6.4 years (0.2-1.76). A total of 48 patients (65.8%) had unilateral RB; 43 patients (63.0%) received systemic chemotherapy; and 57 patients (78.1%) underwent enucleation. At last follow-up, 5 children (6.8%) had bilateral visual acuity (VA) Conclusions Academic difficulties in childhood RB survivors are associated with chemotherapy treatment, a risk factor independent of VA.

Purpose: Differing techniques have been reported for focal laser therapy for patients with small and medium retinoblastoma. We report the technique used at our center; and report the functional and anatomical outcomes for small and medium retinoblastomas treated with focal laser therapy with or without systemic chemotherapy. Methods: A retrospective case study was conducted including pediatric patients with macular retinoblastoma treated with systemic chemotherapy and laser ablation from July 1990 to July 2015 at Washington University School of Medicine/Saint Louis Children’s Hospital. Results: Fourteen eyes (11 patients) with small and medium retinoblastoma tumors were treated with repetitive indirect laser hyperthermia and seven of those patients were treated with systemic chemotherapy as well. Using the International Retinoblastoma classification, one eye was stage A, 10 eyes were stage B, and three eyes were stage C. The mean follow-up time was 7.7 years. There were no recurrences of tumor in the patients. Final visual acuity outcomes were 20/20 to 20/50 in four eyes, 20/60 to 20/200 in four eyes, and 20/400 or less in six eyes. None of the patients developed metastatic disease. Conclusions: The evidence for systemic chemotherapy and diode laser therapy is limited to case series and retrospective reviews, but evidence suggests that it is an effective treatment for small and medium sized retinoblastoma tumors involving the macula with the potential for good visual outcomes.

OBJECTIVE To delineate the impact of treatment exposures and chronic health conditions on psychological, educational, and social outcomes in adolescent survivors of Wilms tumor. METHODS Parent reports from the Childhood Cancer Survivor Study were analyzed for 666 adolescent survivors of Wilms tumor and 698 adolescent siblings. Adjusting for race and household income, survivors were compared to siblings on the Behavior Problems Index and educational outcomes. Multivariable modified Poisson regression estimated relative risks (RR) for therapeutic exposures and chronic health conditions (CTCAE 4.03 graded) among survivors, adjusting for sex, race, income, and age at diagnosis. RESULTS Compared to siblings, adolescent survivors of Wilms tumor were more likely to take psychoactive medication (9.4% vs. 5.1%, p < 0.001) and utilize special education services (25.5% vs. 12.6%, p < 0.001) but did not differ significantly in emotional and behavioral problems. Survivors were less likely to be friendless (7.2% vs. 10.1%, p = 0.04) but were more likely to have difficulty getting along with friends (14.5% vs. 7.8%, p < 0.001). Among survivors, use of special education services was associated with abdomen plus chest radiation (RR = 1.98, CI:1.18-3.34). Those with grade 2-4 cardiovascular conditions had higher risk for anxiety/depression (RR = 1.95, CI:1.19-3.19), headstrong behaviors (RR = 1.91, CI:1.26-2.89), and inattention (RR = 1.56, CI:1.02-2.40). CONCLUSIONS Adolescent survivors of Wilms tumor were similar to siblings with respect to mental health concerns overall but were more likely to require special education. Monitoring of psychosocial and academic problems through adolescence is warranted, especially among those treated with radiation to the abdomen plus chest or with cardiac conditions.

PURPOSE The Children’s Oncology Group (COG) protocol AALL0434 evaluated the safety and efficacy of multi-agent chemotherapy with Capizzi-based methotrexate/pegaspargase (C-MTX) in patients with newly diagnosed pediatric T-cell lymphoblastic lymphoma (T-LL) and gained preliminary data using nelarabine in high-risk patients. PATIENTS AND METHODS The trial enrolled 299 patients, age 1-31 years. High-risk (HR) patients had ≥ 1% minimal detectable disease (MDD) in the bone marrow at diagnosis or received prior steroid treatment. Induction failure was defined as failure to achieve a partial response (PR) by the end of the 4-week induction. All patients received the augmented Berlin-Frankfurt-Muenster (ABFM) C-MTX regimen. HR patients were randomly assigned to receive or not receive 6 5-day courses of nelarabine incorporated into ABFM. Patients with induction failure were nonrandomly assigned to ABFM C-MTX plus nelarabine. No patients received prophylactic cranial radiation; however, patients with CNS3 disease (CSF WBC ≥ 5/μL with blasts or cranial nerve palsies, brain/eye involvement, or hypothalamic syndrome) were ineligible. RESULTS At end-induction, 98.8% of evaluable participants had at least a PR. The 4-year event-free survival (EFS) and overall survival (OS) were 84.7% ± 2.3% and 89.0% ± 2.0%. The 4-year disease-free survival (DFS) from end-induction was 85.9% ± 2.6%. There was no difference in DFS observed between the HR and standard-risk groups ( P = .29) or by treatment regimen ( P = .55). Disease stage, tumor response, and MDD at diagnosis did not demonstrate thresholds that resulted in differences in EFS. Nelarabine did not show an advantage for HR patients. CNS relapse occurred in only 4 patients. CONCLUSION COG AALL0434 produced excellent outcomes in one of the largest trials ever conducted for patients with newly diagnosed T-LL. The COG ABFM regimen with C-MTX provided excellent EFS and OS without cranial radiation.

Background Clostridioides difficile infection (CDI) is a significant source of morbidity in pediatric cancer patients. Few reports to date have evaluated risk factors and short-term outcomes for this population. Methods We retrospectively evaluated pediatric oncology admissions at St Louis Children’s Hospital from 2009 to 2018. All inpatient cases of diagnosed initial CDI were identified. We aimed to investigate the prevalence of CDI and associated risk factors, including coadmission with another patient with CDI, and to evaluate short-term outcomes including length of stay and delays in subsequent scheduled chemotherapy. Results Review of 6567 admissions from 952 patients revealed 109 CDI cases (11.4% of patients). Patients with leukemia or lymphoma, compared to those with solid tumors, were more likely to have CDI (odds ratio [OR], 3 [95% CI, 1.4–6.6], and 3 [95% CI, 1.3–6.8], respectively). Autologous hematopoietic stem cell transplant (HSCT) was also a risk factor (OR, 3.5 [95% CI, 1.7–7.4]). Prior antibiotic exposure independently increased the risk for CDI (OR, 3.0 [95% CI, 1.8–4.8]). Concurrent admission with another patient with CDI also significantly increased the risk (OR, 84.7 [95% CI, 10.5–681.8]). In contrast to previous reports, exposure to acid-suppressing medications decreased the risk for CDI (OR, 0.5 [95% CI, .3–.7]). CDI was associated with increased length of stay (mean difference, 8 days [95% CI, 4.6–11.4]) and prolonged delays for subsequent chemotherapy (mean difference, 1.4 days [95% CI, .1–2.7]). Conclusions CDI in pediatric oncology patients significantly prolongs hospitalization and delays chemotherapy treatment plans. Interventions to control CDI will improve the care of pediatric oncology patients.

With limited data comparing hematopoietic cell transplant outcomes between myeloablative total body irradiation (TBI) containing and non-TBI regimens in children with de novo acute myeloid leukemia, the aim of this study was to compare transplant-outcomes between these regimens. Cox regression models were used to compare transplant-outcomes after TBI and non-TBI regimens in 624 children transplanted between 2008 and 2016. Thirty two percent (n=199) received TBI regimens whereas 68% (n=425) received non-TBI regimens. Five-year non-relapse mortality was higher with TBI regimens (22% vs. 11%, p

BACKGROUND We sought to estimate the frequency of hearing screening failures in pediatric cancer survivors at low risk for hearing loss and evaluate the feasibility of administering screenings in this population. PROCEDURE Survivors in the St. Louis Children's Hospital Late Effects Clinic were recruited. Eligibility included (a) diagnosis of a pediatric cancer treated without platinum chemotherapy or cranial radiation, (b) at least 6 months from completion of therapy, (c) between the ages of 7 and 18 years, (d) cognitively/behaviorally able to participate, and (e) English speaking. Behavioral hearing screenings from 1000 to 8000 Hz were performed by trained personnel using a calibrated audiometer. A failed screen was defined by a participant not responding to two or more of the three screening attempts for at least one frequency in at least one ear. RESULTS One hundred nine patients met eligibility criteria with 78 enrolled (71.5%). Diagnoses included leukemia (57.7%), sarcoma (11.5%), Wilms tumor (14.1%), lymphoma (12.8%), and other solid tumors (3.9%). The median age was 13.2 years (Q1-Q3: 9.6-15.4) and the median time from treatment completion was 3.7 years (Q1-Q3: 2.3-7.4). Eighteen patients (23%) failed the hearing screen (95% CI: 14%-34%). No demographic or treatment-related variables were significantly correlated to screening failure. Six screen failures (33%) underwent formal audiology assessments, with three demonstrating unilateral hearing loss: two conductive and one sensorineural. CONCLUSIONS A significant fraction of pediatric cancer survivors at low risk for hearing loss failed hearing screening. Broader use of hearing screening should be considered.

BackgroundSensorineural hearing loss is a well-known side effect of cisplatin (CDDP). There is limited research on the effect of dosing, infusion times, and schedules of cisplatin administration and their impact on hearing loss.MethodsA retrospective review of 993 pediatric patients’ medical and audiological charts from August 1990 to March 2015 was conducted using stringent inclusion criteria to characterize patients with hearing loss. 248 of these patients received CDDP. Of these, 216 patients had sufficient CDDP infusion data to assess for sensorineural hearing loss attributable to CDDP and its associated risk factors. Chart reviews were performed to extract clinical data including CDDP dosing information. Demographic and clinical characteristics were summarized by descriptive statistics, and univariate and multivariate logistic regressions were performed to examine the relationship between hearing loss and specific parameters of cisplatin administration (amount infused per dose, prescribed infusion time, total number of doses, number of doses per cycle, number of cycles, cumulative cisplatin exposure). Stepwise variable selection procedure was performed in the multivariate model building to extract the best subset of risk factors for the prediction of hearing loss and worsening ototoxicity grade using an established ototoxicity grading scale from the International Society of Pediatric Oncology (SIOP).ResultsA total of 153 patients with complete medical and audiologic data were evaluable for analysis. Hearing loss was identified in 72.6% of the patients. Multivariate analysis revealed that age [OR=0.90 (0.84-0.97), p-value=0.0086], radiation to any part of the body, [OR=3.20 (1.29-7.93), p-value=0.012], amount infused per dose (mg/m2) [OR=1.018 (1.002-1.033), p-value=0.029], and cumulative cisplatin exposure (mg/m 2) [OR=1.004 (1-1.008), p-value=0.027] were associated with hearing loss. Similar associations were also found between these risk factors and worsening SIOP grade.ConclusionIn one of the largest studies examining the influence of CDDP dosing and schedules on hearing loss, we found the amount of CDDP infused per dose is a significant risk factor. Considerations in designing regimens that reduce the amount of CDDP infused per dose may reduce the risk of hearing loss. Randomized prospective trials are needed.

PURPOSE The widely used, risk-based Lymphome Malin de Burkitt (LMB) chemotherapy regimen has improved survival rates for children with mature B-cell non-Hodgkin lymphoma (NHL); however, associated late effects remain understudied. We assessed late health outcomes after LMB treatment in the Childhood Cancer Survivor Study. PATIENTS AND METHODS Multivariable regression models compared chronic health conditions, health status, and socioeconomic and neurocognitive outcomes between survivors of NHL treated with the LMB regimen (n = 126), survivors of NHL treated with non-LMB regimens (n = 444), and siblings (n = 1,029). RESULTS LMB survivors were a median age of 10.2 years (range, 2.5 to 20.5 years) at diagnosis and 24.0 years (range, 10.3 to 35.3 years) at evaluation. Compared with siblings, LMB survivors were at increased risk for adverse health outcomes. However, survivors of NHL treated with LMB and non-LMB regimens did not differ with regard to risk of having any chronic health conditions, impaired health status, neurocognitive deficits, or poorer socioeconomic outcomes. Increased risk for the following specific neurologic conditions was observed in LMB survivors compared with non-LMB survivors: epilepsy (relative risk [RR], 15.2; 95% CI, 3.1 to 73.4); balance problems (RR, 8.9; 95% CI, 2.3 to 34.8); tremors (RR, 7.5; 95% CI, 1.9 to 29.9); weakness in legs (RR, 8.1; 95% CI, 2.5 to 26.4); severe headaches (RR, 3.2; 95% CI, 1.6 to 6.3); and prolonged arm, leg, or back pain (RR, 4.0; 95% CI, 2.2 to 7.1). The survivors from the group C LMB risk group (n = 50) were at the highest risk for these conditions; however, except for worse functional status (odds ratio, 2.7; 95% CI, 1.2 to 5.8), they were not at increased risk for other adverse health status or socioeconomic outcomes compared with non-LMB survivors. CONCLUSION Survivors treated with LMB and non-LMB regimens are largely comparable in late health outcomes except for excess neurotoxicity among LMB survivors. These data inform treatment efforts seeking to optimize disease control while minimizing toxicity.

Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for many nonmalignant disorders (NMD) and is curative or prevents disease progression. Reduced-intensity conditioning (RIC) in HSCT for NMD may reduce regimen-related acute toxicities and late complications. Myeloablation is often replaced by immune suppression in RIC regimens to support donor engraftment. The pace of immune reconstitution after immune suppression by RIC regimens is influenced by agents used, donor source, and graft-versus-host disease prophylaxis/treatment. In a multicenter trial (NCT 00920972) of HSCT for NMD, a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan was substituted for myeloablation. Alemtuzumab was administered early (days −21 to −19) to mitigate major lymphodepletion of the incoming graft and the risk of graft rejection. Immune reconstitution and infectious complications were prospectively monitored for 1-year post-HSCT. Seventy-one patients met inclusion criteria for this report and received marrow or peripheral blood stem cell transplants. Immune reconstitution and infections are reported for related donor (RD) and unrelated donor (URD) transplants at 3 time-points (100days, 6 months, and 1 year post-HSCT). Natural killer cell recovery was rapid, and numbers normalized in both cohorts by day +100. Mean CD3, CD4, and CD8 T-lymphocyte numbers normalized by 6 months after RD HSCT and by 1 year in the URD group. CD4 and CD8 T-lymphocyte counts were significantly higher in patients who received RD HSCT at 6 months and at 1 year, respectively, post-HSCT compared with patients who received URD HSCT. The pace of CD19 B-cell recovery was markedly different between RD and URD cohorts. Mean B-cell numbers were normal by day 100 after RD HSCT but took 1 year post-HSCT to normalize in the URD cohort. Despite these differences in immune reconstitution, the timing and nature of infections did not differ between the groups, presumably because of comparable T-lymphocyte recovery. Immune reconstitution occurred at a faster pace than in prior reports using RIC with T-cell depletion. The incidence of infections was similar for both cohorts and occurred most frequently in the first 100days post-HSCT. Viral and fungal infections occurred at a lower incidence in this cohort, with "early" alemtuzumab compared with regimens administering serotherapy in the peritransplantation period. Patients were susceptible to bacterial infections primarily in the first 100days irrespective of donor source and had no increase in mortality from the same. The overall mortality rate from infections was 1.4% at 1 year. Close monitoring and prophylaxis against bacterial infections in the first 100days post-HSCT is necessary but is followed by robust immune reconstitution, especially in the T-cell compartment.

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P < .001) and grade III to IV acute GVHD (RR, 1.93; P = .006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P = .008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results. ispartof: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION vol:25 issue:1 pages:73-85 ispartof: location:United States status: published

10046 Background: Retinoblastoma (RB) is the most common tumor of the eye in childhood. Intraocular RB cure rates approach 100%. Therefore, treatment now focuses on globe salvage preserving functional vision. The Research Into Visual Endpoints and RB Health Outcomes After Treatment (RIVERBOAT) consortium was established to examine patient health outcomes, including vision, in the contemporary therapy era. Methods: Patients with RB treated at consortium centers from 2007 to present were identified. Medical record abstraction was performed for disease presentation, treatment, and outcomes. A subset of the patients returned to centers and completed functional vision questionnaires (Child Vision Function Questionnaire - ages 0 – 7 and Cardiff Visual Ability Questionnaire for Children - ages > 8) and had visual acuity assessed. For participants who could not yet return for a study evaluation, medical record abstraction alone was performed. Results: Among 463 participants enrolled to date, 270 (58%) had unilateral disease. One patient with metastatic RB did not survive, resulting in overall survival of 99.6. There was one case of secondary leukemia. The eye group distribution (International Intraocular Retinoblastoma Classification) was 0.4% A, 5.6% B, 7.0% C, 36.0% D, 49.0% E and 2.0% not classified. 131 (49%) patients underwent primary enucleation and are not included in further analyses. Among the remaining 139 patients, 3% were treated with local ophthalmic therapy only, 22% with intravenous chemotherapy (IV) only, 53% with intra-arterial chemotherapy (IAC) only, 22% with IV and IAC, and 35% required secondary enucleation. Globe salvage after chemotherapy was successful in 100% A, 93% B, 82% C, 72% D, and 48% E eyes. This salvage was achieved with IV only, IAC only, or both in 22%, 58% and 20% respectively. The mean percentage of patients receiving IAC per year increased from 13% (2008 – 2013) to 21% (2014 – 2017) to 28% (2018 – 2022). In 29 patients without enucleation who reported functional vision to date, the mean scores (survey theoretical ranges) were 0.72 for < 3 years (0.57 to 0.87), 0.82 for 3 -7 years (0.56 to 0.94) and -2.72 for > 8 years (-2.53 to -0.51), all considered good functional vision. In 20 of these 29 patients, 4 eyes had normal vision (20/20-20/40) across A to D groups. Moderate vision loss (> 20/40 – 20/70) was noted in 3 D eyes and low vision (> 20/70 - < 20/200) in 1 D eye. Twelve B through E eyes met criteria for a legally blind eye (>20/200). Conclusions: In this cohort of RB patients with unilateral disease treated from 2007 - 2022, 66% required primary or secondary enucleation. Among 29 patients with globe salvage, self-reported functional vision was good, but 12 eyes in 20 of the patients were legally blind. IAC only or IV plus IAC was most used in those who avoided secondary enucleation. With ongoing cohort accrual and increased IAC use, it will remain to be determined if globe salvage with functional vision will improve.

10045 Background: Retinoblastoma (RB) is the most common tumor of the eye in childhood. Intraocular RB cure rates approach 100%. Therefore, treatment advances have focused on globe salvage preserving functional vision. The Research Into Visual Endpoints and RB Health Outcomes After Treatment (RIVERBOAT) consortium was established to examine patient health outcomes, including vision, in the contemporary therapy era. Methods: Patients with RB treated at consortium centers from 2007 to the present were identified. Medical record abstraction was performed for disease presentation, treatment, and outcomes. A subset of the patients returned to centers and completed functional vision questionnaires (Child Vision Function Questionnaire for ages 0 – 7 and Cardiff Visual Ability Questionnaire for Children for ages >8) and had visual acuity assessed. For participants who could not yet return for a study evaluation, medical record abstraction alone was performed. Results: Among 463 participants enrolled to date, 193 (42%) had bilateral disease. Two each had metastatic RB, trilateral RB, and secondary osteosarcoma. One patient each with metastatic RB and trilateral RB is deceased, with overall survival for the cohort of 99%. The eye group distribution (International Intraocular Retinoblastoma Classification) was 14% A, 22% B, 14% C, 28% D, 19% E and 3% not classified. Primary enucleation was performed in 43 (22%), secondary enucleation in 48 (25%) and bilateral enucleation in 1(0.5%). Intravenous chemotherapy (IV) alone was administered in 58%, intra-arterial chemotherapy (IAC) alone in 4%, with 31% receiving both. Among 145 patients who did not require secondary or bilateral enucleation, the distribution was 16% A, 21% B, 16% C, 28% D, 15% E, and 4% non-classified eyes. This salvage was achieved with IV alone, IAC alone, or both in 55%, 5% and 30% respectively and with ophthalmic therapy only in 10%. The mean percentage of patients receiving IAC per year increased from 6% in 2008 – 2013 to 11% in 2014 – 2022 and was stable at 11% in 2018 – 2022. Among 53 patients who have reported functional vision to date, the mean scores were 0.81 for < 3 years 0.80 for 3-7 years and -1.31 for those >8 years, all considered to be good functional vision. Among 50 eyes in 37 of these 53 patients, 33 had normal vision (20/20-20/40) across A to E groups. Moderate vision loss (> 20/40 – 20/70) was noted in 1 C and 1 B eye and low vision (> 20/70 - < 20/200) in 6 group B, C or D eyes. Nine B or D eyes were legally blind (>20/200). No patients had two legally blind eyes. Conclusions: In this cohort of RB patients with bilateral disease treated between 2007 and 2022, 52% have been successfully treated without enucleation. Self-reported functional vision in 53 of these patients with all group eyes was good. Only 6 of 50 eyes in 37 patients met criteria for legal blindness and 66% of eyes had normal vision. With cohort accrual ongoing, we will determine if these promising outcomes continue.

Background: Children treated for cancer are at risk for neuromuscular dysfunction, but data are limited regarding prevalence, longitudinal patterns, and long-term impact. Methods: Longitudinal surveys from 25,583 childhood cancer survivors ≥5 years from diagnosis and 5,044 siblings from the Childhood Cancer Survivor Study were used to estimate the prevalence and cumulative incidence of neuromuscular dysfunction. Multivariable models adjusted for age, sex, race, and ethnicity estimated prevalence ratios (PR) of neuromuscular dysfunction in survivors compared with siblings, and associations with treatments and late health/socioeconomic outcomes. Results: Prevalence of neuromuscular dysfunction was 14.7% in survivors 5 years postdiagnosis versus 1.5% in siblings [PR, 9.9; 95% confidence interval (CI), 7.9–12.4], and highest in survivors of central nervous system (CNS) tumors (PR, 27.6; 95% CI, 22.1–34.6) and sarcomas (PR, 11.5; 95% CI, 9.1–14.5). Cumulative incidence rose to 24.3% in survivors 20 years postdiagnosis (95% CI, 23.8–24.8). Spinal radiotherapy and increasing cranial radiotherapy dose were associated with increased prevalence of neuromuscular dysfunction. Platinum exposure (vs. none) was associated with neuromuscular dysfunction (PR, 1.8; 95% CI, 1.5–2.1), even after excluding survivors with CNS tumors, cranial/spinal radiotherapy, or amputation. Neuromuscular dysfunction was associated with concurrent or later obesity (PR, 1.1; 95% CI, 1.1–1.2), anxiety (PR, 2.5; 95% CI, 2.2–2.9), depression (PR, 2.1; 95% CI, 1.9–2.3), and lower likelihood of graduating college (PR, 0.92; 95% CI, 0.90–0.94) and employment (PR, 0.8; 95% CI, 0.8–0.9). Conclusions: Neuromuscular dysfunction is prevalent in childhood cancer survivors, continues to increase posttherapy, and is associated with adverse health and socioeconomic outcomes. Impact: Interventions are needed to prevent and treat neuromuscular dysfunction, especially in survivors with platinum and radiation exposure.

The purpose of this study was to describe the academic performance of childhood retinoblastoma (RB) survivors.Retrospective cohort study.Retrospective chart review of children followed in a survivorship clinic.A total of 73 patients with RB (median age at diagnosis: 9.97 months; range: 0.29-65.1) were followed for a median of 6.4 years (0.2-1.76). A total of 48 patients (65.8%) had unilateral RB; 43 patients (63.0%) received systemic chemotherapy; and 57 patients (78.1%) underwent enucleation. At last follow-up, 5 children (6.8%) had bilateral visual acuity (VA)20/70. Seventeen subjects (23.3%) reported school difficulties, and 10 subjects (13.7%) had an individualized education program (IEP). Multivariate analysis revealed that a history of receiving chemotherapy" Multivariate analysis revealed that a history of receiving chemotherapy was associated with self-reported school difficulties (odds ratio [CI]: 5.44; 95% confidence interval [CI]: 1.36-21.69; P = .016), and undergoing an IEP (OR: 11.47; 95% CI: 1.34-98.16; P = .03). The degree of visual impairment and history of enucleation did not influence the risk of self-reported school difficulties or the implementation of an IEP. Among unilateral RB patients, chemotherapy was an independent risk factor for self-reported school difficulties (OR: 12.8; 95% CI: 1.45-113; P = .009) and implementation of an IEP (OR: 15.2; 95% CI: 0.78-292; P = .02).Academic difficulties in childhood RB survivors are associated with chemotherapy treatment, a risk factor independent of VA.

Early T-cell precursor phenotype acute lymphoblastic leukemia (ETP-ALL) is a subtype of T-ALL with a unique immunophenotype and genetic abnormalities distinct from conventional T-ALL. A subset of T lymphoblastic lymphoma (T-LLy) also demonstrates the early T-cell precursor immunophenotype and may be a counterpart of ETP-ALL. Unlike ETP-ALL, the incidence, clinical features, and genomic features of ETP-LLy are unknown. We reviewed the immunophenotyping data of 218 T-LLy patients who enrolled in the Children’s Oncology Group AALL0434 clinical trial and identified 9 cases (4%) exhibiting a definitive ETP immunophenotype. We performed single-nucleotide polymorphism array profiling on 9 ETP-LLy and 15 non-ETP T-LLy cases. Compared with non-ETP T-LLy, ETP-LLy showed less frequent deletion of 9p (CKDN2A/B), more frequent deletion of 12p (ETV6) and 1p (RPL22), and more frequent absence of biallelic T-cell receptor γ deletions. Recurrent abnormalities previously described in ETP-ALL such as deletions of 5q and 13q and gain of 6q were not observed in ETP-LLy cases. There were no failures of therapy among the ETP-LLy subtype with a 4-year event-free survival of 100%. Overall, ETP-LLy does not exhibit unifying genetic alterations but shows some distinct genomic features from non-ETP T-LLy suggesting that ETP-LLy may be a distinct entity from non-ETP T-LLy.

OBJECTIVES Children with malignancies may be exposed to ototoxic therapies resulting in sensorineural hearing loss (SNHL). There is no consensus as to when intervention with amplification is necessary due to a variety of factors such as disease status, speech and language development, perceived difficulty with communication, and limitations of technology to fit these challenging losses. The decision to proceed with amplification after cancer can be difficult for patients and families. The purpose of this study is (1) to understand the decision-making (DM) process of childhood cancer survivors (CCSs) with SNHL and their parents and (2) to identify their decisional needs. DESIGN Semi-structured interviews guided by the Ottawa's decision support framework were recorded and transcribed verbatim. Inclusion criteria were CCSs ages 8 to 30 years old with a Chang grade >1b SNHL and off-therapy; parents of this group were also eligible. Patients with active disease were excluded. Prompts inquired of sources of decisional conflict, role in DM, and DM behaviors. Inductive content analysis of the narrative qualitative data was used. RESULTS Seven parents of CCSs and 6 CCSs participated. Themes in the CCS group included: (1) making sense of ototoxic SNHL; (2) desiring personalized education and treatment of SNHL; (3) playing an active role in the joint DM process; and (4) accepting hearing aids requires time and effort. The parent group shared the first and last theme with the CCS group and had two unique themes: (1) needing experts to respect the individual's journey to SNHL acceptance and (2) moving past the cancer experience to acceptance. Parents more often framed their DM within the context of already experiencing the trauma of cancer, whereas CCSs did not. One parent said, "You see all the rubble and you've lived through the devastation of the storm, but now you got to figure out what's broken." CCSs expressed bodily concerns regarding amplification, such as discomfort to the ear and difficulty in adjusting to the volume. The following needs were identified: early, re-enforced education regarding late effects risks; open communication among providers, CCSs, and parents; and audiogram result interpretations in patient- and parent-friendly language. CONCLUSIONS Understanding the DM process from the CCS and parent's perspectives should be considered when providing counseling for hearing amplification in the setting of cancer-related SNHL. Earlier and consistent delivery of late effects education, open communication regarding risk for SNHL, and improved delivery of audiogram results should be targets for meeting unmet needs. These findings should inform the development of decision aids to reduce decisional conflict in this population.

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.

We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range

Background Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods 9028 recipients of hematopoietic cell autotransplants (1995–2010) for Hodgkin lymphoma (HL; n = 916), non-Hodgkin lymphoma (NHL; n = 3546) and plasma cell myeloma (PCM; n = 4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS. Results 335 MDS/AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR = 4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR = 2.5 [1.1, 2.5]); (2) ≥3 versus 1 line of chemotherapy for NHL (HR = 1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005–2010 versus 1995–1999 (HR = 2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/MDS in HL, NHL and PCM to be 5–10 times the background rate. In contrast, relative risks were 10–50 for AML and approximately 100 for MDS in the autotransplant cohort. Conclusions There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.

IntroductionWe sought to evaluate paediatric oncology simulations intended to improve paediatric residents’ skills and comfort in caring for children with cancer.MethodIn a non-randomised trial, controls (the first three rotations) received a standard set of lectures, and the intervention arm received these lectures plus five simulation training scenarios—fever/neutropaenia, a new leukaemia diagnosis, end-of-life care discussion, tumour lysis syndrome and a mediastinal mass. All residents were tested after the rotation on the first three scenarios; management skills were evaluated independently by two raters. Before and after training, all residents completed an emotional-appraisal questionnaire evaluating each scenario as a perceived challenge or threat. Analysis of variance (ANOVA) measured differences by study arm in skills checklist assessments and appraisals; repeated measures ANOVA measured changes in emotional-appraisal scores.ResultsForty-two residents (9 controls, 33 interventions) participated. Inter-rater agreement for skills checklist scores using average-measures intraclass correlation was high (0.847), and overall mean scores were significantly higher for the intervention than control group across both raters (p=0.005). For all residents, perceived challenge increased in the end-of-life simulation, and perceived threat decreased in all three test scenarios. The intervention group, regardless of training year, evaluated the teaching scenarios favourably and felt that challenging oncology situations were addressed, skills were enhanced and the simulations should be offered to other residents.ConclusionsIt was feasible to introduce residents to difficult paediatric oncology scenarios using simulation. The intervention group performed more skills than controls when tested and perceive threat declined in all residents after their paediatric oncology rotation.

Purpose The purpose of this study was to assess knowledge and perceptions of infertility, reproductive concerns, quality of life, and emotional burden of fertility concerns in adolescent female cancer survivors and their parents. Methods A cross-sectional design was used to investigate reproductive knowledge and concerns among female childhood cancer survivors and their parents. The instruments administered at a single, routine visit were the 13-item knowledge instrument, Adolescent Fertility Values Clarification Tool (VCT), Impact of Event Scale (IES), and Pediatrics Quality of Life Assessment (PedsQL). The knowledge instrument was given to both patients and caregivers, while the PedsQL and VCT were given to only patients and IES only to caregivers. Results Twenty-six survivors and 23 parents completed evaluations. The mean age of survivors was 16. The mean knowledge instrument score for survivors was 9.5 (± 1.9) and 9.96 (± 1.7) for parents with a maximum possible score of 13. The VCT indicated almost all patients agreed or strongly agreed they would like more information on how their treatment may affect their fertility, with 84.6% identified wanting a baby in the future. The mean survivor PedsQL score was 67.7 (± 15.3). While parental IES scores as whole did not endorse symptoms of PTSD, 30% of our sample did fall within the range for PTSD. Conclusion Although this population of women has above average knowledge scores, they still demonstrated a desire for more information on reproduction after cancer therapy. While PedsQL scores fell within a normal range, survivors report infertility would cause negative emotions. Implication for cancer survivors This information can be used refine educational programs within survivorship clinics to improve knowledge of post-treatment reproductive health.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on treatment and management considerations for AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for AYA Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

Background: The prognosis for patients (pts) with relapsed T-ALL and T-LL is dismal. The primary goal of T-ALL/T-LL treatment is to prevent relapse. In the phase 3 Children's Oncology Group (COG) clinical trial AALL1231 (NCT02112916), children, adolescents and young adults (age 1-30 years) with T-ALL and T-LL were treated with a modified augmented BFM (aBFM) backbone that used dexamethasone as the only corticosteroid and included two (rather than one) doses of pegaspargase during induction and delayed intensification. Pts were stratified as standard (SR), intermediate (IR), or very high risk (VHR), primarily based on disease response: morphology, minimal residual disease (MRD) performed by multiparameter flow cytometry at a central reference laboratory) at end of induction and consolidation (T-ALL), and radiographic response for T-LL. Pts were randomized 1:1 to receive/not receive bortezomib during induction and delayed intensification (1.3mg/m 2 x 4 doses per block). VHR T-ALL pts were defined as having day 29 M3 marrow (>25% blasts) or end of consolidation (EOC) MRD >0.1%. 10-15% of T-ALL pts were predicted to be VHR based on COG AALL0434. Pts with induction failure (M3 marrow by morphology) or EOC MRD >0.1% were expected to have 4-yr event-free survival (EFS) of ~66+/-16%. Following consolidation, VHR pts received 3 BFM-based intensification blocks in lieu of interim maintenance (IM). Detectable MRD following the intensification blocks was considered an event and these pts were removed from protocol therapy. VHR ALL pts who had undetectable MRD continued protocol therapy, received delayed intensification, an IM phase with Capizzi escalating methotrexate plus pegaspargase, and maintenance. A secondary aim of AALL1231 was to compare survival in VHR T-ALL pts with EOC MRD ≥ 0.1% but undetectable MRD after intensification of chemotherapy with those who continued to have detectable MRD and were eligible for other treatment strategies, including hematopoietic stem cell transplant (HSCT). This study also analyzed outcomes for pts with M3 marrow at the end of induction. Results: AALL1231 accrued 847 pts (824 eligible and evaluable) of 1400 anticipated from 2014 until early closure. The 3-year EFS for the bortezomib randomization for the SR and IR groups has been reported previously (Teachey, et. al ASH 2020). Because only 2 of 209 T-LL pts were VHR; this report focuses on the outcomes of the 5.2% (32/615) of T-ALL pts who were VHR. In total, 25 VHR T-ALL pts were EOC MRD >0.1%, and 18 of these had MRD sent at the end of HR intensification. Of the 8 pts who became MRD undetectable and continued protocol therapy, only 2 survived (3-year overall survival [OS] 25+15.3%). In contrast, 10 pts who had detectable MRD were taken off protocol and underwent HSCT. Of these 10, only one relapsed (3-year OS 90+12.7%). The 3-year OS for the 10 pts who were M3 at Day 29 was 60.0±17.0%. As there were not enough pts to assess the impact of EOC MRD on pts who were M3 at Day 29, we assessed the impact of EOC MRD on outcomes in M2 (5-25% blasts at Day 29; n = 24) and M3 pts, which defines induction failure in other cooperative groups. M2+M3 T-ALL who were EOC MRD 0.1% (n = 12) pts. Conclusions: T-ALL pts treated on AALL1231 who are EOC MRD ≥0.1% with undetectable MRD after 3 BFM-based intensification blocks had a very poor outcome when treated with standard cytotoxic chemotherapy. In contrast, while patient numbers are small, those pts that remained MRD-positive after 3 intensification blocks and underwent HSCT had an excellent outcome. These data not only impact the recommended treatment for T-ALL pts who are induction and consolidation failures, but also support the importance of the graft-versus-leukemia (GVL) effect in refractory T-ALL. Disclosures Hayashi: Magenta Therapeutics: Consultancy. August: Jazz: Membership on an entity's Board of Directors or advisory committees. Hermiston: Sobi: Consultancy; Novartis: Consultancy. Bollard: Cabeletta Bio: Membership on an entity's Board of Directors or advisory committees; Catamaran Bio and Mana Therapeutics: Other: member and cofounder; SOBI: Other: DSMB. Loh: MediSix therapeutics: Membership on an entity's Board of Directors or advisory committees. Raetz: Pfizer: Research Funding; Celgene: Other: DSMB member. Teachey: BEAM Therapeutics: Consultancy, Research Funding; NeoImmune Tech: Research Funding; Sobi: Consultancy; Janssen: Consultancy.

Date Presented 04/13/21 Children with cancer treated with platinum-based chemotherapy are at risk for developing hearing impairment (HI), one of several late effects associated with treatment. HI is associated with decreased socioemotional development, academic performance, and quality of life (QOL) among survivors of central nervous system (CNS) tumors. This is the first study to examine the impact of ototoxic HI on cognition and QOL among a cohort of survivors of pediatric non-CNS cancers. Primary Author and Speaker: Taniya Easow Varughese Contributing Authors: Julia Ferringer, Emily Grambo, Hannah Murkens, Jillian Smith, and Emily Scifo

Young adult (YA) survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for late psychosocial challenges, including the inability to return to work post-HCT. Work-related outcomes in this population remain understudied, however. We conducted this study to assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YAs and to analyze the patient-, disease-, and HCT-related factors associated with their work status at 1 year post-HCT. Using Center for International Blood and Marrow Transplant Research data, we evaluated the post-HCT work status (full-time, part-time work, unemployed, or medical disability) of 1365 YA HCT survivors who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at 4 time points: 6 months, 1 year, 2 years, and 3 years post-HCT. Percentages of post-HCT work status categories at the 1-year time point were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression. From 6 months to 3 years post-HCT, the percentage of survivors working full-time increased from 18.3% to 50.7% and the percentage working part-time increased from 6.9% to 10.5%. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1 year post-HCT. Female sex (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.40 to 0.77), HCT Comorbidity Index score ≥3 (OR, 0.57; 95% CI, 0.39 to 0.82), pre-HCT unemployment (OR, 0.37; 95% CI, 0.24 to 0.56), medical disability (OR, 0.44; 95% CI, 0.28 to 0.70), development of grade III-IV acute graft-versus-host disease (OR, 0.52; 95% CI, 0.34 to 0.80), and relapse within 1 year post-HCT (OR, 0.34; 95% CI, 0.21 to 0.56) were associated with a lower likelihood of employment at 1 year post-HCT. Compared with myeloablative conditioning (MAC) with total body irradiation (TBI), MAC without TBI (OR, 1.71; 95% CI, 1.16 to 2.53) was associated with a greater likelihood of employment at 1 year post-HCT. Graduate school-level education (OR, 2.47; 95% CI, 1.49 to 4.10) was also associated with a greater likelihood of employment at 1 year post-HCT. Although the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective interventions to support return to work in this population.

BACKGROUND Autologous hematopoietic cell transplantation (auto-HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL); however, long-term outcomes are not well described. METHODS This study analyzed survival, nonrelapse mortality, late effects, and subsequent malignant neoplasms (SMNs) in 1617 patients who survived progression-free for ≥2 years after auto-HCT for cHL or DLBCL between 1990 and 2008. The median age at auto-HCT was 40 years; the median follow-up was 10.6 years. RESULTS The 5-year overall survival rate was 90% (95% confidence interval [CI], 87%-92%) for patients with cHL and 89% (95% CI, 87%-91%) for patients with DLBCL. The risk of late mortality in comparison with the general population was 9.6-fold higher for patients with cHL (standardized mortality ratio [SMR], 9.6) and 3.4-fold higher for patients with DLBCL (SMR, 3.4). Relapse accounted for 44% of late deaths. At least 1 late effect was reported for 9% of the patients. A total of 105 SMNs were confirmed: 44 in the cHL group and 61 in the DLBCL group. According to a multivariate analysis, older age, male sex, a Karnofsky score < 90, total body irradiation (TBI) exposure, and a higher number of lines of chemotherapy before auto-HCT were risk factors for overall mortality in cHL. Risk factors in DLBCL were older age and TBI exposure. A subanalysis of 798 adolescent and young adult patients mirrored the outcomes of the overall study population. CONCLUSIONS Despite generally favorable outcomes, 2-year survivors of auto-HCT for cHL or DLBCL have an excess late-mortality risk in comparison with the general population and experience an assortment of late complications. Cancer 2018;124:816-25. © 2017 American Cancer Society.

Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for year after allogeneic myeloablative HCT for hematologic malignancy at = 1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P