Prevalence and risk factors of cataract after chemotherapy with or without central nervous system irradiation for childhood acute lymphoblastic leukaemia: an LEA study (original) (raw)
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International Journal of Radiation Oncology*Biology*Physics, 2002
Purpose: To determine a dose-effect relationship for cataract induction, the tissue-specific parameter, ␣/, and the rate of repair of sublethal damage, value, in the linear-quadratic formula have to be known. To obtain these parameters for the human eye lens, a large series of patients treated with different doses and dose rates is required. The data of patients with acute leukemia treated with single-dose total body irradiation (STBI) and bone marrow transplantation (BMT) collected by the European Group for Blood and Marrow Transplantation were analyzed. Methods and Materials: The data of 495 patients who underwent BMT for acute leukemia, who had STBI as part of their conditioning regimen, were analyzed using the linear-quadratic concept. The end point was the incidence of cataract formation after BMT. Of the analyzed patients, 175 were registered as having cataracts. Biologic effective doses (BEDs) for different sets of values for ␣/ and were calculated for each patient. With Cox regression analysis, using the overall chi-square test as the parameter evaluating the goodness of fit, ␣/ and values were found. Risk factors for cataract induction were the BED of the applied TBI regimen, allogeneic BMT, steroid therapy for >14 weeks, and heparin administration. To avoid the influence of steroid therapy and heparin on cataract induction, patients who received steroid or heparin treatment were excluded, leaving only the BED as a risk factor. Next, the most likely set of ␣/ and values was obtained. With this set, the cataract-free survival rates were calculated for specific BED intervals, according to the Kaplan-Meier method. From these calculations, cataract incidences were obtained as function of the BED at 120 months after STBI. Results: The use of BED instead of the TBI dose enabled the incidence of cataract formation to be predicted in a reasonably consistent way. With Cox regression analysis for all STBI data, a maximal chi-square value was obtained for ␣/ ؍ 1.75 Gy and ؍ 0.75 h ؊1. When Cox regression analysis was applied for patients who had no steroid treatment after BMT, a maximal chi-square value was obtained for ␣/ ؍ 1 Gy and ؍ 0.6 h ؊1. Cox regression analysis was repeated using the data of patients who had not received posttransplant steroid treatment and also no heparin administration; we found ␣/ ؍ 0.75 Gy and ؍ 0.65 h ؊1. An increased cataract incidence was observed after steroid treatment of >14 weeks and heparin administration. Conclusion: The ␣/ value of 0.75 Gy and a value of 0.65 h ؊1 found for the eye lens are characteristic for late-responding tissues. The incidence of cataract formation can now be quantified, taking into account the values calculated for ␣/ and , TBI dose, and dose rate. Also, the reduction in cataract incidence as a result of lens dose reduction by eye shielding can be estimated.
International Journal of Radiation Oncology*Biology*Physics, 1998
Therefore, evaluation of late complications such as cataracts is of paramount importance. Methods and Materials: We analyzed data of 2149 patients from the EBMT registry. A cohort of 1063 patients were evaluable for survival and ophthalmologic status after transplant for acute leukemia (AL) in first or second complete remission. Conditioning therapy included either single-dose total body irradiation (STBI) or fractionated TBI (FTBI) grouped in different dose rates (low: LDR < 0.04 Gy/min; high: HDR > 0.04 Gy/min). Results: The overall 10-year estimated cataract incidence (ECI) was 50%. It was 60% in the STBI group, 43% in the FTBI group < 6 fractions, and 7% in the FTBI group > 6 fractions (p < 10 ؊4 ). It was significantly lower (30%) in the LDR than in the HDR groups (59%; p < 10 ؊4 ). Patients receiving heparin for veno-occlusive disease prophylaxis had fewer cataracts than those who did not (10-year ECI: 33% vs. 53%, respectively; p ؍ 0.04). The 10-year ECI was 65% in the allogeneic vs. 46% in the autologous BMT patients (p ؍ 0.0018). Factors independently associated with an increased risk of cataract were an older age (> 23 years), higher dose rate (> 0.04 Gy/min), allogeneic BMT, and steroid administration (> 100 days). The use of FTBI was associated with a decreased risk of cataract. Heparin administration was a protective factor in patients receiving STBI. In terms of cataract surgery, the unfavorable factors for requiring surgery were: age > 23 yr, STBI, dose rate > 0.04 Gy/min, chronic graft-vs.-host disease (cGvHD), and absence of heparin administration. Among the patients who required cataract surgery (111 out of 257), secondary posterior capsular opacification was observed in 15.7%. Conclusion: High dose rate and STBI are the main risk factors for cataract development and the need for surgery, and the administration of heparin has a protective role in cataractogenesis. © 1998 Elsevier Science Inc.
Pediatric Blood & Cancer, 2009
IntroductionApproximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors.Approximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors.ProcedureThe Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study investigating health outcomes of 5+ year survivors diagnosed and treated between 1970 and 1986 compared to a sibling cohort. The baseline questionnaire included questions about the first occurrence of six ocular conditions. Relative risks (RR) and 95% confidence intervals (CI) were calculated from responses of 14,362 survivors and 3,901 siblings.The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study investigating health outcomes of 5+ year survivors diagnosed and treated between 1970 and 1986 compared to a sibling cohort. The baseline questionnaire included questions about the first occurrence of six ocular conditions. Relative risks (RR) and 95% confidence intervals (CI) were calculated from responses of 14,362 survivors and 3,901 siblings.ResultsFive or more years from the diagnosis, survivors were at increased risk of cataracts (RR: 10.8; 95% CI: 6.2–18.9), glaucoma (RR: 2.5; 95% CI: 1.1–5.7), legal blindness (RR: 2.6; 95% CI: 1.7–4.0), double vision (RR: 4.1; 95% CI: 2.7–6.1), and dry eyes (RR: 1.9; 95% CI: 1.6–2.4), when compared to siblings. Dose of radiation to the eye was significantly associated with risk of cataracts, legal blindness, double vision, and dry eyes, in a dose-dependent manner. Risk of cataracts were also associated with radiation 3,000+ cGy to the posterior fossa (RR: 8.4; 95% CI: 5.0–14.3), temporal lobe (RR: 9.4; 95% CI: 5.6–15.6), and exposure to prednisone (RR: 2.3; 95% CI: 1.6–3.4).Five or more years from the diagnosis, survivors were at increased risk of cataracts (RR: 10.8; 95% CI: 6.2–18.9), glaucoma (RR: 2.5; 95% CI: 1.1–5.7), legal blindness (RR: 2.6; 95% CI: 1.7–4.0), double vision (RR: 4.1; 95% CI: 2.7–6.1), and dry eyes (RR: 1.9; 95% CI: 1.6–2.4), when compared to siblings. Dose of radiation to the eye was significantly associated with risk of cataracts, legal blindness, double vision, and dry eyes, in a dose-dependent manner. Risk of cataracts were also associated with radiation 3,000+ cGy to the posterior fossa (RR: 8.4; 95% CI: 5.0–14.3), temporal lobe (RR: 9.4; 95% CI: 5.6–15.6), and exposure to prednisone (RR: 2.3; 95% CI: 1.6–3.4).ConclusionsChildhood cancer survivors are at risk of developing late occurring ocular complications, with exposure to glucocorticoids and cranial radiation being important determinants of increased risk. Long-term follow-up is needed to evaluate potential progression of ocular deficits and impact on quality of life. Pediatr Blood Cancer 2010; 54:103–109. © 2009 Wiley-Liss, Inc.Childhood cancer survivors are at risk of developing late occurring ocular complications, with exposure to glucocorticoids and cranial radiation being important determinants of increased risk. Long-term follow-up is needed to evaluate potential progression of ocular deficits and impact on quality of life. Pediatr Blood Cancer 2010; 54:103–109. © 2009 Wiley-Liss, Inc.
Cataract after allogeneic hematopoietic stem cell transplantation in childhood
Acta Paediatrica, 2015
The aim of this study was to study long-term visual outcome and cataract development in children and adolescents after hematopoietic stem cell transplantation (HSCT) in childhood. Methods: Best corrected visual acuity (BCVA), refraction and lens status were examined in a prospective study of 139 children and adolescents. Results: In total, 139 patients (58 female), median age 6.6 years at HSCT (range 0.4-17.5 years), were followed up for a median of 8.0 years (1-19.4 years). Median BCVA in the better eye was 1.0 decimal. Altogether 19 of 131 patients developed cataract requiring surgery, while 46 developed less prominent lens opacities and 66 had clear lenses at time of latest follow-up. Patients conditioned with total body irradiation had a higher risk of developing lens opacities or cataract (p < 0.0001) as did patients with malignant disease, irrespective of irradiation treatment (p < 0.0001). Cumulative analysis showed that 50% of all patients had developed lens opacities/cataract after 10.2 years. Patients who ultimately needed cataract surgery developed cataract earlier than others (p = 0.006). Conclusion: Lens opacities or cataract were more common in children or adolescents with malignant disease and after conditioning with irradiation. Regular ophthalmological followup is important after HSCT for early intervention to avoid amblyopia.
Bone Marrow Transplantation, 2020
Patients given allogeneic hematopoietic stem cell transplantation (alloHSCT) present an increased incidence of long-term toxicities that can be attributed to the preparative regimen. We retrospectively analyzed in a population of 670 children receiving allo-HSCT for acute leukemia the occurrence of different late effects in function of the choice made between total body irradiation (TBI) and busulfan, as part of the preparative regimen. In univariable analysis, we found that patients treated with TBI developed cataract in 24% of the cases compared with 4% in patients treated with BU (p = 0.0001) and that the incidence of secondary malignant neoplasia (SMN) was higher in patients treated with TBI (18%) as compared with those prepared to the allograft with a Bu-based regimen (0%) (p = 0.019). Conditioning regimen did not show a statistically significant correlation with the occurrence of all the other investigated late effects. In multivariable analysis, TBI remained associated with the occurrence of cataracts (Relative Risk: 0.33 p = 0.012) and secondary malignancies (Relative Risk 3.96 × 10e−6 p < 0.001); however, other variables, as GvHD and disease type, were also correlated with these long-term sequels, indicating that in our study population the preparative regimen is not the only factor influencing the incidence of these complications.
Bone Marrow Transplantation, 2003
Loes van Kempen -Harteveld Optimization of total body irradiation: the match between (maximal) leukemic cell kill and (minimal) late effects Chapter 4 62 Summary This is a retrospective analysis on 188 children who underwent total body irradiation (TBI) in one or two fractions before bone marrow transplantation (BMT) for a hematological disorder. While 139 children had eye shielding during TBI to decrease cataract formation, 49 did not. The blocks used for shielding caused cylindrical area of decreased dose intensity in the brain. The aim of the study was to determine if there was an increased risk of relapse in the eyes or in the CNS after shielding of the eyes. The probability and severity of cataract formation with and without shielding were also evaluated. None of the 49 children without shielding had a relapse in their eyes or in the CNS after BMT. Of the children with shielding, none had a relapse in the eyes two of the 139 (1.4%) had a CNS relapse. The incidence of cataracts without shielding was 90% (19 of 21 evaluable patients), while with shielding it was 31% (20 of 64). Severe cataracts were present in eight of 21 (38%) patients without and two of 64 (3%) patients with shielding. The probability of staying cataract free for at least five years was 0.77 with and 0.33 without shielding, at 8 years it was 0.53 and 0.24 respectively. The relative risk of developing a cataract without shielding vs. shielding was three (95% CI = 1.5; 5.9).
Radiother Oncol, 1996
Background: Age at presentation has been reported to be a prognostic factor for the survival of patients with medulloblastoma with very young children carrying a worse prognosis. We analysed the literature data to examine this hypothesis. Material and methods: Included in the analysis were published studies if the radiotherapeutic treatment consisted of a craniospinal irradiation by megavoltage equipment and the minimum follow-up allowed the calculation of at least 5-year survival rates. Results: 2736 evaluable patients were found to match the entrance criteria in 34 publications published from 1979 to 1995. Only 26% of these studies with 1151 patients analysed survival according to age at diagnosis. The cutoff level vaded between 2 and 16 years of age within the studies. 8/9 studies reported lower 5-year survival rates for the younger patient group with two of these showing a statistical significant difference in survival. Failure pattern is charactedsed by local relapse in 64% of all patients. Of these 42% present with multilocal recurrences. The main therapeutic difference for the younger patient group is the reduction of the overall dose by 15-25% compared to the standard dose. of 54-55 Gy to the postedor fosse Literature data suggest that a reduced overall dose of less than 50 Gy reduces survival of patients with medulloblastoma significantly. Conclusion: The hypothesis that age at presentation is a prognostic factor for children with medulloblastoma is widely accepted. One of the major negative therapeutic factors influencing survival is reduced total irradiation dose to the posterior fossa. In very young children postoperative chemotherapy could play a role until standard radiotherapy can be applied without unnecessary severe late sequelae
Ophthalmic manifestations of acute leukaemias: the ophthalmologist's role
Eye, 2004
With evolving diagnostic and therapeutic advances, the survival of patients with acute leukaemia has considerably improved. This has led to an increase in the variability of ocular presentations in the form of side effects of the treatment and the ways leukaemic relapses are being first identified as an ocular presentation. Leukaemia may involve many ocular tissues either by direct infiltration, haemorrhage, ischaemia, or toxicity due to various chemotherapeutic agents. Ocular involvement may also be seen in graft-versushost reaction in patients undergoing allogeneic bone marrow transplantation, or simply as increased susceptibility to infections as a result of immunosuppression that these patients undergo. This can range from simple bacterial conjunctivitis to an endophthalmitis. Leukaemia can present as pathology in the adnexae, conjunctiva, sclera, cornea, anterior chamber, iris, lens, vitreous, retina, choroid, and optic nerve. Recognition of the varied ocular presentations is also important in assessing the course and prognosis of leukaemia. We have presented a systematic approach taking each part of the eye in turn and outlining how leukaemia has been shown to affect it.
CORTICOSTEROID-INDUCED OCULAR HYPERTENSION IN CHILDREN AND ADOLESCENTS WITH ACUTE LYMPHOCYTIC LEUKEMIA AND NON-HODGKIN LYMPHOMA: A SYSTEMATIC REVIEW (Atena Editora), 2022
Objective: Conduct a systematic review to assess the risk of increased intraocular pressure (IOP) associated with corticosteroid use in children and adolescents with acute lymphocytic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). Methodology: A search was performed on PubMed, Scopus, Web of Science, Science Direct Cochrane Library, Google Scholar and OpenThesis databases. Relevant studies were read in full and selected according to eligibility criteria (children and adolescents up to 19 years of age with ALL or NHL, regardless of gender, and who were treated with systemic corticosteroids regularly) and those who reported ocular hypertension due to tumor infiltration, and glaucomatous damage and corticosteroid-induced ocular hypertension in initial testing. Results: 8 studies were selected: three case reports, a series of 5 cases, two prospective observational studies – one with 55 patients and one with 90 patients – and two retrospective observational studies – one with 54 and one with 12 patients. The results demonstrated eventual control of IOP, and consequences ranging from no ocular impairment to complete loss of vision.Conclusion: The possibility of silent ocular hypertension, with risk of irreversible amaurosis, demonstrates the need to evaluate the introduction of an evaluation and treatment protocol in pediatric patients soon after the diagnosis of ALL or NHL. However, given the limited evidence, further studies are warranted evaluating IOP and visual function before treatment initiation, as well as systematic measures during and after treatment.