Cataracts after total body irradiation and bone marrow transplantation in patients with acute leukemia in complete remission: a study of the european group for blood and marrow transplantation (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, 1995
Purpose: To determine the risk of, and risk factors for, developing cataracts after bone marrow transplantation. Methods and Materials: Four hundred and ninety-two adults who underwent bone marrow transplantation in Seattle were followed for 2 to 18 (median, 6) years. Before transplantation, patients received a preparative regimen of chemotherapy plus total body irradiation (TBI) (n = 407) or chemotherapy alone, without TBI (n = 85). TBI was administered in a single dose of 10 Gy (n = 74) or in fractionated doses totaling 12-15.75 Gy (n = 333). The risk of cataracts was determined for groups of patients with respect to the type of preparative regimen received and other pretransplant and posttransplant variables. Results: One hundred and fifty-nine patients (32%) developed cataracts between 0.5 to 11 (median, 2.3) years after transplantation.
Cataract after total body irradiation and bone marrow transplantation
International Journal of Radiation Oncology*Biology*Physics, 2002
Purpose: To assess the degree of visual impairment as a result of cataract formation after total body irradiation (TBI) for bone marrow transplantation. Methods and Materials: The data from 93 patients who received TBI in 1 or 2 fractions as a part of their conditioning regimen for bone marrow transplantation were analyzed with respect to the degree of visual impairment as a result of cataract formation. The probability to develop severe visual impairment (SVI) was determined for all patients, and the degree of visual impairment was assessed for 56 patients with stabilized cataract, using three categories: no, mild, or severe. Results: For all 93 patients, the probability of developing a cataract causing SVI was 0.44. For allogeneic patients, it was 0.33 without and 0.71 with steroid treatment (p <0.001). All SVI-free probability curves reached a plateau distinct from the cataract-free curves. Apparently, cataracts developing late in the follow-up period rarely cause SVI. Of the patients with stabilized cataract, 32% had no visual impairment, 16% had mild, and 52% severe impairment. No or mild visual impairment was present in 61% of all patients with stable cataract and no steroid treatment compared with only 13% of the patients treated with steroids (p ؍ 0.035). Conclusion: SVI occurs in only some of the patients (52%) with stable cataract after TBI for bone marrow transplantation in 1 or 2 fractions. Steroid treatment markedly increases the probability of developing visual problems as result of a cataract after TBI.
Bone Marrow Transplantation, 2002
One hundred and ninety-three patients with hematological malignancies and a follow-up у1 year, treated with stem cell transplantation (45 autologous, 99 allogeneic T cell-depleted matched, 49 allogeneic T cell-depleted mismatched) from July 1985 to May 1998, were considered evaluable for the development of cataracts. Total body irradiation (TBI), administered either according to a hyperfractionated scheme (HTBI) or in a single dose (STBI), was employed in the conditioning regimens. HTBI was prescribed in 94% of patients undergoing allogeneic matched transplant, while STBI was used in 71% of patients receiving allogeneic mismatched and in all patients undergoing autologous transplant. The median follow-up was 7.56 years in the HTBI and 3.02 years in the STBI group. Among the different risk factors analyzed by univariate analysis only the TBI scheme and type of transplant reached statistical significance (P Ͻ 0.0001 and P Ͻ 0.001, respectively). By multivariate analysis only the TBI scheme was an independent factor for cataract development (STBI vs HTBI RR 7.2; P Ͻ 0.01). Our results showed that STBI is more cataractogenic than HTBI. The incidence of cataract we observed was among the lowest described in the literature. T cell depletion, because it prevents graft-versus-host disease and reduces the protracted use of post-transplant steroids, explains the results we obtained.
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).
Cataract incidence after total-body irradiation
International Journal of Radiation Oncology*Biology*Physics, 2000
Purpose: The aim of this retrospective study was to evaluate cataract incidence in a homogeneously-treated group of patients after total-body irradiation (TBI) followed by autologous bone marrow transplantation or peripheral blood stem cell transplantation. Methods and Materials: Between 1982 and 1994, a total of 260 patients received either autologous bone marrow or blood stem cell transplantation for hematological malignancy at the University of Heidelberg. Two hundred nine of these patients received TBI in our hospital. Radiotherapy was applied as hyperfractionated TBI, with a median dose of 14.4 Gy in 12 fractions over 4 days. Minimum time between fractions was 4 h. Photons with an energy of 23 MeV were used with a dose rate of 7-18 cGy/min. Ninety-six of the 209 irradiated patients were still alive in 1996; 86 of these patients (52 men, 33 women) answered a questionnaire and could be examined ophthalmologically. The median age at time of TBI was 38.5 years, with a range of 15-59 years. Results: The median follow-up is now 5.8 years, with a range of 1.7-13 years. Cataract occurred in 28/85 patients (32.9%) after a median of 47 months (1-104 months). In 6 of 28 patients who developed a cataract, surgery of the cataract was performed. Whole-brain irradiation prior to TBI had been performed more often in the group of patients developing cataract (14.3%) versus 10.7% in the group of patients without cataract. However, there was no statistical difference (Chi-square, p > 0.05). Conclusion: Cataract is a common side effect of TBI. Cataract incidence found in our patients is comparable to results of other centers using a fractionated regimen for TBI. To assess the incidence of cataract after TBI, a long-term follow-up is required.
Risk factors for requiring cataract surgery following total body irradiation
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 1994
In order to determine the incidence of cataract surgery following total body irradiation (TBI), questionnaires were mailed to 173 surviving patients who had received single fraction TBI for haematological malignancies. All patients had undergone bone marrow transplantation at the Royal Marsden Hospital, Surrey, between 1977 and 1991. Replies were received from 135 patients (78%). Fifty-four patients had required cataract surgery. The probability of requiring surgery for cataract at 2, 5 and 10 years post TBI was 5%, 39% and 58%, respectively. No cataract surgery was performed at less than 2 years after the time of TBI, and 12 years is the longest interval, prior to surgery, recorded so far. From a number of potential risk factors, those found to predict independently for cataract surgery, and their relative risk (RR) factors, were: cranial radiotherapy preceding TBI (RR 4.2 for patients irradiated in year prior to TBI, 3.3 for others irradiated); skull dose (RR 2.3 for patients over...
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.
A Retrospective Study of Ocular Side Effects in Children Undergoing Bone Marrow Transplantation
European Journal of Ophthalmology, 1996
Bone marrow transplantation (BMT) is recognized as a successful treatment for malignant and non-malignant hematological diseases. Thanks to transplantation, the num-» ber of long-term survivors has risen and with the improved prognosis a problem of ocular side effects has arisen. We carried out a retrospective study to determine the incidence and etiopathogenesis of ocular complications in a series of young patients undergoing BMT. One hundred children (62 males and 38 females) with a mean age of 7.12 (±3.3) years at the time of BMT (autologous in 66 cases, allogenic in 34) were followed for a mean of 4.2 years (range 2-9). The conditioning regimens preceding BMT induced cytoreductive chemotherapy alone (47 cases) or associated with total body irradiation (TBI) (53 cases) in three or six fractions for a total dose of 10-12 Gy. We examined every child before BMT and subsequently every six months. We did not include patients with ocular complications due to the primary disease. Thirty-three children showed several complications after BMT: 17 had subcapsular posterior cataract in both eyes and eight had tear hyposecretion; one had dramatic fungal panuveitis, four had hemorrhagic complications and five optic disk edema. TBI was significantly associated with the development of subcapsular posterior cataract.