Independent risk factors and long-term outcomes for acute kidney injury in pediatric patients undergoing hematopoietic stem cell transplantation: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) remains a frequent complication in children undergoing hematopoietic stem cell transplantation (HSCT) and an independent risk factor of the patient's survival and a prognostic factor of progression to chronic kidney disease (CKD). However, the causes of these complications are diverse, usually overlapping, and less well understood. METHODS: This retrospective analysis was performed in 43 patients (28 boys, 15 girls; median age, 5.5 years) undergoing HSCT between April 2006 and March 2019. The main outcome was the development of AKI defined according to the Pediatric Risk, Injury, Failure, Loss, End-stage Renal Disease (pRIFLE) criteria as ≥ 25% decrease in estimated creatinine clearance. The secondary outcome was the development of CKD after a 2-year follow-up. RESULTS: AKI developed in 21 patients (49%) within 100 days after HSCT. After adjusting for possible confounders, posttransplant AKI was associated with matched unrelated donor (MUD) (HR, 6.26; P = 0.042), but not total body irradiation (TBI). Of 37 patients who were able to follow-up for 2 years, 7 patients died, but none had reached CKD during the 2 years after transplantation. CONCLUSIONS: Posttransplant AKI was strongly associated with HSCT from MUD. Although the incidence of AKI was high in our cohort, that of posttransplant CKD was lower than reported previously in adults. TBI dose reduced, GVHD minimized, and infection prevented are required to avoid late renal dysfunction after HSCT in children since their combinations may contribute to the occurrence of AKI.

Total Body Irradiation and Risk of Breast Cancer After Blood or Marrow Transplantation: A Blood or Marrow Transplantation Survivor Study Report.

PURPOSE: To examine the association between total body irradiation (TBI) and subsequent breast cancer in women treated with blood or marrow transplantation (BMT) for hematologic malignancies. PATIENTS AND METHODS: Participants were drawn from the BMT Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived for ≥ 2 years after BMT. Patients with pre-BMT chest radiation or a history of breast cancer were excluded. Participants completed the BMTSS survey, which included details regarding breast cancer diagnosis. Subsequent breast cancer was confirmed by pathology report review or physician notes. Cox proportional hazards models assessed the association between TBI and subsequent breast cancer. Standardized incidence ratios were calculated to determine the excess risk of subsequent breast cancer compared with that in the general population. RESULTS: A total of 1,464 female BMT survivors (allogeneic: n = 788; autologous: n = 676) participated, with a median follow-up of 9.3 years from BMT. TBI was used in 660 patients (46%). Thirty-seven women developed subsequent breast cancer (allogeneic: n = 19; autologous: n = 18). Multivariable analysis revealed that exposure to TBI was associated with an increased risk of subsequent breast cancer among allogeneic BMT survivors (hazard ratio [HR], 3.7 [95% CI, 1.2 to 11.8]; P = .03) and autologous BMT survivors (HR, 2.6 [95% CI, 1.0 to 6.8]; P = .048). Pre-BMT exposure to alkylating agents was associated with an increased risk of subsequent breast cancer among autologous BMT survivors (HR, 3.3 [95% CI, 1.0 to 9.0]; P = .05). Compared with that in the general population, exposure to TBI at age < 30 years was associated with a 4.4-fold higher risk of subsequent breast cancer in allogeneic BMT survivors and a 4.6-fold higher risk in autologous BMT survivors. CONCLUSION: The association between TBI and subsequent breast cancer, especially among those exposed at a young age, as well as pre-BMT exposure to alkylating agents, should inform breast cancer screening for early detection.

Total body irradiation in Australia and New Zealand: results of a practice survey.

Total body irradiation (TBI) is an important treatment modality for the preparation of patients for bone marrow transplants. It is technically challenging and the actual delivery may vary from clinic to clinic. Knowledge of the pattern of practice may be helpful for clinics to determine future practice. We carried out an email survey from April to September 2019 sending 48 TBI related questions to all radiotherapy clinics in Australia and New Zealand via the Australasian College of Physical Scientists in Medicine email distribution list. Centres not performing TBI were not expected to complete the survey and centres that had participated in a previous survey, or that were known to perform the treatment, were followed up if no response was received. Of a total of approximately 70 centres, 14 clinics responded to the survey. The vast majority of clinics use conventional lateral and/or anterior-posterior beams at extended SSD for TBI treatment delivery. However, treatment planning, ancillary equipment (used for immobilisation/modulation), beam energy and prescribed lung doses vary considerably-with some clinics delivering the prescription dose to the lungs and some aiming to deliver a lung dose which is lower than the prescription dose. Only one clinic reported using an advanced delivery technique with modulated arcs at extended SSD. Centres either said they had no access to outcome data or did not answer this question. Compared with an earlier survey from 2005, 3 clinics have lowered their linac dose rate and 7 are the same or similar. The TBI practice in Australia and New Zealand remains varied, with considerable differences in treatment planning, beam energy, accepted lung doses and delivered dose rates.

Ultrasound is superior to palpation for thyroid cancer detection in high-risk childhood cancer and BMT survivors.

PURPOSE: Thyroid cancer is a common subsequent malignant neoplasm in childhood cancer survivors (CCS). Patients who received radiotherapy (RT) to the head, neck, upper thorax, or total body irradiation (TBI) are considered to be at risk for subsequent thyroid cancer. Current Children's Oncology Group screening guidelines recommend annual neck palpation. Our objective was to determine if ultrasound (US) is more sensitive and specific than palpation to detect thyroid cancer in high-risk CCS and bone marrow transplant (BMT) survivors. METHODS: Electronic medical records of patients followed in a longitudinal survivorship clinic from January 1, 2010 to December 31, 2017 were reviewed. Inclusion criteria included history of RT to the head, neck, upper thorax, or TBI for primary therapy or preparation for BMT prior to the age of 20 years. RESULTS: Two hundred and twenty-five patients had documented palpation and 144 (64%) also had US evaluation. Mean radiation dose was 28.6 Gy. Sixteen of 225 patients (7.1%) developed a subsequent thyroid cancer at a mean of 9.7 years from the completion of RT. Sensitivity of US was 100% compared with 12.5% for palpation. US demonstrated higher accuracy, with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.87 versus 0.56 for palpation (P < 0.0001). CONCLUSION: Routine screening with US was more sensitive than palpation for detection of subsequent thyroid cancer after high-risk RT in CCS and BMT survivors. Screening US may lead to earlier detection of thyroid cancer in this population. Earlier diagnosis has the potential to decrease operative complexity, and earlier definitive therapy reduces the likelihood of metastatic disease.

Defining patterns of care in the management of patients with brain metastases in a large oncology centre: A single-centre retrospective audit of 236 cases.

AIMS: The role of selected treatments for brain metastases (BM) is well documented; however, the prevalence of these is not. We report on the patterns of care in the management of BM in a large oncology centre. MATERIALS AND METHODS: We retrospectively audited 236 cases of newly diagnosed BM from January 2016 to December 2017 by looking at 2 years of radiology reports and gathered data on primary site, survival, treatment received, palliative care input and brain metastases-related admissions. RESULTS: Eighty-two per cent of cases were related to lung, breast and melanoma primaries. Half of patients received a form of treatment with the other half receiving best supportive care. Of these, whole-brain radiotherapy (39%) and stereotactic radiosurgery (40%) were the most common treatment modalities. Most common reasons for admissions were headaches, seizures, weakness and confusion. CONCLUSION: This is the first study in the UK that gives an in-depth overview of the real-world management of brain metastases. We have demonstrated the prevalence of treatment across the spectrum of brain metastases patients. Radiotherapy is the mainstay of treatment in nearly 80% of cases; however, care needs to be taken in ensuring that SRS is offered to those who are suitable.

Effects of Proton Center Closure on Pediatric Case Volume and Resident Education at an Academic Cancer Center.

PURPOSE: To analyze effects of closure of an academic proton treatment center (PTC) on pediatric case volume, distribution, and resident education. METHODS AND MATERIALS: This was a review of 412 consecutive pediatric (age ≤18 years) cases treated at a single institution from 2012 to 2016. Residents' Accreditation Council for Graduate Medical Education case logs for the same years were also analyzed. Characteristics of the patient population and resident case volumes before and after closure of the PTC are reported. RESULTS: Overall pediatric new starts declined by approximately 50%, from 35 to 70 per 6 months in 2012 to 2014 to 22 to 30 per 6 months in 2015 to 2016. Central nervous system (CNS) case volume declined sharply, from 121 patients treated in 2012 to 2015 to 18 patients in 2015 to 2016. In 2012 to 2014 our institution treated 36, 24, and 17 patients for medulloblastoma/intracranial primitive neuroectodermal tumor, ependymoma, and low-grade glioma, respectively, compared with 0, 1, and 1 patient(s) in 2015 to 2016. Forty-nine patients were treated with craniospinal radiation (CSI) from 2012 to 2014, whereas only 2 patients underwent CSI between 2015 and 2016. Hematologic malignancy patient volume and use of total body irradiation remained relatively stable. Patients treated when the PTC was open were significantly younger (9.1 vs 10.7 years, P=.010) and their radiation courses were longer (35.4 vs 20.9 days, P<.0001) than those treated after its closure. Resident case logs showed only a small decline in total pediatric cases, because the percentage of pediatric cases covered by residents increased after PTC closure; however, residents logged fewer CNS cases after PTC closure versus before. CONCLUSIONS: Overall pediatric case volume decreased after PTC closure, as did the number of patients treated for potentially curable CNS tumors. Our findings raise important questions regarding resident training in pediatric radiation oncology as these cases become increasingly concentrated at specialized centers.

Patterns of Relapse in High-Risk Neuroblastoma Patients Treated With and Without Total Body Irradiation.

PURPOSE: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. METHODS AND MATERIALS: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012. Anatomic sites of disease, defined by metaiodobenzylguanidine (MIBG) avidity, were compared at diagnosis and at first relapse. The Fisher exact test was performed to compare relapse in initially involved sites between patients treated with and without TBI. RESULTS: Seventy-four patients with a median age at diagnosis of 3.5 years (range, 0.3-15.3 years) had relapse in 227 sites of MIBG-avid metastatic disease, with a median time to relapse of 1.8 years. Of the 227 sites of first relapse, 154 sites (68%) were involved at diagnosis. When we compared relapse patterns in patients treated with and without TBI, 12 of 23 patients (52%) treated with TBI had relapse in ≥1 previously MIBG-avid site of disease whereas 40 of 51 patients (78%) treated without TBI had relapse in ≥1 previously MIBG-avid site of disease (P=.03). CONCLUSIONS: Patients treated with systemic irradiation in the form of TBI were significantly less likely to have relapse in prior sites of disease. These findings support further investigation into the role of radiopharmaceutical therapies in curative multimodality therapy.

[French experience in paediatric total body irradiation: A study from the radiotherapy committee of the Société française des cancers de l'enfant (SFCE)]. / Expérience française de l'irradiation corporelle totale en pédiatrie : étude du comité de radiothérapie de la Société française des cancers de l'enfant (SFCE).

A survey was conducted in 2015 in France on the care of children in radiotherapy services. We present the results for total body irradiation in children, a specific technique of radiation treatment, which needs dedicated controls for this particular population. Of the 17 centres interviewed, 16 responded, and 13 practiced total body irradiation. Patients are positioned in lateral decubitus in 11 centres and supine/prone in two centres. Doses used for total body irradiation in myeloablative bone marrow transplantation are the same in all centres (12Gy); treatments are always fractionated. Lung shielding is positioned to limit the dose at an average of 8Gy with extremes ranging from 6 to 10Gy. The shape of the shieldings varies depending on departments' protocol, with a smaller size in case of mediastinal mass. Four centres have experience of total body irradiation under general anaesthesia, despite twice-daily fractions. In total, practice is relatively homogeneous throughout France and is inspired by the knowledge obtained in adults.

[Status report of Hungarian radiotherapy based on treatment data, available infrastucture, and human resources]. / A magyar sugárterápia helyzete a betegellátási adatok, a rendelkezésre álló infrastruktúra és emberi eroforrás tükrében.

The purpose of the study is to report the status of Hungarian radiotherapy (RT) based on the assessment of treatment data in years 2012 to 2014, available infrastructure, and RT staffing. Between December 2014 and January 2015, a RT questionnaire including 3 parts (1. treatment data; 2. infrastructure; 3. staffing) was sent out to all Hungarian RT centers (n=12). All RT centers responded to all questions of the survey. 1. Treatment data: In 2014, 33,162 patients were treated with RT: 31,678 (95.5%) with teletherapy, and 1484 (4.5%) with brachytherapy (BT). Between 2012 and 2014, the number of patients treated with radiotherapy increased with 6.6%, but the number of BT patients decreased by 11%. Forty-two percent of all patients were treated in the two centers of the capital: 9235 patients (28%) at the National Institute of Oncology (NIO), and 4812 (14%) at the Municipial Oncoradiology Center (MOC). Out of the patients treated on megavoltage RT units (n=22,239), only 901 (4%) were treated with intensity-modulated RT (IMRT), and 2018 (9%) with image-guided RT (IGRT). In 2014, 52% of all BT treatments were performed in Budapest: NIO - 539 patients (36%); MOC - 239 patients (16%); and BT was not available in 3 RT centers. Prostate I-125 seed implants and interstitial breast BT was utilized in one, prostate HDR BT in two, and head&neck implants in three centers. 2. Infrastructure: Including ongoing development projects funded by the European Union, by the end of year 2015, 39 megavoltage teletherapy units, and 12 HDR BT units will be in use in 13 available Hungarian RT centers. 3. Staffing: Actually, 92 radiation oncologists (RO), 29 RT residents, 61 medical physicists, and 229 radiation therapy technologists are working in 12 RT centers. There are 23 vacant positions (including 11 RO positions) available at the Hungarian RT centers. According to the professional minimal requirements and WHO guidelines, the implementation of 11 new linear accelerators, and 1 BT units are needed in Hungary. Further resources for the development and upgrade of RT infrastructure and capacity should be allocated to RT centers in Budapest. Brachytherapy and modern teletherapy (e.g. IMRT and IGRT) are underutilized in Hungary compared to other European countries. Implementation of continuous education and practical training programs in leading Hungarian and international RT centers are suggested in an effort to a wider implementation of modern RT techniques in Hungarian RT centers.

Relative effectiveness at 1 gy after acute and fractionated exposures of heavy ions with different linear energy transfer for lung tumorigenesis.

Space radiation, which is comprised of high-energy charged (HZE) particles with different high-linear energy transfer (LET), induces more severe biological effects than the Earth's radiation. NASA has mandated that risk estimates of carcinogenesis induced by exposure to HZE particles with different LET be determined before conducting human explorations of Mars. Because lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in humans, it is critical the risk of that radiation-induced lung tumorigenesis be included when estimating the risks of space radiation to astronauts. To address this, we examined the incidence of lung tumorigenesis in wild-type C57BL/6 mice at 1.5 years after 1 Gy exposure (single or fractionated dose) to different types of radiation with different LET (iron, silicon, oxygen and X ray). We chose wild-type mice for this study because previous studies of radiation-induced lung tumorigenesis using mutant mice models (either downregulated tumor suppressors or upregulated oncogenes) may not accurately reflect the response of healthy individuals (astronauts) to space radiation. Our study clearly showed that HZE particles (iron, silicon and oxygen) induced a higher incidence of lung tumorigenesis than X rays, and that their relative effectiveness at 1 Gy was >6. In addition, we found that silicon exposure appears to induce more aggressive lung tumors. These results provide valuable information for future followup experiments to study the underlying mechanism of lung tumorigenesis, which will improve risk estimation of space radiation-induced lung tumorigenesis and help in the development of mitigators to reduce risk if it exceeds NASA guidelines.

Paraphyseal changes on bone-age studies predict risk of delayed radiation-associated skeletal complications following total body irradiation.

BACKGROUND: Children undergoing total body irradiation (TBI) often develop delayed skeletal complications. Bone-age studies in these children often reveal subtle paraphyseal changes including physeal widening, metaphyseal irregularity and paraphyseal exostoses. OBJECTIVE: To investigate whether paraphyseal changes on a bone-age study following TBI indicate a predisposition toward developing other radiation-associated skeletal complications. MATERIALS AND METHODS: We retrospectively reviewed medical records and bone-age studies of 77 children receiving TBI at our institution between 1995 and 2008 who had at least 2 years of clinical follow-up and one bone-age study after TBI. We graded bone-age studies according to the severity of paraphyseal changes. All documented skeletal complications following TBI were tabulated. Kendall's tau-b was used to examine associations between degree of paraphyseal change and development of a skeletal complication. RESULTS: Kendall's tau analyses showed that physeal widening and metaphyseal irregularity/sclerosis (tau = 0.87, P < 0.001) and paraphyseal exostoses (tau = 0.68, P < 0.001) seen on bone-age studies were significantly positively associated with the development of delayed skeletal complications following TBI. Thirty percent of children with no or mild paraphyseal changes developed a delayed skeletal complication, compared with 58% of children with moderate paraphyseal changes and 90% of children with severe paraphyseal changes. CONCLUSION: Paraphyseal changes identified on a bone-age study correlate positively with the development of delayed skeletal complications elsewhere in the skeleton following TBI.

Comparing radiation toxicities across species: an examination of radiation effects in Mus musculus and Peromyscus leucopus.

PURPOSE: Life shortening and pathological complications in similarly irradiated cohorts of the laboratory mouse Mus musculus and the white-footed mouse Peromyscus leucopus were recorded in the course of the Janus studies conducted at Argonne National Laboratory from 1970-1992. This study examines how lifespan, tumor and non-tumor disease incidence, and tumor multiplicity are differentially affected by gamma-rays and neutron radiation exposure in two different animal species. MATERIALS AND METHODS: Survival analyses examined differences in lifespan across species, while decision tree analyses examined statistically significant associations between lifespan, radiation exposure, and specific diseases. Logistic regression models were generated to examine the likelihood of disease incidence in these two species following gamma-ray or neutron radiation exposure. RESULTS: Life shortening in response to radiation was more significant in Peromyscus leucopus than in Mus musculus, irrespective of radiation quality. Many types of tumor and non-tumor diseases were found to be consistently species specific. Tumor multiplicity was observed in both species in response to radiation, although more pronounced in Mus musculus. CONCLUSION: The response to radiation was highly species specific, highlighting the difficulty in extrapolating conclusions from one species to another, irrespective of their phenotypic similarities and ecologic niches.

Medical effects and risks of exposure to ionising radiation.

Effects and risk from exposure to ionising radiation depend upon the absorbed dose, dose rate, quality of radiation, specifics of the tissue irradiated and other factors such as the age of the individual. Effects may be apparent almost immediately or may take decades to be manifest. Cancer is the most important stochastic effect at absorbed doses of less than 1 Gy. The risk of cancer induction varies widely across different tissues; however, the risk of fatal radiation-induced cancer for a general population following chronic exposure is about 5% Sv(-1). Quantification of cancer risk at doses of less than 0.1 Gy remains problematic. Hereditary risks from irradiation that might result in effects to offspring of humans appear to be much lower and any such potential risks can only be estimated from animal models. At high doses (over 1 Gy) cell killing and modification causes deterministic effects such as skin burns, and bone marrow depression, in which case immunosuppression becomes a critical issue. Acute whole body penetrating gamma irradiation at doses in excess of 2 Gy results in varying degrees of acute radiation sickness and doses over 10 Gy are usually lethal as a result of combined organ injury.

Radiation dose associated with renal failure mortality: a potential pathway to partially explain increased cardiovascular disease mortality observed after whole-body irradiation.

Whole-body and thoracic ionizing radiation exposure are associated with increased cardiovascular disease (CVD) risk. In atomic bomb survivors, radiation dose is also associated with increased hypertension incidence, suggesting that radiation dose may be associated with chronic renal failure (CRF), thus explaining part of the mechanism for increased CVD. Multivariate Poisson regression was used to evaluate the association of radiation dose with various definitions of chronic kidney disease (CKD) mortality in the Life Span Study (LSS) of atomic bomb survivors. A secondary analysis was performed using a subsample for whom self-reported information on hypertension and diabetes, the two biggest risk factors for CRF, had been collected. We found a significant association between radiation dose and only our broadest definition of CRF among the full cohort. A quadratic dose excess relative risk model [ERR/Gy(2) = 0.091 (95% CI: 0.05, 0.198)] fit minimally better than a linear model. Within the subsample, association was also observed only with the broadest CRF definition [ERR/Gy(2) = 0.15 (95% CI: 0.02, 0.32)]. Adjustment for hypertension and diabetes improved model fit but did not substantially change the ERR/Gy(2) estimate, which was 0.17 (95% CI: 0.04, 0.35). We found a significant quadratic dose relationship between radiation dose and possible chronic renal disease mortality that is similar in shape to that observed between radiation and incidence of hypertension in this population. Our results suggest that renal dysfunction could be part of the mechanism causing increased CVD risk after whole-body irradiation, a hypothesis that deserves further study.

Radiation doses originating from diagnostic procedures during the treatment and follow-up of children and adolescents with malignant lymphoma.

Children with malignant lymphoma undergo many diagnostic procedures that involve exposure to ionising radiation. In addition, many, but by no means all, undergo further exposure to ionising radiation during radiotherapy. While therapeutic radiation exposures are prescribed, the extent of radiation exposure arising from diagnostic procedures utilised in such children is largely unknown. We completed an audit of the radiation doses arising from diagnostic imaging procedures performed in a cohort of children with malignant lymphoma. The cumulative effective radiation dose associated with radiographic and radioisotopic procedures was derived for 81 children and adolescents with malignant lymphoma during their diagnosis, treatment and follow-up. Thirty-eight of the 42 patients (90%) with Hodgkin lymphoma were alive at study termination, with follow-up periods ranging from 1.9 to 11.7 years (median 5.3). Thirty-three of the 39 patients (85%) with non-Hodgkin lymphoma were alive at study termination with follow-up periods ranging from 2.4 to 12.3 years (median 7.5). The median effective dose was 518 mSv for patients with Hodgkin lymphoma and 309 mSv for those with non-Hodgkin lymphoma. The maximum effective dose was 1.7 Sv. The principal contributors to the effective dose were computed tomography (CT) and nuclear medicine imaging procedures using (67)Ga. Protocols for the management of children and adolescents with malignant lymphoma should be reviewed in order to reduce the radiation detriment without loss of essential diagnostic information.

Stereotactic body radiation therapy for head and neck tumor: disease control and morbidity outcomes.

We evaluated the efficacy and safety of stereotactic body radiation therapy (SBRT) for patients with head and neck tumors. From April 2005 through April 2008, 34 patients with head and neck tumors were treated with CyberKnife SBRT. Twenty-one of them had prior radiotherapy. Treatment sites were orbit (n = 7), cervical lymph nodes (n = 6), nasopharynx (n = 5), oropharynx (n = 4) and others (n = 12). The prescribed dose ranged from 19.5 to 42 Gy (median, 30 Gy) in 3-8 fractions for consecutive days. The target volume ranged from 0.7 to 78.1 cm(3) (median, 11.6 cm(3)). The median follow-up was 16 months. Treatment was well tolerated without significant acute complications in any cases. Complete response rate and partial response rate were 32.4% and 38.6%, respectively. The overall survival rates were 70.6% and 58.3% at 12 and 24 months, respectively. The overall survival was better in patients without prior radiotherapy within the previous 24 months or in case of smaller target volume. Six patients suffered severe late complications. All these patients had prior radiotherapy, and 2 of them developed massive hemorrhage in the pharynx and both died of this complication 5 and 28 months, respectively, after SBRT. Our preliminary results suggest that SBRT is an effective treatment modality for head and neck tumors. However, re-irradiation has significant risk of severe and even fatal late complications in the form of necrosis and hemorrhage in re-irradiated areas.

[Risk factors of graft-versus-host disease in patients after allogeneic stem cell transplantation]. / Czynniki ryzyka wystepowania choroby przeszczep przeciw gospodarzowi u pacjentów po allogenicznym przeszczepieniu macierzystych komórek krwiotwórczych.

BACKGROUND: Graft-versus-host disease (GVHD) is the most common and most serious complication of allogeneic hematopoetic stem cell transplantation (HSCT). The aim of this study was to assess the incidence of GVHD after allogeneic HSCT depending on the diagnosis and risk factors. MATERIAL AND METHODS: The study group comprised 78 patients aged 18 to 61 in whom allogeneic transplantation of hematopoietic stem cell in the Department and Clinic of Hematology, Oncology and Internal Diseases of Medical University in Warsaw (Poland) was performed. RESULTS: Acute form of GVHD was significantly more often occurred after total body irradiation (TBI) for patients with TBI who did not (p < 0.05). CONCLUSIONS: Risk factors for aGVHD were: age of the recipient, acute myeloid leukemia, myeloablative conditioning, TBI and unrelated donor.

Antioxidant diet supplementation starting 24 hours after exposure reduces radiation lethality.

Antioxidants mitigate radiation-induced lethality when started soon after radiation exposure, a delivery time that may not be practical due to difficulties in distribution and because the oral administration of such agents may require a delay beyond the prodromal stage of the radiation syndrome. We report the unexpected finding that antioxidant supplementation starting 24 h after total-body irradiation resulted in better survival than antioxidant supplementation started soon after the irradiation. The antioxidant dietary supplement was l-selenomethionine, sodium ascorbate, N-acetyl cysteine, alpha-lipoic acid, alpha-tocopherol succinate, and co-enzyme Q10. Total-body irradiation with 8 Gy in the absence of antioxidant supplementation was lethal by day 16. When antioxidant supplementation was started soon after irradiation, four of 14 mice survived. In contrast, 14 of 18 mice receiving antioxidant supplementation starting 24 h after irradiation were alive and well 30 days later. The numbers of spleen colonies and blood cells were higher in mice receiving antioxidant supplementation starting 24 h after irradiation than in mice receiving radiation alone. A diet supplemented with antioxidants administered starting 24 h after total-body irradiation improved bone marrow cell survival and mitigated lethality, with a radiation protection factor of approximately 1.18.

Quantifying the survival benefit for allogeneic hematopoietic stem cell transplantation in relapsed acute myelogenous leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the recommended therapy for patients with relapsed acute myelogenous leukemia (AML), despite little evidence showing a survival benefit in patients who undergo HSCT versus chemotherapy alone. Because a prospective randomized trial addressing this issue is unlikely, we retrospectively reviewed all patients receiving initial salvage therapy for AML at M.D. Anderson Cancer Center between 1995 and 2004, focusing on patients undergoing HSCT or chemotherapy without HSCT as second salvage after first salvage failed to produce complete remission (CR) (group A) and patients in first salvage-induced CR (group B). Median survival was 5.1 months for HSCT (n=84) versus 2.3 months for chemotherapy (n = 200; P = .004) in group A and 11.7 months for HSCT (n = 46) versus 5.6 months for chemotherapy (n = 66; P < . 001) in group B. HSCT was associated with a survival benefit in each of 8 subgroups defined by age < or > or = 50, high-risk cytogenetics or not, and treatment in first salvage-induced CR or second salvage, and also in 5 of 6 subgroups defined by age < or > or = 50 years and duration of first CR (CR1) (primary refractory, CR1 < or = 36 weeks, CR1 > 36 weeks). Our data suggest that HSCT is preferable to chemotherapy alone in these patients with poor prognoses, with particular benefits noted in patients under age 50 years.

Incidence of acute myeloid leukemia and hepatocellular carcinoma in mice irradiated with 1 GeV/nucleon (56)Fe ions.

Abstract Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the leukemogenic efficacy of one such HZE species, 1 GeV (56)Fe ions, a component of space radiation, in a mouse model for radiation-induced acute myeloid leukemia. CBA/CaJ mice were irradiated with 1 GeV/nucleon (56)Fe ions or (137)Cs gamma rays and followed until they were moribund or to 800 days of age. We found that 1 GeV/nucleon (56)Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia (AML). However, (56)Fe-ion-irradiated mice had a much higher incidence of hepatocellular carcinoma (HCC) than gamma-irradiated mice, with an estimated RBE of approximately 50. These data suggest a difference in the effects of HZE iron ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis.