Consensus of German transplant centers on hematopoietic stem cell transplantation in Fanconi anemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative therapy for the severe hematopoietic complications associated with Fanconi anemia (FA). In Germany, it is estimated that 10-15 transplants are performed annually for FA. However, because FA is a DNA repair disorder, standard conditioning regimens confer a high risk of excessive regimen-related toxicities and mortality, and reduced intensity regimens are linked with graft failure in some FA patients. Moreover, development of graft-versus-host disease is a major contributing factor for secondary solid tumors. The relative rarity of the disorder limits HSCT experience at any single center. Consensus meetings were convened to develop a national approach for HSCT in FA. This manuscript outlines current experience and knowledge about HSCT in FA and, based on this analysis, general recommendations reached at these meetings.

Outcomes of mismatched and unrelated donor hematopoietic stem cell transplantation in Fanconi anemia conditioned with chemotherapy only.

Fanconi anemia (FA) is a genomic instability syndrome associated with bone marrow failure, myelodysplastic syndrome (MDS), and/or acute myeloid leukemia (AML) requiring hematopoietic stem cell transplantation (HSCT) to restore normal hematopoiesis. Although low-intensity fludarabine-based preparative regimens without radiation confer excellent outcomes in FA HSCTs with HLA-matched sibling donors, outcomes for FA patients with alternative donors are less encouraging, albeit improving. We present our experience with 17 FA patients who completed mismatched related or unrelated donor HSCT using a non-radiation fludarabine-based preparative regimen at Charité University Medicine Berlin. All patients engrafted; however, one patient had unstable chimerism in the setting of multi-viral infections that necessitated a stem cell boost to revert to full donor chimerism. Forty-seven percent of patients developed grade I acute graft-verus-host disease (aGVHD). No grade II-IV aGVHD or chronic graft-versus-host disease of any severity occurred. At a median follow-up of 30 months, 88 % of patients are alive with normal hematopoiesis. Two patients died of infections 4 months post-transplantation. These results demonstrate that short-term outcomes for FA patients with mismatched and unrelated donor HSCTs can be excellent using chemotherapy only conditioning. Viral reactivation, however, was a major treatment-related complication.

Dose point kernel simulation for monoenergetic electrons and radionuclides using Monte Carlo techniques.

Monte Carlo (MC) simulation has been commonly used in the dose evaluation of radiation accidents and for medical purposes. The accuracy of simulated results is affected by the particle-tracking algorithm, cross-sectional database, random number generator and statistical error. The differences among MC simulation software packages must be validated. This study simulated the dose point kernel (DPK) and the cellular S-values of monoenergetic electrons ranging from 0.01 to 2 MeV and the radionuclides of (90)Y, (177)Lu and (103 m)Rh, using Fluktuierende Kaskade (FLUKA) and MC N-Particle Transport Code Version 5 (MCNP5). A 6-µm-radius cell model consisting of the cell surface, cytoplasm and cell nucleus was constructed for cellular S-value calculation. The mean absolute percentage errors (MAPEs) of the scaled DPKs, simulated using FLUKA and MCNP5, were 7.92, 9.64, 4.62, 3.71 and 3.84 % for 0.01, 0.1, 0.5, 1 and 2 MeV, respectively. For the three radionuclides, the MAPEs of the scaled DPKs were within 5 %. The maximum deviations of S(N←N), S(N←Cy) and S(N←CS) for the electron energy larger than 10 keV were 6.63, 6.77 and 5.24 %, respectively. The deviations for the self-absorbed S-values and cross-dose S-values of the three radionuclides were within 4 %. On the basis of the results of this study, it was concluded that the simulation results are consistent between FLUKA and MCNP5. However, there is a minor inconsistency for low energy range. The DPK and the cellular S-value should be used as the quality assurance tools before the MC simulation results are adopted as the gold standard.

Targeted therapy in Ewing sarcoma.

Despite marked improvement in the prognosis of patients with nonmetastatic Ewing sarcoma (ES), the outcome for patients with recurrent or metastatic disease remains poor. Insight into key biologic processes in ES could provide new therapeutic targets. The particular biologic feature of ES, the fusion of the EWS gene with a member of the ETS family of genes, is present in >95% of cases. The EWS-ETS chimeric protein leads to aberrant transcription that promotes tumor initiation and propagation via prosurvival and antiapoptotic pathways. Recent research has identified cooperating mutations important for ES tumorigenesis. This paper provides a summary of the latest research in ES and discusses potential novel targets for therapy.

Auditory abnormalities associated with unilateral renal agenesis.

OBJECTIVE: To evaluate the relationship between unilateral renal agenesis and auditory abnormality, and to determine the clinical spectrum of hearing impairment in such patients. METHODS: Seventy-five children with unilateral renal agenesis underwent auditory examinations. The subjects comprised 35 males and 40 females. Fourteen females had mullerian abnormalities. Another 75 schoolchildren with the same gender profile were selected for audiometric testing as a control group. Children with sonographically evident urogenital system abnormalities were excluded from the control group. RESULTS: The prevalence of auditory abnormalities in children with unilateral renal agenesis (4/75) (5.3%) was higher than in the control group (0%). The prevalence in children with urogenital anomalies was significantly higher in patients with renal agenesis than in the normal population (28.5%). Audiometric results showed that four of the 75 children manifested ipsilateral sensorineural hearing impairment, particularly in the high-frequency range. All were females with coexisting genital abnormalities. Two were diagnosed with mild sensorineural hearing impairment while the other two had moderate hearing loss. CONCLUSIONS: The results of our study suggest that neurosensory hearing loss was found to be associated with renal agenesis. Further audiometric follow-up of children with renal agenesis seems worthwhile.

Image display for collision avoidance of radiation therapy: treatment planning.

Patient treatment in a medical linear accelerator is characterized by many angular and translational movements of the gantry and couch. The direction and orientation of each treatment beam is specified by a set of gantry, turntable, and collimator angles. It is possible that some selected treatment field configurations will result in gantry/couch or gantry/patient collisions that remain undetected during the treatment planning process. In this work, a digital camera has been used to record all the workable gantry/ patient set-up images, and a Windows programming language is used to edit and display these images on a personal computer for the treatment planner to screen the treatment plans. These graphical displays enable the planner to be aware of any potential collision hazards by an actual visualization of each selected gantry/turntable or gantry/patient angle configuration.

Whole body radiation exposure with gamma unit radiosurgery.

BACKGROUND: Stereotactic radiosurgery is the use of external radiation in association with a stereotactic device to precisely locate and destroy inaccessible deep-seated lesions within the brain in a single treatment session. Very little attention has been paid to the extracranial sites of radiation exposure measurements. This study evaluates the extracranial absorbed dose due to leakage and scattered radiation of the Gamma Unit used in radiosurgery. METHODS: The absorbed doses were measured with thermoluminescent dosimetry (TLDs). Single and multiple Gamma Unit treatment with the 18mm collimator helmet was given and a Rando tissue equivalent phantom was in place to simulate a patient treatment. TLDs were placed on the phantom to measure the absorbed doses by the organs at risk. Two TLD chips were placed at each of the following organs: eye, thyroid, sternum and gonads. The irradiated TLDs were read with a Vinten TLD system 654D. The TLD factor was determined by irradiating TLDs with a cobalt-60 teletherapy unit of a known dose of radiation. RESULTS: The average maximum target absorbed dose was 30 Gy. The measured absorbed dose in selected organs from Gamma Unit radiosurgery with one or more isocenters was 21-53 cGy for the eye, 4-8 cGy for the thyroid, 3-4 cGy for the sternum and 2-3 cGy for the gonads. The dose to extracranial sites increased with the number of isocenters. The radiation dose to extracranial sites became much more substantial when multiple isocenters were used. CONCLUSIONS: The potential risk of radiation exposure is radiation induced tumors. No cases have been reported in patients treated with Gamma Unit radiosurgery. Given the benefit of Gamma Unit treatment, the clinical significance of these doses is minimal.