Three-dimensional patient setup errors at different treatment sites measured by the Tomotherapy megavoltage CT.

BACKGROUND AND PURPOSE: Reduction of interfraction setup uncertainty is vital for assuring the accuracy of conformal radiotherapy. We report a systematic study of setup error to assess patients' three-dimensional (3D) localization at various treatment sites. PATIENTS AND METHODS: Tomotherapy megavoltage CT (MVCT) images were scanned daily in 259 patients from 2005-2008. We analyzed 6,465 MVCT images to measure setup error for head and neck (H&N), chest/thorax, abdomen, prostate, legs, and total marrow irradiation (TMI). Statistical comparisons of the absolute displacements across sites and time were performed in rotation (R), lateral (x), craniocaudal (y), and vertical (z) directions. RESULTS: The global systematic errors were measured to be less than 3 mm in each direction with increasing order of errors for different sites: H&N, prostate, chest, pelvis, spine, legs, and TMI. The differences in displacements in the x, y, and z directions, and 3D average displacement between treatment sites were significant (p < 0.01). Overall improvement in patient localization with time (after 3-4 treatment fractions) was observed. Large displacement (> 5 mm) was observed in the 75(th) percentile of the patient groups for chest, pelvis, legs, and spine in the x and y direction in the second week of the treatment. CONCLUSION: MVCT imaging is essential for determining 3D setup error and to reduce uncertainty in localization at all anatomical locations. Setup error evaluation should be performed daily for all treatment regions, preferably for all treatment fractions.

Multimodality image guided total marrow irradiation and verification of the dose delivered to the lung, PTV, and thoracic bone in a patient: a case study.

This work reports our initial experience using multimodality image guidance to improve total marrow irradiation (TMI) using helical tomotherapy. We also monitored the details of the treatment delivery to glean information necessary for the implementation of future adaptive processes. A patient with metastatic Ewing's sarcoma underwent MRI, and bone scan imaging prior to TMI. A whole body kilovoltage CT (kVCT) scan was obtained for intensity modulated TMI treatment planning, including a boost treatment to areas of bony involvement. The delivered dose was estimated by using MVCT images from the helical tomotherapy treatment unit, compared to the expected dose distributions mapped onto the kVCT images. Clinical concerns regarding patient treatment and dosimetric uncertainties were also evaluated. A small fraction of thoracic bone volume received lower radiation dose than the prescribed dose. Reconstructed planned treatment volume (PTV) and the dose delivered to the lung were identical to planned dose. Bone scan imaging had a higher sensitivity for detecting skeletal metastasis compared to MR imaging. However the bone scan lacked sufficient specificity in three dimensions to be useful for planning conformal radiation boost treatments. Inclusion of appropriate imaging modalities improves detection of metastases, which allows the possibility of a radiation dose boost to metastases during TMI. Conformal intensity modulated radiation therapy via helical tomotherapy permitted radiation delivery to metastases in the skull with reduced dose to brain in conjunction with TMI. While TMI reduces irradiation to the lungs, onboard megavoltage computed tomography (MVCT) to verify accurate volumetric dose coverage to marrow-containing thoracic bones may be essential for successful conformal TMI treatment.

Evaluation of bladder dose in intensity-modulated radiation therapy of the prostate.

Day-to-day variation in bladder and rectal filling affects prostate location and positioning accuracy. Systems using ultrasonic localization or gold seed placement are most often used to help correct for these changes. At some institutions, patients are instructed to empty their rectum and fill their bladders prior to treatment in an attempt to standardize the prostate location, displace small bowel out of the radiation field, and move some of the bladder wall away from the high-dose area. Although instructed to come to treatment with a full bladder, it is presumed that there is variability in bladder filling each day of treatment, depending on the amount of fluids consumed and time to treatment. We have reviewed daily bladder volumes on a subset of 5 prostate patients, all of them prescribed to receive 7560 cGy in 42 fractions, and have evaluated the dosimetric consequences of bladder volume changes from full to two-third or one-third filling. All of these patients' positions were verified daily with ultrasonic localization. Those measurements have been used to help analyze the actual treated bladder volumes for comparison with the treatment plan. We find that, in general, maximum filling only occurred on the initial simulation/image acquisition day and was typically smaller on all the following treatment days. Based on our dose-volume model, we estimate that average bladder daily doses were 8-50% higher than predicted by the initial intensity-modulation radiation therapy (IMRT) plan.

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up.

INTRODUCTION: Chemo-potentiation of radiation improves survival in women with cervical cancer. Our group has previously demonstrated the tolerability of weekly paclitaxel combined with cisplatin during radiation therapy. We sought to determine the efficacy of this regimen in patients with "high risk" cervical cancer, and to determine the short- and long-term toxicity of this approach. METHODS: We prospectively enrolled surgically staged patients with positive peritoneal cytology, resectable nodal metastases, or primary tumor > 6 cm. Patients were treated using external beam radiation with concomitant cisplatin (50 mg/m2) during weeks 1, 4, and 7, and weekly paclitaxel (50 mg/m2), followed by four courses of adjuvant cisplatin (50 mg/m2) and paclitaxel (135 mg/m2). Toxicity, overall, and disease-free survival were evaluated. RESULTS: Twenty-three patients were enrolled, and 21 were evaluable. Patient allotment by FIGO stage was: IB1 - seven, IB2 - five, IIA - two, IIB - four, IIIB - two, IV - three. Twenty patients (95%) completed radiation treatment (median dose to point A was 8278 cGy). Seventeen patients (81%) completed all chemotherapy. At a median follow-up of 58 months the overall survival was 68%. Overall survival for patients with clinical Stage I and II disease was 82% at a median of 64 months. Hematologic toxicity was common but rarely resulted in treatment delays. Late complications requiring intervention (obstruction, fistula, significant lymphocyst) occurred in 11 patients (52%). CONCLUSION: The combination of paclitaxel and cisplatin appears efficacious in "high-risk" cervical cancer patients. Hematologic toxicity was common but tolerable. Long-term survival was common in these patients, however late toxicity was significant. This regimen should be investigated in collaborative phase III trials.

Autologous stem cell transplantation for high-risk Ewing's sarcoma and other pediatric solid tumors.

The prognosis for many pediatric and young adult patients with solid tumors that have metastasized at the time of diagnosis or have relapsed after therapy remains very poor. The steep dose-response curve of many of these tumors to alkylating agents makes myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) an attractive potential therapy. The role of ASCT for these high-risk patients is yet to be conclusively determined. We have transplanted 36 patients on two consecutive protocols with a variety of histological diagnoses. Overall survival (OS) was 63% (95% CI: 47-79%) at 1 year and 33% (95% CI: 16-50%) at 3 years. Patients with a diagnosis of Ewing's sarcoma (ES) or desmoplastic small round cell tumor (DSRCT) had significantly better survival than those with other diagnoses with estimated 3-year OS of 54% (95% CI: 29-79%) for this group of patients (P = 0.03). There were two transplant-related deaths both attributable to hepatic veno-occlusive disease. Median follow-up among survivors is 3.5 years (range: 0.6-7.9 years). These data justify continued investigation of ASCT as a consolidation therapy in patients with metastatic or relapsed ES and DSRCT.

Preclinical studies targeting normal and leukemic hematopoietic cells with Yttrium-90-labeled anti-CD45 antibody in vitro and in vivo in nude mice.

A study was undertaken to investigate the suitability of using a high affinity (Kd = 1.1 nM) anti-CD45 monoclonal antibody for delivering the high energy beta-particle emitting isotope (90)Y to lymphohematopoietic target cells in vivo. The antibody, AHN-12, recognized the tyrosine phosphatase CD45 expressed on the surface of normal and malignant hematopoietic cells and studies showed that it reacted with both CD45-expressing normal peripheral blood cells and leukemia cells from patients. The antibody was readily labeled with (90)Y using the highly stable chelate 1B4M-DTPA and the radioimmunoconjugate was designated (90)Y-anti-CD45. The agent selectively bound to CD45(+) B cell line Daudi, but not CD45(-) control cells and significantly (p = 0.007) more bound to Daudi tumors growing in athymic nude mice than did a control non-reactive antibody. Moreover, biodistribution data correlated well to an anti-Daudi effect observed against established tumors in nude mice. The effect was dose dependent and irreversible with the best results in mice receiving a single dose of 137 microCi (90)Y-anti-CD45. These mice displayed a significantly (p < 0.0095) better anti-tumor effect than a control (90)Y-labeled antibody and survived over 135 days with no evidence of tumor. Histology studies showed no significant injury to kidney, liver, or small intestine even at 254 microCi, the highest dose tested. Because radiolabeled anti-CD45 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data indicate that this agent may be used to improve treatment of hematopoietic malignancies, particularly leukemia and lymphoma, when combined with hematopoietic stem cell transplantation in a future clinical trial.

In vivo diode dosimetry for routine quality assurance in IMRT.

Due to the complexity of IMRT dosimetry, dose delivery evaluation is generally done using a treatment plan in which the optimized fluence distribution has been transferred to a test phantom for accessibility and simplicity of measurement. The actual patient doses may be reconstructed in vivo through the use of electronic portal imaging devices or films, but the assessment of absolute dose from these measurements is time-consuming and complicated. In our clinic we have instituted the use of routine diode dosimetry for IMRT patients following the same procedure used for standard radiation therapy patients in which each new treatment field is checked at the start of treatment. For standard cases the dose at dmax is calculated as part of the monitor unit calculation. For the IMRT cases, the dose contribution to the dmax depth for each field is taken from the treatment plan. We found that about 90% of the diode measurements agreed to within +/- 10% of the planned doses (45/51 fields) and 63% (32/51 fields) achieved +/- 5% agreement. By using this direct in vivo method to verify the clinical doses delivered, we have been able to make a uniform startup procedure for all patients while simplifying our IMRT QA process.

Outcome of second hematopoietic cell transplantation in Hurler syndrome.

Hurler syndrome (HS) is an autosomal recessive, inherited metabolic storage disorder due to deficiency of lysosomal alpha-L-iduronidase (IDU) enzyme activity. Untreated patients develop progressive mental retardation and multisystem morbidity with a median life expectancy of 5 years. Allogeneic hematopoietic cell transplantation (HCT) can achieve stabilization and even improvement of intellect, with long-term survival. However, children with HS have an increased incidence of graft failure, usually with concomitant autologous marrow reconstitution. Between 1983 and 2000, 71 Hurler children underwent HCT at the University of Minnesota. Of these 71, 19 (27%) experienced graft failure. We report HCT outcomes in all 11 Hurler patients receiving a second HCT at the University of Minnesota. Median age at second HCT was 25 months (range, 16 to 45 months); median time from first HCT was 8 months (range, 4 to 18.5 months). The conditioning regimen consisted of cyclophosphamide/TBI/ATG (n = 8) or busulfan/cyclophosphamide/ATG (n = 3). The source of bone marrow was an unrelated donor in six, matched sibling in four, and mismatched related in one. Five of the 11 grafts were T cell depleted prior to infusion. Overall, 10 of 11 patients showed donor-derived engraftment, of whom three developed grade 3 to 4 acute GVHD. Five of 11 patients are surviving a median of 25 months (range, 2 months to 12 years) with an overall actuarial survival of 50% (95% CI, 27% to 93%) at 4 years. All five show sustained donor engraftment with normalization of IDU activity levels. Three of five evaluable patients demonstrated stabilization of neuropsychological function after second HCT. Currently, allogeneic donor-derived hematopoiesis provides the only chance for long-term survival and improved quality of life in Hurler patients. While graft failure in Hurler patients requires further investigation, a timely second HCT can be well-tolerated and beneficial.

Using a belly board device to reduce the small bowel volume within pelvic radiation fields in women with postoperatively treated cervical carcinoma.

OBJECTIVE: The purpose of this study was to attempt to reduce the small bowel volume in cervical cancer patients undergoing radiation therapy using the belly board device and a four-field technique. METHODS: From 1994 through 1997, twenty-one patients with cervical cancer were referred to the University of Minnesota Medical Center and underwent surgical staging with or without radical hysterectomy followed by postoperative external beam radiotherapy for various indications including positive nodal disease (n = 11), lymph-vascular space invasion (n = 2), poor histology (n = 3), parametrial disease (n = 4), and positive vaginal margin (n = 1). RESULTS: The median age of the 21 patients was 42 years (25-54 years) and a median external beam pelvic radiation dose of 4775 cGy (range, 4200-5075 cGy) was administered. All patients were evaluated for amount of small bowel in the field in both the supine and prone positions, with and without the belly board device (BBD), using a four-field technique. With a full bladder, abdominal radiographs with contrast were obtained to evaluate the volume of small bowel within the radiation fields. In most patients, the BBD was effective at minimizing the amount of small bowel in the lateral fields, whereas a prone position on the treatment table (without the BBD) spared the most small bowel with the AP/PA fields. Therefore over a 2-day cycle, the most small bowel sparing was obtained with the patients treated prone on the BBD for the lateral fields on Day 1 and prone on the table for the AP/PA fields on Day 2. Patients had FIGO stage IB (n = 18), IA2 (n = 1), and IIA (n = 2). The median follow-up was 37 months (24-65 months). No significant acute gastrointestinal or genitourinary toxicity was experienced and no patients have experienced a bowel obstruction to date. CONCLUSIONS: The BBD may offer a means for positioning the mobile small intestine out of the radiation field and improving the tolerance of radiotherapy. The BBD provides a noninvasive technique for reduction of acute and chronic gastrointestinal morbidity.

A phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of repeated intravenous doses and correlation of pharmacokinetics with pharmacodynamics.

PURPOSE: Preclinical studies indicate that RSR13 oxygenates and radiosensitizes hypoxic solid tumors by decreasing the oxygen (O(2))-binding affinity of hemoglobin (Hb). A Phase I open-label, multicenter dose and frequency escalation study was conducted to assess the safety, tolerance, pharmacokinetics, and pharmacodynamic effect of daily RSR13 administration to cancer patients receiving concurrent palliative radiotherapy (RT). METHODS AND MATERIALS: Eligibility criteria included the following: ECOG performance status < or =2; resting and exercise arterial oxygen saturation (SaO(2)) > or =90%; an indication for palliative RT, 20-40 Gy in 10-15 fractions. RSR13 was administered i.v. via central vein over 60 min immediately before RT. Patients received supplemental O(2) via nasal cannula at 4 L/min during RSR13 infusion and RT. Plasma, red blood cell (RBC), and urine RSR13 concentrations were assayed. The pharmacodynamic effect of RSR13 on Hb-O(2) binding affinity was quantified by multipoint tonometry and expressed as an increase in p50, defined as the partial pressure of O(2) that results in 50% SaO(2). The RSR13 dose in the first cohort was 75 mg/kg once a week for two doses; successive cohorts received higher, more frequent doses up to 100 mg/kg/day for 10 days during RT. RESULTS: Twenty patients were enrolled in the study. Repeated daily doses of RSR13 were generally well tolerated. Two adverse events of note occurred: (1) A patient with pre-existing restrictive lung disease had transient persistent hypoxemia after the sixth RSR13 dose; (2) a patient with a recurrent glioma receiving high-dose corticosteroids had edema after the seventh RSR13 dose, likely due to the daily high-volume fluid infusions. Both patients recovered to baseline status with conservative management. Maximum pharmacodynamic effect occurred at the end of RSR13 infusion and was proportional to the RBC RSR13 concentration. After an RSR13 dose of 100 mg/kg, the peak increase in p50 averaged 8.1 mm Hg, consistent with the targeted physiologic effect, and then diminished with a half-life of approximately 5 h. CONCLUSIONS: RSR13 was well tolerated in daily doses up to 100 mg/kg administered for 10 days during RT. The combined administration of RSR13 with 4 L/min supplemental O(2) yielded pharmacodynamic conditions in which hypoxic tumor radiosensitization can occur. Ongoing Phase II and Phase III studies are evaluating the combination of RT and RSR13 for selected indications, including primary brain tumors, brain metastases, and non-small-cell lung cancer.

A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission.

Intensive, myelosuppressive therapy is necessary to maximize outcomes for patients with acute myeloid leukemia (AML). A comparison was made of 3 aggressive postremission approaches for children and adolescents with AML in a randomized trial, CCG-2891. A total of 652 children and adolescents with AML who achieved remission on 2 induction regimens using identical drugs and doses (standard and intensive timing) were eligible for allocation to allogeneic bone marrow transplantation (BMT) based on matched related donor status (n = 181) or randomization to autologous BMT (n = 177) or to aggressive high-dose cytarabine-based chemotherapy (n = 179). Only 115 patients (18%) refused to participate in the postremission phase of this study. Overall compliance with the 3 allocated regimens was 90%. At 8 years actuarial, 54% +/- 4% (95% confidence interval) of all remission patients remain alive. Survival by assigned regimen ("intent to treat") is as follows: allogeneic BMT, 60% +/- 9%; autologous BMT, 48% +/- 8%; and chemotherapy, 53% +/- 8%. Survival in the allogeneic BMT group is significantly superior to autologous BMT (P =.002) and chemotherapy (P =.05); differences between chemotherapy and autologous BMT are not significant (P =.21). No potential confounding factors affected results. Patients receiving intensive-timing induction therapy had superior long-term survival irrespective of postremission regimen received (allogeneic BMT, 70% +/- 9%; autologous BMT, 54% +/- 9%; chemotherapy, 57% +/- 10%). Allogeneic BMT remains the treatment of choice for children and adolescents with AML in remission, when a matched related donor is available. For all others, there is no advantage to autologous BMT; hence, aggressive nonablative chemotherapy should be used.

Wolman disease successfully treated by bone marrow transplantation.

Wolman disease is characterized by severe diarrhea and malnutrition leading to death during infancy. Lysosomal acid lipase deficiency is the cause of the symptoms and signs. It is inherited in an autosomal recessive manner. All Wolman disease patients have adrenal gland calcification. Previous therapeutic attempts have failed to provide remission. We report successful long-term bone marrow engraftment in a patient with Wolman disease resulting in continued normalization of peripheral leukocyte lysosomal acid lipase enzyme activity. Diarrhea is no longer present. Now, at 4 years of age, this patient is gaining developmental milestones. Cholesterol and triglyceride levels are normal. Liver function is normal. This is the first long-term continued remission reported for Wolman disease.

Matched-pair analysis of peripheral blood stem cells compared to marrow for allogeneic transplantation.

We performed a case-control analysis of 42 patients with advanced leukemia or MDS comparing peripheral blood stem cell (PBSC) with marrow grafts (BMT) from HLA-matched sibling donors. PBSC were mobilized with G-CSF (7.5 microg/kg/day) and yielded a median of 6.7 x 10(6) CD34+ cells/kg (range, 1.6-15.0) and 2.7 x 10(8) CD3+ cells/kg (range, 1.1-7.1) vs marrow grafts with a median of 2.0 x 10(8) nucleated cells/kg (range, 1.8-2.2). Recovery was significantly faster after PBSCT compared to BMT, with a median of 17 (range, 12-26) vs 26 (range, 16-36) days, respectively, to neutrophils >0.5 x 10(9)/l (P < 0.01), and 22 (range, 12->60) vs 42 (range, 18->60) days, for platelet recovery (P < 0.01). Transplantation of >/=7 x 10(6) CD34+ cells/kg accelerated recovery to >20 x 10(9) l platelets; median 17 days (range, 12-19) vs 23 days (range, 17-36) for those receiving <7 x 10(6)/kg (P = 0.01). PBSC and marrow recipients had similar risks of grades II-IV or III-IV acute GVHD or extensive chronic GVHD (all P > 0.3). At 1 year after PBSCT and BMT, the risk of relapse was 41% and 32%, respectively (P = 0.47), and the probability of survival was 46% and 48%, respectively (P = 0.70). HLA-matched sibling PBSCT resulted in faster neutrophil and platelet engraftment compared to BMT, with no subsequent differences in acute or chronic GVHD, relapse or survival. A minimum of 7 x 10(6) CD34+ cells/kg in PBSC grafts may be required for very rapid platelet engraftment. Bone Marrow Transplantation (2000) 26, 723-728.

Haematopoietic cell transplantation in patients with Fanconi anaemia using alternate donors: results of a total body irradiation dose escalation trial.

Allogeneic haematopoietic cell transplantation (HCT) is the only therapeutic modality capable of correcting the haematologic manifestations of Fanconi anaemia (FA). However, HCT from alternative donors has been associated with poor survival. Between June 1993 and July 1998, 29 FA patients (median age 12.1 years; range 3.7-48.5 years) were enrolled in a prospective phase I-II dose escalation study. All patients were treated with cyclophosphamide 40 mg/kg, total body irradiation (TBI) 450 cGy or 600 cGy and antithymocyte globulin (ATG), followed by HCT from an alternative donor. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A for 6 months, short course methylprednisolone (2 mg/kg/day) between days +5 and +19 and marrow T-cell depletion by counterflow elutriation. The probability of developing grade III-IV toxicity was 17% (95% CI 3-31%). For the 25 marrow recipients, the probability of neutrophil engraftment (ANC 0.5 x 109/l by day 45) was 63% (95% CI 42-82%). Probabilities of grade II-IV acute GVHD and chronic GVHD were 32% (95%CI 10-54%) and 0% respectively. With a median follow-up of 18 months, the probability of survival for the entire cohort at 1 year was 34% (95% CI 17-51%). The presence of lymphocyte somatic mosaicism [i.e. the presence of diepoxybutane (DEB)-insensitive cells] was associated with a significantly increased risk of graft failure. Disappointingly, the use of higher dose TBI and post-transplant ATG did not improve engraftment. More effective peritransplant immunosuppression, especially in FA patients with somatic mosaicism, was required to overcome the barrier of graft rejection. New conditioning regimens adapted to each individual's alkylator sensitivity are needed to improve the outcome of alternative donor HCT for FA.

Synovial sarcoma. Large size predicts poor outcome.

A consecutive series of 38 patients with synovial sarcoma diagnosed and treated in a consistent fashion from 1976 to 1994 was reviewed for prognostic variables. The histologic specimens were reviewed and confirmed by one pathologist. There was a minimum 4-year followup for all surviving patients and no patients were lost to followup. The treatment protocol consisted of surgical excision with a wide or radical margin and limb preservation when possible. In those patients in whom the surgical margin was undefined or was less than a wide margin, perioperative radiation therapy was used. Four patients presented with metastatic disease and all died of their disease. Thirty-four patients had localized disease at presentation. Variables considered in stratifying outcomes included histologic grade, histologic subtype, surgical margin, presence or absence of local recurrence, age, and size of tumor. Of the 34 patients without metastasis there was a strong statistical association between size of tumor and survival: 17 patients with tumors less than 5 cm indiameter had a 100% survival, 12 patients with tumors 5 cm to 10 cm had a 75% survival, and five patients with tumors greater than 10 cm had a 20% survival. The authors urge that a multicenter trial for neoadjuvant chemotherapy be initiated for patients presenting with a synovial sarcoma greater than 10 cm in diameter.

Cardiac metastasis of cloacagenic carcinoma of the vagina: a case and review of gynecologic malignancies with cardiac metastasis.

We report of a case of a 44-year-old woman with a vaginal cloacagenic carcinoma who initially presented with a hymenal lesion that metastasized first to the perihilar lymph nodes and then consequently to the right ventricle. The embryological tumor is rare with only a few cases of vaginal or vulvar involvement. We present the first case of cloacagenic cancer of the vagina with metastasis to the heart. The lesion was surgically resected after completion of neoadjuvant therapy. Herein we present this unique case and the clinical manifestations of intracardiac and pericardial lesions from gynecologic malignancies.

Evaluation of eye shields made of tungsten and aluminum in high-energy electron beams.

PURPOSE: To protect the lens and cornea of the eye when treating the eyelid with electrons, we designed a tungsten and aluminum eye shield that protected both the lens and cornea, and also limited the amount of backscatter to the overlying eyelid when using electron beam therapy. METHODS AND MATERIALS: Custom curved tungsten eye shields, 2 mm and 3 mm thick, were placed on Kodak XV film on 8 cm polystyrene and irradiated to evaluate the transmission through the shields. To simulate the thickness of the eyelid and to hold the micro-TLDs, an aquaplast mold was made to match the curvature of the eye shields. Backscatter was measured by placing the micro-TLDs on the beam entrance side to check the dose to the underside of the eyelid. Measurements were done with no aluminum, 0.5, and 1.0 mm of aluminum on top of the tungsten eye shields. The measurements were repeated with 2- and 3-mm flat pieces of lead to determine both the transmission and the backscatter dose for this material. RESULTS: Tungsten proved to be superior to lead for shielding the underlying structures and for reducing backscatter. At 6 MeV, a 3-mm flat slab of tungsten plus 0.5 mm of aluminum, resulted in .042 Gy under the shield when 1.00 Gy is delivered to dmax. At 6 MeV for a 3-mm lead plus 0.5-mm aluminum, .046 Gy was measured beneath the shield, a 9.5% decrease with the tungsten. Backscatter was also decreased from 1.17 to 1.13 Gy, a 4% decrease, when using tungsten plus 0.5 mm of aluminum vs. the same thickness of lead. Measurements using 9 MeV were performed in the same manner. With 3 mm tungsten and 0.5 mm of aluminum, at 3 mm depth the dose was .048 Gy compared to .079 Gy with lead and aluminum (39% decrease). Additionally, the backscatter dose was 3% less using tungsten. Simulating the lens dose 3 mm beyond the shield for the 2-mm and 3-mm custom curved tungsten eye shields plus 0.5 mm of aluminum was .030 and .024 Gy, respectively, using 6 MeV (20% decrease). Using 9-MeV electrons, the dose 3 mm beyond the shield was .048 Gy for the 2-mm shield and .029 Gy for the 3-mm shield (40% decrease). Backscatter was not further decreased using thicker tungsten. With a 6-MeV beam, using the 2-mm or 3-mm custom tungsten eye shields plus 0.5 mm of aluminum, the backscattered doses were 1.03 and 1.02 Gy, respectively. The backscatter dose with 9 MeV was 1.06 Gy using the 2-mm custom shield plus 0.5 mm aluminum and 1.05 Gy with a 3-mm custom shield plus 0.5 mm aluminum. There was very little difference in backscatter dosage under the eyelid using 0.5 vs. 1.0 mm of aluminum. Therefore, for patient comfort, we recommend using 0.5 mm of aluminum. CONCLUSIONS: Tungsten is superior to lead as a material for eye shields due to its higher density and lower atomic number (Z). Using 6- and 9-MeV electrons, tungsten provides the necessary protection for the lens and cornea of the eye and decreases the amount of backscatter to the eyelid above the shield.

Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy.

BACKGROUND: Globoid-cell leukodystrophy is caused by a deficiency of galactocerebrosidase, which results in progressive central nervous system deterioration. We investigated whether allogeneic hematopoietic stem-cell transplantation can provide a source of leukocyte galactocerebrosidase and thereby prevent the decline of central nervous system function in patients with the disease. METHODS: Five children with globoid-cell leukodystrophy (one with the infantile type and four with late-onset disease) were treated with allogeneic hematopoietic stem-cell transplantation. Measurement of leukocyte galactocerebrosidase levels, neurologic examinations, neuropsychological tests, magnetic resonance imaging of the central nervous system, cerebrospinal fluid protein assays, and neurophysiologic measurements were performed before and after transplantation, with follow-up ranging from one to nine years. RESULTS: Engraftment of donor-derived hematopoietic cells occurred in all patients and was followed by restoration of normal leukocyte galactocerebrosidase levels. In the four patients with late-onset disease, the central nervous system deterioration was reversed, and in the patient with the infantile form of the disease, signs and symptoms have not appeared. Magnetic resonance imaging showed a decrease in signal intensity in the three patients with late-onset disease who were assessed both before and after transplantation. Abnormalities in cerebrospinal fluid total protein levels were corrected in three patients with late-onset disease and substantially reduced in the patient with the infantile form. CONCLUSIONS: Central nervous system manifestations of globoid-cell leukodystrophy can be reversed by allogeneic hematopoietic stem-cell transplantation.

Unrelated donor bone marrow transplantation for children with acute leukemia.

PURPOSE: To test the use of unrelated donor bone marrow transplantation (URD BMT) to cure children with high-risk acute leukemias. PATIENTS AND METHODS: Between June 1985 and December 1994, 50 children with acute leukemia (15 acute myelogenous leukemia [AML], 35 acute lymphoblastic leukemia [ALL]; 22 greater than second complete remission [CR]) received BMT from a URD at the University of Minnesota. Ages ranged from 0.9 to 17.5 years (median, 8.8). Median follow-up is 2.1 years (range, 1 to 7.3). Thirty patients (60%) received bone marrow fully matched at HLA-A,B and DRB1; 20 (40%) received bone marrow with a major or minor mismatch at a single HLA-A or B locus. RESULTS: The median time to neutrophil engraftment was day 24 (range, 14 to 42 days) in those receiving matched and day 25 (range, 15 to 32 days) in those receiving mismatched marrow (P = .35). The incidence of grades III to IV graft-versus-host disease (GVHD) was 23% (95% confidence interval [CI], 7% to 39%) in matched and 32% (95% CI, 8% to 52%) in HLA-mismatched patients (P = .57). The incidence of chronic GVHD was 50% (95% CI, 28% to 72%) in matched and 57% (95% CI, 23% to 91%) in mismatched patients (P = .80). Disease-free survival for patients with ALL is 37% (95% CI, 21% to 53%) at 1 year and 30% (95% CI, 15% to 46%) at 2 years; for patients with AML, 53% (95% CI, 28% to 78%) at 1 year and 33% (95% CI, 6% to 60%) at 2 years. CONCLUSION: URD BMT is an effective treatment for children with poor-prognosis acute leukemia and should be considered for all high-risk patients. Early referral of patients is strongly recommended.