Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia.

Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt.

Postremission therapy for children with acute myeloid leukemia: the children's cancer group experience in the transplant era.

We reviewed consolidation therapy results and analyzed postremission outcomes for 1464 children less than 21 years old at diagnosis in five consecutive Children's Cancer Group acute myeloid leukemia trials between 1979 and 1996. Children in remission were allocated to allogeneic bone marrow transplantation (BMT) (N=373) in first remission, if a matched family donor was available. Remaining children were assigned consolidation chemotherapy (N=688) or autologous purged BMT (N=217), or withdrew from study before assignment, or with unknown data (N=186). Overall and disease-free survival were superior for children assigned allogeneic transplants. High (>50,000/microl) diagnostic white blood cell (WBC) count was prognostic for inferior outcome, but French-American-British (FAB) subtypes were not. Inv(16) is a favorable karyotypic feature for children in first remission and t(8;21) is not. Allogeneic transplantation benefit was evident in most children, including those with high or low diagnostic WBC count, each FAB subtype, and t(8;21), but was not seen in children with inv(16). Therefore, these data suggest reserving matched related donor allogeneic transplantation for children with inv(16) for second remission, but not those with t(8;21).

Prognostic variables in newly diagnosed children and adolescents with acute myeloid leukemia: Children's Cancer Group Study 213.

The objective of this study was to identify biologic parameters that were associated with either exceptionally good or poor outcome in childhood acute myeloid leukemia (AML). Among the children with AML who entered Children's Cancer Group trial 213, 498 patients without Down syndrome or acute promyelocytic leukemia (APL) comprise the basis for this report. Univariate comparisons of the proportion of patients attaining complete remission after induction (CR) indicate that, at diagnosis, male gender, low platelet count (< or =20 000/microl), hepatomegaly, myelodysplastic syndrome (MDS), French-American- British (FAB) category M5, high (>15%) bone marrow (BM) blasts on day 14 of the first course of induction, and +8 are associated with lower CR rates, while abnormal 16 is associated with a higher CR rate. Multivariate analysis suggests high platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 are independent prognostic factors associated with better CR. Univariate analysis demonstrated a significant favorable relationship between platelet count at diagnosis (>20 000/microl), absence of hepatomegaly, low percentage of BM blasts (< or =15%), and abnormal 16 with overall survival. Absence of hepatomegaly, < or =15% day 14 BM blast percentage, and abnormal 16 were determined to be independent prognostic factors associated with better survival.

Second malignant neoplasms after successful treatment of childhood cancers.

Improved treatment and supportive care have increased the survival of children diagnosed with cancer. This success has resulted in a growing population at risk of long-term complications of therapy, including secondary malignancy. These neoplasms may result from the direct effect of the modalities used in treatment of the primary tumor, more indirect effects of the treatment or supportive care, the genetic predisposition of the patient, or to interactions among these factors. The increasing success of cancer therapy is producing a rapidly growing population of patients at risk of second malignancy. This is a result of the increasing intensity of treatments and the increasing duration of survival, which provides the time to manifest the late effects of therapy. The concept that a patient is "cured" at some arbitrary time after treatment does not diminish the need for follow-up of all cancer survivors to identify and treat secondary malignancies. These risks have led to an increased effort to define phenotypic and genotypic categories of patients that may be cured with less intensive therapy and to develop molecularly targeted drugs that have fewer noxious effects on normal tissues.

Congenital thrombocytopenia and radio-ulnar synostosis: a new familial syndrome.

The association of bone marrow failure and skeletal defects has been frequently noted, however, the genetic basis for most of these syndromes remains unclear. We describe a previously uncharacterized autosomal dominant syndrome of amegakaryocytic thrombocytopenia associated with radial-ulnar synostosis. The clinical features of this syndrome appear to be distinct from other similar conditions, including Fanconi's anaemia and thrombocytopenia-absent radii (TAR). The physical findings at diagnosis and clinical management of each case are detailed, as well as a discussion of this disorder in the context of other syndromes in which marrow failure and skeletal defects are prominent features. We also review recent developments in molecular genetics that may provide important clues to the underlying aetiology of this condition.

Unrelated umbilical cord stem cell transplantation for X-linked immunodeficiencies.

Banked unrelated umbilical cord blood matched at 5 of 6 human leukocyte antigen loci was used to reconstitute the immune system in 2 brothers with X-linked lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-M syndrome. Pretransplant cytoreduction and posttransplant graft-versus-host prophylaxis were given. Hematopoietic engraftment and correction of the genetic defects were documented by molecular techniques. Two years after transplantation, all 3 patients have normal immune systems. These reports support the wider use of banked partially matched cord blood for transplantation in primary immunodeficiencies.

Stereotactic core-needle breast biopsy: a multi-institutional prospective trial.

PURPOSE: To assess the accuracy of stereotactic core-needle biopsy (CNB) of nonpalpable breast lesions within the context of clinically important parameters of anticipated tissue-sampling error and concordance with mammographic findings. MATERIALS AND METHODS: CNB was performed in 1,003 patients, with results validated at surgery or clinical and mammographic follow-up. Mammographic findings were scored according to the American College of Radiology Breast Imaging Reporting and Data System with a similar correlative scale for histopathologic samples obtained at either CNB or surgery. Agreement of CNB findings with surgical findings or evidence of no change during clinical and mammographic follow-up (median, 24 months) for benign lesions was used to determine results. Three forms of diagnostic discrimination measures (strict, working [strict conditioned by tissue sampling error], applied [working conditioned by concordance of imaging and CNB findings) were used to evaluate the correlation of CNB, surgical, and follow-up results. RESULTS: Strict, working, and applied sensitivities were 91% +/- 1.9; 92% +/- 1.8, and 98% +/- 0.9, respectively; strict, working, and applied specificities were 100%, 98% +/- 0.8, and 73% +/- 0.9; strict, working, and applied accuracies were 97%, 96%, and 79%. CONCLUSION: Percutaneous stereotactic CNB is an accurate method to establish a histopathologic diagnosis of nonpalpable breast lesions. Accuracy increases when additional surgery is performed for lesions with anticipated sampling error or when CNB findings are discordant with mammographic findings. An understanding of the interrelationship among these parameters is necessary to properly assess results.

Relationship between phantom failure rates and radiation dose in mammography accreditation.

The American College of Radiology Mammography Accreditation Program (ACR MAP) reviews both clinical mammograms and a phantom image to assess clinical and technical quality from each mammography unit. The phantom contains details representing fibers (speculations), speck groups (microcalcifications), and masses. The depiction of these structures by the mammographic system is scored by medical physicists. The phantom image is taken using the facility's exposure technique for a 4.2-cm thick breast of average composition. The mean glandular dose (MGD) is determined from a set of thermoluminescent dosimeters placed on top of the chest wall edge of the phantom. Phantom scores and MGD data collected from 1993 to 1999 based on 31 535 unit evaluations are presented in this paper. The relationship between the failure rate for phantom image quality and MGD has been analyzed. While over all doses the phantom failure rate was 11%, for doses of 0.26 to 0.50 mGy the failure rate was 43%. The phantom failure rate fell continuously to about 6% for MGDs in the range of 1.51-2.0 mGy. With further increases in dose, failure rates began to rise. Factors that may account for these results are presented and discussed.

Ductal carcinoma in situ. Implications for screening mammography.

Ductal carcinoma in situ (DCIS) now represents 20% of all newly diagnosed breast cancers because of increased detection by screening mammography. Twenty year relative survival rates are 97%. Postsurgical and histological studies and recent molecular biological studies indicate that most cases of DCIS will progress to invasive carcinoma if not detected by mammography. Screening mammography studies support the need for annual versus less frequent screenings to detect DCIS before further progression.

An introduction to economic issues in breast imaging.

Marked increases in national health care costs, along with governmental coverage of health care costs for the elderly under Medicare, have resulted in increased government regulation of medical reimbursement rates. Private insurers and HMOs now provide reimbursements that are frequently the same or lower than those from Medicare. Reimbursement rates for mammography have been particularly restricted. Although screening mammography appears to be as cost-effective as other commonly accepted medical interventions, some third-party payors have been reluctant to reimburse screening mammography because of its perceived effect on overall health care costs. An objective analysis shows that inclusion of coverage for screening mammography, however, even beginning at age 40 years, has only a slight effect on total health care costs. Adequate reimbursement for screening mammography supports an effort that provides substantial reduction in deaths from breast cancer.

Economic challenges in breast imaging. A survivor's guide to success.

Most breast imaging centers today operate under financial strain. Among strategies designed to improve their bottom line, more efficient use of the radiologist's time is the most fundamental strategy and the one most likely to succeed in all breast imaging centers. Tasks performed by the radiologist that are not directly related to interpretation and consultation should be shifted to other personnel. Other strategies that may help some breast imaging centers include accepting only self-paying patients, renegotiating the hospital contract, performing more interventional procedures, and extending the hours of operation. Measures that can improve the economic efficiency of screening mammography include batch interpretation of mammograms; paperwork reduction; brief automated reports; limiting requests for previous films from other facilities to only potentially necessary cases; dedicated screening mammography examination rooms; reduction in recall rates; and, in certain circumstances, extension of breast center hours. Measures that can improve the economic efficiency of diagnostic mammography performance and interpretation include dedicated diagnostic mammography examination rooms, automated film rotators, improved scheduling, and efficient work-flow patterns for examination performance. Measures that can improve the economic efficiency of both screening and diagnostic mammography include improved triage of screening and diagnostic patients, reminder telephone calls to confirm mammography appointments, greater use of medical assistants to help the radiologists and technologists, and streamlined film library procedures and operations. Measures that can improve the economic efficiency of breast interventional procedures include preprocedure work-up, establishment of scheduling protocols, and greater involvement of technologists and medical assistants in assisting the radiologist who performs the interventional procedures. All of these methods are intended to create a breast imaging center that is cost efficient while maintaining a patient-friendly atmosphere and diagnostic accuracy.

Society of Breast Imaging residency and fellowship training curriculum.

A recently developed Society of Breast Imaging curriculum for residency training is intended to provide guidance to residents and their mentors, and to practicing radiologists who want to keep up to date in screening, diagnosis, and interventional procedures. The curriculum contains lists of key concepts in 14 subject areas: epidemiology; anatomy; pathology, and physiology; equipment and technique; quality control; interpretation; problem-solving mammography; ultrasound; interventional procedures; reporting and medicolegal aspects; screening; MR imaging; therapeutic considerations; and patient management principles. The curriculum also makes recommendations about residency training, including the number of examinations the resident should interpret, and the time the resident should spend in breast imaging. Recommendations for fellowship training are also discussed.

Radiologists' preferences for digital mammographic display. The International Digital Mammography Development Group.

PURPOSE: To determine the preferences of radiologists among eight different image processing algorithms applied to digital mammograms obtained for screening and diagnostic imaging tasks. MATERIALS AND METHODS: Twenty-eight images representing histologically proved masses or calcifications were obtained by using three clinically available digital mammographic units. Images were processed and printed on film by using manual intensity windowing, histogram-based intensity windowing, mixture model intensity windowing, peripheral equalization, multiscale image contrast amplification (MUSICA), contrast-limited adaptive histogram equalization, Trex processing, and unsharp masking. Twelve radiologists compared the processed digital images with screen-film mammograms obtained in the same patient for breast cancer screening and breast lesion diagnosis. RESULTS: For the screening task, screen-film mammograms were preferred to all digital presentations, but the acceptability of images processed with Trex and MUSICA algorithms were not significantly different. All printed digital images were preferred to screen-film radiographs in the diagnosis of masses; mammograms processed with unsharp masking were significantly preferred. For the diagnosis of calcifications, no processed digital mammogram was preferred to screen-film mammograms. CONCLUSION: When digital mammograms were preferred to screen-film mammograms, radiologists selected different digital processing algorithms for each of three mammographic reading tasks and for different lesion types. Soft-copy display will eventually allow radiologists to select among these options more easily.

Reasons for failure of a mammography unit at clinical image review in the American College of Radiology Mammography Accreditation Program.

PURPOSE: To identify the most common deficiencies in the quality of mammograms submitted for clinical image evaluation (evaluation of image from actual patient referred for mammography). MATERIALS AND METHODS: In 1997, the American College of Radiology Mammography Accreditation Program reviewed clinical images for 2,341 mammography units. For each mammography unit, the facility submitted bilateral mediolateral oblique and craniocaudal mammograms obtained in a woman with fatty breasts and a woman with dense breasts. Images were reviewed independently by two experienced radiologists. Reviewers listed the general categories and specific deficiencies that led to a decision to fail the unit that produced the clinical images. RESULTS: Of the 2,341 mammography units, 1,034 (44%) failed the clinical image evaluation process. Of 6,128 categories cited by reviewers as deficient, 1,250 (20%) involved problems in positioning; 944 (15%), exposure; 887 (14%), compression; 806 (13%), sharpness; 785 (13%), contrast; 703 (11%), labeling; 465 (8%), artifacts; and 288 (5%), noise. A significantly higher proportion of failures was attributed to positioning deficiencies for fatty breasts than for dense breasts (P =.028). Higher proportions of failures in dense breasts were related to compression (P <.001) and exposure (P <.001) deficiencies. CONCLUSION: Common problems in clinical image quality have been identified. This information should be useful for educators and facilities striving to improve the quality of mammography.

Potential contribution of computer-aided detection to the sensitivity of screening mammography.

PURPOSE: To determine the false-negative rate in screening mammography, the capability of computer-aided detection (CAD) to identify these missed lesions, and whether or not CAD increases the radiologists' recall rate. MATERIALS AND METHODS: All available screening mammograms that led to the detection of biopsy-proved cancer (n = 1,083) and the most recent corresponding prior mammograms (n = 427) were collected from 13 facilities. Panels of radiologists evaluated the retrospectively visible prior mammograms by means of blinded review. All mammograms were analyzed by a CAD system that marks features associated with cancer. The recall rates of 14 radiologists were prospectively measured before and after installation of the CAD system. RESULTS: At retrospective review, 67% (286 of 427) of screening mammography-detected breast cancers were visible on the prior mammograms. At independent, blinded review by panels of radiologists, 27% (115 of 427) were interpreted as warranting recall on the basis of a statistical evaluation index; and the CAD system correctly marked 77% (89 of 115) of these cases. The original attending radiologists' sensitivity was 79% (427 of [427 + 115]). There was no statistically significant increase in the radiologists' recall rate when comparing the values before (8.3%) with those after (7.6%) installation of the CAD system. CONCLUSION: The original attending radiologists had a false-negative rate of 21% (115 of [427 + 115]). CAD prompting could have potentially helped reduce this false-negative rate by 77% (89 of 115) without an increase in the recall rate.

Children's cancer group trials of interleukin-2 therapy to prevent relapse of acute myelogenous leukemia.

PURPOSE: Up to 80% of children with acute myelogenous leukemia treated with intensive chemotherapy achieve remission; however, a large proportion of patients develops recurrent disease. Because interleukin (IL)-2 can induce remission in patients with overt evidence of acute myelogenous leukemia, we hypothesized that it might prevent relapse when administered to patients in first remission after intensive consolidation chemotherapy. A pilot Children's Cancer Group (CCG) trial (CCG-0941) demonstrated the feasibility of this approach, and we initiated a prospective randomized trial (CCG-2961) to further evaluate the safety and potential efficacy of IL-2 therapy in preventing relapse of acute myelogenous leukemia. PATIENTS AND METHODS: In trial CCG-0941, 21 pediatric patients in complete remission following induction and consolidation chemotherapy on protocol CCG-2941 received IL-2 therapy. In CCG-2961, 79 patients in complete remission were randomized as of February 1999 to receive either IL-2 (n = 39) or no further therapy. In both trials, recombinant IL-2 was given at a dose of 9 million IU/m2/d by continuous intravenous infusion for 4 days. After 4 days of rest, IL-2 was resumed at a dose of 1.6 million IU/m2/d for 10 days by continuous infusion. We monitored patients for toxicity and relapse. RESULTS: The majority of patients treated with IL-2 in these two trials experienced some degree of fever. Seven of 60 patients (12%) had clinically significant rashes, and grade 3 vascular leak syndrome and hypotension have each been observed in five patients (8%). Hypotension resolved promptly after treatment with intravenous fluids. No patients have experienced renal toxicity or required cardiac vasopressors or transfer to an intensive care unit; there have been no treatment-related deaths. Overall, the incidence and severity of adverse events remain similar in the two trials. Total projected accrual to the IL-2 randomization is anticipated to be 326 patients, and relapse and survival data remain blinded. CONCLUSION: The dose and schedule of IL-2 used in these two trials continue to be reasonably well tolerated by children with acute myelogenous leukemia in first remission. Any conclusions with regard to efficacy must await completion of the randomized trial.

Immune thrombocytopenia after umbilical cord progenitor cell transplant: response to vincristine.

An 8-month-old male with X-linked lymphoproliferative disease underwent an unrelated, partially matched (with major mismatch at DR locus), cord blood stem cell transplant. Four months following the transplant, he developed immune thrombocytopenia with hemolytic anemia (Evans syndrome). He received multiple courses of intravenous immunoglobulin, anti-Rh D immunoglobulin, a pulse of high-dose corticosteroids and cyclosporine with some improvement of hemolytic anemia, but no improvement of the thrombocytopenia. Addition of vincristine, resulted in long-term resolution of thrombocytopenia and anemia. No major toxicity was observed during treatment. Vincristine should be considered as a treatment for refractory immune thrombocytopenia after hematopoietic stem cell transplantation.

Developing asymmetric breast tissue.

PURPOSE: To show that benign asymmetric breast tissue detected mammographically may increase over time. MATERIALS AND METHODS: Serial mammograms obtained in 21 women with negative physical examination results and mammographically detected developing asymmetric breast tissue were reviewed, and findings were correlated with results of biopsy (n = 16), ultrasonography (US) (n = 8), and contrast material-enhanced magnetic resonance (MR) imaging (n = 3). Five patients who did not undergo biopsy were followed up for 13-84 months. Thirteen of 16 biopsy specimens were reviewed. RESULTS: At the time of mammographic change, 12 patients without baseline asymmetric tissue had a mean age of 41.7 years and a mean size of asymmetric tissue of 2.4 cm. The mean age of nine patients with baseline asymmetric tissue was 46.9 years. In eight patients, the mean size increase was 2.5 cm. One patient showed increased tissue density but stable size. All US and MR images were negative. Pseudoangiomatous stromal hyperplasia was present in all 13 biopsy specimens reviewed and extensive in 12. No malignancies have been reported in five of the followed-up patients, and two have had continued enlargement of asymmetric tissue. CONCLUSION: Pseudoangiomatous stromal hyperplasia is a common histopathologic finding in developing asymmetric breast tissue. Follow-up, rather than biopsy, is a management option if benign imaging and clinical criteria are met.