Immunosuppressive therapy of severe aplastic anemia.
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Biomedical subjects
Publications and source records attributed to S Dahlberg.
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The estimation of gene frequencies, linkage disequilibrium and disease associations for the human leukocyte antigen (HLA) system is considered. Comprehensive models for HLA data are introduced and contrasted with simpler approaches to the analysis of such data.
The accuracy of data coded from the medical records of 985 patients from 22 major U.S. cancer centers was checked by recoding during 1978-81. The 29 items covered demographics, diagnosis, and therapy. Original codes were compared to recodes, and disagreements were classified as major or minor. The highest rate of major disagreements, 23%, was for stage of disease, followed by 10% for histology and 7% for site. Major disagreement rates for most other items were under 7%. Only 3% of a large sample of major disagreements involved justifiable differences in interpretation; the others were due to errors in the use of records. Major disagreement rates varied by a factor of 10 across sites, 4 across centers, and 2 across stage of disease. For several items the code "unknown" was overused and led to disagreements. A new procedure is presented for analysis of disagreement rates. The results from this procedure can guide training effort to improve coding accuracy.
Ninety-five patients with advanced non-Hodgkin's lymphoma were treated with four courses of cyclophosphamide, adriamycin, vincristine and prednisone, with or without procarbazine [CHOP(P)] chemotherapy; either 150 rad total body irradiation (for "extensive" disease) or 3,500 rad local radiation therapy (for "limited" disease); and a final four courses of CHOP(P) chemotherapy. Sixty-four patients had stage IV, 22 stage III, and 9 abdominal stage II disease. Histologic material was available in 80 patients for review according to the new Working Formulation: 16 had low grade, 38 intermediate grade (20 large cell, 18 diffuse small cleaved and mixed cell), and 26 high grade (12 lymphoblastic, 8 immunoblastic, 6 small noncleaved) malignancies. Complete remission was achieved in 78% of 92 evaluable patients. The remission duration curve for diffuse large cell lymphoma patients showed a plateau at 72% after 2 yr, but a pattern of continued relapse (median 3 yr) was seen in the other histologies. Multivariate analysis showed that "B" symptoms, bulky abdominal masses, and stage IV disease adversely affected survival. Overall survival by Kaplan-Meier analysis showed that 67% of diffuse small cleaved and mixed cell, 49% of large cell and immunoblastic, and 44% of lymphoblastic lymphoma patients survive 6 yr after diagnosis. When compared to reported remission duration and survival with CHOP chemotherapy alone, these data suggest a possible advantage for combined modality treatment.
The Centralized Cancer Patient Data System is the system which the 21 comprehensive cancer centers in the U.S. have established in order to report and to analyze demographic, diagnostic, treatment and survival data on all new patients. We propose that this closely monitored standardized 36 item dataset can be used to profile the categories of initial treatment that are given to patients having all types and stages of cancer: the data may be displayed for all centers or used to compare the approaches used at different centers. Differences in the frequency with which surgery, radiation, chemotherapy, and no specific treatment are used for patients having any of three common histologic types of lung cancer serve to illustrate the method. Opportunities now exist to utilize this new resource to study trends in the use of treatment modalities and their relationship to survival, which in turn should enhance the accessibility of treatment information about all patients at cancer centers, rather than only those which are reported from selected treatment protocols. This approach may also be uniquely useful in obtaining treatment and survival information about patients with rare sites or types of cancer.
Patients with non-Hodgkin's lymphoma (NHL) who fail conventional chemotherapy have a dismal outcome. Reports from single institutions utilizing high-dose chemoradiotherapy plus Autologous Bone Marrow Transplantation (ABMT) in this setting suggest three-year disease-free survival between 15-60 per cent. From 1985 to 1989 the Southwest Oncology Group performed a prospective multi-institutional study involving ABMT in relapsed/refractory NHL. Forty-five patients, ages 6-60 (median 38), with relapsed NHL were treated with high-dose cyclophosphamide (60 mg/kg/d x 2), total body irradiation (200 cGy/d x 6), and autologous unpurged bone marrow. Histologic subtypes included high grade lymphoma (10), intermediate grade lymphoma (33), and low grade lymphoma (2). Disease status pre-ABMT was sensitive relapse (16), resistant relapse (13), and untreated relapse (16). The actuarial three-year event-free survival and overall survival for all patients were 27 per cent and 38 per cent respectively. Causes of failure included regimen-related deaths (4), lack of response (10), or tumour progression (20) which occurred at a median of 5 months (1-22) post-ABMT and usually at previous sites of involvement. Response to salvage therapy pre-ABMT, a reflection of a tumour's biological behaviour, was the most important predictor of good outcome post-ABMT. This study confirms that a significant number of patients with recurrent NHL can achieve prolonged disease-free survival after ABMT.
BACKGROUND: Significant hepatobiliary accumulation of technetium 99m-labeled cardiac perfusion agents has been shown to cause alterations in the apparent localization of the agents in the cardiac walls. A Monte Carlo study was conducted to investigate the hypothesis that the cardiac count changes are due to the inconsistencies in the projection data input to reconstruction, and that correction of the causes of these inconsistencies before reconstruction, or including knowledge of the physics underlying them in the reconstruction algorithm, would virtually eliminate these artifacts. METHODS AND RESULTS: The SIMIND Monte Carlo package was used to simulate 64 x 64 pixel projection images at 128 angles of the three-dimensional mathematical cardiac-torso (MCAT) phantom. Simulations were made of (1) a point source in the liver, (2) cardiac activity only, and (3) hepatic activity only. The planar projections and reconstructed point spread functions (PSFs) of the point source in the liver were investigated to study the nature of the inconsistencies introduced into the projections by imaging, and how these affect the distribution of counts in the reconstructed slices. Bull's eye polar maps of the counts at the center of the left ventricular wall of filtered back-projection (FBP) and maximum-likelihood expectation-maximization (MLEM) reconstructions of projections with solely cardiac activity, and with cardiac activity plus hepatic activity scaled to have twice the cardiac concentration, were compared to determine the magnitude and location of apparent changes in cardiac activity when hepatic activity is present. Separate simulations were made to allow the investigation of stationary spatial resolution, distance-dependent spatial resolution, attenuation, and scatter. The point source projections showed significant inconsistencies as a function of projection angle with the largest effect being caused by attenuation. When consistent projections were simulated, no significant impact of hepatic activity on cardiac counts was noted with FBP, or 100 iterations of MLEM. With inconsistent projections, reconstruction of 180 degrees resulted in greater apparent cardiac count losses than did 360 degrees reconstruction for both FBP and MLEM. The incorporation of attenuation correction in MLEM reconstruction reduced the changes in cardiac counts to that seen in simulations in which attenuation was not included, but resulted in increased apparent localization of activity in the posterior wall of the left ventricle when scatter was present in the simulated images. CONCLUSIONS: The apparent alterations in cardiac counts when significant hepatic localization is present is due to the inconsistency of the projections inherent in imaging. Prior correction of these, or accounting for them in the reconstruction algorithm, will virtually eliminate them as causes of artifactual changes in localization. Attenuation correction and scatter correction are both required to overcome the major sources of apparent count changes in the heart associated with hepatic uptake.
The appearance of acute non-lymphocytic leukemia (ANLL) in patients with other hematologic and non-hematologic malignancies is now a well recognized syndrome. These patients have an unusual form of leukemia with distinct clinical and morphological features. With improved therapy many cancer patients have experienced prolonged survival and cure. Some of these patients will develop ANLL as a consequence of their previous therapy, or for reasons associated with their primary tumor (host factors or common oncogenic virus). It is also possible that a fraction of these patients will develop the usual form of leukemia (de novo ANLL) that is unrelated to the underlying malignancy. Indeed, a statistical analysis assuming ANLL incidence rates to be unaffected by breast cancer or cancer therapy, predicted the occurrence of three new ANLL cases with a history of breast cancer in Wisconsin per year. Eleven patients with ANLL and a history of breast cancer were seen at the University Hospitals over a ten-year span (1969-1978). Clinical, morphological and cytogenetic features were examined and it was found that five of the eleven patients had features atypical for therapy related leukemia. Indeed, two of the patients had not received breast cancer therapy. The distinction between de novo and therapy related leukemia is important because remission and prolonged survival are more likely in the former and morbidity and mortality associated with therapy are more likely in the latter. We suggest that if features of de novo leukemia exist, despite previous therapy for underlying malignancy, intensive antileukemia therapy should be considered.