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Biomedical subjects

C D Bloomfield

Publications and source records attributed to C D Bloomfield.

At least 217 records · Page 12Linked to original sources
PubMed1981

Daunorubicin-prednisone in the treatment of acute nonlymphocytic leukemia.

In 1967 we first started to use daunorubicin and prednisone in the treatment of acute nonlymphocytic leukemia. In this review we describe our results with this regimen in 72 adults who were treated at the University of Minnesota between 1967 and 1977. Fifty-five patients were previously untreated and 17 had received prior cytotoxic chemotherapy. Complete remissions were obtained in 21 (29%) of the 72 patients. The patients achieving complete remission were significantly younger and had lower pretreatment leukocyte and absolute myeloblast counts than the nonresponders. Patients with acute promyelocytic leukemia had a higher response rate (67%) and longer duration of complete remission compared to patients with the morphologic subtypes. Their median duration of complete remission was 29 months compared to 6 months for the other patients. The 21 patients who achieved complete remission survived longer (20 months) than those who failed to enter remission (2 months). Our experience suggests that daunorubicin is an effective drug in the treatment of acute promyelocytic leukemia, but should be combined with additional agents in the treatment of other types of acute nonlymphocytic leukemia.

Acute Disease↗
PubMed1981

Classification and prognosis of acute lymphoblastic leukemia.

It is clear that a substantial percentage of both children and adults with ALL are currently being cured with appropriate treatment. Certain clinical characteristics and the morphology and biologic features of the lymphoblast at diagnosis can be used to identify those patients who are likely to be long-term disease-free survivors with current therapy and those who need new therapeutic approaches (Table VIII). It is hoped that continued studies, such as described in this review, will allow even better separation of good and poor responders. Such identification and separation will, it is hoped, allow the good responders to be cured with minimal toxicity and the poor responders to benefit from new therapies that may allow them too to be cured.

Adolescent↗
PubMed1981

Chromosomal abnormalities in acute lymphoblastic leukemia.

Chromosome abnormalities in acute lymphoblastic leukemia (ALL) and their possible clinical significance are briefly reviewed based upon the literature and 60 cases studied at the University of Minnesota. Almost all cases of ALL appear to demonstrate clonal abnormalities; the major abnormal clone is usually hyperdiploid or pseudodiploid. Among cases of non-T, non-B ALL, at least four translocations appear to be present with an increased frequency: t(9;22); t(4;11); t(11;14); and t(1;3). Patients with these translocations appear to have unique clinical and laboratory findings. Although the presence of abnormal clones does not seem to influence remission duration, the nature of the abnormality does. Patients whose leukemias demonstrate predominantly a pseudodiploid abnormal clone or a translocation have significantly shorter first remissions. Most importantly, among patients with non-T, non-B ALL, the presence or absence of translocations may separate poor responders from good responders.

Acute Disease↗
PubMed1981

Long-term survival of patients with Hodgkin's disease. Treatment with cyclophosphamide, vinblastine, procarbazine, and prednisone.

Thirty-eight patients with advanced Hodgkin's disease were treated with a combination of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP); the minimum period of observation for surviving patients was five years. Twenty-eight patients (74%) achieved complete remission; in 17 (61%), remissions lasted at least five years. Twenty-five (66%) of the 38 patients survived more than five years from the initiation of CVPP. There were no differences in either rates or duration of response when evaluation was performed for multiple pretreatment clinical features. However, survival was adversely influenced by advanced age, nodular sclerosis histologic subtype, and pretreatment bone marrow involvement. Two patients died, in remission, of overwhelming viral infections, and acute nonlymphocytic leukemia developed in one patient. In another patient, aseptic necrosis of the heads of both femora developed. Our data suggest that treatment with CVPP may result in long-term disease-free survival for patients with advanced Hodgkin's disease.

Adult↗
PubMed1981

Glucocorticoid receptors and in vitro responses to glucocorticoid in acute nonlymphocytic leukemia.

Early clinical studies in which glucocorticoids were used alone in the treatment of acute nonlymphocytic leukemia (ANLL) reported a wide range of responses from remission in some patients to dramatic aggravation of the disease in others. In the hopes of identifying those patients likely to derive therapeutic benefit from glucocorticoids, we have studied glucocorticoid receptors and in vitro responses to glucocorticoids in 36 previously untreated adults with ANLL. The leukemic blasts of all patients contained glucocorticoid receptors (range, 4,300 to 28,400 total receptor sites per cell; median, 8,800). These receptors were similar in all respects studied to those from a variety of other normal and malignant tissues. There was little difference between receptor levels among the various French-American-British categories. In vitro responses to glucocorticoid were observed in leukemic blasts of 26 of 28 cases studied. These responses varied from near complete cell killing to stimulation of proliferation. Since the cells of patients with ANLL have about the same number of receptors as do cells from patients with acute lymphoblastic leukemia and these receptors are capable of mediating physiological responses in vitro, it is unlikely that qualitative or quantitative receptor defects underlie the relative resistance to glucocorticoid therapy of ALL compared to acute lymphoblastic leukemia. However, the broad range of in vitro responses and receptor levels suggests that these studies might be useful in identifying those patients with ANLL likely to derive benefit from steroid therapy.

Acute Disease↗
PubMed1980

Prognostic significance of mediastinal involvement in Hodgkin's disease treated with curative radiotherapy.

We evaluated the prognostic significance of mediastinal involvement in Hodgkin's disease in 79 consecutive newly diagnosed patients treated with curative-intent, nodal radiotherapy. Mediastinal masses were classified large or small depending on whether the ratio of the largest transverse diameter of the mass to the transverse diameter of the thorax at T5-6 was greater than or equal to 35. Forty-eight patients had mediastinal disease; 20 had large masses, and 28 small masses. Complete remissions were achieved in 19 patients with large masses, 26 with small masses and all patients with no mediastinal masses. Relapse have occurred in 74% of patients with large masses but in only 27% with small masses and 19% without masses (P < .001). This high recurrence rate among patients with large masses could not be explained by other known adverse prognostic factors. Survival was adversely influenced by mediastinal mass size (P = .03). We conclude that curative-intent, nodal irradiation is inadequate therapy for patients with large mediastinal masses. Controlled studies are needed to determine if survival can be improved by the addition of chemotherapy or whole lung irradiation.

Adolescent↗
PubMed1980

Intensive five-drug combination chemotherapy for adult acute non-lymphocytic leukemia.

Twenty-two newly diagnosed adults with acute non-lymphocytic leukemia (ANLL) and 18 who had relapsed from a prior complete remission (CR) obtained with intensive chemotherapy were treated with a combination of Adriamycin, cytosine arabinoside, 6-thioguanine, prednisone, and vincristine. Eighteen (82%) of the patients undergoing initial induction therapy, including 4 of 6 patients over 60 years of age, achieved CR. Twelve patients (67%) undergoing reinduction therapy also achieved CR. Twenty-three (77%) of the 30 CRs were obtained with only one course of chemotherapy. The median time to CR for those undergoing initial treatment was 32 days, and the median duration of CR is 10+ months. The median survival for all 22 newly diagnosed patients is 15+ months. This intensive five-drug regimen is highly effective for the remission induction of both newly diagnosed and previously treated patients with ANLL producing a high percentage of CRs with only one course of therapy.

Acute Disease↗
PubMed1980

In-vitro glucocorticoid studies for predicting response to glucocorticoid therapy in adults with malignant lymphoma.

Neoplastic tissues from 28 adults with malignant lymphoma were examined for glucocorticoid receptors and in-vitro sensitivity to glucocorticoids. The patients were then treated with desamethasone for 5--14 days. 13 patients achieved at least a partial remission, and 15 had no significant tumour response. Lymphoma cells from patients who responded had more glucocorticoid-receptor sites per cell and greater in-vitro sensitivity as measured by glucocorticoid inhibition of incorporation of leucine and uridine than did tumour cells from non-responders. Study of tumour glucocorticoid receptors and glucocorticoid sensitivity in vitro may allow selection of those patients with lymphoma who should receive glucocorticoids as part of combination chemotherapy.

Adolescent↗
PubMed1980

Clinical trial of VP 16--213 (NSC 141540) I.V. twice weekly in advanced neoplastic disease: a study by the Cancer and Leukemia Group B.

The epipodophyllotoxin derivative VP 16--213 (NSC 141540) was studied by the Cancer and Leukemia Group B in a broad phase II trial at three dose levels: 60 mg/m2, 90 mg/m2, and 135 mg/m2 I.V. twice weekly. No correlation between dose of VP 16--213 and response frequency in a particular disease category could be demonstrated. Of the 382 patients, 8% obtained a complete (CR) or partial remission (PR), 8% showed improvement, and 14% had stable disease. By tumor type the best responses were obtained in lymphomas (8/31 CR + PR), uterus (2/9), prostate (1/5), rhabdomyosarcoma (2/6), neuroblastoma (2/4), colon/rectum (5/81), other gastrointestinal (4/32). In lung tumors, 4/80 patients obtained CR or PR. VP 16--213 has definite antineoplastic activity but the response frequency with the twice weekly schedule may be lower than that reported with other schedules.

Adult↗
PubMed1980

Relationship of clinical staging and lymphocyte morphology to survival in chronic lymphocytic leukaemia.

The value of the Rai clinical staging system and lymphocyte morphology in predicting survival in chronic lymphocytic leukaemia was examined in 83 patients who had been followed for at least 5 years. Patients with less clinical evidence of disease (Stages 0 and I) had significantly longer survivals than patients with more evidence of disease (Stages II, III and IV). Patients in whom greater than 35% of the lymphocytes resembled benign atypical lymphocytes had longer survivals than those in whom most of the lymphocytes had narrow rims of cytoplasm and coarsely clumped chromatin. The survival differences in the morphologic groups were less striking than those in the clinical stages, and when the morphological groups were corrected for clinical stage, no significant differences in survival among the morphologic groups remained.

Humans↗
PubMed1980

DNA nucleotidylexotransferase of normal persons and leukemic patients.

We describe a relatively simple and rapid assay for DNA nucleotidylexotransferase (EC 2.7.7.31) activity in normal lymphocytes and leukemic cells from blood and (or) bone marrow of patients with various types of leukemia. We followed the method of Beutler and Kuhl (Am. J. Clin. Pathol. 70: 733, 1978) but separated the product of the reaction by precipitation on filter-paper disks instead of by centrifugation. Normal lymphocytes had a mean activity of 13.5 (SD = 9.21; range 3 to 35) pU/10(8) cells. Leukemic cells from the peripheral blood of patients with acute myelogenous leukemia had a mean activity slightly greater than normal (48 pU/10(8) cells); those from patients with acute lymphoblastic leukemia had a mean activity of 863 pU/10(8) cells, or 62-fold the normal mean. Similarly, cells from patients with chronic myelogenous leukemia in acute phase had a normal activity when the cell proliferation was myelogenous, but much higher activities when the cell proliferation was lymphoblastic. Cells from patients with chronic lymphocytic leukemia had normal activity. In leukemic patients, approximately similar results were obtained with cells isolated from bone marrow.

Bone Marrow↗
PubMed1980

Curative radiotherapy for localized diffuse histiocytic lymphoma.

Ten newly diagnosed patients, with localized diffuse histiocytic lymphoma classified according to the Lukes-Collins classification, were evaluated for response to treatment with extended-field radiation. All classified tumors were of follicular center cell type (four large cleaved, four large noncleaved, and one small noncleaved). There were nine patients with stage I disease and one with stage II disease. The patient with stage II disease had only two sites of involvement. The disease was nodal in six patients and extranodal in four. All patients are alive without evidence of disease recurrence from 19 to 102 months since diagnosis (median survival, 58 + months). No differences were found in response or survival rates between histologic categories. No significant immediate or long-term complications have occurred. These results suggest that radiotherapy alone is curative for localized diffuse histiocytic lymphoma and may be superior to recently advocated chemotherapeutic approaches.

Adult↗
PubMed1979

Clinical utility of lymphocyte surface markers combined with the Lukes-Collins histologic classification in adult lymphoma.

To determine whether analysis of lymphocyte surface markers adds clinically useful information to the Lukes-Collins classification of lymphomas, tumors from 107 adults were histologically classified and studied for surface markers. Ninety-six cases were histologically classified as Lukes-Collins B-cell lymphomas; 87 showed B and one showed T surface markers, whereas eight had neither marker. Eleven lymphomas were histologically T-cell tumors; four of the 11 showed T surface markers, and seven had neither marker. Both the Lukes-Collins classification and surface markers identified patient groups with different clinical characteristics, chemotherapeutic responsiveness and survival. However, by combining surface markers and histologic features, additional important therapeutic and prognostic information was obtained. In each histologic class, patients whose lymphomas failed to express immunologically the histologically predicted marker had fewer responses to chemotherapy and shorter survivals than patients whose lymphomas expressed the predicted marker. Our data suggest that the analysis of surface markers in combination with the Lukes-Collins classification identifies many patients who respond poorly to current therapy and who thus require new therapeutic approaches.

Aged↗
PubMed1979

Predictability of immunologic phenotype of malignant lymphomas by conventional morphology: a study of 60 cases.

In order to test the immunologic validity of the Lukes-Collins (L-C) classification of the non-Hodgkin's lymphomas (ML), 60 ML in adult patients were studied and their B- or T-cell nature was predicted on a morphologic basis, without knowledge of the clinical history or the results of surface marker (SM) studies (SIg, C', Fc and E-rosettes), which were performed on cell suspensions and cryostat sections from the same specimens used for histology. There was a good correlation between morphologic types and SM (97% for the nodular ML, 81% for the diffuse). The predictions were not confirmed in 6 instances: one nodular ML typed as T; one convoluted lymphocytic ML typed as histiocytic; and four diffuse ML, predicted to be of B-type, bore no detectable SM ("Null" ML). It is concluded that the L-C morphologic criteria do allow in most cases the recognition of the B- or T-cell nature of ML, but cannot detect variations of the SM pattern which seem to affect the clinical behavior of these neoplasias. Thus, while the L-C classification seems immunologically sound, its clinical relevance still needs to be demonstrated.

Adult↗
PubMed1979

Therapy-related leukemia: a panmyelosis.

Fifteen patients developed acute nonlymphocytic leukemia (ANLL) 31 to 182 months following chemotherapy and/or radiotherapy for various malignancies and one non-neoplastic disorder. The ANLL was commonly heralded by a brief preleukemic phase consisting of cytopenias and a variety of morphologic abnormalities. At diagnosis of ANLL, all of the patients had a panmyelosis with variation in the predominant abnormal cell line. Neutrophilic and erythroid abnormalities were most striking in 12 of the patients, megakaryocytic abnormalities predominated in 2 and monocytic abnormalities in 1. Pancytopenia, marked anisopoikilocytosis, normoblastemia, large hypogranular platelets, hypogranular neutrophils, pseudo-Pelger-Huet nuclei, low myeloblast counts and basophilia were the most common abnormalities in the blood. Bone marrows were hypercellular with increased myeloblasts and basophils, abnormal neutrophil precursors, occasional monocytoid blasts, dyserythropoiesis with PAS positive erythroblasts, ring sideroblasts and micromegakaryocytes. All of the 7 patients who had bone marrow chromosome studies exhibited major chromosomal abnormalities. Response to anti-leukemic therapy was poor. The morphologic and clinical findings of these 15 patients appear to define a clinical-pathologic entity.

Adult↗
PubMed1979

Neutrophil function in lymphoreticular malignancy.

Neutrophil chemotaxis, phagocytosis, and metabolic stimulation were studied in 25 patients with untreated lymphoreticular malignancies, 8 patients with untreated carcinomas, and 8 patients undergoing therapy for lymphoreticular tumors. Phagocytic activity and metabolic stimulation during phagocytosis were comparable to controls in all patient groups. Slight, but significant, differences were found in chemotactic responsiveness of untreated patient groups when compared to controls. In almost all instances, chemotactic responsiveness reverted to normal in most patients studied after therapy for the malignant process. In patients with intact immunologic function these minor differences in chemotactic responsiveness are probably not sufficient to predispose to infection. However, this defect could be additive, and when present in combination with impaired immunity may contribute to compromised host defense.

Adolescent↗