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C D Bloomfield

Publications and source records attributed to C D Bloomfield.

At least 109 records · Page 6Linked to original sources
PubMed1992

Cytogenetics and oncogenes in leukemia.

Cytogenetic and molecular studies have assumed an increasing role in the evaluation and management of patients with leukemia. Many cytogenetic findings have become well established as important independent indicators of prognosis in the acute leukemias. There has been a recent explosion of knowledge about the genes involved in leukemogenesis and the manner in which their structure or expression is altered by chromosomal translocations or point mutations. Application of newer techniques such as the polymerase chain reaction and in situ hybridization has begun to allow quantitation of residual leukemia cells after therapy. Cytogenetic and molecular findings should allow us to use more individualized therapy in treating leukemia, as well as therapy targeting leukemia-specific abnormal gene products.

Chromosome Aberrations↗
PubMed1992

A phase II study of recombinant interleukin-2 with or without recombinant interferon-beta in non-Hodgkin's lymphoma. A study of the Cancer and Leukemia Group B.

Interleukin-2 (IL-2) and interferon-beta (IFN-beta) have demonstrated activity against lymphoid malignancies, presumably mediated by the augmentation of lymphokine-activated killer (LAK) cell and natural killer (NK) cell activity. There is in vitro and in vivo evidence to suggest that the combination of IL-2 and IFN-beta is synergistic. The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II trial of IL-2 with or without IFN-beta in 49 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Overall toxicity was severe, with 17 patients experiencing life-threatening toxicity. Three patients had treatment-related deaths. Responses were noted in seven patients (17%). There were no meaningful differences between treatment arms in toxicity profile, response rate, or modulation of in vivo NK and LAK activity. We conclude that IL-2 with or without IFN-beta is not effective therapy for NHL in the doses and schedule used in this study.

Adult↗
PubMed1992

Trisomy 13 in acute leukemia.

Trisomy 13 occurring as a sole cytogenetic abnormality has recently been demonstrated to have adverse prognostic significance in acute leukemia. Trisomy 13 is seen primarily in an older male population, and has been reported in treatment-associated acute leukemia and acute leukemia evolved from myelodysplastic syndromes, as well as in de novo leukemia. The 36 cases of acute leukemia with trisomy 13 reported to date include 26 AML, 6 AUL, 2 ALL and 2 mixed lineage patients. Immunophenotyping studies have demonstrated an undifferentiated phenotype or biphenotypic markers in most cases. Trisomy 13 is associated with a low complete remission rate and with brief remission duration. The role of the additional copy of chromosome 13 in the pathogenesis of these cases of acute leukemia and the gene(s) of importance on chromosome 13 are yet to be determined.

Acute Disease↗
PubMed1992

Predictive value of flow cytometric analyses of blast cells in assessing the phenotype of the leukemia colony-forming cell (L-CFC) population in acute myeloid leukemia.

Acute myeloid leukemia (AML) blast cells (BC) express antigens that are commonly found on their normal counterparts. The leukemia colony-forming cell (L-CFC) subpopulation, identified by its ability to form leukemia colonies in vitro, is thought to be the stem cell population that produces BC. To ascertain the association between myeloid antigens on the BC and the L-CFC from the same patient, we compared the expression of CD14, CD15, CD33, p124 and HLA class I from 17 cases of AML. These particular myeloid antigens were studied because they are suitable targets in purging bone marrow for autotransplantation. We found no significant difference in the expression of CD14, CD15, CD33, and HLA class I on the BC and L-CFC from the same patient, although we observed considerable heterogeneity among different AML cases. Analysis of the progenitor cell antigen p124 revealed significant within-patient differences on the BC and L-CFC (p = 0.007), with a greater tendency for expression on the L-CFC. This heterogeneity may be due to differences in maturation stage of the L-CFC and BC. This information is important when L-CFC phenotype is used to determine the appropriate selection of antibodies for purging of residual disease in the context of auto-transplantation.

Antigens, Differentiation↗
PubMed1992

Leukemias and myelodysplastic syndromes secondary to drug, radiation, and environmental exposure.

The median latency of 2 degrees MDS/AL is 4 to 5 years. A high percentage of patients with 2 degrees MDS/AL convert to 2 degrees AL. Survival of either is less than 1 year. A constellation of morphologic abnormalities from all 3 cell lines produces a unique appearance. Both 2 degrees MDS and 2 degrees AL are difficult to classify by the FAB system. With the exception of the identification of karyotypic abnormalities, the biology of 2 degrees MDS/AL remains largely unexplored. Alterations of chromosomes 5 and 7 predominate, but other associated cytogenetic abnormalities are being increasingly recognized. A synthesis of data regarding 2 degrees MDS/AL resulting from the treatment of several primary malignancies generates the tentative conclusions that (a) many of the alkylating agents, and the nonclassic alkylating agent procarbazine, are leukemogens; (b) melphalan is a more potent leukemogen than cyclophosphamide. None of the other alkylating agents has been clearly established to be more or less potent than another; (c) increasing duration or amount of alkylator-based chemotherapy increases the risk of leukemogenesis; (d) low doses of radiation delivered to large volumes of bone marrow are weakly leukemogenic. High doses of radiation delivered to small volumes are not. Due to the latter, there is minimal additive risk for 2 degrees MDS/AL among studies using alkylator-based chemotherapy and radiotherapy, either concurrently or sequentially; (e) the older patient (greater than 40) is at increased risk for 2 degrees MDS/AL, at least in Hodgkin's disease. Children may be at lesser risk than adults, and younger children at lesser risk than older children; (f) the risk of 2 degrees MDS/AL peaks within the first decade after treatment for the primary malignancy. The incidence rates during the second decade are low. Identified occupational/environmental risks for 2 degrees MDS/AL include benzene, ambient and diagnostic radiation exposure, and perhaps ethylene oxide. The similarities in karyotype abnormalities among leukemic cells of those whose occupations expose them to chemical hazard, and those who are exposed to cytotoxic agents, suggest that many more environmental leukemogens have yet to be discovered. Karyotype is an important prognostic factor for both achievement of CR and for survival. Nonaggressive treatment approaches have not proven useful, although the use of hematopoietic growth factors offers promise in this area. Combination chemotherapy is justified in patients with adequate performance statuses and "favorable" karyotypes. Allogeneic bone marrow transplantation is currently the only curative approach, and can be applied without attempts to first reduce the leukemic burden.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Expression of the CD15 antigen on normal and leukemic myeloid cells: effects of neuraminidase and variable detection with a panel of monoclonal antibodies.

Normal and malignant myeloids cells are known to express cell surface molecules having in common the carbohydrate antigen lacto-N-fucopentaose-III (LNF-III--termed CD15). We used flow cytometry to examine the variability of CD15 expression in normal cells and acute myeloid leukemia (AML) cells as detected by 24 murine monoclonal antibodies (mAb). Important differences in the levels of binding were observed with the various mAb. Titrations of each mAb were performed to confirm that these differences in binding were due to increased antigen detection and not differences in concn. In studies of CD15 expression on AML cells selected from a large prospective study, anti-CD15-1 (also known as PM-81) showed the highest binding to each case. Neuraminidase was added to cells from seven AML patients that we had previously found to be low in CD15 expression, in order to determine if cryptic CD15 was present on these cells. Neuraminidase enhanced binding of each of the entire panel of mAb on five patients' cells, thus demonstrating the ubiquitous expression of CD15 on AML cells. In two cases, binding of only some of the mAb was increased, indicating exposure of unusual epitopes on those cells. Subpopulations of normal peripheral blood lymphocytes, cells not associated with CD15 expression, also substantially increased their level of binding to some of the mAb after the addition of neuraminidase. Two-color flow cytometry was used to determine the immunologic phenotype of the lymphocytic population that expressed CD15. This technique revealed that 9.5% normal lymphocytes coexpressed the CD15 and CD3 (T cell) antigens. In addition, by gating on large granular lymphocytes we found that 24.4% of these cells coexpressed CD15 (detected by PM-81) and CD2 (sheep erythrocyte receptor), while 50.3% expressed CD15 and CD16 (type III Fc receptor, natural killer cell-associated). This is consistent with the notion that sialylated CD15 is expressed on some natural killer cells and T cells.

Antibodies, Monoclonal↗
PubMed1991

The clinical significance of biological characteristics of the cells in acute myeloid leukemia.

An understanding of the biological heterogeneity of acute myeloid leukemia has been gained from studies of morphology, cytogenetics, cell surface antigen expression, level of leukemic transformation, responsiveness to hematopoietic growth factors, in vivo and in vitro differentiation, and protooncogene expression. Knowledge acquired from these studies has begun to lead to stratification of therapy and to new avenues of treatment.

Cell Differentiation↗
PubMed1990

A randomized comparison of methotrexate dose and the addition of bleomycin to CHOP therapy for diffuse large cell lymphoma and other non-Hodgkin's lymphomas. Cancer and Leukemia Group B study 7851.

In 1978, Cancer and Leukemia Group B initiated a randomized study to determine the usefulness of the addition of bleomycin and/or high-dose methotrexate to standard therapy for the treatment of certain adult non-Hodgkin's lymphomas. Between 1978 and 1985, 177 patients with diffuse large cell lymphoma (DLCL) and 97 patients with other intermediate-grade non-Hodgkin's lymphoma were randomized to receive therapy with three courses of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) every 3 weeks with or without low-dose bleomycin by continuous IV infusion. Responders after three courses were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 gm/m2/week intravenously with leucovorin rescue) or standard-dose methotrexate (30 mg/m2/week orally without rescue). Therapy was concluded with three additional courses of CHOP. Neither the addition of low-dose infusion bleomycin nor the use of high-dose rather than low-dose methotrexate had significant effects on response for patients with DLCL; complete response rates for the four treatment programs ranged from 47% to 51%. Median failure-free survival (FFS) for the entire group of DLCL patients was 12 months; 5-year FFS was 27%. There was no significant effect on FFS from the addition of either low-dose bleomycin to CHOP (5-year FFS: CHOP, 28%; CHOP-B, 26%, P = 0.81), or from the use of different doses of methotrexate (5-year FFS: high-dose, 34%; standard-dose, 33%, P = 0.51). Patients with follicular large cell lymphoma, with or without diffuse areas, had a better FFS (5-year FFS, 47%) than patients with DLCL (5-year FFS, 27%), while the patients with the other histopathologic subtypes of diffuse lymphomas had the poorest FFS (5-year FFS, 16%).

Aged↗
PubMed1990

Induction of differentiation in blast cells and leukemia colony-forming cells from patients with acute myeloid leukemia.

The characteristic lesion in acute myeloid leukemia (AML) is the failure of myeloid cells to differentiate normally, leading to the accumulation of immature blast cells (BC) in the bone marrow. We determined whether BC and leukemia colony-forming cells (L-CFC) from AML patients could differentiate in vitro after short-term culture with interferon-gamma (IFN gamma), 1,25 dihydroxyvitamin D3 (D3), retinoic acid (RA), tumor necrosis factor-alpha (TNF alpha), and granulocyte-monocyte colony-stimulating factor (GM-CSF). Expression of myeloid differentiation antigens CD15, CD14, CD33, and p124 was determined on the BC by immunofluorescence and on the L-CFC by monoclonal antibody (MoAb) and complement (C')-mediated cytotoxicity followed by cloning in methylcellulose. We found that 26 of 39 (67%) cases demonstrated changes in the expression of myeloid differentiation antigens on the BC, and 6 of 7 (86%) cases showed an altered L-CFC myeloid antigen phenotype after short-term culture with differentiating agents. Alterations in myeloid antigen expression in the L-CFC population correlated with a reduction in L-CFC cloning potential. In the BC, alterations of myeloid differentiation antigens occurred in a manner consistent with those observed during normal myelopoiesis. For example, CD14 antigen expression (a late-stage monocyte antigen) increased on BC from 12 of 39 (31%) cases, and p124 (an antigen expressed both by myeloid progenitor cells and by a subset of monocytes) increased on 15 of 39 (38%) cases. Changes in the expression of CD33 antigens (expressed normally by myeloid progenitor cells and by mature monocytes) on the BC were variable, with 7 of 29 cases (24%) showing a decrease and 7 of 29 cases (24%) showing an increase. When comparisons were made between pairs of differentiation agents that caused the altered expression of an antigen on either the BC or L-CFC of a patient, the majority of changes were in the same direction (either both "increased" or both "decreased"). This suggests that the direction of antigen change is characteristic of the leukemia cell subpopulation for each patient and not of the stimulatory agent. This study demonstrates that cells from more than two thirds of AML cases examined responded to various differentiation agents in vitro as measured by changes in the expression of myeloid cell-associated surface antigens and by alterations in cloning potential of the L-CFC, a finding of potential clinical significance.

Antigens, CD↗
PubMed1990

Prognostic factors at relapse for adults with acute myeloid leukemia.

To identify prognostic factors for patients with acute myeloid leukemia in first relapse we have analyzed the courses of 57 patients undergoing intensive reinduction therapy. The median duration of first remission was 9 months. A second complete remission was achieved by 31 patients (54%). The median duration of second remission was 5 months (range 1-142 + months). Two patients are still disease-free with 42 months and 142 months follow-up. Clinical, laboratory, and treatment variables at the time of original diagnosis and at relapse were examined for possible associations with the outcome of reinduction chemotherapy. Only duration of first remission consistently correlated with ability to achieve a second remission, second remission duration, and overall survival from reinduction. The second complete remission rate was 69% for those with a first remission longer than 9 months but only 39% for those with a first remission less than 9 months (P less than 0.05). The patients with longer first remissions also had longer second remissions (8 months median vs. 4 months, P = 0.02) and a longer median survival following reinduction chemotherapy (8 months vs. 5 months, P = 0.02). We conclude that the duration of a patient's first remission should be considered a useful prognostic factor both in treatment planning and in the interpretation of clinical trials of patients in relapse.

Antineoplastic Agents↗
PubMed1990

Prognostic factors for patients with diffuse large cell or immunoblastic non-Hodgkin's lymphomas: experience of the non-Hodgkin's Lymphoma Pathologic Classification Project.

Prognostic factors for long-term survival of 312 patients with diffuse large cell or immunoblastic non-Hodgkin's lymphoma are presented based on analysis of the multiinstitution clinicopathologic study sponsored by the National Cancer Institute. At the time of analysis, 75% of the patients had died and the median follow-up for patients still alive was 11 years. The distribution of Ann Arbor stages was 21% stage I, 32% stage II, 17% stage III, and 30% stage IV. Factors of prognostic significance for survival included age, stage, histologic subtype, presence of B symptoms, size of the largest lesion, number of extra-lymphoid organs involved, and extent of lymphatic involvement. Recursive partitioning analysis suggested a prognostic classification system based on stage, age, size of the largest lesion, and presence of mediastinal involvement. Stage I patient less than 50 years of age had a 10 year survival rate of 65% compared to 36% for older stage I patients. Stage II patients less than 65 years old without bulky lesions or mediastinal involvement had a 10 year survival rate of 45% compared to 10% for the poorer risk stage II patients. Although statistically significant prognostic factors were identified for the stage III/IV patients, they were not strong discriminants of 5-10 year survival rate. Because of the correlation among potential prognostic factors, there is no uniquely best classification system. Reasons for discrepancies among reported prognostic factor analyses are discussed, and a prognostic grouping that synthesizes our results with those of others is proposed.

Adult↗
PubMed1990

Nosocomial septicemia in the cancer patient: the influence of central venous access devices, neutropenia, and type of malignancy.

Nosocomial septicemias that occurred over a 32-month period on an inpatient medical oncology service were reviewed. One hundred four episodes of septicemia occurred in 84 patients, 33% with solid tumors and 67% with leukemia or lymphoma. Sixty were primary septicemias, with the remainder being secondary. Of the 118 isolates recovered, 42% were Gram-positive organisms, 45% Gram-negative organisms, and 13% were fungi. Coagulase-negative staphylococci and Escherichia coli were the most common Gram-positive and Gram-negative isolates, respectively. The effect of the type of malignancy, neutropenic status, and presence of a central venous access device (CVAD) on the isolate(s) recovered was studied. Coagulase-negative staphylococci were more commonly isolated from leukemia-lymphoma patients (26% vs. 3%, P less than .01), while Gram-negative isolates (63% vs. 36%, P = .01), specifically Klebsiella species (21% vs. 5%, P = .02), were more common in solid tumor patients. Staphylococcus aureus was isolated more frequently from non-neutropenic patients than from those with neutropenia (19% vs. 4%, P = .02). Gram-positive isolates were more commonly found in patients with a CVAD (51% vs. 29%, P = .03), in particular coagulase-negative staphylococci (29% vs. 2%, P less than .001). In contrast, Gram-negative isolates (62% vs. 34%, especially Klebsiella species (22% vs. 3%, P less than .01) and S. aureus (18% vs. 5%, P = .07) were more commonly isolated from patients with no CVAD. Neither neutropenia nor the presence of a CVAD predisposed to early mortality. Our data suggest that empiric antimicrobial coverage for presumed nosocomial septicemia in the febrile cancer patient should include vancomycin for patients with a CVAD to cover coagulase-negative staphylococci and a cephalosporin for patients with solid tumors, especially those without a CVAD, to cover Klebsiella species.

Adolescent↗
PubMed1990

Curative radiotherapy for laparotomy-staged IA, IIA, IIIA Hodgkin's disease: an evaluation of the gains achieved with radical radiotherapy.

Between 1970 and 1983, 179 patients with pathologically staged IA, IIA, and IIIA Hodgkin's disease were treated with curative radiotherapy. From 1970 to 1974, patients were treated with standard extended or total nodal field irradiation (Treatment Group 1). Since 1975, because of the high prevalence of recurrences in patients with large mediastinal mass and/or hilar disease and/or splenic involvement (LMM &/or H+ &/or S+), treatment was modified to include low-dose lung irradiation within the mantle field for those patients with LMM &/or H+ and low-dose liver irradiation within the infradiaphragmatic field for patients with S+ (radical XRT). Patients who did not have those characteristics were treated with standard radiotherapy (standard XRT). A total of 122 patients were treated from 1975 to 1983 (Treatment Group 2), of whom 61 received radical XRT and 61 received standard XRT. An analysis was done to evaluate whether the progressive-improvement in outcome since 1970 at the University of Minnesota Hospital resulted from the contribution of modified treatment or from progressive improvement in treatment overall. There was a statistical improvement in recurrence-free survival (RFS) in Treatment Group 2 (Tr Gr 2) compared to Treatment Group 1 (Tr Gr 1), with 10-year RFS of 80% versus 57% (p less than 0.001 for time to event). The improvement in RFS was attributed to treatment modification consisting of radical XRT for those patients with LMM &/or S+. There was no change in RFS for those patients without LMM &/or H+ &/or S+ who were treated in Tr Gr 1 and Tr Gr 2, with 10-year RFS of 78% versus 86% (p = 0.29), respectively. However, treatment results for patients with LMM &/or H+ &/or S+ improved considerably in the radical XRT group. Comparing standard versus radical XRT, 10-year RFS was 36% versus 78% (p = 0.001), and 10-year OS was 72% versus 92% (p = 0.034). Patterns of relapse also changed for patients with LMM &/or H+ &/or S+ who were treated with radical XRT. Rather than showing a high frequency of intrathoracic recurrence as was seen in those patients with LMM &/or H+ &/or S+ after standard XRT, the relapse pattern was similar to patients without LMM &/or H+ &/or S+. Salvage treatment was well tolerated for patients who failed after radical XRT. Delayed, life-threatening effects, such as pulmonary and cardiovascular complications and SMN, were equivalent for patients in Tr Gr 1 versus 2, and for those who received standard and radical XRT.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗