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Biomedical subjects

E D Ball

Publications and source records attributed to E D Ball.

At least 91 records · Page 5Linked to original sources
PubMed1990

Autologous bone marrow transplantation for acute myeloid leukemia following in vitro treatment with neuraminidase and monoclonal antibodies.

Although monoclonal antibodies (MoAbs) to CD15, especially PM-81, react with leukemic blasts from the majority of patients with acute myeloid leukemia (AML), a small subset of patients have cells that are CD15 negative or dim. We determined previously that neuraminidase will increase the reactivity of PM-81 with AML blasts, as well as blasts from many patients with acute lymphoblastic leukemia (ALL). In this report, we describe the laboratory results and clinical course of the first patient with AML whose harvested bone marrow was treated with neuraminidase prior to MoAbs and complement treatment. Neuraminidase increased the percentage of the patient's leukemia cells that reacted with PM-81 from 18% to 90% and more than doubled the percentage of AML blasts that were lysed by PM-81 and complement. The patient suffered no acute toxicity, engrafted rapidly, and was transfusion independent by day 21 post-ABMT. This report demonstrates the probable safety and efficacy of pretreatment of bone marrow with neuraminidase, and increases the number of patients with AML or ALL who may benefit from ABMT using marrow purging with MoAb to CD15.

Acute Disease↗
PubMed1990

Immunophenotyping of acute myeloid leukemia cells.

This article considers the expression of myeloid cell-associated antigens on both normal and malignant myeloid cells. Progress in the use of monoclonal antibodies to myeloid cell surface antigens for the diagnosis, subclassification, and treatment of acute myeloid leukemia is discussed. The results of bone marrow purging with monoclonal antibodies to remove leukemia cells for the purpose of autologous bone-marrow transplantation are promising.

Antigens, Differentiation↗
PubMed1989

Expression of the three myeloid cell-associated immunoglobulin G Fc receptors defined by murine monoclonal antibodies on normal bone marrow and acute leukemia cells.

Monoclonal antibodies (MoAbs) have been prepared recently that recognize the three cell-surface receptors for the Fc portion of immunoglobulin (Ig), termed Fc gamma RI (MoAb 32.2), Fc gamma R II (MoAb IV-3), and Fc gamma R III (MoAb 3G8) that are expressed on selected subsets of non-T lymphocyte peripheral blood leukocytes. In the blood, Fc gamma R I is expressed exclusively on monocytes and macrophages, Fc gamma R II on granulocytes, mononuclear phagocytes, platelets, and B cells, and Fc gamma R III on granulocytes and natural killer (NK) cells. We have examined the expression of these molecules on normal bone marrow (BM) cells and on leukemia cells from the blood and/or BM in order to determine their normal ontogeny as well as their distribution on leukemic cells. BM was obtained from six normal volunteers and from 170 patients with newly diagnosed acute leukemia. Normal BM cells were found to express Fc gamma R I, II, and III with the following percentages: 40%, 58%, and 56%, respectively. Cell sorting revealed that both Fc gamma R I and Fc gamma R II were detectable on all subclasses of myeloid precursors as early as myeloblasts. Cell sorting experiments revealed that 66% of the granulocyte-monocyte colony-forming cells (CFU-GM) and 50% of erythroid burst-forming units (BFU-E) were Fc gamma R II positive with only 20% and 28%, respectively, of CFU-GM and BFU-E were Fc gamma R I positive. Acute myeloid leukemia (AML) cells expressed the three receptors with the following frequency (n = 146): Fc gamma R I, 58%; Fc gamma R II, 67%; and Fc gamma R III, 26% of patients. Despite the fact that Fc gamma R I is only expressed on monocytes among blood cells, AML cells without monocytoid differentiation (French-American-British [FAB]M1, M2, M3, M6) were sometimes positive for this receptor. However, Fc gamma R I was highly correlated with FAB M4 and M5 morphology (P less than .001). Fc gamma R II was also correlated with FAB M4 and M5 morphology (P = .003). Cells from 11 patients with acute lymphoblastic leukemia were negative for Fc gamma R I, but six cases were positive for Fc gamma R II and III (not the same patients). These studies demonstrate that Ig Fc gamma R are acquired during normal differentiation in the BM at or before the level of colony-forming units. In addition, we show that acute leukemia cells commonly express Fc gamma R.

Acute Disease↗
PubMed1989

Morphologic and cytochemical characteristics of acute promyelocytic leukemia.

The existence of two distinct subtypes of acute promyelocytic leukemia was confirmed and characterized based on morphologic features of leukemic cells in a series of 63 patients studied by the Cancer and Leukemia Group B (CALGB). Seventeen patients (27%) had microgranular leukemic cells (M3V), and 46 patients (73%) had hypergranular leukemic cells (M3). These patient cohorts were studied for other laboratory and clinical features. Leukemic cells from M3V patients stained less frequently than leukemic cells from M3 patients for myeloperoxidase (median, 93% vs. 99%; P = .006), periodic acid-Schiff (median, 57% vs. 92%; P = .0001), ASD-chloroacetate esterase (median, 45% vs. 87%; P less than .0001), and alpha-naphthyl acetate esterase (0% vs. 37%; P = .0003). Patients with M3V had a higher platelet count (median, 50 vs. 30 x 10(9)/L; P = .01) and tended to have a higher leukocyte count (median, 7.4 vs. 2.2 x 10(9)/L; P = .06) than M3 patients. The patients with M3V morphology were more likely to be nonwhite (29% vs. 7%; P = .03), female (71% vs. 37%; P = .02), and to be infected at the time of presentation (71% vs. 35%; P = .02). No differences in the frequency of the t(15;17) karyotype or the immunophenotypic expression of the leukemic cells were noted in the two morphologic subtypes of acute promyelocytic leukemia. Fewer patients with M3V tended to enter complete remission (65% vs. 80%; P = .20), but no significant differences were found in the duration of complete remission (P = .81; 1 year rate, 50% vs. 85%), or probability of survival (P = .67; 1 year rate, 49% vs. 68%).

Adolescent↗
PubMed1989

Utility of flow cytometric reticulocyte quantification as a predictor of engraftment in autologous bone marrow transplantation.

Flow cytometric reticulocyte quantification with thiazole orange (TO) was used to study erythropoiesis in 20 patients following autologous bone marrow transplantation for the treatment of acute myelogenous leukemia. Flow cytometric reticulocyte analysis provided not only the reticulocyte percentage and absolute reticulocyte count but a quantitative reticulocyte maturity index (RMI) proportional to the amount of RNA in the reticulocytes. The RMI values, but not the reticulocyte percentage or absolute counts, correlated temporally with the rise in the absolute neutrophil counts in the posttransplantation period. In the majority of patients (12/20), the RMI value was the earliest indicator of bone marrow engraftment. The findings of this study demonstrate an important clinical utility of TO reticulocyte analysis by flow cytometry and indicate the diagnostic importance of the RMI measurement in the evaluation of erythropoietic activity in bone marrow transplant patients.

Adolescent↗
PubMed1989

Restricted usage of VH and V kappa genes by murine monoclonal antibodies against 3-fucosyllactosamine.

We are studying the structure and regulation of murine antibodies against the 3-fucosyllactosamine antigenic determinant. Analysis of the sequences of seven BALB/c IgM, kappa monoclonal antibodies (mAb), obtained from four fusions, indicates that these antibodies exhibit restriction in their usage of VH and VL genes. Based on a combination of mRNA sequences and Southern filter hybridization data, all seven light chains are encoded by V kappa 24B and J kappa 1 gene segments. Complete mRNA sequences of the heavy chains revealed that all seven mAb are encoded by VH441, six antibodies are encoded by JH4 and one uses a JH3 gene segment. The VH441 gene segment and all seven mAb contain a potential glycosylation site at Asn 58 in complementarity-determining region (CDR)2. In contrast to the similarity of the VH regions, the heavy chain CDR3 segments exhibit considerable heterogeneity. They are encoded by three D segments, they vary in length from 7-9 amino acids and display differences in their deduced amino acid sequences. The VH441 gene segment also encodes antibodies against four other carbohydrate antigens, levan, galactan, dextran and galactosyl globoside. The use of a single gene segment to encode antibodies against five different antigens suggests that the domain encoded by VH441 might be particularly well adapted for forming sites that bind carbohydrate determinants. Glycosylation of CDR2 might contribute to the unique properties of this VH domain.

Amino Acid Sequence↗
PubMed1989

Effects of anti-myeloid antibodies on the generation of hematopoietic colony-forming units in long-term bone marrow culture.

We have prepared and characterized several monoclonal antibodies (MoAbs), PM-18 (CD 15),AML-2-23 (CD 14), and AML-1-99 (no cluster designation) reactive with antigens expressed on myeloid cells. Previous studies using complement-dependent lysis have determined the reactivity of these MoAbs with hematopoietic cells in vitro. PM-81 and AML-2-23 react with variable percentages of CFU-GM but not BFU-E or CFU-Mix. AML-1-99 reacts with greater than 90% of CFU-GM. CFU-E, and CFU-Mix. In order to determine the reactivity of these MoAbs with the bone marrow-derived precursors of in vitro colony-forming cells we have performed complement-dependent lysis and fluorescence activated cell sorting of bone marrow cells followed by long-term culture of surviving or sorted cells. Bone marrow cells from four normal subjects were subjected to various combinations of MoAbs and complement and assayed for residual colony-forming cells. Total surviving cells were then placed in flasks which contained a monolayer of irradiated bone marrow-derived adherent cells previously obtained from allogeneic donors. The cultures supported production of non-adherent colony-forming cells for up to 6 weeks as determined by serial in vitro colony-forming assays in methylcellulose. Cultures treated with one, two or three MoAbs and complement demonstrated variable reductions in colony-forming cells at the initiation of the experiments. However, cumulative production of colony-forming cells in anti-MoAb-treated cultures was usually at least as great as in control cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1989

Continuous infusion of complement by an automated cell processor enhances cytotoxicity of monoclonal antibody sensitized leukemia cells.

We report the use of the Haemonetics cell processor for monoclonal antibody (MoAb) and complement (C')-mediated lysis of leukemia cells. Using the HL-60 promyelocytic leukemia cell line, we can achieve a six-log depletion of HL-60 colony-forming cells in cell mixtures containing 1% HL-60 cells and 99% normal peripheral blood or bone marrow leukocytes at 10(7)/ml after a single 60-min treatment with an anti-myeloid MoAb, PM-81, plus C'. In this procedure, we continuously infuse a solution of fresh C' while removing medium containing spent C'. We have utilized this procedure to purge remission bone marrow from patients with acute myelogenous leukemia in preparation for autologous bone marrow transplantation. There were no adverse effects to normal progenitor cells of the granulocyte, monocyte and erythrocyte lineages as measured in colony-forming assays. Other potential benefits of using the cell processor method of cytotoxicity include reduction in treatment time and the amounts of costly reagents.

Antibodies, Monoclonal↗
PubMed1988

A novel monoclonal antibody, SCCL 175, with specificity for small cell neuroendocrine carcinoma of the lung.

The murine monoclonal antibody SCCL 175, which is one of several monoclonal antibodies directed against small cell neuroendocrine carcinoma developed by one of us (E.D.B.), was studied for its immunohistochemical reactivity against normal human tissues and a spectrum of bronchopulmonary and metastatic carcinomas using the avidin-biotin complex technique. SCCL 175 reacted with 40 of 44 small cell carcinomas including both primary and metastatic sites and was distributed both on the cell surface and intracytoplasmically. Staining was seen in fresh frozen tissues, cytology preparations, and in a limited number of paraffin-embedded tissue sections after trypsin pretreatment. It was nonreactive with all non-small cell lung carcinomas, neuroendocrine carcinomas from other primary sites, and nonpulmonary carcinomata studied to date. Its distribution in normal adult human tissues was limited to some hypothalamic neurons and the apical membranes of renal proximal tubular epithelium. Cytotrophoblastic and syncytotrophoblastic cells from placental tissue demonstrated variable SCCL 175 immunoreactivity. Of choriocarcinomas studied, one of three demonstrated focal staining. These findings demonstrate the diagnostic utility of SCCL 175 in phenotyping small cell carcinoma of lung, and its specificity suggests a potential role in the therapy of this disease.

Antibodies, Monoclonal↗
PubMed1988

Monoclonal antibodies to carbohydrate antigens in autologous bone marrow transplantation.

Normal and malignant myeloid cells express a highly immunogenic oligosaccharide, lacto-n-fucopentaose-III (LNF-III), that has been identified by numerous monoclonal antibodies (MoAb). We have been interested in the use of a particular monoclonal antibody to LNF-III, PM-81, in the treatment of patients with acute myelogenous leukemia using the antibody to treat bone marrow in vitro. Following in vitro treatment of bone marrow with PM-81 and another MoAb, AML-2-23, the remaining cells are used as an autograft in a patient treated with high-dose chemotherapy and radiotherapy. In order to enhance the ability of the MoAb to lyse leukemic cells in the remission bone marrow, we have explored the effect of neuraminidase treatment on leukemia cells. In this paper we describe that myeloid leukemia cells expressing low levels of LNF-III by immunofluorescence can be shown to have high levels of LNF-III after neuraminidase treatment. In addition, we show that normal bone marrow progenitor cells do not have cryptic LNF-III antigen, thus allowing the application of this finding to the clinical setting. Moreover, we have shown that leukemia colony-forming cells from one patient with acute myelogenous leukemia express cryptic LNF-III and that after exposure to neuraminidase there was an increased ability of PM-81 in the presence of complement to eliminate these colony forming cells. These data indicate that the LNF-III moiety is almost universally expressed on myeloid leukemia cells and their progenitors but not expressed on normal progenitors. Thus, it may be possible to enhance leukemia cell kill in vitro by neuraminidase treatment of bone marrow.

Antibodies, Monoclonal↗
PubMed1988

Mitoxantrone in relapsed or refractory acute nonlymphocytic leukemia.

Seventeen patients with relapsed or refractory acute nonlymphocytic leukemia were treated with 14 mg/m2 of mitoxantrone given in a 30-minute infusion daily for three days. If the day fourteen bone marrow showed residual leukemia, a second course was given at the same dose for two days. Eight patients (47%) entered complete remission. Three patients (17%) had a partial response, four (24%) did not respond, and two (12%) died with hypoplastic marrows during treatment. Seven of the 12 relapsed patients entered a complete remission, as did one of the five refractory patients. Toxicity was acceptable; prolonged myelosuppression, moderate hepatic toxicity, and stomatitis were the only problems. Several dose schedules of mitoxantrone have been studied by other investigators with varying results. The three-day schedule in the present study is similar to the schedule used for common induction regimens employing anthracycline drugs. On the basis of its activity and acceptable toxicity in relapsed and refractory ANLL patients, we feel that this schedule could be safely combined with other agents in future studies.

Acute Disease↗
PubMed1988

Immunotoxins for ex vivo marrow purging in autologous bone marrow transplantation for acute nonlymphocytic leukemia.

Two potent antimyeloid immunotoxins (IT) were generated by conjugating AML-2-23 (anti-CD14) and MCS-2 (anti-CD13) monoclonal antibodies (mAb) to the ribosome-inactivating phytotoxin, ricin. Both IT selectively bound to target cells, inhibited protein synthesis, and prevented the clonogenic growth of fresh marrow blasts from acute nonlymphocytic leukemia patients as well as KG-1 (ANLL) cells. Cryopreservation did not inhibit IT activity. We conclude that AML-2-23-ricin and MCS-2-ricin show potential for effective ex vivo marrow purging in autologous bone marrow transplantation (ABMT) for ANLL. To our knowledge, this study represents the first evidence of the clinical potential of IT in high-risk ANLL.

Acute Disease↗
PubMed1988

In vitro purging of bone marrow for autologous marrow transplantation in acute myelogenous leukemia using myeloid-specific monoclonal antibodies.

Autologous bone marrow transplantation (ABMT) for acute myelogenous leukemia has gained new popularity recently due to the availability of techniques to purge the autograft of residual leukemia cells. One of the methods of purging involves the use of monoclonal antibodies (mAbs) directed to antigens expressed on the surface of leukemia cells. Several mAbs lend themselves to this use because of their high degree of reactivity with leukemia cells and their lack of reactivity with normal pluripotent hematopoietic progenitor cells. Candidate mAbs include those directed to the CD14, CD15, and CD33 molecules. This review focuses on the pre-clinical data concerning the use of mAbs to these antigens and on the results of on-going clinical trials of ABMT using mAb-mediated purging.

Antibodies, Monoclonal↗
PubMed1988

Distribution of the 124-kd antigen defined by monoclonal antibody AML-1-99 on normal and leukemic myeloid cells.

We have produced a monoclonal antibody (MoAb), AML-1-99, that defines a novel 124-kd protein antigen expressed on a subpopulation of monocytes and on the majority of hematopoietic progenitor cells of the granulocyte-monocyte (CFU-GM), erythroid, and mixed-lineage classes. AML-1-99 is lytic to bone marrow (BM)- and peripheral blood-derived progenitor cells in the presence of rabbit complement (C'). AML-1-99 is not toxic to progenitor cells in the absence of C', nor does it modify their growth when included in colony-forming cultures. Several leukemia cell lines, including HL-60, U937, KG-1a, and Daudi cells, express the antigen on the majority of cells. Freshly isolated leukemia cells from patients with acute myelogenous leukemia (AML) react variably with AML-1-99. Leukemia colony-forming cells from several AML patients express the antigen and could be eliminated by treatment with AML-1-99 and C'. Cell sorting and immune rosette techniques were successfully applied to normal BM and chronic myelocytic leukemia cell populations using AML-1-99 with the result that significant enrichment of CFU-GM could be accomplished. The pattern of reactivity of this MoAb and its apparent molecular weight suggests that AML-1-99 recognizes a newly defined myeloid-associated cell surface antigen.

Antibodies, Monoclonal↗
PubMed1987

Expression of antigens associated with small cell carcinoma of the lung on hematopoietic progenitor cells.

We have previously described a panel of four monoclonal antibodies (MoAbs) reactive with antigens expressed on tumor cells from small cell carcinoma of the lung (SCCL). These IgM MoAbs are cytotoxic to SCCL cells in the presence of complement and thus have potential as reagents for the removal of SCCL cells contaminating bone marrow autografts. Therefore, we examined the cytotoxicity of these MoAbs against normal hematopoietic progenitor cells as a preliminary step toward their use in clinical trials. In this paper we report the results of treating normal bone marrow and peripheral blood mononuclear cells with the four IgM MoAbs, as well as an IgG2a MoAb that we have recently prepared against an SCCL cell line, DMS 406. Peripheral blood and bone marrow mononuclear cells were treated with the MoAbs alone or in combination, in the presence of rabbit complement, and then plated into colony-forming assays. Notably, only one MoAb, SCCL-1, had any demonstrable cytotoxicity against progenitor cells. This toxicity was limited to bone marrow burst-forming unit-erythroid and all classes of blood progenitor cells. A MoAb cocktail containing a combination of either four or five MoAbs + complement spared most marrow progenitor cells. These studies extend the base of information regarding the expression of SCCL-associated antigens on hematopoietic cells and indicate that selected MoAbs may be used safely for the removal of SCCL cells from autografts by complement-dependent lysis or other means.

Antibodies, Monoclonal↗
PubMed1987

Magnetic affinity colloid (MAC) cell separation of leukemia cells from autologous bone marrow aspirates.

A colloidal suspension of Co2B with avidin irreversibly adsorbed to the surface has been used with biotinylated antibodies and lectins to eliminate specific cell populations from mixtures with peripheral blood or bone marrows. Using the monoclonal antibodies CF-1 and PM-81 with this magnetic affinity colloid (MAC), we can eliminate five logs of K562 cells from mixtures with peripheral blood or marrow cells as determined by a linear limiting dilution clonogenic assay. We have also used this separation to eliminate clonogenic leukemia cells from fresh samples of peripheral blood and bone marrow from relapsed acute leukemia patients. Using CF-1 alone or in combination with PM-81, we eliminated two logs of colonies and clusters of leukemia cells from the fresh samples. The same antibodies used with MAC separation of hematologically normal marrows allow recovery of greater than 30% of the hematopoietic progenitors.

Bone Marrow Cells↗