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Biomedical subjects

B Koziner

Publications and source records attributed to B Koziner.

At least 109 records · Page 6Linked to original sources
PubMed1982

Combination chemotherapy of advanced chronic lymphocytic leukemia: the M-2 protocol (vincristine, BCNU, cyclophosphamide, melphalan, and prednisone).

The M-2 protocol (vincristine, cyclophosphamide, BCNU, melphalan, and prednisone) was administered monthly to 63 evaluable patients with advanced chronic lymphocytic leukemia. Complete remission (absence of all clinical and bone marrow evidence of leukemia) and partial response (greater than 50% decrease in organ enlargement and reduction of WBC count to below 15,000 x 10(6)/liter) were achieved in 17% and 44%, respectively, for a total response rate of 61%. The median survivals from therapy of patients achieving a CR, RR, or no response were 73+, 40, and 14 mo respectively. The median survival time from onset of treatment for stages II, III, and IV disease were 47, 20 and 19 mo, respectively, which was not statistically different from historical controls. However, when untreated patients are compared to this latter group, a significant survival advantage from diagnosis was found (p = 0.01), stressing the importance of prior therapy as the only unfavorable prognostic factor. Although complete remissions in CLL, as reflected in apparently normal bone marrow B-lymphocyte markers, can be induced wih acceptable morbidity, the majority of patients relapse after cessation of therapy. An alternative approach to the M-2 protocol will be needed to eradicate the disease.

Antineoplastic Agents↗
PubMed1982

Analysis of T-cell differentiation antigens in acute lymphatic leukemia using monoclonal antibodies.

Leukemic cells in 134 patients with ALL were analyzed by a panel of mouse monoclonal antibodies. Two antibodies are reactive with all peripheral blood T cells but define different surface antigens (Leu-1 and Leu-4). Two other antibodies react with antigens that are restricted to suppressor/cytotoxic T cells (Leu-2) and to helper T cells (Leu-3). We also used antibodies to the receptor for sheep red blood cells (SRBC) (Leu-5) and to a human "TL-like" antigen that is found on most thymocytes but not in peripheral T cells (Leu-6). An antibody to the human p29.34 "Ia-like" molecule was also tested. Of the 134 ALL patients, 17 had a predominance of SRBC-rosetting (Leu-5+) lymphoblasts ("T" ALL), expressing different surface phenotypes defined by this panel of monoclonal antibodies. These phenotypes were not readily classifiable according to a scheme of sequential stages of normal differentiation proposed. Moreover, the lymphoblasts in 8 of 113 patients not expressing conventional B- to T-cell markers ("null" ALL) reacted with the monoclonal anti-T-cell antibodies. This study suggests that the classification of lymphoblasts in ALL based on the reactivities observed with this panel of mouse monoclonal antibodies is not easily reconciled with current models of normal T-cell differentiation. However, it should be emphasized that the precise sequence of antigenic expression by cells undergoing thymic differentiation is still not fully known, and further phenotypic analysis of ALL cells might contribute to an improved understanding of this malignancy.

Adolescent↗
PubMed1982

Multidisciplinary treatment of advanced Hodgkin's disease by an alternating chemotherapeutic regimen of MOPP/ABDV and low-dose radiation therapy restricted to originally bulky disease.

Ninety-one evaluable patients with advanced Hodgkin's disease (patients with stages IIB, IIIB, or IV disease and patients with IIIA disease who were greater than 35 years old or had mixed cellularity or lymphocyte depletion histology) received chemotherapy with MOPP and ABDV given in alternating months; radiation therapy (RT) (2000 rad in 2 weeks) was given during Month 5 of therapy to the previously untreated patients through ports that were limited to the originally bulky disease. The complete remission rates observed were: 88% in previously untreated patients, 69% in patients who had had prior RT but minimal chemotherapy, and 50% in patients who had had prior heavy chemotherapy. The actuarial relapse-free survival rates at 4 years, for patients who had complete remission, are: previously untreated, 84%; prior RT, 70%; and prior heavy chemotherapy, 30%. The total actuarial survival rates at 5 years for all 118 patients, evaluable and nonevaluable, who were entered in the study, are: previously untreated, 80%, prior RT, 57%; and prior heavy chemotherapy, 40%.

Adolescent↗
PubMed1981

T-cell growth factor (interleukin 2) and terminal transferase activity in human leukemias and lymphoblastic cell lines.

Mononuclear blood cells from patients with different types of leukemia, and from controls as well as cells from established lymphoblastic cell lines were analyzed with respect to terminal transferase (TdT) activity and T-cell growth factor (TCGF; Interleukin 2, IL-2), to determine the significance of TCGF production and response as functional markers for human leukemias. The data obtained so far suggest that the aberrant proliferation and lack of maturation observed in these leukemias may be associated with or be the result of a break-down in cellular-mediated control of proliferation.

Acute Disease↗
PubMed1981

The treatment of advanced hodgkin's disease.

Between January, 1975, and December, 1978, 118 patients with advanced Hodgkin's disease were treated with 8 months of alternating MOPP and adriamycin, bleomycin, dacarbazine and vinblastine (ABDV) combined with 1 month of low-dose radiation therapy (2,000 rad) to areas initially involved with bulky disease. Among 57 evaluable previously-untreated patients, 50/57 (88%) achieved complete and 7/57 (12%) partial remissions. The estimated relapse rate among the complete responders was 16% at 36 months from date of remission. Toxicity was comparable to that of other combination chemotherapy regimens. These results are among the best reported for the treatment of patients with advanced Hodgkin's disease.

Adolescent↗
PubMed1981

The extracerebral dopamine antagonist domperidone block the suppressive effect of bromocriptine on prolactin and TSH secretion in man.

The effects of a single oral dose of 2.5 mg bromocriptine on serum level of TSH and prolactin were studied in a group of normal male subjects. Bromocriptine effectively inhibited basal TSH and prolactin concentration as well as the prolactin and TSH response to TRH given 4 hours later. The prior administration of the extracerebral dopamine antagonist domperidone reversed the endocrine effects of bromocriptine. The results suggest that dopamine receptors located at the pituitary may regulate TSH (and prolactin) release in man.

Adult↗
PubMed1981

Induction of giant fat cells in human bone marrow culture by human serum factor.

Evidence is presented below that normal human sera contain a potent non-dialyzable factor inducing abundant giant fat cells in human bone marrow culture, normal as well as CML. Media with 20% heated (56 degrees C) human serum induce during 7-14 days almost complete monolayer of fat cells on the bottom of the plastic flasks or dishes. Fetal bovine sera do not exhibit this effect and shift cultures to the proliferation of fibroblasts. We are studying the functions of fat cells in hemopoiesis as well as the biochemical nature of fat cell-inducing factor in human sera.

Adipose Tissue↗
PubMed1980

Analysis of multiple cell markers in acute leukemia complicating Hodgkin's disease.

A multidisciplinary methodology was applied to study 6 patients with acute leukemia (AL) following treatment for Hodgkin's disease. All 6 patients developed acute monocytic leukemia according to cytochemical criteria; morphologically, 3 cases were undifferentiated monoblastic leukemia; 3 cases were partially differentiated monocytic leukemia. In 3 of the 6 cases, cell suspensions from peripheral blood and/or bone marrow bore predominantly surface receptors for the Fc fragment of IgG and/or C-3 fraction of complement and exhibited variable degrees of phagocytosis. Two cases lacked any recognizable membrane markers or phagocytic activity. Terminal transferase enzymatic activity was not diagnostically elevated. Soft agar bone marrow culture studies revealed no growth or a characteristic leukemic cluster pattern. Chromosome analysis done in 1 of the 2 patients studied revealed hypodiploidy and structural rearrangement. Prospective studies, done serially, will help determine whether development of AL in patients with Hodgkin's disease results from the influence of intensive and potentially oncogenic therapy or represents progression from a preleukemic stage inherent to the original tumor.

Adult↗
PubMed1980

The eight-drug/radiation therapy program (MOPP/ABDV/RT) for advanced Hodgkin's disease: a follow-up report.

Eighty-four evaluable patients with advanced Hodgkin's disease (Stages IIB, IIIA age greater than 35 or mixed cellularity or lymphocyte depletion histology, IIIB, IVA, and IVB) were treated with alternating monthly MOPP and Adriamycin, bleomycin, dacarbazine, and vinblastine (ABDV). Radiation therapy (RT), 2000 rads in two weeks, was given to areas of initial bulky disease in untreated patients. Complete remission (CR) rates were 80% for previously untreated, 65% for prior RT or minimal chemotherapy treated, and 50% for heavily pretreated patients. Among 49 previously untreated patients there were no primary treatment failures. The estimated two-year relapse rate for the CR group was 9%. The therapeutic effectiveness of this program may have been due to either or both of the following elements: (1) two non-cross-resistant drug combinations, (2) low dose adjuvant RT to initial sites of bulky disease. These early results are among the best reported for the treatment of advanced Hodgkin's disease.

Adolescent↗
PubMed1980

Subpopulations of human T lymphocytes. VI. Analysis of cell markers in acute lymphoblastic leukemia with special reference to Fc receptor expression on E-rosette-forming blasts.

A variety of surface markers, terminal deoxynucleotidyl transferase (TdT) activity, morphologic appearance, and cytochemical composition were studied in a group of 16 patients (13 children, 3 adults) with acute lymphoblastic leukemia (ALL). In 9 children, no surface markers were detected on lymphoblasts (null-type ALL). Leukemic blasts of 4 children formed E-rosettes. These E-rosette-forming blasts from 3 adult patients with ALL, were studied for the presence of Fc receptors. Of the leukemic blasts from these 7 patients, 2--76% expressed receptors for IgG Fc. Only 3 of 7 patients showed 9--42% receptors for IgM Fc. In addition, complement receptors were investigated in 6 of those 7 patients with T-cell ALL. Complement receptors were detected on 9--70% of the E rosette forming blasts from all 6 patients. TdT activity was elevated in T-cell ALL and in children with null-type ALL. The heterogeneity of Fc receptor expression on leukemic blasts in these patients demonstrates a malignant proliferation of T cells in different stages of differentiation or maturation. This observation might be helpful in subclassifying T-cell leukemias with regard to prognosis and the response to therapy.

Adult↗
PubMed1980

Bone marrow transplantation for the therapy of refractory adult T cell acute lymphoblastic leukemia.

Two adult patients with T cell acute lymphoblastic leukemia (ALL) received an intensive multiagent therapeutic regimen and failed to enter remission. Following cytoreduction with cyclophosphamide (60 mg/kg x 2) and total body irradiation (1000 rads) they underwent bone marrow transplantation. One patient received marrow from his identical twin brother and the other from his HLA-matched sister. Both patients promptly went into remission. The identical twin recipient is alive and free of disease at 20+ months, but the allogeneic patient died of P. carinii pneumonia at eight months with no evidence of leukemia. These results suggest that even some refractory patients whose disease has multiple negative prognostic features may respond to pretransplant chemoradiotherapy and attain a clinically useful complete remission. Additional patients with longer follow-up will be necessary before the curative potential of bone marrow transplantation in T cell ALL can be assessed.

Adult↗
PubMed1980

A micromethod for determination of terminal deoxynucleotidyl transferase (TdT) in the diagnostic evaluation of acute leukemias.

A micromethod for the determination of TdT in peripheral leukocytes and bone marrow cells has been developed that allows unequivocal identification and quantitation of TdT in less than 1 X 10(6) leukocytes from ALL patients, i.e., in 1 ml of peripheral blood and/or 0.5 ml of bone marrow obtained during routine clinical sampling. The method involves disruption of cell pellet with high salt and detergent followed by centrifugation of extracts at 12,000 X g and partial purification on phosphocellulose matrix by a batch elution technique using a standard laboratory microcentrifuge. Using this microassay, TdT activities have been determined in 500 samples of peripheral blood and bone marrow of 240 adult patients with acute leukemias (86 ALL, 108 ANLL, 44 blastic CML, two acute leukemias following P. vera). From an analysis of our data based on TdT activity, cell surface markers and growth patterns in soft agar and observations published in the literature, it can be concluded that the frequencies of TdT + phenotypes in the various clinical-morphological diagnostic groups are approximately 95% in ALL, 10% in ANLL, 50% in AUL, and 35% in blastic CML. Since the presence of high TdT activity is clearly associated with clinical response to specific forms of chemotherapy in blastic CML and most probably, also in ANLL, the determination of TdT should be considered in all cases of acute leukemias to objectively define prognostically important subgroups which can not be diagnosed by conventional means.

Acute Disease↗
PubMed1980

The acute monocytic leukemias: multidisciplinary studies in 45 patients.

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

Adolescent↗
PubMed1980

Heterogeneity of cell lineages in L3 leukemias.

Five cases of adult leukemia with L3 morphology in bone marrow were studied for the presence of immunologic, metabolic, and enzymatic markers. Among the five patients, there were four males and female. Median age was 66 with a range of 16-80 yr. Median survival was only 5 mo. Serum lactate dehydrogenase (LDH) levels, 3H-thymidine labeling indices, and DNA/RNA content of the L3 lymphoblasts were markedly elevated. B-cell markers were found in three cases, two exhibiting surface membrane IgM-lambda, and one IgG-K. Terminal deoxynucleotidyl transferase (TdT) enzymatic activity was consistently low in this group. In one case, the L3 lymphoblasts displayed only surface Fc receptors demonstrated by the binding of aggregated IgG. TdT activity was found to be significantly increased. In another instance, the lymphoblasts formed spontaneous rosettes with sheep erythrocytes and exhibited paranuclear staining with acid phosphatase. TdT activity was found to be low. Although most of the L3 leukemias are neoplasias of B lymphocytes, other lineages may also express this morphology.

Adult↗