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Biomedical subjects

B Koziner

Publications and source records attributed to B Koziner.

At least 37 records · Page 2Linked to original sources

Phorbol ester-induced hairy cell features on chronic lymphocytic leukemia cells in vitro.

Leukemic cells from eight patients with chronic lymphocytic leukemia were isolated and cultured in the continuous presence of 12-O-tetradecanoylphorbol 13-acetate (TPA) at a concentration of 1.6 x 10(-9) M for 4-10 days. Aliquots of cells were then analyzed at intervals of 24-72 hr for changes in morphology, acid phosphatase staining (AP), and expression of two hairy cell-associated surface antigens, HCL1 (CD22, Leu 14) and HCL3 (CD11c, Leu M5). All cases studied showed typical B-CLL phenotype, and only a small proportion of cells expressed CD22 and CD11c (mean 7% and 4.9%, respectively). TPA treatment induced the coexpression of CD22 (mean 49%) and CD11c (mean 48%) and tartrate-resistant acid phosphatase in seven of eight cases. Morphologically, cells in TPA cultures expressed hairy cell features that were evident in light and electron microscopic studies. Collectively these changes indicate that TPA can induce hairy cell features on CLL cells in vitro, suggesting the later maturational stage of HCL compared with CLL.

Acid Phosphatase↗

Treatment results with an aggressive chemotherapeutic regimen (MACOP-B) for intermediate- and some high-grade non-Hodgkin's lymphomas.

Seventy previously untreated patients with stage II, III, and IV intermediate- or high-grade lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between September 1985 and November 1987. Forty-nine of these patients had diffuse large-cell lymphoma (DLCL), and eight of these patients were human immunodeficiency virus (HIV)-positive. Complete responses were achieved in 54% of all patients and 52% of those with DLCL. With follow-up extending to 36 months, 45% of all DLCL patients are alive, and 50% are still living, if the HIV-positive patients are excluded from the analysis. Chemotherapy was quite toxic. Seventy-five percent of patients had severe mucositis, 42% had peripheral neuropathy, 50% required hospitalization, and 54% experienced leukopenia with a WBC count below 1,000/microL. Seven percent (five patients) died of toxicity related to the chemotherapy. Our analysis of prognostic parameters indicated that B symptoms, a performance status below 80, and, to a lesser extent, elevation of serum lactic acid dehydrogenase (LDH) (in HIV-negative DLCL patients) were associated with an inferior survival. Advanced age, sex, and bulky disease were not found to have a statistically significant effect on survival. Our preliminary results indicate that MACOP-B chemotherapy is an effective regimen for high- and intermediate-grade lymphomas. However, the survival for patients with DLCL treated with MACOP-B is no different than that achieved with previous regimens at our institution.

Adolescent↗

Detection of intracytoplasmic immunoglobulin by flow cytometry in B-cell malignancies.

The aim of this study was to compare the results of flow cytometric (FCM) determination of heavy and light chain cytoplasmic immunoglobulin (cIg) with those obtained by the peroxidase-antiperoxidase (PAP) method. Fifty-one patients, including five non-T-acute lymphoblastic leukemias, 16 B-chronic lymphocytic leukemias (CLL), 13 non-Hodgkin's lymphomas, seven hairy cell leukemias, four multiple myeloma/plasma cell leukemias, and six T-cell leukemia/lymphomas, as well as 12 normal controls, were studied. Saponin-permeabilized cell suspensions were indirectly stained with monoclonal antibodies and analyzed by flow cytometry. Acetone-fixed cytocentrifuge smears were stained for cIg by the PAP method. The results obtained indicate that: (a) detection of cIg by FCM is a feasible and useful technique to confirm the B-cell lineage of leukemias and lymphomas, particularly those characterized by low-density surface immunoglobulin, such as CLL; and (b) cIg detection by FCM and PAP staining are complementary methods to recognize with certainty the monoclonality of B-cell malignancies.

B-Lymphocytes↗

Detection of terminal deoxynucleotidyl transferase (TdT) by flow cytometry in leukemic disorders.

We applied a new technique to the detection of intracellular TdT in 26 leukemic patients, including 16 non-T acute lymphoblastic leukemia (ALL), four T-ALL, one T-lymphoblastic lymphoma in leukemia phase, one undifferentiated leukemia, one de novo lymphoblastic phase of chronic myeloid leukemia, and three acute monocytic leukemias (AMOL). Mononuclear cell suspensions were incubated in saponin to permeabilize the cell membrane. The cells were then stained by indirect immunofluorescence (IF) using anti-human TdT monoclonal antibodies and were analyzed by flow cytometry (FCM). The TdT results were compared with those obtained by biochemical TdT assay (26 cases), immunoperoxidase determination (PAP) (12 cases), and fluorescence microscopy (seven cases). The results obtained by PAP and fluorescence microscopy were 100% concordant with those obtained by FCM and biochemical assay. TdT determination by FCM allows the analysis of large numbers of cells in a fast, objective, and reliable manner, as compared with biochemical assay, PAP, and fluorescence microscopy determinations.

DNA Nucleotidylexotransferase↗

AIDS-related lymphoid neoplasia. The Memorial Hospital experience.

The clinical features and laboratory results of 63 patients with or at risk for AIDS with lymphoid neoplasias seen from November 1980 through November 1986 are reviewed. Forty-three had systemic non-Hodgkin's lymphoma (NHL), nine had primary large cell lymphomas of the brain, 11 had Hodgkin's disease (HD), and one had plasmacytoma evolving to myeloma. Those with systemic NHL included 40 (93%) with intermediate or high-grade histologies, 35 (81%) with advanced stage (III, IV), and 28 (65%) with extranodal disease at presentation (predominantly marrow and meninges). Overall survival was short (median, 10.5 months from diagnosis) with the majority of deaths attributable to AIDS-related opportunistic infections (OI). However, 17 patients with diffuse NHL achieved a complete clinical remission, and nine now have been disease-free for more than 1 year (median follow-up, 28 months; range, 12 to 73 months). Early stage and lack of systemic symptoms were features associated with prolonged disease-free survival. Primary brain NHL was a uniformly lethal manifestation of AIDS, being diagnosed at postmortem in seven of nine severely immunosuppressed homosexual men. As with NHL, a propensity towards advanced disease and extranodal involvement was also observed in HD, suggesting that the atypical clinical behavior of HD may be an additional epiphenomenon of AIDS. This experience tends to argue for the use of intensive therapy in at least some patients with AIDS-related systemic NHL since it has resulted in a proportion of long-term disease-free survivors.

Acquired Immunodeficiency Syndrome↗

Autologous bone marrow transplantation for patients with poor-prognosis lymphoma.

Review of prognostic factors at Memorial Hospital in New York City has shown that adult patients with large-cell lymphoma (diffuse histiocytic lymphoma by Rappaport classification) who have high lactic dehydrogenase (LDH) and/or bulky mediastinal or abdominal disease are destined to do poorly with conventional combination chemotherapy, with a 2-year disease-free survival of about 20%. Patients who relapse after conventional combination chemotherapy have a similar poor prognosis. Thirty-one such patients with lymphoma were studied to evaluate the efficacy of intensive radiotherapy (hyperfractionated total body irradiation [TBI] [1,320 rad]), and cyclophosphamide (60 mg/kg/d for two days) followed by autologous bone marrow transplantation (ABMT). Our results show a disease-free survival advantage (P = .002) for 14 patients who underwent ABMT immediately after induction of remission with 79% surviving at a median follow-up 49.2+ months, compared with a median survival of 5.2 months for 17 patients administered ABMT while in relapse and/or after failing conventional treatment. Our results support the use of aggressive therapy as early treatment for patients with poor prognostic features.

Adolescent↗

Hodgkin's disease after treatment of non-Hodgkin's lymphoma.

A review of the clinical data base of the Hematology/Lymphoma Service at Memorial Hospital was carried out to determine the incidence of Hodgkin's disease (HD) after treatment of non-Hodgkin's lymphoma (NHL). Five patients (four men, one woman) developed HD after treatment for NHL, with an interval ranging from 60 months to 23 years (median, 7.6 years). All but one had no evidence of NHL, when HD was diagnosed. Three patients in whom the diagnosis of HD was made soon after or concomitantly with the diagnosis of NHL also are reported. Supervening HD was more frequently of nodular sclerosis type. The patients were older (median, 63 years) than patients with HD as the first cancer (median, 32 years). The occurrence of HD after NHL has been observed so infrequently that it is unlikely that it may be related to the treatment of the first neoplasia.

Adult↗

Non-Hodgkin's lymphomas: characteristics of long-term survivors following conservative treatment.

A most important set of prognostic factors for survival among 467 patients with non-Hodgkin's lymphoma receiving conservative treatment was determined statistically by the Cox proportional hazards model. Non-Hodgkin's lymphoma was diagnosed in these patients between 1958 and 1969. Initial biopsy material was classified according to the Working Formulation, and the Rappaport, Kiel, and Lukes-Collins systems. The Cox analysis identified a group of 37 patients with a median survival of 150 months. These patients had the following characteristics: small lymphocyte, plasmacytoid lymphocyte, small cleaved, large cleaved or non-cleaved follicular center cell histologic subtype (Lukes-Collins); no bulky involvement of mesenteric nodes or critical organs--kidney, urinary tract, or pleura; stages I to III disease (78 percent stage I or IE); no B symptoms; age below 60 years; initial resection as a reflection of localized disease. Patients with advanced-stage non-Hodgkin's lymphoma receiving conservative treatment have a relatively short survival (median, less than five years) regardless of histologic subtype.

Adolescent↗

Multiparameter characterization of L3 leukemia cell populations.

Multiparameter analysis of 14 consecutive patients with L3 cell populations (FAB classification) in bone marrow showed consistently high mean cellular RNA content but heterogeneity with respect to percent cels in S- and G2M-phases of the cell cycle, cell surface phenotype, cytogenetic abnormalities, cellular DNA content, and nuclear activities of terminal deoxynucleotidyl transferase. Five of the 14 patients had the characteristic profile of L3 leukemia with high RNA content, a typical t(8;14) or t(8;22) translocation, low Tdt, B-cell surface phenotype, pseudodiploid modal number of chromosomes, high proliferation and normal DNA index. The remaining 9 patients had features thought to be unusual and they were very heterogeneous. Median survival time from time of diagnosis was 115 days with no patient alive after 474 days. The survival times exhibited excellent correlation with a parametric model assuming exponential distribution. Accordingly, the presence of abnormal DI predicted for decreased, and the presence of t(8;14) or pseudodiploidy was associated with increased survival rates. However, due to the small number of patients in this study, generally applicable conclusions should be drawn only from a collection of larger numbers of cases of this rare type of leukemia.

Adult↗

Semen cryopreservation and artificial insemination for Hodgkin's disease.

Seventy-nine men with Hodgkin's disease were treated with chemotherapy protocols at Memorial Sloan-Kettering Cancer Center and had pretreatment semen analysis performed at the area semen bank. The patients were evaluated to determine: the quality of pretreatment semen, the effect of treatment on spermatogenesis, and the success rate of artificial insemination after semen cryopreservation. Pretreatment sperm concentration, fresh motility, fresh progression, postthaw motility and postthaw progression were all significantly decreased in men with Hodgkin's disease compared with normal controls. Posttreatment semen analysis in 44 men showed azoospermia in 80%, sperm concentration, less than or equal to 10 X 10(6)/mL in 11%, and sperm concentration greater than 10 X 10(6)/mL in 9%. Eleven couples attempted artificial insemination using cryopreserved semen, thus far resulting in three pregnancies. Semen cryopreservation and artificial insemination offer a partial solution to posttreatment azoospermia in this population, but further methods are needed to minimize gonadal toxicity without compromising therapy for Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗

Cytogenetic and histologic correlations in malignant lymphoma.

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.

Chromosome Aberrations↗