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Biomedical subjects

B Koziner

Publications and source records attributed to B Koziner.

At least 91 records · Page 5Linked to original sources

The non-Hodgkin's lymphomas. I. A retrospective clinical and pathologic analysis of 499 cases diagnosed between 1958 and 1969.

A retrospective clinical and histopathological review was made of 499 previously untreated cases of non-Hodgkin's lymphoma with adequate initial biopsy material diagnosed at Memorial Hospital between 1958 and 1969. Three hundred-eighty-four cases (77%) had diffuse, 104 (21%) nodular, nine (2%) nodular and diffuse, and two (less than 1%) unclassifiable histologic types. Overall median survival was 16 months, and 79% of the patients died with lymphoma. For all treatments, survival of responding patients was the same as that of nonresponders, a reflection of the palliative approach. Significant differences in survival were found between patients in the various Ann Arbor stages. Median survival was 42 months for the nodular group and 11.5 months for the diffuse (P less than 0.001). The ten-year survival was 12% for the diffuse and 22% for the nodular patients. The overall difference in survival was due to early deaths in the diffuse group. Long-term follow-up is necessary to appreciate the usual fatal course of patients with all types of non-Hodgkin's lymphomas treated conservatively.

Adolescent↗

Combination chemotherapy for the treatment of Hodgkin's disease in relapse. Results with lomustine (CCNU), melphalan (Alkeran), and vindesine (DVA) alone (CAD) and in alternation with MOPP and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV).

Vindesine (desacetyl vinblastine amide sulfate, DVA) was used in combination with CCNU (lomustine) and melphalan (Alkeran) (CAD) to treat 15 heavily pretreated patients with Hodgkin's disease in relapse. The patients were treated with up to six cycles, depending upon their response. Two patients (13%) achieved a complete remission (CR) and five (33%) patients a partial remission (PR). The major toxicity was prolonged thrombocytopenia, which was decreased by a reduction in the initial drug doses for patients who had received extensive prior chemotherapy and radiotherapy (RT). The CAD regimen was then alternated with nitrogen mustard or cyclophosphamide, vincristine, procarbazine, and prednisone (MOPP, C-MOPP) and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV) for a total of nine cycles in 25 patients with Hodgkin's disease in relapse with somewhat more favorable prognostic features. Two patients also received low-dose RT to areas of bulky nodal disease. Eleven patients (44%) achieved a CR and seven (28%) a PR. Of the 11 CR patients, six remain in remission. The serious toxicity was comparable to that seen with other combination chemotherapy regimens. These results indicated that the CAD/MOPP/ABVD regimen is as active as other so-called 'salvage' regimens for Hodgkin's disease in relapse, and suggest that it might be useful for newly diagnosed Hodgkin's disease.

Adolescent↗

Defective T-cell response to PHA and mitogenic monoclonal antibodies in male homosexuals with acquired immunodeficiency syndrome and its in vitro correction by interleukin 2.

We studied the ability of phytohemagglutinin (PHA) and two anti-T-cell monoclonal antibodies OKT3 and Pan T2, to induce proliferation and interleukin 2 (IL2) production in peripheral blood lymphocytes (PBL) from 21 homosexual patients: 12 with Kaposi's sarcoma (KS), 4 with reactive lymphadenopathy, and 5 with opportunistic infections. All patients with KS and opportunistic infections had significantly lower mitogen-stimulated DNA synthesis, as compared to the controls, irrespective of the mitogen used (P less than 0.01). The patients with lymphadenopathy exhibited significantly lower responses only in the OKT3 assay as compared to normals (P = 0.009). The production of endogenous IL2 was significantly lower in PBL cultures from patients with KS and with opportunistic infections, irrespective of the mitogen used, as compared to healthy male controls, and also significantly lower in the Pan T2-stimulated cultures from patients with lymphadenopathy. The addition of highly purified IL2 was able to restore partially lymphocyte proliferation in vitro in the presence of these mitogens in all patients. Our studies demonstrate (1) that male homosexuals even without clinical manifestations of immunodeficiency frequently exhibit a proliferative T-cell defect when anti-T-cell monoclonal antibodies rather than PHA are used as mitogens, (2) that this proliferative defect is associated with defective IL2 production, and (3) that this defect is at least in part correctable in vitro by highly purified IL2.

Acquired Immunodeficiency Syndrome↗

Analysis of T cell subsets in cancer patients treated with interferon.

T cell subsets were analyzed in 33 patients with advanced cancer who were treated with either of two interferon preparations: a partially purified human leukocyte interferon (HulFN-alpha (Le] and a highly purified recombinant interferon (lFLrA). Included in the lFLrA-treated group were eight patients with immunodeficiency and Kaposi's sarcoma. The OKT4+/OKT8+ ratio was used to define the balance between helper/inducer and suppressor/cytotoxic T cell subsets. With both interferon preparations, the mean OKT4+/OKT8+ ratio decreased 24 hours after the first interferon dose. Within the HulFN-alpha (Le) group, the decrease in ratio was related to an increase in OKT8+ cells; in the lFLrA group, it was accompanied by a small decrease in the proportion of OKT4+ cells that was greater than the decrease in OKT8+ cells. Patients treated with lFLrA were followed for the first three weeks of therapy. Most patients treated with lFLrA at all dose levels, ranging from 1 X 10(6) to 54 X 10(6) units per day, had a decrease in OKT4+/OKT8+ ratio on Day 1. No substantial change in the ratio was observed on Days 7, 14, and 22. Patients with immunodeficiency and Kaposi's sarcoma had responses similar to those of patients with other cancers treated with lFLrA. In conclusion, although both HulFN-alpha (Le) and lFLrA induce immediate decreases in the OKT4+/OKT8+ ratio, the T cell subset(s) primarily responsible for the decrease varies with the source of interferon.

Acquired Immunodeficiency Syndrome↗

Non-T, non-B acute lymphoblastic leukemia (L3) with t(8;22) and two 14q+ chromosomes.

A patient with L3 leukemia is reported whose leukemic cells were characterized cytogenetically by a duplication of the long arm segment 1q25 leads to q42, trisomy for chromosome 7, t(8;22)(q24;q11), and two 14q+ chromosomes. Immunologic marker analysis revealed the leukemic cells to be of the non-T, non-B ("null") type. This observation, when considered in conjunction with a previous report of heterogeneity in cell lineages of L3 leukemias, raises the possibility of some lymphoid neoplasms arising in stem cells.

Adult↗

Phenomenon of formation of giant fat-containing cells in human bone marrow cultures induced by human serum factor: normal and leukemic patterns.

Normal human sera induce the formation of fat-containing cells (FCC) in human bone marrow cultures. A nearly complete monolayer of FCC is formed after 7-14 days of cultivation with 20% human sera in the medium. FCC-inducing activity (FCCIA) is nondialyzable through 14,900-dalton cutoff membrane and is stable at 56 degrees C for 30 min. Abundant FCCIA was found in 83% of normal human sera but in only 20% of sera from untreated patients with different hemopoietic disorders and in 32% of treated leukemic patients. It is suggested that FCCIA may be involved in regulation of the bone marrow microenvironment an that it varies in normal individuals and in patients with different diseases.

Adolescent↗

Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.

Acute Disease↗

Treatment of acute lymphoblastic leukemia in adults: results of the L-10 and L-10M protocols.

Two successive protocols (L-10 and L-10M) employing multidrug induction therapy with vincristine, prednisone, and doxorubicin (Adriamycin) plus an intensive consolidation phase and maintenance program have led to a significant improvement in the prognosis of adult acute lymphoblastic leukemia (ALL). The complete remission (CR) rates for the 34 patients entered on the L-10 protocol and the 38 patients entered on the L-10M protocol were 85% and 84%, respectively. The median duration of remission has not yet been reached for either the L-10 (median follow-up, 5.5 years; range, 3.5-7.5 years) or the L-10M protocol (median follow-up, 2.5 years; range, 1-3.5 years). The median survival time has not yet been reached for the L-10M protocol. Central nervous system prophylaxis with intrathecal methotrexate alone was effective in preventing central nervous system relapse. An analysis of possible prognostic factors indicated that patients less than 25 years of age had a higher CR rate than older patients (p = 0.02). Patients with an initial leukocyte count below 15,000/microL experienced longer remissions than patients with a leukocyte count above 15,000/microL (p = 0.008), and patients who achieved CR within the first month of therapy were in remission longer than those requiring a longer time to achieve CR (p = 0.04). Patients with T cell ALL did not have a poorer prognosis than other patients treated on these protocols. The L-10 and L-10M protocols were well tolerated with minimal morbidity.

Adolescent↗

Prognostic significance of receptors for the third component of complement an heavy chain phenotype in diffuse B-cell lymphomas.

As part of a larger study to determine the prognostic significance of cell marker phenotype in diffuse lymphomas, 51 patients with monoclonal B-cell lymphoma were further characterized by receptors for C3 (EAC rosettes) as well as heavy and light chain phenotypes. Patients with greater than 10% EAC rosette-forming cells were found to have a statistically significant longer survival than those with less than 10% EAC rosettes (p = 0.005). A similar trend in survival duration was found for patients whose cells expressed mu heavy chain on their surfaces when compared to those with gamma heavy chain on their cell surfaces (p = 0.05). No difference was observed for light chain phenotype. No correlation was observed between these prognostic groups and any of the three most frequently used histologic classifications (i.e., Rappaport, Lukes, Kiel).

Adult↗

Specific translocations characterize Burkitt's-like lymphoma of homosexual men with the acquired immunodeficiency syndrome.

A Burkitt's-like B-cell lymphoma (BLL) has recently been shown to be associated with the acquired immunodeficiency syndrome (AIDS), which affects homosexual men. We report cytogenetic studies of two BLL tumors in homosexual men. Both tumors had chromosome translocations characteristic of Burkitt's lymphoma (BL), one the t(8;14) and the other the t(8;22). The pathway of lymphomagenesis in this disorder is discussed in the light of recent data on chromosome change and localization of immunoglobulin genes and oncogenes.

Acquired Immunodeficiency Syndrome↗

Lymphomatoid granulomatosis: an analysis of clinical and immunologic characteristics.

Six patients with lymphomatoid granulomatosis were studied. Two patients had eye involvement, a rare manifestation of this disease. Both had complete disappearance of disease in this area after radiation therapy. One patient presented with an autoimmune hemolytic anemia, which remitted completely with chemotherapy. The use of corticosteroids or chemotherapy was effective in bringing about a decrease in pulmonary infiltrates in all six patients, although the duration of response was limited. One patient did have a prolonged period of clinical remission, and died of an unrelated cause. Evidence of profound immunologic abnormalities was found in these patients by a variety of tests. The extensive immunologic dysfunction present in patients with lymphomatoid granulomatosis has not previously been described. Most strikingly, patients with lymphomatoid granulomatosis have a severe impairment in T-lymphocyte function, confirmed by their inability to react to common skin test antigens or dinitrochlorobenzene, decreased in vitro lymphocyte responsiveness to mitogens and antigens and changes in T-cell subset populations. This may account for the frequent development of malignant lymphomas in patients with this condition.

Aged↗

Treatment of advanced diffuse histiocytic lymphoma: an analysis of prognostic variables.

Sixty-five patients with Stages III and IV diffuse histiocytic lymphoma (DHL) were treated with two different and successive combination chemotherapy protocols. Twenty-seven patients were treated with the cyclophosphamide (CTX) L2 protocol, which included maintenance chemotherapy for three years. Thirty-eight patients received the NHL-3 program. Both protocols included radiotherapy (1350--4000 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system prophylaxis with intrathecal methotrexate or cytosine arabinoside in patients with bone marrow involvement. Two-year survival rates were 44 and 56%, respectively, for the CTX-L2 and NHL-3 protocols. Of the 65 patients, 59 were evaluable for response to therapy. The CTX-L2 produced a 58% total response (TR) rate, 39% complete (CR), and 19% partial (PR). The patients on NHL-3 achieved a TR rate of 82%, 33% CR, and 48% PR. The difference in TR was significant (P = 0.05), but in CR was not. Prior chemotherapy (P = 0.077) and serum lactic dehydrogenase (LDH) level above 500 U/liter (P = 0.01) significantly lessened the chances for achievement of a CR. However, sex, age, the presence of systemic symptoms, stage (III vs. IV), and prior RT were not found to be significantly related to CR rate. This analysis suggests that a high level of serum LDH characterizes a subgroup of patients with particularly aggressive DHL that requires a more intensive modality of treatment.

Adolescent↗

Characterization of B-cell type chronic lymphocytic leukemia cells by surface markers and a monoclonal antibody.

This study was carried out to determine the reactivity of the Leu-1 mouse monoclonal antibody with B-chronic lymphocytic leukemia and other B-cell leukemias. This antibody has been previously reported to recognize a surface antigen expressed by almost all human thymocytes and peripheral T cells. It was also detected on surface immunoglobulin-bearing cells of most patients with chronic lymphocytic leukemia but was not detectable in normal B-cells and B-cell lines. In the present series, the neoplastic lymphocytes in 33 cases of B-chronic lymphocytic leukemia expressed surface immunoglobulin, Ia antigen, and receptors for Fc, C3, and mouse erythrocytes. All but one case expressed the Leu-1 antigen as detected by indirect immunofluorescence using flow cytometry. In three other cases, the leukemic cells in the peripheral blood reacted with anti-Leu-1, whereas the bone marrow lymphocytes did not. Moreover, quantitative differences in the surface density of Leu-1 were apparent by flow cytometry. The peripheral blood and bone marrow lymphocytes in other B-cell leukemias, including 15 cases of leukemic B-cell lymphomas and three cases of hairy-cell leukemia, failed to stain positively with the anti-Leu-1 antibody. The recognition of the Leu-1 antigen adds to the phenotypic characterization of b-chronic lymphocytic leukemia and may contribute to a better understanding of the pathogenesis of the disease and its expression in different tissues.

Antibodies, Monoclonal↗