Benjamin Koziner

Non-Hodgkin's lymphoma in 90 homosexual men: relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome

We describe the histologic and clinical features of non-Hodgkins lymphoma diagnosed between January 1980 and December 1983 in 90 homosexual men from San Francisco, Los Angeles, Houston, and New York. The median age was 37 years, with an age distribution identical to that for cases of AIDS reported to the Centers for Disease Control. Sixty-two per cent of the patients had high-grade (aggressive) subtypes of lymphoma, 29 per cent had subtypes of intermediate grade, and 7 per cent had low-grade subtypes. Histologic subtypes and malignant cell phenotypes were consistent with a B-cell origin. All but two men had extranodal lymphoma: central-nervous-system, bone-marrow, bowel, and mucocutaneous sites were most commonly involved. Thirty-five of 66 evaluable men (53 per cent) had complete responses to combination chemotherapy or radiotherapy or both, and thus far, 19 (54 per cent) of them have had a relapse. Mortality and morbidity were closely related to prodromal manifestations; death or illness have occurred in 19 (91 per cent) of the 21 men who presented with AIDS, in 26 (79 per cent) of the 33 who presented with generalized lymphadenopathy, and in 5 (42 per cent) of the 12 who had no prodromal manifestations. Mortality rates analyzed according to histologic grade were higher than currently reported rates in other patient populations. Kaposis sarcoma or severe opportunistic infections characteristic of AIDS developed in 14 of 33 men (42 per cent) who presented with generalized lymphadenopathy and in 3 of 12 (33 per cent) without prodromal manifestations. We conclude that non-Hodgkins lymphoma in members of an AIDS risk group is a serious manifestation of AIDS and the AIDS-related complex.

Preliminary Observations on the Effect of Recombinant Leukocyte a Interferon in Homosexual Men with Kaposi's Sarcoma

Preliminary clinical trials have shown that both natural and recombinant-DNA-produced human interferons are occasionally capable of inhibiting the growth of some tumors.1 2 3 4 Although the tumors ...

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‐Hodgkins lymphoma (NHL), nine had primary large cell lymphomas of the brain, 11 had Hodgkins 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 postmorten 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.

The Natural History of Kaposi's Sarcoma in the Acquired Immunodeficiency Syndrome

Kaposis sarcoma is a multifocal systemic neoplasm histologically characterized by proliferating fibroblastic and microvascular elements. Initial signs include macules, papules, or nodules on the skin or mucosal surface. Lesions are frequently found on the trunk, arms, and head and neck. In general, sites of involvement and tumor load do not correlate with prognosis. A general decrease in the functional capacities of T and B cells is found in most patients. Kaposis sarcoma is reported as the initial manifestation of the acquired immunodeficiency syndrome (AIDS) in approximately 30% of cases. Most cases are in men, although it has been reported in all risk groups. Kaposis sarcoma in AIDS is more frequent among whites and homosexuals than blacks and intravenous drug abusers. Overall mortality is approximately 41%, with over 60% of patients alive at 1 year and 50% at 22 months. Overall survival is 18 months; however, some patients who have had the disease for 3 to 4 years are still doing well.

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 Kaposis 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<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 proliferationin 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 correctablein vitro by highly purified IL2.

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‐Hodgkins 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 (< 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 < 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‐Hodgkins lymphomas treated conservatively.

Characterization of malignant lymphomas in leukemic phase by multiple differentiation markers of mononuclear cells: Correlation with clinical features and conventional morphology

Abstract Peripheral blood and bone marrow cells of 38 patients with malignant lymphoma in the leukemic phase were defined by multiple immunologic markers and determination of the enzyme terminal deoxynucleotidyl transferase (TdT). Despite shared B cell markers (surface immunoglobulins, binding of aggregated immunoglobulin G [IgG]) distinctions could be made between the cells of patients with chronic lymphocytic leukemia (CLL) and those of patients with other B-lymphoproliferative disorders on the basis of morphology, intensity of surface immunofluorescence and number of mouse rosette-forming cells (MRFC). In 15 patients with CLL, the mean value for MRFC was 47.5 per cent, differing significantly (p

Interleukin-2 correction of defectivein vitro T-cell mitogenesis in patients with common varied immunodeficiency

We studied the ability of phytohemagglutinin (PHA) and two anti-T-cell monoclonal antibodies, OKT3 and Pan T2, to induce interleukin-2 (IL2) production and proliferation in peripheral blood lymphocytes (PBL) from 14 patients with combined varied immunodeficiency (CVI). The median values of endogenous IL2 produced by mitogen-stimulated PBL was significantly lower in patients than controls irrespective of the mitogen used. The patients, taken as a group, had a significantly decreasedin vitro PBL response to mitogen stimulation when compared to controls. With the addition of a highly purified human IL2 preparation, the proliferative response in the majority of patients was significantly improved with all mitogens. Three patient groups could be distinguished: Group A (3/14) had full restoration of proliferative response with the addition of IL2, Group B (5/14) had partial restoration, and Group C (6/14) had no significant response. The monoclonal antibody, Pan T2, recognized a T-cell proliferative defect in 5 of 14 patients which neither PHA nor OKT3 recognized. This was not significantly corrected by the addition of IL2. This T-cell proliferative defect correlated with the lack of B-cell proliferation and immunoglobulin production in response to B-cell mitogens in three-fourths of the patients assayed. These data show that CVI patients are a heterogeneous group but have in common a decreasedin vitro production of IL2 resulting in a proliferative defect which is correctable at least in part,in vitro, in the majority by the addition of purified IL2.

A study of malignant lymphomas using light and ultramicroscopic, cytochemical and immunologic technics: Correlation with clinical features

Abstract Light microscopic and ultrastructural morphology, enzyme cytochemistry, cell surface and functional markers were used to further characterize the nature of the proliferating cells in 50 patients with malignant lymphoma. Appropriate clinical information was also included. In 40 patients (80 per cent), a predominant population of monoclonal B cells was found. Within this group, one cell type was recognized morphologically by its characteristic faint surface membrane immunofluorescence. This type appeared identical to the cells in chronic lymphocytic leukemia. A second cell type, recognized by its bright surface immunoglobulin, contained two subtypes delineated by light microscopic and ultrastructural features. A third cell type, characterized by its ability to phagocytize, positive staining for nonspecific esterases and dense cytoplasmic granules, was recognized in one leukemic patient. A fourth cell type (two patients) formed sheep red blood cells (SRBC) rosettes at 4 °C and 37 °C, indicating a T cell lineage. A fifth cell type, defined by the absence of any cell marker, was identified in two other leukemic patients. In five patients no clearly identifiable clonal proliferation could be established. Technical limiting factors and the necessity of using multiple cell markers are discussed. These data clearly suggest the usefulness of cell markers for the more precise identification of cellular types, providing more objective bases for prognosis and treatment.

Lymphoblastic Neoplasia in a Homosexual Patient with Kaposi's Sarcoma

Abstract The bone marrow aspirate from a leukopenic homosexual patient with Kaposis sarcoma showed a minimal increase (10%) in the blast count with 25% of mononuclear cells positive for terminal d...