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Biomedical subjects

S M Lippman

Publications and source records attributed to S M Lippman.

At least 217 records · Page 12Linked to original sources
PubMed1988

HLA-DR (Ia) immune phenotype predicts outcome for patients with diffuse large cell lymphoma.

The clinical utility for establishing the immune phenotype in patients with non-Hodgkin's lymphoma is controversial. To help resolve this dilemma, we studied 104 consecutive patients with diffuse large cell lymphoma, the most common subtype of potentially curable non-Hodgkin's lymphomas. The presence or absence of the human class II histocompatibility antigen was determined using the monoclonal antibody anti-HLA-DR (Ia), and the results correlated with pretreatment clinical features and survival. We found that eight HLA-DR negative patients had similar pretreatment clinical characteristics compared with 96 HLA-DR positive patients, but HLA-DR negative patients had a significantly shorter survival duration compared with HLA-DR positive patients (P = 0.003 log-rank). The median survival of the HLA-DR negative patients was 0.5 years compared to 2.8 yr for the HLA-DR positive patients. No HLA-DR negative patient survived beyond 1.5 yr. A multi-variate analysis, adjusting for prognostic factors of known clinical significance, confirmed the importance of HLA-DR as a prognostic factor (P = 0.016). We conclude that determining the presence of HLA-DR is a relatively simple pretreatment study that identifies a small but important group of patients who are not curable using currently available combination chemotherapy.

Aged↗
PubMed1988

The aberrancy of immunophenotype and immunoglobulin status as indicators of prognosis in B cell diffuse large cell lymphoma.

To assess the prognostic significance of the immunophenotype in diffuse large cell lymphoma (DLCL), 105 DLCL patients were studied between 1978 and 1987 using a panel of 40 monoclonal antibodies applied to frozen tissue. Eighty-three patients were found to have B cell phenotypes, and 20 patients had T cell phenotypes. Focusing on markers relevant to clinical outcome among B cell LCL showed that lack of expression of the pan B antigens Leu14 and Leu16 were correlated with decreased survival (Leu14, P = 0.01; Leu16, P = 0.06; log-rank). HLA-DR activity also showed that lack of expression of this antigen correlated with poor survival (P = 0.004, log-rank). Kappa light chain immunoglobulin lack of expression showed predictive value for decreased survival as well (P = 0.005, log-rank). Multivariate analyses of known clinically important variables and the immune phenotypes confirm that the loss of HLA-DR and B cell aberrancy are independent factors predicting a poor clinical outcome. Losing some B activation/kappa antigens appears to be a broad biologic phenomenon linking surface antigen lack of expression with decreased survival. This suggests that aberrancy of immunophenotype and immunoglobulin status are key predictors of survival in B-LCL.

Antigens, Surface↗
PubMed1988

Clonal ambiguity of human immunodeficiency virus-associated lymphomas. Similarity to posttransplant lymphomas.

Initial biopsy specimens from two patients with lymphadenopathy and human immunodeficiency virus antibody-positive serum presented considerable difficulty in making specific histologic and immunologic diagnoses, although subsequent biopsy specimens revealed clear progression to acquired immunodeficiency syndrome (AIDS)-associated lymphomas. The initial biopsy specimens revealed multifocal clusters of large blastic lymphoid cells, with some clusters showing a monoclonal lambda light chain predominance, whereas other clusters showed a kappa predominance, indicating considerable phenotypic ambiguity suggestive of polyclonality. This initial clonal ambiguity was followed within two to three months by overt histologic, phenotypic, and clinical malignant transformation to a diffuse high-grade monoclonal B-cell lymphoma. These data have significant implications for the clonality and pathogenesis of AIDS-associated lymphoproliferative disorders. AIDS-related lymphomas may evolve from an initial multiclonal B-cell expansion similar to that described in other severely immunosuppressed patients (eg, with posttransplantation lymphoma).

AIDS-Related Complex↗
PubMed1988

The prognostic significance of the immunotype in diffuse large-cell lymphoma: a comparative study of the T-cell and B-cell phenotype.

The clinical significance of immunophenotyping of the non-Hodgkin's lymphomas is controversial. Therefore, we conducted the present study of 103 consecutively accrued diffuse large-cell lymphoma (DLCL) patients to define, independently of histologic subtypes, the prognostic importance of phenotyping. We used an extensive panel of monoclonal antibodies to T- and B-cell antigens to assign all patients immunologically into the T-cell (20 patients) or B-cell group (83 patients). The only significant differences in pretreatment clinical variables between the two patient groups were the higher frequency of bulky disease (greater than 10 cm) in B-cell patients (P = .008) and more frequent skin involvement in the T-cell group (P less than or equal to .001). Multiagent doxorubicin-containing chemotherapy regimens were employed as initial therapy in over 83% of the patients in each group. Our study revealed that disease-free survival (DFS) was significantly shorter in the T-cell patients than in the B-cell DLCL patients (median DFS, 10.8 months for T-cell and 42.7 months for B-cell; P = .01, log rank). No patient with T-cell DLCL remained disease free for longer than 2 years, whereas 55% of the B-cell group were disease free at 2 years. Univariate and multivariate analyses of all major prognostic factors of DFS suggest that the T-cell phenotype indicates an incurable subset of DLCL patients. Although the B-cell group had a twofold advantage in median survival (35 months v 18 months), actuarial overall survival was not significantly different between the two patient groups (P = .23). Our results indicate the need for new approaches in the search for a curative treatment for T-cell DLCL.

Adolescent↗
PubMed1988

Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67.

To assess the prognostic significance of the growth fraction in diffuse large cell lymphoma (DLCL), we studied 105 DLCL patients with the monoclonal antibody Ki-67 applied to frozen tissue sections. Ki-67 detects a nuclear antigen associated with cell proliferation not found in resting cells. Ki-67 findings and other clinical prognostic factors were correlated with outcome using univariate and multivariate analyses in the proportional hazards model. High proliferative activity, defined as nuclear Ki-67 expression in greater than 60% of malignant cells (Ki-67 greater than 60), was found to be a strong predictor of poor survival among these patients (P = .003, log-rank). The 19 patients with Ki-67 greater than 60% had a median survival of 8 months compared with a median survival of 39 months for the 86 patients with Ki-67 less than or equal to 60%. Examination of pretreatment clinical variables indicated the patient groups were similar with regard to age, sex, stage, B symptoms, tumor bulk, and lactate dehydrogenase (LDH). Both patient groups received comparable curative intent therapy and showed comparable complete response rate precluding treatment differences as modifying outcome. Multivariate analysis indicated Ki-67 is an independent predictor of survival (multivariate P = .006). Further statistical analysis using only B-cell DLCL patients treated with CHOP (63 patients) indicated that Ki-67 greater than 60 retained strong prediction of poor outcome (P = .002, log-rank) among this homogeneous group. We conclude that high proliferative activity (Ki-67 greater than 60) is an independent factor allowing laboratory prediction of probable poor outcome of DLCL.

Adolescent↗
PubMed1987

Lethal midline granuloma with a novel T-cell phenotype as found in peripheral T-cell lymphoma.

Lethal midline granuloma (LMG), initially a clinical description, includes an uncommon group of disorders characterized by a relentless, destructive process involving the upper respiratory structures. Its etiology and pathogenesis are uncertain, probably varied, and the distinction between inflammatory and malignant processes is difficult despite extensive clinical and histopathologic evaluation. The need for new techniques for rapid diagnosis has important therapeutic implications. Using an extensive panel of T- and B-cell monoclonal antibodies the authors describe a patient with clinically and pathologically typical LMG demonstrating an "activated" T-cell phenotype with a "novel" pattern characteristic of peripheral T-cell lymphoma, strongly implying that some cases of LMG are more closely related to neoplastic T-cell lymphoproliferative disorders than to inflammatory conditions. Further studies using these immunotyping techniques may help clarify the pathogenesis of LMG, and may uncover specific diagnostic and prognostic phenotypic patterns.

Adult↗
PubMed1987

Post-transplantation T cell lymphoblastic lymphoma.

Immunosuppressed renal transplant recipients are at increased risk for large cell lymphoma of B cell phenotype. This report describes a case of post-transplantation lymphoma presenting with a mediastinal mass causing superior vena cava syndrome, tracheal obstruction, and pleural effusion. Cytospin preparations of pleural fluid documented high-grade lymphoblastic lymphoma morphology and immature T cell (cortical thymocyte) phenotype: Leu 1-6-positive, Leu 9-positive, Tdt-positive, B-negative, Calla-positive. The occurrence of post-transplantation lymphoma of T cell lineage is inconsistent with the postulated Epstein-Barr virus origin and raises important questions regarding the development of lymphoproliferative disorders in immunosuppressed organ transplant recipients.

Adult↗
PubMed1987

Evans' syndrome as a presenting manifestation of atypical paroxysmal cold hemoglobinuria.

Paroxysmal cold hemoglobinuria is a rare and potentially life-threatening acquired hemolytic anemia occurring either as an acute transient anemia following several different viral syndromes, or in a chronic idiopathic form. Episodic hemolysis in paroxysmal cold hemoglobinuria is usually associated with a biphasic (Donath-Landsteiner) IgG cold-reactive complement-fixing autohemolysin with anti-P specificity. Paroxysmal cold hemoglobinuria has not previously been associated with malignancy nor has it been clearly shown to be steroid-responsive. This report describes a patient with steroid-responsive autoimmune hemolytic anemia and immune thrombocytopenia (Evans' syndrome) associated with oat cell carcinoma of the lung and a unique biphasic anti-IgM autohemolysin. This case extends the spectrum of biphasic antibody-mediated immune cytopenias and widens both the clinical and the serologic definition of paroxysmal cold hemoglobinuria.

Anemia, Hemolytic, Autoimmune↗
PubMed1987

Salvage therapy of advanced Hodgkin's disease. Critical appraisal of curative potential.

The therapeutic outcome in patients with advanced Hodgkin's disease has improved considerably since the advent of MOPP chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone) and MOPP-like regimens. Still, failure will eventually occur in approximately 50 percent of these patients. The optimal approach to treating these patients is not well established. Currently, the six major salvage approaches available are: (1) chemotherapy reinduction with the same initial regimen: (2) chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine); (3) non-ABVD second-line regimens; (4) third-line chemotherapy regimens; (5) wide-field radiation therapy alone or combined with second-line chemotherapy; and (6) autologous and allogeneic bone marrow transplantation. This review provides a critical evaluation of the curative potential of each therapeutic modality and outlines recommendations for the best current therapeutic approach and for future clinical study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Danazol in the treatment of myelodysplastic syndromes.

20 patients with myelodysplastic syndromes (MDS) were treated with danazol, 800 mg daily in 4 divided doses. 18 patients were evaluable for response. 3 patients (17%), whose principal problem was anemia, responded to treatment, but only with an increase in platelet count. Responses were short-lived and lacked clinical significance. No patients with anemia or leukopenia responded to treatment and none of the 7 patients with a platelet count less than 30 x 10(9)/l responded. Danazol appears to have limited clinical utility in the treatment of MDS. However, occasional patients with thrombocytopenia may benefit.

Clinical Trials as Topic↗
PubMed1987

Radiation therapy salvage of Hodgkin's disease following chemotherapy failure.

Between 1972 and 1984, 17 patients with advanced Hodgkin's disease failing intensive combination chemotherapy in previously unirradiated nodal and/or pulmonary sites were treated with salvage radiotherapy. Treatment consisted of comprehensive wide field radiotherapy to all known areas of disease. Doses administered to these fields ranged from 1,700 to 5,000 rad, with only three patients (18%) receiving less than 3,000 rad to any field. With a median follow-up of over 4 years, 88% achieved a complete response, with median actuarial disease-free survival (DFS) of 19 months (range, 4 to 61+). Actuarial median survival was 64 months, with a range of 4 to 134+ months. Nine patients (53%) are currently alive with three (18%) in continuous complete remission (CR) for 24, 30, and 61 months. In addition, four patients relapsing after salvage radiotherapy are now in CR following additional therapy. Patients younger than 35 years of age had a significantly increased overall survival when compared with older patients (P less than .005). An initial complete response to chemotherapy lasting 12 or more months appeared to be a favorable prognostic factor, although small patient numbers preclude statistical significance. Comprehensive salvage radiotherapy is of significant benefit in patients with advanced Hodgkin's disease relapsing after combination chemotherapy in nodal and/or pulmonary sites.

Actuarial Analysis↗
PubMed1987

Treatment of advanced squamous cell carcinoma of the skin with isotretinoin.

STUDY OBJECTIVE: To determine the efficacy of oral isotretinoin in refractory advanced squamous cell carcinoma of the skin. DESIGN: Case series trial. SETTING: Tertiary care center at a university hospital. PATIENTS: A consecutive collection of four patients with advanced squamous cell carcinoma of the skin who failed to respond to standard surgical or radiation therapy. INTERVENTIONS: Isotretinoin in gelatin capsules was given at a total daily dose of 1 mg/kg body weight in two divided doses for at least 4 weeks. MEASUREMENTS AND MAIN RESULTS: Bidimensional tumor measurements at monthly intervals showed striking responses to isotretinoin in all four patients. Response durations ranged from 2 to more than 23 months. The drug produced reversible moderate mucocutaneous side effects and asymptomatic laboratory abnormalities. CONCLUSIONS: Impressive responses to isotretinoin occurred in our four patients and in six of ten other reported patients. Retinoic acid's mechanisms of action in cutaneous squamous cell carcinoma is not precisely known, but may involve the modulation of epidermal growth factor receptors and certain protein kinases. These in-vitro findings and the clinical data suggest that retinoids may be an effective and well-tolerated therapy for refractory advanced squamous cell carcinoma of the skin. The absence of any other effective systemic therapy indicates the need for continuing trials with retinoids in this disease.

Aged↗
PubMed1987

Retinoids as preventive and therapeutic anticancer agents (Part I).

Retinoids, the synthetic and natural analogs of vitamin A, frequently block the phenotypic expression of cancer in vitro; they also inhibit growth and induce differentiation in many animal and human malignant cell types. Only recently has it become possible to propose a unifying mechanism of retinoid action, which involves the protein kinase-C cascade system. This system may mediate retinoids' many diverse actions, including their effects on enzyme synthesis, membrane properties, growth factors, binding proteins, genomic and postgenomic expression, the extracellular matrix, and immunologic responses. Ongoing in vitro studies of retinoid structure-activity relationships, effects on oncogene expression, reversal of drug-resistance, and, especially, the protein kinase-C cascade system should help clarify the precise mechanism of their anticancer action. Many in vitro and in vivo assay systems are available for testing the 2000 + synthetic retinoids. These assays indicate specific drug sensitivities, which may help focus future clinical trials. In human cancer prevention, retinoids have been most effective for skin diseases, including actinic keratosis, keratoacanthoma, and basal cell carcinoma; however, nondermatologic premalignancies, such as oral leukoplakia, bronchial metaplasia, laryngeal papillomatosis, cervical dysplasia, myelodysplastic syndromes, and the urinary bladder, also respond to retinoid therapy. Significant therapeutic advances are also occurring with this class of drugs in refractory malignancies, including advanced cutaneous squamous and basal cell cancer, mycosis fungoides, and acute promyelocytic leukemia. Newer third-generation retinoids, such as the highly potent retinoidal benzoic acid derivatives, are demonstrating therapeutic indexes far higher than earlier-generation retinoids. Current in vitro testing is also demonstrating that retinoids have synergistic activity in combination with other agents (eg, biologic modifiers, hormones, and DNA synthesis inhibitors) and treatment modalities (eg, irradiation). Notwithstanding the progress already made with retinoids in human cancer, many in vitro questions remain, and clinical work is just beginning.

Animals↗
PubMed1986

Efficacy of danazol in pure red cell aplasia.

Twenty-one unselected patients with refractory chronic anemias of various etiologies were treated with danazol, a synthetic attenuated androgen. All had previously failed treatment with hematinics, androgens, corticosteroids, high-dose intravenous immunoglobulin, antithymocyte globulin, cytotoxic immunosuppressive agents, and/or plasmapheresis. Three patients with pure red cell aplasia and one with aplastic anemia responded. No responses were observed in 11 patients with myelodysplastic syndromes, two patients with myelofibrosis, and two with paroxysmal nocturnal hemoglobinuria. Remission in pure red cell aplasia was maintained with danazol alone in one patient and required combined low-dose prednisone in two. Objective responses occurred in 2 to 3 weeks and therapy generally was well tolerated. To date, one patient with pure red cell aplasia remains in complete remission at 9 months on low-dose danazol alone. We conclude that danazol alone or combined with prednisone may induce and maintain remission in severe refractory pure red cell aplasia and possibly other chronic cytopenias characterized by immunologic marrow suppression. Further trials of danazol in treating these disorders are indicated.

Adult↗