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Biomedical subjects

R S Neiman

Publications and source records attributed to R S Neiman.

At least 73 records · Page 4Linked to original sources

Remissions in hairy-cell leukemia with pentostatin (2'-deoxycoformycin).

The Eastern Cooperative Oncology Group conducted a study of pentostatin (2'-deoxycoformycin) in 37 patients with hairy-cell leukemia. Among the 27 patients who met all the study's entry criteria, the response rate was 96 percent, with 16 patients (59 percent) entering complete remission and 10 patients (37 percent) partial remission. In one patient no response was observed. These results were not significantly changed by the inclusion of nine additional patients who were found retrospectively not to have fulfilled the entry criteria. When complete remission was attained, maintenance therapy was not given. Despite this, no patient has had a relapse, and the duration of complete remission ranges from 1 to 375 days. Pentostatin appears to be equally effective in untreated patients and in those who have progressive disease after splenectomy or after both splenectomy and treatment with interferon. Whether pentostatin is superior to splenectomy or interferon as therapy for hairy-cell leukemia will have to be assessed by direct comparison in randomized studies. Lengthy follow-up will be required to determine a median duration for the responses of hairy-cell leukemia to pentostatin.

Antineoplastic Agents↗

Lymphocyte predominance Hodgkin's disease. A clinicopathologic reassessment.

A clinicopathologic analysis of 35 cases of lymphocyte predominance Hodgkin's disease (LPHD) was performed, and the relationship between various histologic features and stage at presentation was examined. The series comprised 31 male and 4 female patients with a median age of 32 years. Twenty patients had Ann Arbor Stage I disease; 5, Stage II; 8, Stage III; and 2, Stage IV. Eight cases showed a multifocal epithelioid histiocytic reaction; six of these had advanced-stage (III or IV) disease (P = 0.003). Five cases contained relatively frequent atypical mononuclear cells; four of these were Stage III or IV (P = 0.017). A purely diffuse growth pattern was also associated with high stage (P = 0.031). Presence of nodularity correlated with low stage (P = 0.031). During follow-up (median, 4 years; range, 2.5 months-18 years) there was a high incidence of second neoplasms (2 large cell lymphomas, 3 non-hematologic malignancies). LPHD manifests greater diversity of stage at presentation than originally thought. A high content of epithelioid histiocytes, relatively frequent atypical mononuclear cells, and diffuse histology appear to define subsets associated with advanced-stage disease. The correlation of nodular growth pattern with low-stage disease is consistent with the distinctive behavior and derivation of nodular LPHD.

Adolescent↗

The histologic features of hyperplastic lymphadenopathy in AIDS-related complex are nonspecific.

Follicular hyperplasia is the most common histologic finding in lymph nodes of patients with AIDS-related complex (ARC) and persistent generalized lymphadenopathy. To determine the specificity of the published features considered characteristic of this condition, we compared two sets of lymph-node biopsy specimens with follicular hyperplasia. Thirty-eight specimens were from human immunodeficiency virus (HIV/HTLV3/LAV) positive homosexual men with persistent generalized lymphadenopathy, and 87 specimens were from patients free of AIDS risk. Polykaryocytes, epithelioid histiocytes, and follicle mantle zone effacement were significantly more common in the ARC group. Dermatopathic change and so-called follicle lysis were significantly more common in control, non-ARC nodes. No statistically significant difference between the two groups could be demonstrated for the following features: irregularity of follicles, burnt-out follicles, sinus monocytoid cells, marked plasmacytosis, and the toxoplasmosis triad. Most importantly, no feature was seen exclusively in either of the two groups. Although some features considered characteristic of the hyperplastic form of ARC lymphadenopathy are seen more commonly in this condition than in lymph nodes showing follicular hyperplasia unrelated to ARC, none of these features is specific for ARC and there is no histologic picture diagnostic of this condition.

AIDS-Related Complex↗

Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma.

Three hundred thirty-two eligible patients with advanced (Ann Arbor stage III or IV) non-Hodgkin's lymphoma of aggressive histologic subtype (Rappaport classification diffuse histiocytic [DH], diffuse poorly differentiated lymphocytic [DPDL], diffuse mixed [DM], or diffuse undifferentiated [DU]) were randomly assigned to receive induction chemotherapy with one of three intensive regimens in a clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) between 1978 and 1983. Chemotherapy regimens consisted of cyclophosphamide, vincristine, prednisone, and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (COPA) administered in 3-week cycles; cyclophosphamide plus doxorubicin plus prednisone beginning day 1, with vincristine plus bleomycin day 15 of each 3-week cycle (COPA + Bleo); or cyclophosphamide plus doxorubicin plus procarbazine beginning day 1, and bleomycin plus vincristine plus prednisone beginning day 15 of each 4-week cycle (CAP-BOP). The median patient follow-up from study entry for patients still alive is 5 years. The three regimens were not significantly different with respect to complete response (CR) rates (43% to 46%), time to progression of malignant disease (median, 1.0 to 1.7 years), or survival (5-year survival, 34% to 45%), although duration of complete remission appeared to be shorter in patients receiving COPA (P = .03). COPA + Bleo and CAP-BOP were significantly more toxic than the COPA regimen. This study did not demonstrate any substantial therapeutic advantage associated with the addition of a fifth or sixth chemotherapy drug, or with treatment administered on a more frequent administration schedule, compared with the COPA regimen in this population of patients with advanced diffuse non-Hodgkin's lymphoma. The relatively small proportion of long-term disease-free survivors treated with COPA underscores the need for prospective clinical trials of new and more effective treatments for patients with these potentially curable tumors.

Adult↗

Bone marrow morphology and immunology in systemic amyloidosis.

Bone marrow specimens from 45 patients presenting with signs and symptoms of systemic amyloidosis were studied to assess the degree and pattern of plasmacytosis and its clonality, using immunohistologic technics. Twenty-four of 35 patients with primary amyloidosis had monoclonal plasma cells, while 11 had polyclonal plasma cells. Five patients with secondary amyloidosis and five with familial amyloidosis had a mild polyclonal plasmacytosis. The authors' data suggest that there may be two subgroups of patients with primary amyloidosis: those with monoclonal plasmacytosis representing part of the spectrum of plasma cell dyscrasias, and those in which a monoclonal plasmacytosis cannot be documented. Immunohistologic staining of bone marrows in patients with amyloidosis may be of future value in characterizing subtypes of amyloidosis and evaluating their relationship to multiple myeloma.

Amyloidosis↗

Malignant lymphoma presenting with prominent splenomegaly. A clinicopathologic study with special reference to intermediate cell lymphoma.

Although non-Hodgkin's lymphoma presenting with prominent splenomegaly is a well-recognized clinical syndrome, previous reports of such cases create confusion today because of the use of outdated pathologic classifications, awkward or inappropriate terms, and imprecise diagnostic criteria. The authors have studied 31 such cases and have classified them according to the modified Rappaport and Lukes-Collins classifications as well as the recently introduced International Working Formulation. Most of our cases (30/31) of malignant lymphoma presenting with prominent splenomegaly were of the small cell type, with morphologic and/or immunologic evidence of B-cell origin. The single largest subtype in our series (19/30) was intermediate lymphocytic lymphoma (IL), a recently described entity in which this mode of presentation has not been previously emphasized. Although such cases have been termed "primary splenic lymphoma," almost all are disseminated diseases that pursue a progressive course and require multiagent chemotherapy and/or radiotherapy.

Adult↗

The pathology of the spleen in steroid-treated immune thrombocytopenic purpura.

The spleen is a central organ in the pathophysiology of immune thrombocytopenic purpura (ITP). Splenic lymphoid tissue synthesizes anti-platelet IgG, and splenic cordal macrophages destroy platelets coated with anti-platelet antibodies. The morphologic features of the spleen in this disease reflect this splenic function: hypertrophied lymphoid follicles with secondary germinal centers in the white pulp, with perivascular plasma cells in the red pulp and evidence of increased platelet phagocytosis in cords of the Billroth. Foamy macrophages and evidence of a variable degree of extramedullary hematopoiesis also have been noted. The authors have studied 17 spleens removed for therapeutic purposes in patients with proven ITP previously treated with varying amounts of corticosteroids. In all cases there was little or no morphologic evidence of follicular hyperplasia or plasmacytosis. However, platelet sequestration and phagocytosis were demonstrated easily in all cases, both in histologic sections and in touch imprints. The authors' findings indicate that morphologic evidence of lymphoid activation characteristic in spleens from patients with ITP usually is ablated by prior corticosteroid therapy but that the characteristic platelet sequestration and phagocytosis persists.

Adult↗

m-AMSA in refractory lymphoma. A phase II trial of the Eastern Cooperative Oncology Group.

m-AMSA (4'-[9'-acridinylamino]-methansulfon-m-anisidide) is an acridine derivative which has shown a wide spectrum of activity in preclinical testing. The mechanism of action is thought to be via interference with synthesis and integrity of DNA chains by intercalation between base pairs and external binding. Initial phase I clinical trials revealed granulocytopenia to be the dose limiting toxicity with occasional thrombocytopenia. Phlebitis, liver function abnormalities, and cardiac abnormalities have also been noted. Early reports suggested activity in leukemia and lymphoma. Based on these results ECOG evaluated m-AMSA in a phase II trial of Hodgkin's disease and non-Hodgkin's lymphoma.

Adolescent↗

Myelofibrosis with myeloid metaplasia: pathophysiologic implications of the correlation between bone marrow changes and progression of splenomegaly.

We undertook a study of 35 cases of myelofibrosis with myeloid metaplasia to assess the histopathologic findings in the bone marrow of patients with this disorder, to ascertain if changes in morphology occurred with time, and to attempt to correlate marrow findings with splenic size. We reviewed 71 bone marrow biopsies and studied 13 splenectomy specimens. Sequential bone marrow biopsies were obtained in 21 cases over intervals ranging from two to ten years (mean, 4 1/2 years). We noted a patchy nature and variable degree of stromal proliferation in most marrow biopsies, and were unable to demonstrate a correlation between the extent of medullary fibrosis and duration of disease, splenic weight, or degree of splenic myeloid metaplasia. We were unable to document a progression of medullary fibrosis as a cause for increasing splenomegaly. However, the alteration in the marrow stroma in this disorder is responsible for the presence of distended marrow sinusoids with intravascular hematopoiesis, a phenomenon we observed in all cases. We believe that this morphological feature, not emphasized by previous investigators, is of significance in understanding the pathophysiology of myeloid metaplasia.

Adult↗

Lymphoplasmacytic lymphoma. A clinicopathologic study of a previously unrecognized composite variant.

Six cases are reported of a previously undescribed unusual composite variant of lymphoplasmacytic lymphoma that is not readily classifiable by either the Rappaport or the Lukes and Collins classifications, or by the recently proposed Working Formulation. These cases are characterized by a partly nodular, partly diffuse proliferation of lymphoid cells surrounded by a separate, zonally distinct proliferation of large plasmacytoid cells. The latter cells are located in medullary and paracortical areas in lymph nodes and in the marginal zone of the white pulp and in the red pulp in the spleen. This distinct zonal characteristic was noted in the small bowel as well in one case. Five of our six patients were male, and their ages ranged from 46 to 68 years. Three had a monoclonal serum IgM and one had hyperglobulinemia that was not further characterized. Three had evidence of an altered immune state. In all cases, monoclonal IgM was demonstrated in involved tissues by an immunoperoxidase technique. These cases are unusual because of the unique topographic segregation of the varying types of tumor cells in all cases, and because of the association of paraproteinemia with nodular lymphoma in three. The resemblance of this tumor to the plasma cell variant of giant lymph node hyperplasia with which two cases were originally confused, and to lymph nodes in patients with autoimmune diseases, may be responsible for its lack of recognition.

Aged↗

Identification of early relapsing patients with adult acute nonlymphocytic leukemia by bone marrow biopsy after initial induction chemotherapy.

Bone marrow biopsies obtained from 69 adult patients with acute nonlymphocytic leukemia (ANLL) six to 10 days after initial induction chemotherapy were reviewed blindly to detect the presence of residual leukemia. Discrimination between the presence or absence of leukemic cells was provided by assessment of the numbers, clustering, and nuclear morphology of blasts and promyelocytes. Twenty-six patients had frank leukemia, 25 had no apparent leukemic cells, and 18 had focal residual leukemia. Of 25 patients whose bone marrow contained no detectable residual leukemic cells, 21 gained complete remission without further chemotherapy. These patients had a median duration of remission of 278 days, with five patients still remaining in remission for 578-882 days. Similarly, all of the 18 patients who had focal residual leukemia achieved complete remission without additional chemotherapy; however, all have relapsed with a median duration of remission of 163 days. This study indicates that patients with foci of residual leukemia in their one-week posttreatment bone marrow samples readily achieve remission, but carry a substantial leukemic burden that increases the likelihood of early relapse.

Acute Disease↗

Peripheral T-cell lymphoma: a clinicopathologic study of nine cases.

The clinicopathologic features of nine cases of peripheral T-cell lymphoma were analyzed. Although the youngest patient was 18 years old, the median age was 59.8 years. They usually presented with widespread disease and had an aggressive course. Seven have died with a median survival of 10.9 months. Five cases were of mixed cell type, sharing certain histopathologic features that we believe are characteristic of peripheral T-cell lymphomas. Three cases were of large cell type; one was a small cell (PDL) type. This latter patient lived symptom-free without treatment for over 3 years, despite stage III disease. Another patient, whose tumor had nodular sclerosis-like fibrosis, is in complete remission two years after chemotherapy for stage III B disease. Because peripheral T-cell lymphoma is morphologically heterogeneous, it may be clinically heterogeneous as well. We believe that classification according to a modified Rappaport system may clarify possible variations in biologic behavior.

Adolescent↗

Evidence to suggest that the human fetal spleen is not a hematopoietic organ.

The human fetal spleen commonly is regarded as an organ of hematopoiesis. Because of the authors' interest in myelofibrosis with myeloid metaplasia (MMM) and because the myeloid metaplasia commonly is regarded as a reactivation of embryonic sites of blood formation, spleens from 48 fetuses and stillborn infants were studied, in an attempt to evaluate splenic hematopoiesis (myelopoiesis). The authors employed immunohistologic and cytochemical technics to identify granulocytic, erythroid, and megakaryocytic cells, in contrast to previous studies that have relied solely on conventional morphology. The authors found surprisingly little evidence of hematopoiesis. Virtually no hematopoietic cells of the dividing cell pool were identified, in spite of the fact that the technic used is capable of detecting such immature forms. The results suggests that the spleen is not a significant organ of hematopoiesis in the human fetus but that immature hematopoietic cells found there merely reflect trapping of circulating precursors in the fetal blood. These findings have significant implications for the pathophysiology of MMM.

Erythrocytes↗

T8 chronic lymphocytic leukemia. A distinctive disorder related to T8 lymphocytosis.

A case of T chronic lymphocytic leukemia (CLL) was first suspected on histologic and cytochemical examination of a splenectomy specimen. Later the patient became frankly leukemic with an E+/T3+/T8+/T4- phenotype. From our case and other reported cases of T-CLL studied with monoclonal antisera, the authors conclude that there are significant clinical and morphologic differences between T4 CLL and T8 CLL. In contrast to T4 CLL, T8 CLL characteristically presents with relatively low lymphocyte counts, little organ involvement, and often only discreet bone marrow involvement, and has a long clinical course. The leukemic cells are often large and have abundant cytoplasm with azurophilic granules. Similar features in cases reported as T8 lymphocytosis with neutropenia lead us to consider both entities part of a spectrum of the same disorder.

Aged↗

Malignant lymphoma, mixed cell type, diffuse.

This retrospective study of diffuse mixed (DM) cell lymphoma was undertaken as a collaborative study between the Repository Center for Lymphoma Clinical Studies and four cooperative oncology groups (CALGB, ECOG, SECSG, SWOG), and was based on 62 patients from the files of the Repository Center. We wanted to ascertain whether there were any significant clinical differences among the various morphological subtypes of this lymphoma. All patients were treated according to different protocols of the Cooperative Oncology Groups sponsored by the National Cancer Institute. In 16 patients (26%), the malignant lymphoma (ML) had morphological features consistent with follicular center cell origin (FCC); in 34 patients (55%), the ML did not have features of follicular center cell type (non-FCC), but had morphology described for peripheral T-cell-derived ML. In 8 of the patients (13%), no agreement could be reached by the 7 histopathologists who participated in the study, and these were classified as unresolved; the remaining 4 (6%) were unclassifiable. We compared the survival times of the 16 patients having the morphological features of the FCC subtype with the survival times of the 34 patients with the non-FCC subtype and found that patients with FCC lived longer (p = 0.07 Cox's regression). In the FCC group, all patients who had complete remissions (CR) were alive; however, their survival times were similar to those who had a partial or no response (p = 0.32). In contrast, in the non-FCC group, the median survival was 20 mo, and patients with a CR had a significantly longer survival than did incomplete responders (p = 0.003). According to these results the non-FCC diffuse mixed cell lymphoma appears to be a high-grade malignant lymphoma, whereas the FCC type is not.

B-Lymphocytes↗