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Biomedical subjects

H Rappaport

Publications and source records attributed to H Rappaport.

At least 73 records · Page 4Linked to original sources
PubMed1985

Peripheral T cell lymphoma: immunologic and cell-kinetic observations associated with morphological progression.

Peripheral T cell lymphomas (PTCLs) form a morphologically heterogeneous group of non-Hodgkin's lymphomas that are generally considered to have immunophenotypes associated with mature T cells, usually those of helper T cells. We now describe and correlate the clinical, morphological, immunologic, and cell-kinetic findings based on the evaluation of eight tissue samples obtained at various times from a 13-year-old girl with PTCL. The early morphological expressions of this patient's PTCL were those of diffuse mixed-cell lymphoma and focal large-cell lymphoma (LCL) evolving from the histologic picture of an atypical immune response (AIR). These morphological findings were associated with an immature T cell immunophenotype associated with cortical thymocytes--namely, sheep erythrocyte rosette (sER)+, T11+, Leu-2a+, Leu-3a+, HLA-DR+, OKT6-, OKT9+, OKT10+--and with cell-kinetic findings that showed no evidence of aneuploidy and few cells in S phase. Diffuse pleomorphic LCL developed, which was associated with further dedifferentiation of the neoplastic T cells to the immunophenotype sER-, T11+, Leu-2a-, Leu-3a-, HLA-DR+, OKT6-, OKT9+, OKT10- and with cell-kinetic findings that demonstrated a distinct aneuploid population and a dramatic increase in the percentage of cells in the S phase. The immunophenotype of the PTCL at the time of the patient's death was T11-, Leu-2a-, Leu-3a-, HLA-DR+, OKT6-, OKT9+, OKT10-, an immunophenotype indistinguishable from that of a non-B non-T cell lymphoma. The immunologic findings in this case also suggest that an AIR in some cases may represent a prelymphomatous state or may be a morphological expression of PTCL. These observations indicate that PTCLs may be characterized by rapidly changing clinical, morphological, immunologic, and cell kinetic findings which are best evaluated by multidisciplinary studies.

Adolescent↗
PubMed1984

Treatment of acute myeloid leukemia with a combination of intensive induction chemotherapy, early consolidation, splenectomy and long-term maintenance chemotherapy.

The authors developed a therapeutic regimen in which 33 patients aged 11 to 61 years (mean +/- SE, 35.9 +/- 2.3 years) with acute myeloid leukemia (AML) were given intensive induction chemotherapy with Adriamycin (doxorubicin) (ADM), vincristine (VCR) and cytosine arabinoside (ARA-C). Twenty-nine of these patients (88%) attained a complete remission (CR) after 1, 2, or 3 courses and were then subjected to an early consolidation course of chemotherapy, identical to that for induction. After consolidation, all patients in CR received a long-term continuous maintenance therapy in which 6-mercaptopurine (6-MP) and methotrexate (MTX) were alternated, associated with periodic reinforcements with daunorubicin (DNR) and VCR. Twenty-five of the 29 patients who achieved a CR were splenectomized soon after the consolidation course. Histologic sections of the spleens, liver biopsy specimens, and lymph nodes, stained routinely and with the naphthol AS-D chloroacetate esterase (NCA) method, showed mature granulocytes and a few NCA positive mononuclear cells, but no proved leukemic infiltrates. For the 25 splenectomized patients, the probability of remaining in CR at 36 and 54 months was 75% and 66%, respectively; the probability of survival at 36 and 54 months was 85% and 75%, respectively. Age older than 40 years and evidence of extramedullary involvement at presentation appeared to carry a bad prognosis for disease-free survival.

Acute Disease↗
PubMed1984

"Monocytoid" cells in reactive follicular hyperplasia with and without multifocal histiocytic reactions: an immunohistochemical study of 21 cases including suspected cases of toxoplasmic lymphadenitis.

The presence of "monocytoid" cells in toxoplasmic lymphadenitis is a distinctive histopathologic finding, but the exact nature and immunologic properties of these cells have not been characterized clearly. The authors have evaluated the immunohistochemical features of monocytoid cells in fresh-frozen and paraffin-embedded, fixed lymph node material from 21 cases of reactive follicular hyperplasia including suspected cases of toxoplasmic lymphadenitis. This study revealed that monocytoid cells contain (1) the B lymphocyte surface membrane differentiation antigens B-1 and BA-1, and (2) surface membrane-associated immunoglobulin light chains in a polyclonal distribution. No positive reaction was observed when monocytoid cells were studied with monoclonal antibodies specific for peripheral T cells or with antibodies considered to be specific for cells of the monocytic/histiocytic cell line. The results indicate that monocytoid cells, despite their distinct morphologic appearance, have surface marker characteristics of polyclonal B lymphocytes. Therefore, "monocytoid B lymphocytes" would be a more appropriate designation for these cells.

Histiocytes↗
PubMed1984

Atypical lymphoplasmacytic and immunoblastic proliferation in lymph nodes of patients with autoimmune disease (autoimmune-disease-associated lymphadenopathy).

This study is based on an analysis of the morphologic, clinical, and laboratory findings in 26 patients whose pretherapy lymph node biopsies showed some, but not all, of the diagnostic features of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD). Partial or complete effacement of nodal architecture by a diffuse lymphoplasmacytic and immunoblastic proliferation was a constant histologic finding. In contrast to the findings in AILD, lymphocytic depletion and pronounced arborizing vascular proliferation were often lacking. Clinically, many of the patients had fever, sweats, weight loss, skin rashes, generalized lymphadenopathy, hepatosplenomegaly, and, in some cases, pulmonary infiltrates. Of the 26 patients, 23 had clinical and/or laboratory evidence of autoimmune disease or immune complex disease. In 12 patients (Group I--idiopathic), various autoantibodies or immune complexes were demonstrable, but these patients did not manifest a well-defined immunologic disease or syndrome. In 11 patients (Group II--secondary), the lymphadenopathy occurred secondary to a well-defined, clinically recognized immunologic disease. Three patients (Group III) had neither a well-defined autoimmune disease nor demonstrable autoantibodies, but two of them had a history of exposure to antibiotics. We suggest that patients whose lymph nodes have the morphologic features described here frequently have an autoimmune disorder, and that the pathogenesis of this clinicopathologic picture is probably related to a deficiency in suppressor T-cell function which results in an unopposed proliferation of B cells with autoantibody formation and polyclonal gammopathy. Our observations should stimulate clinicians to consider the possibility of an autoimmune pathogenesis for a lymphadenopathy in which a florid lymphoplasmacytic and immunoblastic proliferation similar to that observed in AILD is demonstrated, even though the sections may not meet all the histologic criteria reported for the diagnosis of AILD. Clinical and laboratory investigations necessary to confirm the presence of autoimmunity are indicated in these cases. Moreover, since there is evidence of genetic factors predisposing to autoimmune disease (17, 43), it would be important to investigate close relatives of patients whose lymph nodes showed the histologic changes described in this paper in prospective studies which include suppressor T-cell function, autoantibodies, HLA type of blood lymphocytes and chromosomal analysis. The median survival of the 23 patients with stigmata of autoimmune disease or immune complex disease was 36 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

The diagnosis and differential diagnosis of hairy cell leukemia in bone marrow and spleen.

In this study we reviewed the morphologic features of marrow biopsies and aspirates as well as splenic sections derived from 28 patients with hairy cell leukemia. Marrow biopsies proved reliable in establishing and/or confirming the diagnosis in every patient, when available for review. Regardless of the degree of marrow involvement, the hairy cell infiltrates consistently exhibited wide spacing of their nuclei due to relatively abundant pale to clear cytoplasm. Hairy cells appeared homogeneous and bland, without mitotic activity or prominent nucleoli; nuclear contours characteristically were ovoid and to a lesser extent slightly indented or reniform. The splenic histology of hairy cell leukemia was equally distinctive. The splenic red pulp was diffusely infiltrated by a uniform population of cytologically monotonous mononuclear cells that expanded the red pulp cords, filled the sinuses, and generally led to atrophy or obliteration of the white pulp. Moreover, the clear cytoplasm of hairy cells usually was highlighted in sinusoidal blood-filled lakes. Despite the employment of these characteristic morphologic criteria for the diagnosis of hairy cell leukemia in marrow and spleen, these pathologic changes may vary and may be simulated in part by a variety of other hematologic disorders. Accuracy of diagnosis requires not only knowledge of the usual pathologic features of hairy cell leukemia but also knowledge of the unusual. Awareness of these pathologic variations will aid in the improvement of diagnosis and will provide a foundation for understanding the clinical and biologic aspects of hairy cell leukemia.

Adult↗
PubMed1983

Angioimmunoblastic lymphadenopathy. Long-term follow-up study.

The clinical course of 41 previously reported patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) on whom follow-up information has been obtained for five or more years is described. Of the 41 patients, 27 achieved a complete remission (CR). The durations of the CR ranged from two to 214 months, with a median of 48 months. Nine of these 27 complete responders are still alive and well without evidence of disease, whereas the remaining 18 patients have died of pneumonia, septicemia, immunoblastic lymphoma, or unrelated causes. These 27 patients had a significantly longer median survival (51 mos) than did the 14 patients who had partial or no response (9 mos) (P = 0.0006). Only two of these 14 patients who did not initially achieve a CR are alive (survivals, 66 months and 70 months). There was a trend suggesting that patients who received combination chemotherapy which included prednisone had a slightly longer survival than did the remaining patients (P = 0.087). Lymphocytopenia was evident in a higher proportion of dead patients than in those who remained alive (P = 0.089).

Follow-Up Studies↗
PubMed1983

Natural killer cell activity and spontaneous development of lymphoma. Effects of single and multiple injections of interferon into young and aged C57BL/6 mice.

The capacity of interferon (IFN) given once or repeatedly to augment natural killer (NK) cell activity in the spleen was tested in young and aged C57BL/6 mice. Multiple injections of 10(4) u IFN i.p. into 3-month-old or 12-month-old mice did not augment cytotoxicity mediated by NK cell activity; rather it reduced this activity in relation to the effect obtained with a single injection. When T and B cells or macrophages were removed in vitro, no restoration of NK-cell activity, and therefore no suppressor cells, could be found in this system. In a long-term experiment, B6 mice were chronically injected with 10(4) u of IFN or mock-IFN from 5 months of age until death. No difference in the modification of NK-cell activity was observed after IFN and mock-IFN, regardless of the duration of treatment. However, the capacity of spleen cells to generate cytotoxic T cells after allogeneic stimulation in vitro or in vivo was increased in IFN-treated mice. The median survival time was improved by 7 weeks through treatment with IFN compared to mock-IFN, but was reduced by 9 weeks compared to the survival after treatment with saline. No significant difference in the incidence of spontaneous lymphoma resulted from IFN treatment, but the percentage of tumors observed in mice receiving mock-IFN (68.1%) was higher than that in mice receiving saline (44.1%). These results indicate that, while a stimulating effect resulting in a delay in mortality and in tumor development can be attributed to IFN itself, the contaminating antigenic products are plausibly responsible for the deleterious effect of the total preparation.

Age Factors↗
PubMed1983

The demonstration of terminal deoxynucleotidyl transferase on frozen tissue sections and smears by the avidin-biotin complex (ABC) method.

A method using avidin-biotin complex (ABC) to detect the presence of the enzyme terminal deoxynucleotidyl transferase (TdT) is described and compared with a proven indirect immunofluorescence method. The material studied consisted of: (1) peripheral blood and bone marrow smears from 17 patients with leukemia (ALL, 8; CLL, 3; AML, 6), six normal controls, one T-ALL cell line, and (2) frozen tissue sections from four patients with lymphoblastic lymphoma (LL), two patients with nodular poorly differentiated lymphocytic lymphoma (NLPD), two patients with reactive follicular hyperplasia (RFH) and one calf thymus. The slides from patients with ALL had from 30 to 90% cells with nuclear positively by the ABC technique. Slides from patients with CLL were negative, as were the normal peripheral blood smears. Normal bone marrow smears contained less than 5% positive cells. The T-ALL cell line was 100% positive. The frozen tissue sections from the patients with LL and the calf thymus contained numerous positive cells, while all of the sections from the patients with NLPD and RFH were negative. A good correlation existed between the ABC and the indirect immunofluorescence methods. The ABC method described is both more specific and more sensitive than the previously described techniques in detecting TdT in tissue sections and smear preparations.

Antigens, Surface↗
PubMed1983

Alloimmunization-activated suppressor cells. I: Abrogation of lethal graft-versus-host reaction directed against non-H-2 antigens.

Incompatibility for DBA/2 (D2) minor histocompatibility antigens (MiHA) alone leads to a severe lethal graft-versus-host reaction (GVHR) in adult (D2 X B10.D2)F1 recipients of B10.D2 bone marrow and spleen cells. In this genetic combination, mortality is completely abrogated by preimmunization of the graft donor against unrelated H-2b antigens and specific D2 MiHA a short time before grafting. Protection against GVHR mortality is elicited by immunizing the donors with a single transfusion of incompatible spleen cells or whole blood. Abrogation of GVHR mortality is due mainly to the immunization with specific MiHA, and only to a much lesser degree to the immunization with unrelated H-2 antigens; the protective effect induced by association of these two types of immunization, however, is significantly better than that elicited by either type of immunization alone. It is unlikely that this abrogation of GVHR mortality results from "dilution" of specifically reactive cells; rather, suppressor cells appear to be a contributing factor, because the preimmunization activates, in the donor spleen, suppressor cells capable of decreasing the severity of the GVHR developed against MiHA by normal cells. Histopathologic observations indicated that the lesions induced in various tissues after grafting of preimmunized donor cells were considerably less severe than those induced by grafting of normal donor cells. However, simultaneous immunization with specific MiHA and unrelated H-2 antigens may also exacerbate the GVHR, depending upon the conditions used for preimmunization; abrogation of GVHR mortality is favored by a single immunization with unrelated H-2b antigens and specific MiHA administered simultaneously a short time before grafting, whereas an acceleration of GVHR mortality is favored by long intervals and multiple immunizations. It is suggested that, depending upon the conditions used for the preimmunization, the allogeneic effect produced by stimulation with unrelated H-2 antigens may augment the response to MiHA or it may enhance the activation of suppressor cells that contribute to the abrogation of GVHR mortality.

Animals↗
PubMed1983

Coincidence of B-cell chronic lymphocytic leukemia and cutaneous T-cell lymphoma (mycosis fungoides): immunologic characterization by monoclonal antibodies.

Although rare cases of chronic lymphocytic leukemia (CLL) of the T-cell type have been reported, CLL is more commonly found to be a neoplastic lymphoproliferative disease of B-cell origin. In this article, we describe a patient with long-standing CLL that was immunologically shown to be of the B-cell type, who, during the course of his disease, developed cutaneous T-cell lymphoma (CTCL), which was shown to be of the helper/inducer subtype. The neoplastic lymphoid cells in the skin infiltrate differed morphologically and immunologically from those in the peripheral blood. The occurrence of CTCL during this patient's clinical course represents a second neoplasm arising from a different cell line, rather than a tissue manifestation of the patient's CLL. To our knowledge, this is the first report in which the occurrence of CTCL is documented in a patient with immunologically known B-cell CLL. In addition to establishing the presence of B-cell CLL and CTCL of the helper/inducer T-cell type in the same patient, this case report demonstrates the usefulness and necessity of evaluating lymphoproliferative disorders by means of a multidisciplinary approach.

Aged↗
PubMed1983

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↗
PubMed1982

[Treatment of acute myeloid leukemia with a protocol combining intensive induction chemotherapy, early consolidation treatment, splenectomy and long-term maintenance chemotherapy. Preliminary study].

Twenty-seven patients aged from 10 to 60 years (mean 34.4 +/- 13 years) in the first perceptible phase of acute myeloid leukemia were subjected to intensive induction chemotherapy consisting of adriamycin (ADM), vincristin (VCR) and cytosine arabinoside (ARA-C). Twenty-four patients (89%) attained complete remission (CR) after 1 to 3 cycles and were then given an early consolidation treatment with one of the previous cycles. This was followed by long-term continuous maintenance chemotherapy with 6-mercaptopurine (6-MP) and methotrexate (MTX) alternatively and 3-monthly reinforcement courses of donaurubicin (DNR) and VCR. Twenty of these 24 patients were splenectomized soon after the consolidation treatment. None of the spleens were enlarged, and histological sections of the spleens, liver biopsies and mesenteric lymph-nodes stained with routine dyes and by the naphthol AS-D chloroacetate esterase method revealed mature granulocytes but no demonstrable leukaemic cells. In the group of splenectomized patients, the probabilities of staying in complete remission at 27 and 44 months were 70 +/- 12.6% and 52 +/- 18.5% respectively, and the probabilities of remaining alive at 32 and 55 months were 79 +/- 11% and 57 +/- 19% respectively. Age over 40 and evidence of extramedullary infiltration at presentation appeared to leave little hope of disease-free survival. The rationale for the present therapeutic study is discussed.

Adolescent↗
PubMed1982

Flow cytometry in the diagnosis and classification of malignant lymphoma and leukemia.

DNA content and light scatter were measured by flow cytometry (FCM) in 103 patients including 43 patients with non-Hodgkin's lymphoma (NHL), eight patients with Hodgkin's disease (HD), 17 patients with acute lymphoblastic leukemia (ALL), ten patients with acute nonlymphocytic leukemia (ANLL), and 25 patients with chronic lymphoid leukemias. Controls consisted of 42 nonneoplastic specimens obtained from lymph nodes, spleen, bone marrow, and peripheral blood. Each specimen was analyzed after staining with a hypotonic solution of propidium iodide using nuclei isolated from chicken erythrocytes as an internal standard. The DNA content and light scatter of the human populations was expressed as a ratio between the DNA content (or light scatter) of the human G0--G1 cells and that of the chicken erythrocytes nuclei. The mean DNA ratio for the 42 nonneoplastic samples was 2.58 +/- 0.045 (SD). In these samples the DNA coefficient of variation of the human G0--G1 peak ranged from 1.48--3.28% (mean, 2.33 +/- 0.54%). The FCM data in the NHL was compared to morphologic diagnoses made according to the "working formulation of NHL for clinical usage" recently proposed by a panel of international experts. Eight of 17 (47%) low grade NHL, one of two (50%) mycosis fungoides, ten of 14 (71%) intermediate grade NHL, nine of ten (90%) high grade NHL, nine of 17 (53%) ALL, three of ten (30%) ANLL, and seven of 25 (28%) chronic lymphoid leukemias had abnormal DNA ratios indicative of aneuploidy. In addition, several cases had normal DNA ratios but G0--G1 coefficients of variation outside of the normal range. All cases of HD had normal DNA values except one case with a small percentage of near tetraploid cells. The mean percentage of cells with S-phase DNA content for the low grade NHL (2.2 +/- 0.8%) was significantly lower than that of the intermediate grade NHL (12.1 +/- 4.9%; P less than 0.0001). The mean S-phase value for the intermediate grade NHL was significantly lower than that of the high grade NHL (22.6 +/- 11.1%; P less than 0.001). The three prognostic categories of NHL designated by the new formulation were clearly distinguishable by the FCM data. Light scatter was not particularly useful for distinguishing nonneoplastic from neoplastic populations. The mean light scatter coefficient of variation of the ALL (15.2%) was significantly lower than that of ANLL (20.5%), however (P less than 0.04).

Bone Marrow↗
PubMed1982

Noncutaneous peripheral T-cell lymphoma histologically resembling mycosis fungoides.

We have studied the clinical and pathologic features of three patients with a distinctive non-Hodgkin's lymphoma of the diffuse mixed cell type. The tumors were characterized by a mixture of lymphoid cells of widely varying size and degree of nuclear transformation. A distinctive feature of the neoplastic cells was the presence of cerebriform nuclear contours identical to those seen in mycosis fungoides. Immunologic studies performed on lymph nodes from two patients revealed that the neoplastic cells were T-cells. Characteristic clinical features of the patients were an advanced stage of disease at diagnosis, absence of skin lesions, presence of lung involvement, poor response to aggressive chemotherapy, and a short survival time (9-13 months). The features described closely resemble those of the pleomorphic variant of Japanese adult T-cell leukemia-lymphoma.

Adult↗
PubMed1982

Mantle-zone lymphoma: a follicular variant of intermediate lymphocytic lymphoma.

A clinicopathologic analysis of 12 cases of a morphologically distinctive non-Hodgkin's malignant lymphoma which appeared to arise from the mantle zones of secondary lymphoid follicles is presented. In lymph node and spleen sections, atypical small lymphoid cells with slightly irregular and indented nuclear contours proliferated as wide mantles around non-neoplastic-appearing germinal centers. Surface marker analysis performed on lymph nodes revealed a monoclonal B-cell proliferation in two cases. Clinically, the patients usually had advanced disease (Stage III or IV) associated with splenomegaly. This lymphoma appears to be relatively low-grade, since nine of 12 patients are alive with a median follow-up period of 28.5 months. We believe that thie "mantle-zone lymphoma" represents a nodular or follicular variant of intermediate lymphocytic lymphoma.

Adult↗
PubMed1982

Acid phosphatase and alpha-naphthyl acetate esterase in neoplastic and non-neoplastic lymphocytes. A statistical analysis.

Acid phosphatase and alpha-naphthyl acetate esterase reaction patterns were evaluated in lymphocytes from patients with a variety of neoplastic and non-neoplastic conditions: leukemia, 59; NHL, 53; and reactive follicular hyperplasia, 23. Fifteen individuals with normal peripheral blood were also studied. For both enzymes, statistical analysis showed a strong correlation between a globular reaction pattern and T lymphocytic origin in both non-neoplastic lymph nodes and normal peripheral blood specimens (P less than 0.0001). A similarly strong correlation was found between a granular acid phosphatase pattern and T lymphocytic origin in cell isolated from non-neoplastic lymph nodes (P less than 0.0001) but not in those obtained from normal peripheral blood where this pattern was observed with equal frequency in B, T, and "null" lymphocytes (P = 0.415). A granular alpha-naphthyl acetate esterase pattern was correlated with non-T lymphocytes from normal peripheral blood (P less than 0.0001), but was observed with equal frequency in B, T, and "null" lymphocytes fron non-neoplastic lymph nodes (P = 0.76). In the eight T cell neoplasias studied, a globular pattern was evident in the majority of cells for both enzymes. In the majority of the B cell neoplasias, however, a granular pattern was observed for both enzymes.

Acid Phosphatase↗