Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Utilizing a panel of monoclonal and polyclonal antibodies, routine paraffin sections in 68 cases of Hodgkin's disease were examined for the presence of immunoreactivity in Reed-Sternberg (R-S) and related cells by the avidin-biotin-peroxidase complex (ABC) technique. In 14 cases of lymphocyte-predominant Hodgkin's disease (LPHD), R-S cells and the polyploid lymphocytic and histiocytic (L & H) variants of R-S cells were immunoreactive for L26 and alpha 1-antitrypsin (alpha 1-AT) in 9 (64%) and 6 (43%), respectively, whereas the remaining antibodies were negative or rarely positive against L & H variants of R-S cells. R-S cells in 24 cases of mixed cellularity Hodgkin's disease (MCHD) were positive with alpha 1-AT in 63% of cases, positive with LN3 in 71% of cases and positive for BerH2 in 92% of cases. The lacunar cell type of R-S cells in 19 cases of nodular sclerosing Hodgkin's disease (NSHD) were reactive for alpha 1-AT in all cases, BerH2 in 18 cases (95%), and LN3 in 17 cases (89%). Pleomorphic variant of R-S cells in 11 cases of lymphocyte depleted Hodgkin's disease (LDHD) showed reactivity with alpha 1-AT in 9 cases (82%), BerH2 in 6 cases (55%), and LN3 in 9 cases (82%). The incidence of L26 in R-S cells was higher in LPHD than in other three subtypes, whereas the immunohistochemical finding of alpha 1-AT had reverse relevance to the result of L26. The incidence of BerH2 in MCHD and NSHD was higher than that of this antibody in the whole of Hodgkin's disease. R-S cells in NSHD and LDHD were highly positive to LN3, and detection rate of these two types was higher than that in the whole of Hodgkin's disease. No cases showed immunoreactivity with anti-T-cell antibodies (CD3, UCHL1 and DFT1), a marker for natural killer cell (Leu7), and a marker for interdigitating reticulum cell (S-100 protein). These results suggest that correlation between predominant staining pattern and R-S cells and variants thereof in each histological subtype of Hodgkin's disease are as follows: LPHD shows L26+, alpha 1-AT-, BerH2-; MCHD and NSHD show L26-, alpha 1-AT+, BerH2+; and LDHD shows L26-, alpha 1-AT+, BerH2+ or L26+, alpha 1-AT+, BerH2-.
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PMID:Immunophenotypes of Reed-Sternberg cells and their variants: a study of 68 cases of Hodgkin's disease. 896 16

Anaplastic large cell lymphoma (ALCL) is composed of large, frequently bizarre, cells of T- or null-cell phenotype that show a preferential sinusoidal growth pattern and consistent CD30 positivity. Whether these tumors represent a single entity or several, and what the exact cell origin, is controversial. Recently, granzyme B, a cytotoxic granule component, was reported in a small percentage of ALCL, suggesting that some cases may originate from cytotoxic lymphocytes. To further investigate this possibility, we performed an immunohistochemical study of 33 ALCLs of T- and null-cell type, using monoclonal antibodies to cytotoxic cell-associated antigens, including CD8, CD56, CD57, and the cytotoxic granular proteins perforin and TIA-1. In addition, CD4 expression was also evaluated. ALCL cases included 27 classical systemic forms and variants, 3 primary cutaneous (PC) forms, and 3 acquired immunodeficiency syndrome-associated forms. Cytotoxic antigen expression was also studied in 51 cases of Hodgkin's disease (HD) and 17 large B-cell lymphomas (LBCLs) with anaplastic cytomorphology and/ or CD30 positivity. We found that 76% of ALCLs, representing all subtypes except the PC forms, expressed either TIA-1, perforin, or both proteins. Expression of TIA-1 and perforin were highly correlated (P < .001). On the basis of their immunophenotypic profiles, several subtypes of cytotoxic antigen positive and negative ALCL could be recognized. Fifty-five percent of ALCLs (18 of 33) displayed an immunophenotypic profile consistent with cytotoxic T cells. Six cases expressed cytotoxic granular proteins in the absence of lineage specific markers, and one case expressed both T-cell- and natural killer cell-like markers. These 7 cases (21%) were placed into a phenotypic category of cytotoxic lymphocytes of unspecified subtype. Twenty-four percent (8 cases) of ALCLs were cytotoxic granule protein negative. All but one of these displayed a T-cell phenotype. Cytotoxic granule protein expression did not correlate with the presence of the NPM-ALK fusion transcript. Only 10% of the 51 HD cases were found to be TIA-1+, and none expressed perforin. Cytotoxic antigen expression was absent in LBCL. The expression of cytotoxic granule proteins in the majority of ALCL implies a cytotoxic lymphocyte phenotype and suggests that most cases originate from lymphocytes with cytotoxic potential. Furthermore, the demonstration of cytotoxic cell related proteins may be a useful addition to the current panel of antibodies used to distinguish ALCL, HD, and anaplastic LBCL.
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PMID:Cytotoxic cell antigen expression in anaplastic large cell lymphomas of T- and null-cell type and Hodgkin's disease: evidence for distinct cellular origin. 902 30

Fifteen patients with refractory Hodgkin's disease were treated in a phase I/II trial with the natural killer (NK)-cell-activating bispecific monoclonal antibody HRS-3/A9, which is directed against the Fc(gamma)-receptor III (CD16 antigen) and the Hodgkin's-associated CD30 antigen, respectively. Median counts of NK cells and of all lymphocyte subsets were considerably decreased in the patients before therapy. HRS-3/A9 was administered 4 times every 3 to 4 days, starting with 1 mg/m2. The treatment was well tolerated, and the maximum tolerated dose was not reached at 64 mg/m2, the highest dose administered because of the limited amounts of HRS-3/A9 available. Side effects were rare and consisted of fever, pain in involved lymph nodes, and a maculopapulous rash. A total of 9 patients developed human antimouse Ig antibodies, and 4 patients developed an allergic reaction after attempted retreatment. A total of 1 complete and 1 partial remission (lasting 6 and 3 months, respectively) [corrected], 3 minor responses (1 to 11+ months), and 1 mixed response were achieved. There was no clear-cut dose-side effect or dose-response correlation. Our results encourage further clinical trials with this novel immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the murine bispecific antibodies.
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PMID:Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody. 905 26

A group of 15 patients with refractory Hodgkin's disease were treated in a phase I/II trial with the natural-killer (NK)-cell-activating bispecific monoclonal antibody HRS-3/A9, which is directed against the Fc gamma receptor III (CD16 antigen) and the Hodgkin's associated CD30 antigen. The antibody was given four times every 3-4 days, starting with 1 mg/m2. The treatment was well tolerated and the maximum tolerated dose was not reached at 64 mg/m2. Side-effects were rare and consisted of fever, pain in involved lymph nodes and a maculopapulous rash. Nine patients developed human anti-(mouse immunoglobulin) antibodies. One complete and one partial remission (lasting 5 and 3 months, respectively), three minor responses (1 to 11+ months), and one mixed response were achieved. There was no clear-cut dose side-effect or dose/response correlation. NK cell activity increased in most of the patients treated with 4 mg/m2 or higher doses but lasted no longer than 6 weeks after therapy. Our results encourage further clinical trials with this novel immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the antibody to allow retreatment of responding patients.
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PMID:Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody. 943 69

Relapse after high-dose chemotherapy supported by peripheral blood stem cell transplantation (HDC-PBSCT) is the main cause of therapeutic failure in patients with lymphoma and breast cancer. Adoptive immunotherapy with activated natural killer (A-NK) cells and interleukin 2 might eliminate surviving residual tumor without adding to toxicity. Eleven patients with relapsed lymphoma and one with metastatic breast cancer were entered on a pilot clinical trial of HDC-PBSCT followed on day 2 after transplant by infusion of cultured autologous A-NK cells. Simultaneously, recombinant human interleukin 2 (rhIL-2) was initiated as a 4-day continuous i.v. infusion at 2 x 10(6) IU/m2/day, referred to as high-dose rhIL-2. Therapy with high-dose rhIL-2 was followed by a 90-day continuous i. v. infusion at 3 x 10(5) IU/m2/day, referred to as low-dose rhIL-2. All patients engrafted and nine completed treatment. Posttransplant days to a neutrophil count of 500/microliter and to a platelet count of 50,000/microliter were similar to comparable patients treated with HDC-PBSCT alone. Generation of A-NK cells for therapy was feasible in all patients except the three patients with Hodgkin's disease, whose cells did not proliferate in culture. Overall toxicity associated with early posttransplant transfer of A-NK cells and interleukin 2 did not differ from that observed with peripheral blood stem cell transplantation alone in comparable patients. There was early amplification of natural killer cell activity in the peripheral blood of four patients that appeared to result from the transfused A-NK cells. Adoptive transfer of A-NK cells and rhIL-2 during the pancytopenic phase after HDC-PBSCT was feasible and well tolerated, did not adversely affect engraftment, and resulted in amplified natural killer activity in the peripheral blood during the immediate posttransplantation period.
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PMID:Autologous peripheral blood stem cell transplantation and adoptive immunotherapy with activated natural killer cells in the immediate posttransplant period. 981 22

Fifteen patients with refractory Hodgkin's disease were treated in a phase I/II dose escalation trial with the NK-cell activating bispecific monoclonal antibody HRS-3/A9 which is directed against the Fcgamma-receptor III (CD16 antigen) and the Hodgkin's associated CD30 antigen, respectively. HRS-3/A9 was given four times every 3-4 days starting with 1 mg/m2. The treatment was well tolerated and the maximum tolerated dose was not reached at 64 mg/m2, the highest dose given due to limited amounts of HRS-3/A9 available. Mild to moderate side effects occured in six patients and consisted of fever, pain in involved lymph nodes, and a maculopapulous rash. Median counts of NK-cells and of all lymphocyte subsets were considerably decreased in the patients before therapy and showed no consistent changes under therapy. Eight patients developed human anti-mouse immunoglobulin antibodies, and five patients showed an allergic reaction after attempted retreatment. One complete and one partial remission (lasting 6 and 3 months, respectively), three minor responses (lasting 1 to 15 months), two disease stabilizations (for 2 and 17 months, respectively), and one mixed response were achieved. There was no clearcut dose-side effect or dose-response correlation. Our results encourage further clinical trials with this novel immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the murine bispecific antibodies.
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PMID:Anti-CD16/CD30 bispecific antibodies as possible treatment for refractory Hodgkin's disease. 986 3

It has been known for 30 years that Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, is the etiologic agent of acute infectious mononucleosis and is closely associated with the genesis of Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma. Recent studies have demonstrated that EBV is also implicated in a variety of other diseases, such as EBV-associated hemophagocytic syndrome, chronic active EBV infection, T-cell lymphoma, natural killer cell leukemia/lymphoma, lymphoproliferative diseases in immunocompromised hosts, Hodgkin's disease, pyothorax-associated B-cell lymphoma, smooth-muscle tumors, and gastric carcinoma. Thus, the virus continues to attract worldwide attention, and it is now appropriate for a reappraisal of the relation between EBV and human diseases. This review summarizes the recent progress in research on EBV and the clinical findings of EBV-associated diseases and provides a basis for the development of new therapeutic strategies.
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PMID:Epstein-Barr virus--associated diseases in humans. 1074 21

We have used severe combined immunodeficiency (SCID) (c.b.-17, ICR/SCID) mice to develop xenotransplantation (XT) models for human intermediate-and-low-grade non-Hodgkin's lymphomas (NHL). In the past, SCID mice have provided a variety of useful XT models for human hematopoietic neoplasms that primarily involve the acute leukemias and some nonhematopoietic tumors, but only rare reports exist on use of the SCID mouse model in the study of primary tumor cells from NHL. Intermediate-grade and low-grade NHL are the most common lymphomas seen in adults. There is no effective therapy for those types of NHL, and they have not been established in an animal model to date. The lack of an animal model has hampered studies that can evaluate the disease process in vivo as well as the definition of therapeutic parameters involved in treatment. We report in this study that primary patient samples of NHL ( intermediate grade and low grade) have been successfully established in SCID mice after XT. NHL include intermediate-grade (mantle cell lymphoma) and low-grade (eg, small lymphocytic lymphoma/chronic lymphocytic lymphoma and marginal zone lymphoma) forms. Studies have been directed toward creating appropriate conditions for the optimal grafting of these NHL in SCID mice so that the disease process in humans could be accurately simulated. These studies indicate that development of XT-human lymphoma cells in SCID mice appear to be linked to their biologic and/or clinical behavior, transplanted lymphoma cell number, and age, as well as to the natural killer cell status of the SCID mouse recipients. Evidence has also shown that NHL cells can exhibit homing or trafficking patterns in SCID recipients that resemble those observed in patients with gastrointestinal lymphomatous involvement (particularly that of mantle cell lymphoma). Our studies also indicate that artefactual influences, such as the outgrowth of Epstein-Barr virus-associated lymphoblastoid lesions, are rare occurrences in the human NHL/SCID models that we have established.
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PMID:Development of intermediate-grade (mantle cell) and low-grade (small lymphocytic and marginal zone) human non-Hodgkin's lymphomas xenotransplanted in severe combined immunodeficiency mouse models. 1078 Jun 72

Fifteen patients with refractory Hodgkin's disease were treated in a dose-escalation trial with the bispecific monoclonal antibody (bi-mAb) HRS-3/A9, which is directed against the Fc gamma receptor III (CD16 antigen) and the Hodgkin's-associated CD30 antigen. Treatment consisted of four cycles of four bi-mAb infusions given over 1 h every 3-4 days at different dose levels ranging from 1 mg/m2 to 64 mg/m2. Measurable serum levels (above 0.1 microgram/ml) of circulating bi-mAb could be detected in patients treated with doses above 4 mg/m2, reaching peak levels of 9.5 micrograms/ml immediately after the end of antibody infusion on the highest dose level. Bi-mAb elimination corresponded to second-order kinetics with a terminal half-life time (t1/2, beta) of 28-32 h. Bi-mAb treatment induced the occurrence of human anti-(mouse Ig) antibodies (HAMA) in 6 out of 13 patients initially testing negative. All 6 patients not only developed anti-isotypic anti-(mouse Ig) but also anti-idiotypic and anti-anti-idiotypic antibodies. While no consistent changes of peripheral blood cell counts, or of any lymphocyte subpopulation including natural killer (NK) cells, has been observed, 4 out of 6 evaluable patients treated with doses of at least 4 mg/m2 showed an increase of NK cell activity within 2 weeks after treatment, which lasted for a maximum of 12 weeks. Circulating amounts of soluble CD30 antigen could be detected in the serum of 6 patients. However, like the results and time courses of all the other immunological parameters evaluated, this was not predictive for treatment outcome.
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PMID:Initiation of humoral and cellular immune responses in patients with refractory Hodgkin's disease by treatment with an anti-CD16/CD30 bispecific antibody. 1088 97

For the treatment of Hodgkin lymphoma, bispecific monoclonal antibodies (bi-mAbs) were established which recognize the Hodgkin-associated CD30 antigen with one arm and the CD3 or CD28 antigen on T lymphocytes or the CD16 antigen on natural killer (NK) cells with the second arm. The NK cell-activating alpha-CD16/CD30 antibody was able to retarget human NK cells toward CD30- target cells and induce their lysis. Sixty percent of Hodgkin tumor-bearing severe combined immunodeficient mice responded to a combined treatment with bi-mAb and human NK cells, leading to a final cure rate of 20%. T cell-activating bi-mAbs were more effective, resulting in the cure of all mice treated. The in vivo administration of both alpha-CD3/CD30 and alpha-CD28/CD30 antibodies resulted in the specific activation of resting human T cells infiltrating the CD30+ Hodgkin tumors. Tumor-infiltrating lymphocytes in the group of mice treated with both T cell-activating bi-mAbs expressed high levels of cytokines and cytotoxic molecules such as perforin and the cytotoxic serine esterases granzyme A and B. More importantly, activated T cells did not home to CD30 tissue and did not enter the circulation. Encouraged by these preclinical data, 15 patients with treatment-refractory Hodgkin lymphoma were included in a phase I/II dose-escalation study and treated four times every 3 or 4 days with increasing doses of the alpha-CD16/CD30 bi-mAb ranging from 1 mg/m2 to 128 mg/m2. No dose-limiting toxicity occurred even at the highest doses. Of these 15 patients, one had a complete response, one a partial response, three a mixed response, two stable disease, and eight patients had progressive disease. Treatment with immunological effector cell-recruiting bi-mAbs is a promising new approach to the treatment of Hodgkin disease refractory to standard therapy.
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PMID:Immune recruitment by bispecific antibodies for the treatment of Hodgkin disease. 1095 Jan 45


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