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)

Fludarabine, an analogue of arabinosyl adenine, used since 1986 proved to be a new agent effective particularly in chronic lymphocytic leukaemia. About 35% of patients refractory to previous cytostatic treatment and about 75% of untreated patients obtained complete remissions. Nearly 90% of them revealed no minimal residual disease and no relapse during 2 years of observation. Worse response was found in patients with other low grade non-Hodgkin's lymphomas.
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PMID:[Fludarabine in the treatment of chronic lymphocytic leukemia and other lymphoproliferative disorders]. 852 71

Despite a common origin from mature lymphoid cells, non-Hodgkin lymphomas (NHL) represent a surprisingly heterogeneous group of lymphoid malignancies whose classification is continuously being remodeled. The most recent proposal, the Revised European-American classification, introduces pathogenetic features among the classification criteria. In this respect, knowledge of the molecular pathogenesis of NHL, which is based upon genetic lesions leading to activation of proto-oncogenes (e.g. BCL-1, BCL-2, BCL-6, c-MYC) or disruption of tumor suppressor genes (e.g. p53), is becoming increasingly relevant for the clinician. These lesions combine into multiple molecular pathways which are selectively associated with distinct NHL types. Thus, for example, rearrangements of BCL-1, BCL-2, BCL-6, and c-MYC ar the genetic hallmarks of mantle cell, follicular, diffuse large cell, and Burkitt's lymphoma, respectively. Overall, from clinical perspective, NHL genetic lesions serve three purposes: a) they assist and complement histologic diagnosis; b) they provide a molecular marker with prognostic relevance; c) they allow evaluation of minimal residual disease through highly specific and highly sensitive technologies.
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PMID:Molecular pathogenesis of non-Hodgkin lymphoma: a clinical perspective. 856 91

Recent developments in the past decade such as the advent of recombinant DNA technology, discovery of immunoglobulin gene rearrangements and recognition of the association of specific cytogenetic abnormalities with certain lymphoma subtypes have led to a better understanding of lymphoproliferative disorders. As the vast majority (80%) of non-Hodgkin's lymphomas are of the B-cell subtype, this is the focus of the article. By definition, tumours are clonal proliferations of a single, abnormal cell. Hence, B-lymphoid malignancy represents a monoclonal proliferation of B-lymphocytes. Immunophenotyping may be used to establish clonality for B-cell proliferations but may fail in some cases where surface antigens are not expressed or if the malignant clone is obscured by reactive lymphoid cells. Molecular methods are far more sensitive and do not require gene expression for detection, hence they are increasingly used for clonality assessment. Either Southern blot analysis or polymerase chain reaction can be used for this purpose. These techniques can also be used to detect specific cytogenetic abnormalities associated with certain lymphomas such as the bcl-2 gene rearrangement and follicular lymphoma. This is useful in the subtyping of lymphomas in cases where morphologic diagnosis is uncertain. Thus, with growing awareness and availability of molecular DNA analysis, these techniques are increasingly employed for the diagnosis of lymphomas as well as for the detection of minimal residual disease.
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PMID:Molecular genetics of B-cell lymphomas: a review. 877 44

Anaplastic large cell lymphoma (ALCL) is a distinct clinicopathologic variant of intermediate grade non-Hodgkin's lymphomas (NHL) composed of large pleomorphic cells that usually express the CD30 antigen and interleukin (IL)-2 receptors, and is characterized by frequent cutaneous and extranodal involvement. With variable frequency ALCL bear the t(2;5)(p23;q35) chromosomal translocation that fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a novel protein kinase gene, Anaplastic Lymphoma Kinase (ALK), on chromosome 2p23. We determined the frequency of this translocation with a novel DNA polymerase chain reaction (PCR) technique using 0.5 microgram of genomic DNA, 5'-primers derived from the NPM gene and 3'-primers derived from the ALK gene and hybridization with internal probes. The presence of amplifiable DNA in the samples was tested with the inclusion in the PCR reaction of oligonucleotide primers designed to amplify a 3016-bp fragment from the beta-globin locus. NMP-ALK fusion amplicons were detected using DNA isolated either from all three ALCL cell lines tested, or from all four primary ALCL tumors known to contain the t(2;5)(p23;q35) translocation. Nested amplicons were detected by hybridization in 100% of specimens diluted 10(4)-fold and in 20% of those diluted 10(5)-fold. We subsequently examined archival genomic DNA from 20 patients with ALCL, 39 with diffuse large cell, 2 with mantle cell, 20 with peripheral T cell, 13 with low-grade NHL, 31 with Hodgkin's disease (HD), and 6 with lymphomatoid papulosis. Fusion of the NPM and ALK genes was detected in three of 18 patients with ALCL who had amplifiable DNA (17%, 95% confidence intervals 4% to 41%), but not in any patients with other NHL, HD, or lymphomatoid papulosis. The amplicon sizes were different in all cell lines and patients reflecting unique genomic DNA breakpoints. We conclude that with genomic DNA-PCR the rearrangement of the NPM and ALK loci is restricted to patients with ALCL. Further studies are needed to determine the prognostic significance of the NPM-ALK rearrangement, to determine whether its detection can aid in the differential diagnosis between ALCL. Hodgkin's disease, and lymphomatoid papulosis, and to establish the usefulness of the genomic DNA PCR in the monitoring of minimal residual disease in those patients whose tumors bear the t(2;5).
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PMID:Amplification of genomic DNA demonstrates the presence of the t(2;5) (p23;q35) in anaplastic large cell lymphoma, but not in other non-Hodgkin's lymphomas, Hodgkin's disease, or lymphomatoid papulosis. 926 95

The success of radiation therapy (XRT) in the management of early-stage Hodgkin's disease (HD) has led to its use in a variety of programs for the management of advanced disease. This article includes discussion of these roles of radiation in advanced disease: 1) use of XRT as an adjuvant after chemotherapy; 2) use of XRT to convert patients who are 'partial responders' (PRs) after chemotherapy to 'complete responders' (CRs); 3) use of XRT as an integrated component of combined modality therapy; 4) use of XRT as a 'salvage' treatment after failure of primary chemotherapy; and 5) incorporation of XRT into programs of high-dose therapy with autologous stem cell (or marrow) rescue. 1) Randomized trials of adjuvant XRT after completion of chemotherapy in advanced disease have been conducted by the Southwest Oncology Group (SWOG), German HD Study Group, and the European Organization for the Research and Treatment of Cancer/Group Pierre Marie Curie (EORTC/ GPMC). The SWOG study shows improvements in disease-free survival, but not overall survival with the addition of XRT. The German Study Group trial was negative, but the number of patients reported in the abstract of the trial was too small to be conclusive. The EORTC/GPMC study has not been reported. 2) Both the SWOG and EORTC/GPMC trials treated "PRs' with XRT. Results in both show conversion to CR in > 80% of patients. Conversion to CR was most likely for patients with just minimal residual disease after chemotherapy. 3) Planned XRT in advanced disease (especially bulky sites) may permit reduction in chemotherapy doses (e.g., the Stanford V chemotherapy program) and maintain excellent outcome (freedom-from-progression > 80%). Reduction in total doses of chemotherapy as well as dose and extent of radiation should limit potential long-term toxicity. 4) Very selected patients with asymptomatic limited nodal relapse may be "salvaged' with XRT, but published reports include only a small number of patients and this should not be considered a standard approach. 5) XRT may be used as total body, total lymphoid, or local field in high-dose therapy programs. Since HD at relapse is still often a local-regional problem, local field irradiation is probably the most rational approach to use in this setting. Recent Stanford data show an improvement in outcome with the inclusion of local field treatment in these patients.
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PMID:Hodgkin's disease--the role of radiation therapy in advanced disease. 883 19

Molecular analysis of leukemias has been demonstrated to be useful for understanding the pathogenesis of leukemias or for detection of minimal residual disease. We present studies on the application of molecular diagnosis in malignant lymphomas. Although follicular lymphomas, a part of non-Hodgkin's lymphomas (NHL), often involve a t (14;18) chromosomal translocation, it is difficult to detect the translocation in some cases by conventional chromosomal analysis. We showed the usefulness of amplification of mbr/JH and mcr/JH junction by PCR to detect the translocation. The PCR products of mbr/JH junction were positive in 7 out of 8 cases of follicular lymphomas some of which were negative in tests on the translocation in the malignant cells. However, most NHL do not have cytogenetically specific translocations, indicating the necessity for another way to diagnose the malignant lymphomas. We used IgH gene probes as tumor specific markers in B-cell lineage malignant lymphomas. We determined DNA sequences for complementarity-determining region 3 (CDR3) of IgH in the malignant clone of each case. Then, we prepared a unique 5' primer for PCR or an oligonucleotide probe for detecting the clone-specific VH gene in each case, amplified the DNA by PCR and finally tried to detect minimal disease in bone marrow or peripheral blood, which brought into sequential detection of minimal residual disease in NHL. Thus, molecular diagnosis in hematopoietic malignancy will be more important in diagnosis, staging, and clinical management of patients with NHL.
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PMID:[Molecular diagnosis in hematopoietic malignancy]. 885 Nov 93

We investigated 23 patients for their chimerism status who underwent allogeneic transplantation using peripheral blood progenitor cells (PBPCT) for chronic myelogenous leukemia (CML) (n = 14), acute myelogenous leukemia (AML) (n = 5), acute lymphoblastic leukemia (n = 1), myelodysplasia (MDS) (n = 1), and Hodgkin's disease (HD) (n = 2). These data were compared with those of patients after allogeneic BMT after matching them for disease and disease stage, sex of donor and recipient, GVHD prophylaxis, conditioning therapy and degree of HLA disparity. Patients were studied monthly up to 16 months post-transplant. In 11 of 23 (48%) patients who were transplanted with PBPCs and in 18 of 23 (78%) patients after BMT a mixed chimerism was detected at 1 month post-transplant. After 3 months, six of 21 (29%) evaluable patients after PBPCT remained mixed chimeric as opposed to 12 of 21 (57%) patients after BMT. We also assessed minimal residual disease using detection of the chimeric BCR/ABL transcripts by PCR of CML patients in this study. In four of 14 (29%) patients who underwent PBPCT, the BCR/ABL chimeric transcript was detected, while after BMT eight of 14 (57%) CML patients remained BCR/ABL positive. In two of these BMT patients, a cytogenetic relapse developed subsequently, and one other patient suffered a hematological relapse, whereas one of the CML patients relapsed after PBPCT. The present data may indicate that after PBPCT the incidence of leukemic relapse is similar or even lower than after BMT.
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PMID:Molecular studies of chimerism and minimal residual disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation. 886 52

We investigated the in vitro antitumor activity of monocytes derived from autologous bone marrow transplanted (ABMT) patients treated in vivo with granulocyte-macrophage colony-stimulating factor (GM-CSF). Thirty-four patients (17 female, 17 male), median age 42 (range 3-57) years, were enrolled in the study. Fourteen patients were diagnosed with non-Hodgkin's lymphoma (NHL), eight with Hodgkin's disease (HD), nine with breast cancer and three with neuroblastoma. Six patients who did not receive GM-CSF post-ABMT served as controls. We assessed cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), expression of the activation antigen CD16, and cytokine production by an enriched population of monocytes (> 90% CD+14) pre-, during and post-GM-CSF administration. Within the group of patients receiving treatment, ADCC was significantly higher during in vivo GM-CSF administration than post-therapy (P < 0.05) and in 50% of these patients, ADCC increased during in vivo GM-CSF administration over pretreatment values. In addition, in vivo GM-CSF administration caused the monocytes to secrete elevated levels of tumor necrosis factor-alpha (TNF-alpha) and GM-CSF (P < 0.05). We conclude that GM-CSF augments monocyte-mediated cytotoxicity post-ABMT, and therefore may have a role in controlling minimal residual disease post-transplant.
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PMID:Granulocyte-macrophage colony-stimulating factor dependent monocyte-mediated cytotoxicity post-autologous bone marrow transplantation. 891 16

The success of autologous stem cell transplantation (ASCT) for hematologic malignancy is limited largely by a high relapse rate. It is postulated that IL-2 administered after ASCT may eliminate minimal residual disease and thereby reduce relapses. A phase I/II study was performed to identify a regimen of IL-2 (Chiron) that could be given early after ASCT in phase III trials. In the phase I study, beginning a median of 46 days after ASCT for hematologic malignancy, cohorts of three to four patients received escalating doses of 'induction' IL-2 of 9, 10, or 12 x 10(6) IU/m2/day for 4 or 5 days by continuous i.v. infusion (CIV), followed by a 4-day rest period, and then 1.6 x 10(6) IU/m2/day of maintenance IL-2 by CIV for 10 days. The maximum tolerated dose (MTD) of induction IL-2 was 9 x 10(6) IU/m2/day x 4. In the phase II study, 52 patients received the MTD. Eighty percent of patients completed induction IL-2. Most patients exhibited some degree of capillary leak. One patient died of CMV pneumonia and one died of ARDS. Maintenance IL-2 was well tolerated. In the phase I/II study, 16 of 31 patients with non-Hodgkin lymphoma (NHL), 3/8 with Hodgkin disease (HD), 4/17 with AML, and 4/5 with ALL remain in CR. Two of six multiple myeloma (MM) patients remain in PR. Although the regimen of IL-2 identified had significant side-effects in some patients, it was well tolerated in the majority of patients. Phase III prospectively randomized clinical trials are in progress to determine if this IL-2 regimen will decrease the relapse rate after ASCT for AML and NHL.
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PMID:Interleukin-2 after autologous stem cell transplantation for hematologic malignancy: a phase I/II study. 905 8

Immune-mediated effects appear to play a major role in controlling minimal residual disease (MRD). We, therefore, investigated the role of recombinant human interleukin-2 (rIL-2) given concomitantly with interferon-alpha (IFN-alpha) in malignant lymphoma (ML) patients with responding disease following autologous bone marrow or blood stem cell transplantation (ABSCT). Fifty-six patients were included in this investigation. Thirty-two patients had non-Hodgkin's lymphoma (NHL) and 24 patients had Hodgkin's disease (HD). Sixty-one patients (NHL 36, HD 25) served as historical controls. Patients from both groups had similar demographic characteristics, the same stage of disease at presentation, status of disease at transplantation, conditioning regimens, and type of transplant. rIL-2 and IFN-alpha were self-administered in two cycles beginning 2.5 to 10.5 months (median, 4 months) posttransplant and separated by a 4-week interval. Each cycle consisted of IFN-alpha subcutaneously (SC) 3 x 10(6) U/d x 5 d/wk combined with rIL-2 SC 3 to 6 IU/m2/d x 5 d/wk for 4 weeks. The incidence of survival and disease-free survival (DFS) was significantly higher in the group under investigation than in the historical controls (P < .01). Of 56 patients with ML treated with IFN-alpha + rIL-2, 45 patients are DFS (80.4%) after a follow-up of 7 to 78 months (median, 34 months), whereas in the historical controls, 32 of 61 (52.5%) patients are disease free, in a follow-up of 4 to 84 months (median, 23 months) posttransplant (P < .01). Our preliminary results are encouraging and suggest that home administered immunotherapy with IFN-alpha and rIL-2 is relatively well tolerated and may intensify remission in ML patients with MRD following ABSCT.
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PMID:Immunotherapy with recombinant human interleukin-2 and recombinant interferon-alpha in lymphoma patients postautologous marrow or stem cell transplantation. 916 32


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