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)

The non-Hodgkin's lymphomas are a diverse group of neoplasms, pathological prognostic groupings, based on survival, are essential to facilitate clinical comparisons of therapeutic trials. In addition, a model, based on important prognostic factors, is also necessary for predicting therapeutic outcome in patients with certain pathological prognostic group. In this paper, four models of pathological prognostic groupings, such as Working Formulation classification, National Cancer Institute classification, lymphoma clinico-pathologic(LCP) classification, and LCP schema, are reviewed for clinical usage. Comments on international prognostic index as a predictive model for aggressive lymphoma are described with its perspective for predictive capacity of therapeutic outcome.
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PMID:[Prognostic factors and predictive model of non-Hodgkin's lymphoma: pathological prognostic groupings and international prognostic index]. 1074 Nov 32

Large B-cell neoplasms represent one of the most frequent groups of non-Hodgkin-lymphomas (30-40%). They are characterized by an aggressive clinical course. These lymphomas may evolve either de novo or secondary during the course of a less aggressive lymphoma. In addition to primary nodal, a primary extranodal manifestation is rather common. The neoplastic cells, even within one given case, show a broad morphological spectrum. Several findings of the last two decades have revealed that the large B-cell lymphomas represent an inhomogeneous group. This fact has been taken into account by the new WHO classification of malignant lymphomas. There are two groups identified, that of the variants and that of the subtypes. The various variants (centroblastic, immunoblastic, anaplastic, T-cell/histiocyte-rich) correspond to lymphomas without reproducible discriminating criteria lacking characteristic clinical, immuno-phenotypical and genetic findings. In contrast, the primary mediastinal, the intravascular, the primary effusion and primary central nervous system lymphomas represent distinct disease entities. A number of recently described large cell lymphoma types, i.e. plasma-blastic, ALK-positive and primary gastric, are included in the classification, their designation as distinct entities is still under discussion.
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PMID:[Large B-cell lymphomas: variants and entities]. 1084 Aug 22

Aggressive non-Hodgkin's lymphona include diffuse large B-cell lymphoma, anaplastic large cell lymphona, and different peripheral T-cell lymphomas. An international prognostic index has been developed including age, serum LDH, performance status, and extranodal involvement. For localized aggressive lymphoma, the preferred treatment is 3-4 CHOP and radiation therapy, with a cure rate of 70-80%. For disseminated aggressive lymphoma, current regimens have a cure rate of less than 40%. Innovative strategies, including dose escalation, autologus stem cell support, new drugs, and immunotherapy are being explored to improve these results.
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PMID:The management of adult aggressive non-Hodgkin's lymphomas. 1086 50

Advances in chemotherapy have led to a favorable long-term prognosis in approximately 50% of patients with aggressive non-Hodgkin lymphoma (NHL). However, the remaining patients do not enjoy such prolonged survival after standard treatment. New prognostic factors are needed to define this poor-prognosis group and to plan an appropriate treatment strategy. It has been reported that serum nm23-H1 protein may be a new prognostic factor for aggressive NHL. In the present study involving multiple institutions and a large number of patients, the level of nm23-H1 protein was compared among different types of lymphoma; it was lowest for indolent lymphoma, followed by aggressive lymphoma and then highly aggressive lymphoma. In addition, patients with aggressive NHL and higher nm23-H1 levels had worse overall and progression-free survival rates than those with lower nm23-H1 levels. The nm23-H1 level was also compared between patients with diffuse large B-cell lymphoma and patients with peripheral T-cell lymphoma. The results suggest that the level of nm23-H1 could serve as a prognostic factor in both groups. Moreover, the prognosis of lymphoma patients could be ascertained even more precisely by combining soluble interleukin-2 receptor or soluble CD44 and nm23-H1 levels. A multivariate analysis confirmed that the nm23-H1 level is an independent and important prognostic factor in aggressive NHL. Therefore, it may provide useful information for clinicians to determine the appropriate therapy for each type of lymphoma.
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PMID:Serum nm23-H1 protein as a prognostic factor in aggressive non-Hodgkin lymphoma. 1122 61

Autologous transplantation with haematopoietic blood stem cells (ASTx) is increasingly performed in blood cell disorders, in solid tumours and recently, in severe autoimmune disorders. In acute leukaemia, ASTx is usually offered to patients in complete remission who lack an HLA-identical donor. The chances and risks must be weighed against a transplant from a matched, unrelated donor. ASTx are routinely performed in aggressive lymphoma. Indications for ASTx in intermediate and low grade lymphoma await results of clinical trials. In Hodgkin's disease and myeloma, ASTx are routinely performed in first or subsequent remission, and in early stages, respectively. Among solid cancers, ASTx is an established part of the therapeutic measures in germ cell tumours. Patients with breast cancer may undergo ASTx in an adjuvant setting after complete tumour resection or in a palliative setting after progression. Initial enthusiasm has switched to a more awaiting view of this indication. Severe autoimmune disorders may undergo haemolymphatic ablation from conditioning and a stem cell transplant. The scientific evaluation of this approach should employ three sequential steps: The first step should employ vigorous immunosuppression followed by ASTx; the second step should employ stem cell autografts depleted from autoreactive immune cells; the third step should employ allogeneic stem cells from normal donors. A truly curative approach after complete haemolymphatic reconstitution is conceivable.
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PMID:[Autologous transplantation of hematopoietic stem cells--therapeutic spectrum and future developments]. 1126 Dec 70

Ifosfamide is an alkylating agent with proven efficacy in the treatment of solid tumours and malignant lymphomas. Because it causes only mild to moderate myelosuppression, ifosfamide is often used in combination regimens with other agents. Ifosfamide has been mainly used in therapy of lymphoma as a component of salvage regimens, but high-dose ifosfamide is also effective in the mobilization of peripheral stem cells for treatment of patients with relapsed or refractory lymphoma with regimens containing autologous stem cell transplantation. Based on promising data with a new combination regimen containing idarubicin, etoposide and ifosfamide (IIVP-16) in patients with poor-risk non-Hodgkin's lymphoma, we have performed a phase II study using DIZE (dexamethasone 20 mg i.v. days 1-4, idarubicin 8 mg/m2 i.v. days 1 + 2, ifosfamide 1.0 g/m2 continuous infusion (c.i.) days 1-4, and etoposide 160 mg/m2 c.i. days 1-4) in patients with relapsed or refractory Hodgkin's and non-Hodgkin's lymphoma. In 43 evaluable patients, the response rate was 58%, including 11 complete remissions (CR) and 14 partial remissions (PR). The mean duration of response was 8 months (1-30). Myelosuppression was generally mild with mean duration of neutropenia < 1000/microL of 2.5 days (range 0-18) and thrombocytopenia < 25,000/microL of 1.5 days (0-17). Thus, DIZE is an effective and safe regimen for pretreated patients with aggressive lymphoma. These results appear to compare favourably with other salvage regimens such as IMVP-16 or DHAP. In conclusion, salvage regimens containing ifosfamide can play an important role in patients who are not eligible for high-dose chemotherapies. Moreover, ifosfamide might also have a role in reducing tumour burden and selecting those patients who qualify for HDCT.
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PMID:The role of ifosfamide in the treatment of relapsed and refractory lymphoma. 1148

Mantle cell lymphoma is a distinct subtype and accounts for approximately 5 to 10% of non-Hodgkin lymphomas. The malignant cells express pan B-cell markers, including CD19, CD20 and CD22, and the T-cell marker CD5, whereas CD10 and CD23 expression are usually absent. By cytogenetic analysis, the t(11;14)(q13;q32) translocation is commonly observed, resulting in overexpression of cyclin D1. This entity often combines some unfavorable clinical features of the indolent and aggressive lymphoma subtypes, as it is generally incurable and relatively aggressive. It is most commonly observed in men 50 to 70 years of age and is characterized by disseminated disease, usually involving lymph nodes, bone marrow, and spleen. Frequently, there is extranodal involvement including the gastrointestinal tract. These tumors are incurable with the currently available therapeutic options, with usual time to progression after chemotherapy of approximately 1 year. Newer chemotherapy regimens (including stem cell transplantation) and monoclonal antibody-based therapies have shown limited evidence of additional benefit. Overall, the prognosis for patients with mantle cell lymphoma remains poor, and novel strategies are needed.
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PMID:Biology and management of mantle cell lymphoma. 1155 10

The CHK2 gene encodes a protein kinase that is important for the regulation of cell cycle arrest after DNA damage. CHK2 acts downstream of ataxia teleangiecstasia mutated (ATM), modulates the function of p53 and may help mediate cell cycle arrest at G2/M by phosphorylation of Cdc25C. Recently, the human homolog of the checkpoint kinase Cds1 (CHK2) has been suggested to be a tumor suppressor gene. Heterozygous germline mutations have been reported in Li-Fraumeni syndrome (LFS), a highly penetrant familial cancer phenotype, and in sporadic colon cancer. LFS is associated with the development of lymphoid malignancies, especially childhood ALL. Therefore, we analyzed the DNA from 143 lymphoid malignancies to determine whether they had mutations of the CHK2 gene. The 14 exons of CHK2 were studied by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing of aberrantly migrating bands. One missense mutation changing serine to phenylalanine (codon 428) in an evolutionarily highly conserved domain was found in a non-Hodgkin's aggressive lymphoma. Another point mutation in the non-coding region was identified in one of adult T-cell leukemias (ATL) samples. This result suggests that mutation of the CHK2 gene may rarely be involved in the development of selected lymphomas.
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PMID:Analysis of the CHK2 gene in lymphoid malignancies. 1169 18

Pulmonary involvement due to disseminated non Hodgkin lymphoma (LNH), is an unusual cause of lung disease in AIDS patients. We report a 38 years old male patient, with advanced AIDS, who, in the course of three weeks, developed cough, dyspnea and fever. The chest X ray film showed diffuse thickening of the peribronchovascular connective tissue with possible mediastinal lymph node enlargement. The evolution was unfavorable with hypoxemia, severe anemia, liver damage and elevated levels of lactic dehydrogenase. The presumptive initial diagnoses were Pneumocystis carinii pneumonia, pulmonary tuberculosis with hematogenous dissemination and Kaposi sarcoma. Definitive diagnosis was made through a transbronchial biopsy performed the day before his death. The pathological and inmunohistochemical report demonstrated a highly aggressive lymphoma (lymphoblastic, B precursor). This finding was confirmed by autopsy that revealed multiple organ involvement.
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PMID:[Pulmonary involvement due to disseminated non Hodgkin lymphoma in one patient with AIDS]. 1183 85

Treatment of aggressive lymphoma in relapse is difficult. Patients who initially present with these diseases often know they have a malignancy considered curable in many cases, and diagnosis of relapse can be devastating. For this reason, it is useful to know the individual patient's risk of relapse prior to starting initial therapy, since it may be appropriate to treat patients with poor prognoses with intensive programs or investigational studies. In the private practice setting, most patients with these diseases receive CHOP or similar cyclophosphamide and doxorubicin-containing regimens at the time of initial diagnosis. However, there are certain disease-related features which determine whether these patients have a high or low risk of relapse, and investigators are now using combinations of these features to determine which patients may be safely treated with CHOP and which may benefit from more intensive chemotherapy management. For example, the International Prognostic Factor Index system, now in common usage, delineates four different groups of patients with differing complete remission, freedom from progression, and overall survival rates. The Tumor Score System, developed at MDACC, delineates only two groups with very different survival rates, and may be a better scoring system for patients with diffuse large cell lymphomas, primarily because of its inclusion of the serum beta(2)-microglobulin level prior to treatment, an important predictor of relapse. In addition to pretreatment features, certain treatment-related factors are also important in determining the risk of relapse, including the dose of chemotherapy administered and the rapidity of response. Results of a gallium scan with SPECT imaging may be an important method of confirming complete response, and should be incorporated into treatment programs, whether the treatment is standard CHOP or an investigational program. For the patient with relapse or progressive disease following induction with CHOP or a similar regimen, the type of response to initial therapy plays an important role in determining potential response to salvage therapy, including high-dose therapy followed by stem cell rescue. Patients for whom initial treatment fails to achieve any response have a very poor chance of responding to any currently used standard-dose program for relapse. Those with partial responses have a better chance of responding to relapse therapy, but a high risk of disease progression or early relapse, and those with a prior complete response to initial therapy have a good chance of responding to relapse therapy, especially those in whom the complete response lasted more than a year. For these reasons, stem cell transplant (SCT) protocols routinely require complete response with initial therapy as a requirement for entry, although "good partial remission" may be acceptable at certain centers. Other limitations for SCT protocols include age greater than 60 or 65 years, significant chronic obstructive pulmonary, renal, or cardiac disease, a poor performance status, and central nervous system or marrow involvement. For these reasons, there is a continued need for newer treatment programs which offer the potential for higher response rates and better survival rates, not only for those for whom SCT is not an option, but also for those who must have an adequate response to "standard dose therapy" prior to selecting SCT as a treatment option. Three broad groups of relapse therapy for aggressive lymphoma have been described, based upon the drugs contained within these regimens. These include platinum-based, mitoxantrone-based, and ifosfamide-based chemotherapy regimens. Results with these programs vary widely and are likely different because of tumor-related features prior to relapse therapy, including size of mass, beta(2)-microglobulin level, LDH level, and type of response to initial therapy. Other features, such as dose of therapy, specific drugs utilized, and number of prior treatments also play important roles in determining results with relapse therapy. In a study of DHAP followed by transplant or more DHAP, DHAP induced a response in 56% of patients, and at 5 years, significantly more of the responders to DHAP who were subsequently treated with high-dose therapy and bone marrow transplant were free of disease compared to those who continued to receive DHAP after response to this regimen. Therefore, high-dose therapy is clearly better for DHAP responders than is continued DHAP. However, results for the overall population are still not good when non-responders are included in the analysis, and DHAP, a first-generation platinum regimen, may not be the optimal regimen to use prior to high-dose therapy followed by peripheral stem cell rescue. At MDACC, we have extensively investigated various combinations containing ifosfamide and etoposide. The most recently reported regimen, MINE-ESHAP, contains mesna, ifosfamide, mitoxantrone, and etoposide, followed after adequate response with etoposide, methylprednisolone, high-dose cytarabine, and continuous infusion as cis-platinum, a second-generation platinum regimen. This strategy resulted in a complete response in 47% of the patients treated, with a 44% complete response in patients with intermediate-grade lymphoma, 56% in those with low-grade lymphoma and 36% in those with transformed lymphoma. Results varied according to type of response achieved with initial therapy, and serum LDH and beta(2)-microglobulin levels prior to treatment with MINE-ESHAP. Using more intensive doses of ifosfamide and etoposide, we have described therapy for 36 patients with relapsed aggressive lymphomas, prior to pheresis and SCT. Results of this study are encouraging: 42% entered complete response with ifosfamide-etoposide and the overall survival was 52%, with a progression-free survival of 32%. Therapy with a similar regimen, combining ifosfamide, carboplatin, and etoposide in standard doses (ICE) has also been described. This regimen has been extensively studied in patients with relapsed aggressive lymphomas and Hodgkin's disease, followed by SCT. In patients with relapsed lymphomas, ICE has achieved a 66% complete response rate, with 89% undergoing transplant. Overall survival in these studies is affected by the quality of the response to ICE. The same program was used to treat 65 patients with Hodgkin's disease. The response rate to ICE was 88%, and the 5-year event-free survival for those transplanted was 68%. These factors predicted outcome: B symptoms, extranodal disease, and complete response less than 1 year. Finally, we have recently studied paclitaxel in combination with topotecan for relapsed and refractory aggressive lymphomas. These and newer combinations should be further developed to treat patients in relapse of aggressive lymphomas.
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PMID:Treatment of relapsed aggressive lymphomas: regimens with and without high-dose therapy and stem cell rescue. 1204 84


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