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 serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in 116 patients with non-Hodgkin's lymphomas (NHL) tested previously for soluble intercellular adhesion molecule-1 (sICAM-1). In contrast to Hodgkin's disease and chronic lymphocytic leukaemia, the sVCAM-1 levels in NHL patients were not significantly different from the levels of healthy controls (n = 31). However, sVCAM-1 was elevated in advanced stage disease, i.e. stages III + IV. Elevated serum levels of sVCAM-1 were associated with significantly poorer disease-free (p = 0.024) and overall (p = 0.02) survival. sVCAM-1 correlated poorly with other known prognostic variables (LDH, sTK and beta 2m) and with sICAM-1. None of the tested markers added prognostic information for disease-free survival independently of Ann Arbor stage and B-symptoms. The expression of VCAM-1 and ICAM-1 in tumour biopsies from 15 patients representing 7 different histologies were examined and compared with the serum levels of the soluble adhesion molecules. No correlation was found between the adhesion molecule expression by vascular endothelium and the corresponding serum levels.
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PMID:Serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) are elevated in advanced stages of non-Hodgkin's lymphomas. 985 46

The biological markers of non-Hodgkin's lymphomas (NHL) are distinguished in three categories: serological, immunophenotypic, and molecular markers. The clinical importance of biological markers in NHL is based on their support of morphologic diagnosis, their role in staging and prognostic assessment, and their contribution to monitoring minimal residual disease (MRD). The most important serological markers reflect the tumor load (beta-2 microglobulin, beta 2-M), proliferative activity (lactic dehydrogenase, LDH), and invasive potential of lymphomas (CA 125). LDH and beta 2-M are included as important prognostic parameters in widely used staging systems. Immunophenotypic analysis identifies specific markers of lineage (B or T-cells), maturation level, cell proliferation, and clonality. Results of immunophenotyping are particularly useful in low to intermediate-grade NHLs to support the morphologic diagnosis and facilitate the detection of MRD after treatment. The molecular markers are genetic lesions involved in the pathogenesis of some categories of NHL. Their use as markers for diagnosis is justified by the selective association with specific lymphoma categories: follicular, mantle cell, diffuse large cell, and anaplastic large cell lymphomas. Molecular lesions are the most specific and sensitive markers for evaluating MRD. Today the biological markers of NHL are widely employed for diagnosis, staging, and prognostic assessment. Their systematic use may complement clinical parameters in the stratification of NHL patients, who may thus become candidates for treatments of different intensity. The detection of MRD after first-line treatment identifies patients at high risk of relapse who require additional therapy to cure their disease.
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PMID:The biological markers of non-Hodgkin's lymphomas: their role in diagnosis, prognostic assessment and therapeutic strategy. 1056 36

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

We have correlated the serum levels of TNF alpha and soluble TNF receptor superfamily members with clinico-pathologic parameters in patients of Hodgkin's disease (HD, N = 26) and non-Hodgkin's lymphoma (NHLs, N = 35). HD patients had significantly higher levels of TNF alpha, sTNFRI, and sTNFRII in serum while NHL patients had significantly higher levels of sTNFRI, sTNFRII, sCD27, and sFas as compared to controls. In NHL patients the levels of sCD27 correlated directly and significantly with the high-stage disease, bone marrow involvement, lymph nodal presentation, and serum LDH levels. Similarly in NHL patients, levels of sFas also correlated directly and significantly with the presence of high stage disease. HD patients with B symptoms had significantly higher levels of sTNFRII.
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PMID:Circulating levels of TNF alpha and TNF receptor superfamily members in lymphoid neoplasia. 1099 26

Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.
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PMID:Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR). 1131 68

The results of autografting in patients with relapsed low grade non-Hodgkin's Lymphoma (NHL) have generally been disappointing due to the failure to maintain remission and the late development of myelodysplasia. Most series have used regimens that include total body irradiation and purged stem cells. We evaluated the outcome in 32 patients with low grade NHL autografted using chemotherapy-only busulfan-based conditioning and unpurged stem cells. Seven of 10 patients with poor prognostic features at diagnosis remain alive in CR a median of 78 months (range 14-129) post-transplant. Twenty two patients with relapsed, chemosensitive, low bulk disease, most of whom did not have marrow involvement or an elevated LDH, were transplanted. Only five of the 22 have relapsed, with an 86 +/- 8% overall survival and 72 +/- 10% event free survival (EFS) after a median follow-up of 56.5 months. All but one patient has an EFS period longer, often substantially so, than their previous longest remission. No patient has developed myelodysplasia. These data suggest that in selected patients with poor prognosis or relapsed low grade NHL autografting has a favourable impact on the natural history of their disease and may result in long-term disease control.
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PMID:Prolonged disease-free survival after autografting for chemosensitive non-bulky low grade non-Hodgkin's Lymphoma. 1134 8

Vinorelbine (Navelbine is a semisynthetic vinca alkaloid devoid of serious neurotoxicity. When given weekly vinorelbine has documented activity against many tumors, including lymphomas. Since weekly schedules cannot be easily incorporated in combination regimens, we tested an infusional schedule of vinorelbine given every 21 days in adults with relapsed or refractory lymphoma. Patients with inadequate organ or bone marrow reserve, HIV or other serious infection, central nervous system disease, or prior stem cell or bone marrow transplantation were ineligible. In the phase I part, patients received a constant intravenous bolus of 8 mg/m(2), followed by intravenous continuous infusion over 24 hours daily for four days increasing from 10, 12, to 14 mg/m(2) /d in successive three-patient cohorts. Cycles were repeated every 21 days, and the daily continuous infusion dose was adjusted for toxicity. Dose-limiting mucositis and neutropenia were reached at the continuous dose of 14 mg/m(2) /d. Consequently, for the Phase II trial the starting continuous infusion dose was 12 mg/m(2) /d. After the first 19 patients were entered in the phase II study, the starting infusion dose was reduced to 10 mg/m(2) /d because of frequent grade (3/4) myelosuppression and mucositis. Forty-four patients were entered in the phase II study, of whom 41 are evaluable. Median age was 61 years, 23 were males, with clinically aggressive non-Hodgkin's lymphoma (NHL) in 22, indolent NHL in 18, and Hodgkin's Disease in one patient. The median number of prior regimens was 3 (range 1-11). The lymphoma was refractory to the initial regimen in nine patients, and to the regimen immediately before vinorelbine in 20 patients. Serum LDH was high in 2(1/4)1, and serum beta(2) -microglobulin > 3.0 mg / L in 16/31 patients. Responses were observed in four of 22 patients with aggressive NHL (18%, 95% confidence interval 5%-40%), and in six of 18 with indolent NHL (33%, 95% confidence interval 13%-59%). Median progression-free survival was 6 months for responders. During the Phase II trial 114 vinorelbine courses were administered. Neutrophil nadir was < 1000/microl in 65% and < 100/microl in 35% of courses, respectively. Platelet nadir was < 100,000/microl in 30% and < 20,000/microl in 8% of courses, respectively. Grade (3/4) mucositis was seen in 18% of courses, and neutropenic fever in 13%, and was complicated by death in one patient. We conclude that this dosage and schedule of vinorelbine has modest activity in patients with relapsed or refractory NHL. Myelosuppression is frequent but reversible, but there is no significant neurotoxicity. The role of vinorelbine in combination regimens for patients with relapsed lymphomas, particularly those of indolent histology, should be further investigated.
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PMID:Infusional vinorelbine in relapsed or refractory lymphomas. 1134 9

Primary vaginal non-Hodgkin's lymphomas (NHL) are rare, and are clinically difficult to differentiate from inflammatory diseases or vaginal cancer. Here, we present such a case in a 74-year-old woman complaining of fever and difficulty with urination. Pelvic examination revealed a tumor involving most of the vaginal wall, and pelvic MRI demonstrated vaginal wall thickening. A biopsy of this lesion confirmed NHL (diffuse large B-cell lymphoma), and the patient was admitted. Abdominal CT and MRI detected a vaginal tumor, and Ga scintigraphy confirmed accumulation in the pelvis, but no abnormalities were seen in other areas. Therefore, the patient was diagnosed as having NHL at clinical stage IB with low-intermediate risk (international prognosis index) (LDH 1,309 IU/L). The patient underwent three courses of CHOP therapy followed by radiotherapy, and complete remission was achieved. Primary vaginal NHL often affects women younger than 50 years of age, and abnormal hemorrhage is the initial symptom in many cases. There have been a number of reports of long-term survival following appropriate early chemotherapy and radiation therapy, suggesting that early diagnosis and treatment based on vaginal biopsy findings greatly influence the prognosis.
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PMID:[Primary lymphoma of the vagina]. 1152 48

The results were evaluated of the management of non-Hodgkin's lymphomas in 46 out of 150 patients relapsing after first complete remission, following early-stage chemoradiotherapy. Polychemotherapy of recurrent tumors was given to 85% (39/46), repeat combined treatment--13% (6/46) and radiotherapy--2% (1/46). Remission was reported in 91% (42/46): complete--69% (32) and partial--22% (10). Remission frequency and duration directly depended on degree of risk (IPI), stage of recurrence development and advancement, tumor size and general symptoms of intoxication. There was no relationship between frequency and duration, on the one hand, and sex and age, tumor pattern or number of involvement areas, on the other. Instead, the efficacy was influenced by the general condition of the patient, damage to the lymph nodes rather than adjacent areas as well as number of such areas. LDH blood level impacted the end results.
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PMID:[Effectiveness of treatment of recurrences of non-Hodgkin's lymphoma after combined chemoradiotherapy depending on prognostic indicators]. 1182 3

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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