Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

This prospective study was undertaken to evaluate the efficacy and toxicity of combination chemotherapy with alternating cycles of vincristine, doxorubicin and dexamethasone (VAD) and cyclophophamide, doxorubicin, etoposide and prednisone (CHEP) in patients over 60 years old with previously untreated and advanced non-Hodgkin's lymphoma (NHL) of intermediate- and high-grade malignancy. Eighty one consecutive, patients with NHL referred from April 1992 to October 1997 to GOELAMS centers were enrolled in this study and their outcome updated to June 1, 1999. Of 81 enrolled patients, 77 were eligible and assessable for response. The median age was 70 years (61 to 78), 85.7% were stage III or IV, 39% were of performance status > or = 2, 27.3% > or = 2 involved extra-nodal sites and 57.3% had higher LDH levels than normal. The immunophenotype was B in 87% and T in 13%. Fifty-one (66.2%) patients received the scheduled eight cycles of therapy and treatment was withdrawn in only 6 patients (7.8%) because of toxicity. Neutropenia grade 3-4 occurred in 11.1% after VAD courses vs 40.6% after CHEP courses. The mean cumulative dose of doxorubicin was 269 mg/m2 and the relative dose intensity was 84%. The overall response and complete response rates were 66.2% and 51.9% respectively, and after a median follow-up of 52 months the 3 year overall survival (OS) and event-free survival rates (EFS) were 43.5% and 33.0% respectively. In multivariate analysis, OS and EFS were statistically influenced by IPI (p = 3 x 10(-3); p < 1 x 10(-4)) and phenotype (p = 2 x 10(-3); p < 1 x 10(-4)). Our findings support the alternation of 4 courses of VAD and CHEP as it is well tolerated in patients over 60 years old with advanced intermediate- or high-grade NHL and provides response and survival rates comparable to 6 courses of CHOP.
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PMID:Continuous infusion of vincristine-doxorubicin with bolus of dexamethasone(VAD) alternated with CHEP in the treatment of patients over 60 years old with aggressive non-Hodgkin's lymphoma. 1142 26

We analyzed 104 patients with non-Hodgkin's lymphoma, follicular or diffuse large-B-cell-type lymphoma, in order to evaluate the correlation between clinical characteristics and immunohistochemical parameters. Immunostaining was performed by means of monoclonal antibodies against Ki-67, bcl-2, and p53 expression. Forty-nine of the patients showed follicular lymphoma. A high expression of bcl-2 was found in 93%, high expression of p53 in 57%, and low expression of Ki-67 in 96%. Follicular lymphoma grade III showed a p53 expression (p = 0.07) slightly higher than follicular lymphoma grades I and II, not reaching statistical significance. Follicular lymphoma grades I and II tended to express lower Ki-67 and higher levels of bcl-2 expression than grade III (p = 0.06). Fifty-five cases showed diffuse large-B-cell lymphoma. Among them, bcl-2 was absent in 39%, whereas p53 and Ki-67 expression were high in 38%. In the diffuse large-B-cell lymphomas, a high bcl-2 expression correlated with stages III and IV (p = 0.03) and involvement of more than one extranodal area (p = 0.03). High Ki-67 expression was also associated to extranodal involvement of more than one area (p = 0.03). Overall survival of patients did not show statistically significant differences regarding Ki-67, bcl-2, and p53 tumoral expression. Prognostic factors for overall survival in the multivariate analysis were age (p = 0.02) and LDH (p = 0.003). Time to progression was worse among follicular lymphoma with high p53 expression than with mild/moderate p53 expression (p = 0.009).
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PMID:Prognostic significance of Ki-67 nuclear proliferative antigen, bcl-2 protein, and p53 expression in follicular and diffuse large B-cell lymphoma. 1177 65

Complete remission can be achieved in 60-80% of adults with diffuse aggressive non-Hodgkin's lymphoma. However, 20-40% of them will subsequently relapse. Nevertheless, formal follow-up guidelines for recurrence detection have never been advocated. We analyzed the pattern of relapse in 30 patients with intermediate- and high-grade non-Hodgkin's lymphoma and the value of intensive protocol for relapse detection. This protocol includes frequent follow-up visits, complete blood count, and serum LDH tests along with annual chest, abdominal, and pelvic CT scans. The median duration of complete remission was 12 months. Twenty-five relapses (83%) were suspected after an interim history and/or physical examination, whereas only 5 relapses (17%) were detected by routine radiographic or laboratory follow-up studies. The majority of relapses (19/30) were detected in sites that included the sites of prior disease. For the first 12 months of complete remission, the estimated cumulative save in charge for a follow-up strategy, based on regular visits in the hematology clinic and performing laboratory and radiologic studies as clinically indicated, is 44% of the cost of a routine intensive evaluation. A reliable and cost-effective follow-up method for non-Hodgkin's lymphoma patients in complete remission should include frequent history and physical examination. Complementary studies should be performed according to clinical indications.
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PMID:Detection of relapse in non-Hodgkin's lymphoma: role of routine follow-up studies. 1183 30

Bone marrow necrosis (BMN) is a relatively uncommon clinicopathologic entity. The etiology is diverse, and malignancy, especially hematopoietic in origin, is the most common underlying disease of BMN. In this retrospective analysis, cases with BMN were re-evaluated for etiology, histopathologic details, and clinical manifestations. In the last 8 years, 23 cases of BMN were detected among the 1,083 bone marrow (BM) biopsies, and the prevalence was found to be 2.2%. Three of these 23 cases with BMN were children, and 20 cases were in adults. Sixteen of these cases (80%) had underlying malignant disease, and four (20%) had nonmalignant disease. Among the malignant cases, three cases had acute myeloblastic leukemia (AML), four had relapsed Hodgkin's disease (R-HD), one had acute lymphoblastic leukemia (ALL), two had chronic myelocytic leukemia (CML), two had non-Hodgkin's lymphoma (NHL), three had disseminated intravascular coagulation (DIC) associated with metastatic solid tumor, and one had myelodysplastic syndrome/myeloproliferative syndrome (MDS/MPS). Among the nonmalignant cases, two had tuberculosis infection, one had anti-phospholipid syndrome (APS), and one had a history of drug ingestion. The most common symptoms were bone pain, fever, fatigue, and jaundice. The most common laboratory findings were variable and associated with underlying disease, but anemia, leukopenia, thrombocytopenia, and high LDH and alkaline phosphatase levels were detected in the majority of the cases, as was also seen in other series. BMN was graded according to the extent of necrosis in the BM biopsy, and necrosis was extensive in 12 cases, moderate in five cases, and mild in three cases. Increased reticulin was found in 16 cases; four cases had severe, eight had moderate, and four had mild fibrosis, and this was found to be an interesting accompanying finding in BMN. In conclusion malignancy is the most common cause of BMN but some nonmalignant conditions such as tuberculosis and APS may be the underlying cause of BMN.
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PMID:Bone marrow necrosis: clinicopathologic analysis of 20 cases and review of the literature. 1221 Aug 11

Soluble transferrin receptor levels in serum (s-sTfR) may be useful in differentiating between iron deficiency anemia and anemia of chronic disease. However, there is both theoretical and clinical evidence for elevated s-sTfR levels in patients with various hematological malignancies. In the present study, routine bone marrow aspirations were performed in 82 patients with malignant lymphomas (63 with non-Hodgkin's lymphoma and 19 with Hodgkin's disease). Smears were stained for evaluation of iron stores and graded. Patients were also given a disease score based on bone marrow morphology, erythrocyte sedimentation rate and LDH. s-sTfR levels correlated better with disease score [partial Spearman rank correlation coefficient (r(s)) controlled for iron stores was 0.51 (95% confidence interval 0.39-0.65); p < 0.001] than with iron stores [partial r(s) controlled for disease score was -0.25 (95% confidence interval -0.44 to -0.03); p = 0.027]. This study showed elevated s-sTfR levels in patients with malignant lymphomas without any signs of iron deficiency anemia. The diagnosis of iron deficiency anemia should not be established upon the basis of s-sTfR alone in this group of patients.
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PMID:Serum levels of soluble transferrin receptor correlate with severity of disease but not with iron stores in patients with malignant lymphomas. 1221 95

Only recently both the Revised European American Lymphoma (REAL) and World Health Organization (WHO) classifications clearly identified indolent non-follicular non-Hodgkin's lymphoma (NHL) as a distinct group of precise histological entities. Therefore, prognostic models, specifically designed for this NHL subset, are still lacking. In this study, we prospectically evaluated the prognostic criteria proposed by the Gruppo Italiano per lo studio dei linfomi (GISL) to identify patients with an indolent non-progressive clinical course, eligible for a watch and wait policy within this histological subset defined according to stringent criteria of histomorphology and immunophenotype. Fifty-three patients affected with small lymphocytic, marginal zone, lymphoplasmacytic lymphoma and lacking at presentation the following: B symptoms, bulky disease, anemia, thrombocytopenia, diffuse pattern of bone marrow infiltration and short tumor doubling time, were registered in a prospective therapeutic GISL trial and addressed to a watch and wait program. After 41.3 months of median follow-up, the median progression free survival (PFS) was not reached and 73% of cases did not progress. When additional variables were considered, in order to improve the prognostic model, it was evident that LDH level and the number of extranodal sites were of statistical significance in the multivariate analysis. Based on this finding, a prognostic score was devised which was able to further identify a small group of patients more likely to undergo early progression, and thus suitable for immediate treatment. In conclusion, the GISL definition of indolent disease is a reliable tool to design the appropriate therapeutic strategy in this histological setting.
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PMID:Prospective study of indolent non-follicular non-Hodgkin's lymphoma: validation of Gruppo Italiano per lo studio dei linfomi (GISL) prognostic criteria for watch and wait policy. 1248 87

Our objectives were to assess survival and predictors for survival among lymphoma patients whose disease had progressed after autologous bone marrow (ABMT) or stem cell transplantation (ASCT). Patients transplanted at Hadassah University Hospital between October 1983 and February 1999 were included. We compared survival of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) after relapse or progression. Predictors for survival were assessed in a multivariate model. Of 88 transplanted patients with HD and 152 with NHL, relapse/progression occurred in 27 (31%) and 75 (49%), respectively. Median survival postrelapse was 25 months for HD and 7.5 months for NHL (P=0.12). Seven relapsed patients with HD (26%) and 10 (13%) with NHL survived >4 years. In NHL, longer postrelapse survival was associated with indolent histologies (P=0.007). On multivariate analysis, factors associated with survival included attainment of remission postrelapse (for both diseases), use of prophylactic immunotherapy (for HD), LDH level and time from transplant to relapse (for NHL). The short-term prognosis for patients with disease progression postautologous transplant may be somewhat better for HD compared to NHL. Long-term survival is poor in both diseases. However, the survival times in the current study are twice as long as those previously reported. Treatment regimens with the potential for achieving remission may have an impact on survival.
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PMID:Factors associated with survival in patients with progressive disease following autologous transplant for lymphoma. 1269 22

The effect of poor blood stem cells mobilization on the outcome of autologous stem cell transplantation (ASCT) has not been well studied. Our aim is to evaluate poor mobilization as a prognostic factor in lymphoma patients undergoing ASCT. We analyzed 90 consecutive patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL) who underwent ASCT. Poor mobilization was defined as the inability to obtain > or = 1 x 10(6) CD34+ cells/kg ideal body weight with two large volume aphereses. Patients were divided into 2 groups: group 1 = poor mobilizers, and group 2 = good mobilizers. The poor mobilizers received lower median transplant CD34+ cell dose (2 x 10(6) vs. 4.5 x 10(6)/kg for good mobilizers, P = 0.001), were more heavily pretreated (P = 0.01), and required higher number of aphereses for PBSC collection (P = 0.0006). The median progression-free survival (PFS) in groups 1 and 2 was 10 and 41 months (P = 0.04), while the median overall survival (OS) was 38 months and not reached (P = 0.02), respectively. Univariate analysis showed that > or = 3 pre-transplant treatments, CD34+ cell dose < or = 2 x 10(6), elevated LDH before transplant, and poor mobilization were significant prognostic factors for poor PFS, while only the first three were significant for worse OS. Multivariate analysis using these same four factors revealed that number of pre-transplant treatments (HR = 6.03, P = 0.001), CD34+ cell dose (HR = 0.1, P = 0.0007) were the only independent predictive factors for worse overall outcome. In conclusion, our data show that poor mobilization could indicate poor outcome in lymphoma patients undergoing ASCT, however, it is more likely to be a reflection of the heavy pre-transplant therapy and lower CD34+ cell dose re-infused in this group of patients.
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PMID:Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation. 1280 19

We report a rare case of bilateral primary adrenal non-Hodgkin's lymphoma with adrenal failure. A 66-year-old woman developed symptoms of adrenal failure. The cause of adrenal failure was suspected to be malignant lymphoma based on the high levels of serum soluble interleukin-2 receptor and LDH. Bilateral adrenalectomy was performed and pathological examination showed intravascular large B-cell lymphoma (IVL). Although complete remission was achieved, recurrence occurred three months later with brain metastases. IVL should be suspected in patients with bilateral adrenal tumors who present with rapidly progressive adrenal failure.
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PMID:Primary bilateral adrenal intravascular large B-cell lymphoma associated with adrenal failure. 1287 56


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