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)

For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose therapy with peripheral blood progenitor cell (PBPC) support may become a first-line treatment. The duration of severe cytopenia in this setting is inversely related to the number of PBPCs autografted. In a retrospective analysis, we therefore looked for factors influencing the yield of PBPCs in 61 patients (16 with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL], and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6 micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45 were in partial remission (PR) or complete remission (CR) after conventional therapy. A median of three leukaphereses (range, one to 10) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+ cells/kg per leukapheresis in nonirradiated patients, while large-field radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg CD34+ cells. The collection efficiency was also significantly lower in patients with Hodgkin's disease. However, except for one, all had been previously irradiated. In contrast, age, sex, disease status, bone marrow involvement during mobilization, and the time since the last chemotherapy or radiotherapy were not significantly related to the collection efficiency. Following high-dose conditioning therapy, 42 patients were autografted with filgrastim-mobilized PBPCs. Hematological recovery (neutrophils > or = 0.5 x 10(9)/L and an unsupported platelet count > or = 20 x 10(9)/L) within 2 weeks was observed in patients autografted with > or = 2.5 x 10(6) CD34+ cells/kg. In seven patients, the quantity of CD34+ cells reinfused was below this threshold. They required a median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil and platelet recovery, respectively. If autografting with PBPCs in malignant lymphoma with poor prognosis is being considered, mobilization and harvesting should be planned early after initial diagnosis to avoid exhaustion of hematopoiesis by cumulative toxicity.
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PMID:Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma. 751 21

Peripheral blood progenitor cells (PBPC) can be mobilized using cytotoxic chemotherapy and cytokines. There is a substantial variability in the yield of hematopoietic progenitor cells between patients. We were looking for predictive parameters indicating a patient's response to a given mobilization regimen. Multiparameter flow-cytometry analysis and clonogenic assays were used to examine the hematopoietic progenitor cells in bone marrow (BM) and peripheral blood (PB) before filgrastim (R-metHuG-CSF; Amgen, Thousand Oaks, CA)-supported chemotherapy and in PB and leukapheresis products (LPs) in the recovery phase. Fifteen patients (four with high-grade non-Hodgkin's lymphoma [NHL], two with low-grade NHL, two with Hodgkin's disease, two with multiple myeloma, three with breast cancer, one with ovarian cancer, and one with germ cell tumor) were included in this study. The comparison of immunofluorescence plots showed a homogenous population of strongly CD34+ cells in steady-state and mobilized PB whereas in steady-state BM, the CD34+ cells ranged from strongly positive with continuous transition to the CD34- population. Consistent with the similarity in CD34 antigen expression, a correlation analysis showed steady-state PB CD34+ cells (r = .81, P < .001) and colony-forming cells (CFCs; r = .69, P < .01) to be a measure of a patient's mobilizable CD34+ cell pool. Individual estimates of progenitor cell yields could be calculated. With a probability of 95%, eg, 0.4 steady-state PB CD34+ cells x 10(6)/L allowed to collect in six LPs 2.5 x 10(6) CD34+ cells/kg, the reported threshold-dose of progenitor cells required for rapid and sustained engraftment after high-dose therapy. For the total steady-state BM CD34+ cell population, a weak correlation (r = .57, P < .05) with the mobilized CD34+ cells only became apparent when an outlier was removed from the analysis. Neither the CD34+ immunologic subgroups defined by the coexpression of the myeloid lineage-associated antigens CD33 or CD45-RA or the phenotypically primitive CD34+/HLA-DR- subset nor the BM CFC count had a predictive value for the mobilization outcome. This may be caused by the additional presence of maturing progenitor cells in BM, which express lower levels of the CD34 antigen and do not circulate. Our results permit us to recognize patients who are at risk to collect low numbers of progenitor cells and those who are likely to achieve sufficient or high progenitor cell yields even before mobilization chemotherapy is administered.
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PMID:Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy. 860 80

Autologous bone marrow transplantation (ABMT) is used increasingly for the treatment of acute leukemias, lymphomas and solid tumors. Since ABMT is burdened by high risk of relapse, mafosfamide or 4-hydroperoxycyclophosphamide chemical marrow purging is employed. Mafosfamide acts by exerting a potent cytotoxic effect and by promoting apoptosis of leukemic cells. A third proposed mechanism of action involves an effect on immune regeneration in vivo. It was the aim of this study to investigate natural killer (NK) cell regeneration in a group of patients undergoing mafosfamide-purged ABMT. Fifteen patients (8 acute myelogenous leukemia, AML; 4 acute lymphoblastic leukemia, ALL; 3 non-Hodgkin's lymphoma, NHL) were treated with high-dose chemotherapy followed by transplantation with marrow purged with mafosfamide. Prior to ABMT and at different intervals thereafter, NK cell number and function were studied by evaluating the percentage of circulating CD16 positive cells and cytotoxic activity against the leukemic cell line, K562. In comparison to pre-ABMT values, AML patients showed a significant increase in cytotoxic activity, expressed as percentage of chromium release (42.5 +/- 3 vs 32.5 +/- 6, P < or = 0.025 at 4 months) which still persisted at 12 months post-ABMT (54 +/- 6, P < or = 0.05). The behavior of NK functional activity was paralleled by an increase of the percentage of CD16-positive cells (8.4 +/- 2.2 vs 5 +/- 1.3, P < or = 0.05 at 4 months; 12.8 +/- 2.4, P < or = 0.005 at 12 months post-ABMT). Similar significant and long-lasting increments in NK cells were also found in NHL patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Natural killer cell regeneration after transplantation with mafosfamide purged autologous bone marrow. 758 Nov 36

To analyze the transition of an autoimmune disease into a mucosa-associated lymphoid tissue-non-Hodgkin's lymphoma (MALT-NHL), we investigated a total of 27 cases of clinically diagnosed autoimmune thyroiditis with lymphoid hyperplasia. Three cases of thyroid hyperplasia served as controls. Monoclonal B cells were detected by studying rearrangement patterns of the hypervariable CDR III regions within the immunoglobulin heavy chain gene locus and the T-cell receptor gamma chain gene (TCRG). We used a seminested polymerase chain reaction (PCR) to demonstrate immunoglobulin rearrangements and a multiplex PCR for TCRG rearrangements. The PCR products were analyzed by temperature gradient gel electrophoresis to expand mixtures of homo- and hetero-duplices within heterogeneous populations of B cells. With this approach we found monoclonality in 14 of the 27 cases of Hashimoto's disease. In a reinvestigation we discovered additional histological and immunohistochemical features of MALT-NHL in 17 cases. The 14 cases of thyroiditis with clonally expanded B cells clearly demonstrate the transition from autoimmune disease to non-Hodgkin's lymphoma.
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PMID:Temperature gradient gel electrophoresis for analysis of clonal evolution in non-Hodgkin's lymphoma of the thyroid. 758 52

Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with promising therapeutic activity in the lymphoproliferative disorders and in particular in low-grade non-Hodgkin's lymphoma (LG-NHL). In order to evaluate FLU in combination with other antineoplastic agents, we used a three-drug combination of FLU, mitoxantrone and prednisone (FMP) to treat 18 patients with recurrent LG-NHL. The FMP regimen was as follows: FLU, 25 mg/m2 i.v. on days 1 to 3; mitoxantrone, 10 mg/m2 i.v. on day 1; prednisone 40 mg i.v. on days 1 to 5. Of the 18 patients, 4 (22%) achieved complete response (CR), 9 (50%) partial response, and the remaining 5 showed no benefit from the treatment. The 4 CR patients are still in remission after 4, 6, 6, and 8 months, respectively. The median duration of overall survival of all patients was 9 months. The major toxic effects observed were neutropenia (50%) and infections and/or febrile episodes (17%); no fatalities due to drug side effects occurred. These results confirm the efficacy of the fludarabine-mitoxantrone combination-containing regimen in inducting a good remission rate with moderate side effects in recurrent LG-NHL.
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PMID:FMP regimen (fludarabine, mitoxantrone, prednisone) as therapy in recurrent low-grade non-Hodgkin's lymphoma. 758 45

Mobilization of peripheral blood stem cells (PBSC) can be accomplished with cytokines or rebound from myelo-suppressive chemotherapy. In this study, patients were mobilized with cyclophosphamide (CY) 4 g/m2 either alone or followed by GM-CSF 250 micrograms/m2 or G-CSF 600 micrograms. Colony-stimulating factors were administered subcutaneously. Eligibility included patients with non-Hodgkin's lymphoma (NHL; n = 29), Hodgkin's disease (n 4) and acute lymphoblastic leukemia (n = 2). One patient died from mobilization-related complications. Admission for neutropenic fevers and other complications occurred in 73% of patients receiving CY alone compared with 32% received CY + G-CSF or GM-CSF (P < 0.05). Apheresis was initiated when the white blood count approached 1 x 10(9)/l and continued until approximately 6 x 10(8) mononuclear cells/kg were collected. Mobilization with CY + GM-CSF led to significantly greater numbers of collected CFU-GM than with CY alone. Colony-stimulating factors were not administered after transplantation. collected progenitor cells correlated with the peak cell counts after mobilization. Following transplantation, an ANC > = 500 x 10(6)/l was achieved at 14.5 days and a platelet count > = 50 x 10(6)/l was achieved on day 20. Days to achieve an ANC > = 500 x 10(6)/l did not correlate with any of the analyzed variables. Platelet engraftment correlated with harvested BFU-E, thawed CD34+ cells and peak counts following mobilization. for patients with NHL, CR was obtained in 82% of evaluable cases. Median time to relapse was 343 days. Twenty five per cent of patients remain disease-free at 900+ days of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclophosphamide-mobilized peripheral blood stem cells in patient with lymphoid malignancies. 759 69

The use of unconjugated monoclonal antibodies to treat patients with non-Hodgkin's lymphoma by targeting specific antigenic determinants on malignant cells has been an area of intense laboratory and clinical research. Although occasional clinical successes have been seen, many limitations of such therapy have been identified, including the low endogenous cytotoxicity of most of the antibodies. More recently, investigators have attempted to employ monoclonal antibody-toxin conjugates (immunotoxins) to deliver specific cytotoxins to the lymphoma cell surface. This article describes the preclinical development of immunotoxin therapy as well as the initial results from selected Phase I and II clinical trials in patients with NHL. In addition, future directions are suggested for the use of these agents as adjuvant therapy and as treatment for patients with human immunodeficiency virus-related NHL.
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PMID:Prospects for immunotoxin therapy of non-Hodgkin's lymphoma. 761 29

The management of patients with treated malignant lymphomas requires functional methods to differentiate a residual soft tissue mass. Patients with treated Hodgkin's lymphoma (HL, n = 20, 68 malignant lesions, three benign lesions) or non-Hodgkin's lymphoma (NHL, n = 26, 46 malignant lesions, one benign lesion) were studied with positron emission tomography (PET) and fluorine-18 deoxyglucose (FDG). Oxygen-15 labelled water was used (n = 14, 25 lesions) in addition to FDG in order to obtain information on the tissue perfusion. Long-term follow-up studies with PET and FDG were performed in nine patients up to 511 days after the initiation of second-line therapy. Fourteen patients underwent single-photon emission tomography (SPET) with technetium-99m sestamibi immediately prior to the first PET examination. PET with FDG displays a high sensitivity for the detection of viable tumour tissue, all the malignant lesions being correctly classified in this study. The possible limitations are inflammatory processes, which may obscure tumour detection due to increased FDG uptake, and malignant lesions with low FDG uptake due to reduced perfusion. Difficulties exist in the prognosis of long-term response, since the change in FDG uptake may be variable. Long-term therapy outcome was correlated with the slope values obtained from the standardized integral uptake (SIU) data, which provides a new approach for the evaluation of PET follow-up studies. 99mTc-sestamibi, which should reflect the multidrug resistance, was evaluated with respect to therapy outcome. A high uptake of 99mTc-sestamibi was observed in patients with stable disease or better. The data support the hypothesis that sestamibi may reflect multidrug resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of tumour metabolism and multidrug resistance in patients with treated malignant lymphomas. 764 52

B cell non-Hodgkin's lymphoma (B-NHL) occurring in immunocompromised hosts, such as acquired immune deficiency syndrome (AIDS) patients, is a high-grade malignancy resistant to regular chemotherapy. To determine whether immunotherapy with public anti-Ig idiotype antibodies can be used to treat these NHL, the Ig idiotype specificity of six NHL in AIDS patients (AIDS-ML) and 23 B-NHL experimentally induced in immunocompromised mice (SCID mice) was investigated. One of the six AIDS-ML and two of the 23 experimental B-NHL reacted monoclonally with a single public antibody, while one AIDS-ML and three experimental B-NHL reacted polyclonally with two or three different antibodies. The presence of Ig idiotypic polyclonality requires special consideration with regard to the introduction of anti-Ig idiotype immunotherapy in these cases.
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PMID:Immunoglobulin idiotypic specificity of AIDS-associated lymphomas and their experimental model. 764 34

From 1986 through 1990, 13 previously untreated pediatric patients with advanced diffuse large-cell non-Hodgkin's lymphoma (LC-NHL) were treated with a 12-week MACOP-B regimen at St Jude Children's Research Hospital. Although 12 patients (92%) achieved a complete response, and one had a partial response, the 2-year event-free survival was only 54 +/- 15% (SE). Seven patients remain in continuous complete remission at a median of 40 months after therapy (range 23-57 months). Relapses occurred at sites of initial involvement in five patients at a median of 3.0 months after remission (range 1.2-8.5 months). Salvage therapy with radiation, and high-dose chemotherapy and bone marrow transplantation produced four durable second remissions. The 2-year overall survival for the entire group is 84 +/- 10% (SE). The 12-week MACOP-B regimen proved feasible in an ambulatory clinic setting with only minimal toxicity. We found that MACOP-B is an effective and tolerable treatment for pediatric patients with LC-NHL but did not provide improved survival over that of a similar group of children treated in previous trials at this institution.
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PMID:MACOP-B treatment in children and adolescents with advanced diffuse large-cell non-Hodgkin's lymphoma. 767 78


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