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)

Between September 1991 and April 1995, high-dose therapy with peripheral blood progenitor cell (PBPC) support was administered to 105 patients with non-Hodgkin's lymphoma (NHL). Thirty-three patients had high-grade NHL, while 72 patients had different forms of low- or intermediate-grade NHL. Except for three patients who received G-CSF during steady-state hematopoiesis, PBPCs were collected following cytokine-supported cytotoxic chemotherapy. This included G-CSF or the sequential administration of interleukin 3 (IL-3) and GM-CSF. Assessing bone marrow (BM) samples before the start of chemotherapy and leukapheresis (LP) products collected during cytokine-enhanced marrow recovery, a 2.3-fold greater mean concentration of CD34- cells was found in peripheral blood (p < 0.005). The blood-derived progenitor cells were enriched with a particular subset of more primitive progenitors, as the mean proportion of CD34+/Thy-1+ cells in LP products was three-fold greater in comparison to premobilization BM samples, respectively (p < 0.001). In contrast, the mean proportion of CD34+/CD19+ and CD19+ cells in LP products was 8.8- and 80-fold smaller compared to BM samples, respectively (p < 0.001). Following high-dose conditioning therapy including TBI in 74 patients, reinfusion of PBPC resulted in rapid and sustained engraftment in the majority of patients, while in seven patients an unsubstituted platelet count of greater than 20 x 10(9)/l was reached between 31 and 51 days. Five patients died of treatment-related complications between 13 and 188 days following transplantation. The probability of long-term disease-free survival at 30 months in patients autografted while they were in first remission was 70% in high-grade and 83% in low-grade NHL, respectively. The data may provide the rationale for the use of PBPC-supported high-dose regimens as first-line treatment for patients at high risk of treatment failure.
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PMID:High-dose therapy with peripheral blood progenitor cell support in patients with non-Hodgkin's lymphoma. 874 86

It was the aim of this study to examine the prognostic value of the detection of minimal residual disease (MRD), with the help of the polymerase chain reaction (PCR), in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) who underwent sequential high-dose therapy with peripheral blood progenitor cell (PBPC) support, and in patients with acute myeloid leukemia (AML) of the subclass M4Eo who underwent high-dose consolidation therapy. Basis for the application of a PCR assay in these disease entities are the following specific gene rearrangements: the t(14;18) translocation in a high percentage of NHL, the clonal rearrangement of the Ig heavy chain locus resulting in a unique complementary determining region 3 (CDR3) for MM region and the inversion 16 characteristic for the M4Eo subclass of AML. Before the G-CSF-supported cytotoxic chemotherapy was given, 65% of the 52 patients with low- and intermediate-grade NHL enrolled into the study had PCR+ bone marrow (BM) and/or peripheral blood (PB) samples. The majority of patients (29 of 52) were autografted with a PCR+ transplant. The proportion of harvests containing t(14;18)+ cells was two-fold less in patients mobilized in first remission than in those with a history of previous treatment failure. This was also reflected when examining the B cell contents of the harvests measured as CD19+ cells with a 3.3-fold smaller proportion of CD19+ cells in leukapheresis (LP) products of patients mobilized in first remission. Patients who received a PCR- transplant are in remission and remained PCR- in BM and PB samples post-transplantation. Conversion to PCR-negativity in BM and PB samples post-transplantation was observed in 11 of 19 patients who were also in remission. In contrast, 6 of 29 patients who were autografted with PCR+ products relapsed, while 4 of them presented with PCR- samples on several occasions post-transplantation. In patients with MM, the assessment of MRD in PBPC harvests was based on the CDR3 regions of the Ig heavy chain locus as a marker for clonality. The great majority of LP products (17 out of 19) contained tumor cells. To prove positive enrichment procedures for the elimination of tumor cells, CD34+ and CD19+ cell fractions obtained from LP samples in an experimental setting via preparative flow cytometry were analyzed for MRD resulting in PCR-negativity for all CD34+ fractions. The results of the four patients with AML M4Eo and inversion 16 are preliminary, with a tendency of persistence of PCR-positivity after finishing the high-dose consolidation therapy. In one case, recurrence of disease was accompanied by an increase of the signal strength in the PCR assay. Longer follow-up periods are necessary to determine the prognostic value of these PCR findings in the different disease entities.
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PMID:Detection of minimal residual disease by polymerase chain reaction in B cell malignancies. 874 88

The toxicity and feasibility of a high-dose sequential (HDS) chemotherapy programme delivered with growth factor support were evaluated in patients with intermediate and high-grade non-Hodgkin's lymphoma (NHL) or with progressive Hodgkin's disease. The scheme includes the sequential administration of single cytotoxic drugs at very high doses followed by intensified treatment with circulating progenitor autograft. In some instances, the original HDS scheme, initially designed at the Milan Cancer Center, was partially modified and intensified with a preliminary debulking phase. The use of G-CSF (filgrastim) made toxicity in the high-dose phase acceptable and allowed good harvests of peripheral blood progenitor cells (PBPC); the use of PBPC in the final autografting phase resulted in low haematological toxicity. Of 71 patients with NHL treated at our institution with either the original or the intensified HDS version, the overall toxicity-related mortality was 5.6%, thus comparable to lethal toxicity commonly associated with conventional chemotherapy. Adequate PBPC harvests are crucial for good tolerability of the programme. Optimal harvests are generally obtained in patients without neoplastic marrow infiltration while patients with marrow disease often have a poorer mobilisation. However, an optimally time-spaced chemotherapy debulking might also restore sufficient mobilisation in these latter patients. In terms of therapeutic efficacy, HDS had produced promising results since the initial experience in relapsed patients. More recently, HDS was evaluated as first-line treatment in a series of 22 consecutive patients, presenting with advanced-stage, intermediate-grade NHL other than diffuse large cell subtype. A CR rate of 82% was obtained following HDS, with a projected survival of 86% at five years. Thus, delivery of an intensive high-dose chemotherapy programme with haematopoietic growth factor support was found to be feasible and reasonably safe. The high anti-tumour efficacy of such a scheme makes it suitable for wider applicability in all those chemosensitive tumours where a dose increase might enhance the chance of cure.
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PMID:Haematological support of high-dose sequential chemotherapy: clinical evidence for reduction of toxicity and high response rates in poor risk lymphomas. 875 Jan 37

We report the clinical experience in 451 patients with HIV related non-Hodgkin's lymphoma (HIV-NHL) observed within the Italian Cooperative Group on AIDS and Tumors (GICAT: Gruppo Italiano Cooperativo AIDS e Tumori), a significant number of them being treated at the Aviano Cancer Center (ACC). High grade histology according to the Working Formulation, stages III-IV and B symptoms were detected in the majority of patients. The median survival was 6 months. Based on the Cox model, three factors appeared to influence survival: advanced stage, treatment received and failure to obtain complete remission (CR). In another study aimed at comparing between chemotherapy with or without G-CSF it was shown that G-CSF significantly reduced white blood cells (WBC) nadir duration, the mean delays between cycles, the mean hospitalization time for toxicity per patient treated, without increasing significantly the overall costs. Furthermore, of 77 GICAT patients treated at the ACC with (group A) or without (group B) long-lasting CR, performance status and the mean CD4+ cell count at time of NHL diagnosis were the only parameters of statistical relevance. Based on our data HIV related NHLs are highly aggressive malignancies which are associated with a poor prognosis per se, and because of the underlying HIV infection. Long-term survivals and possible cures can, nonetheless, be obtained in a subgroup of patients, who have a better performance status and a less advanced immune dysfunction related to HIV infection.
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PMID:Clinical evaluation of 451 patients with HIV related non-Hodgkin's lymphoma: experience on the Italian cooperative group on AIDS and tumors (GICAT). 875 Jun 28

The present study demonstrated that a human B-cell line derived from non-Hodgkin's lymphoma. HCF-MLpN. constitutively expressed G-CSF receptor on the cell surface. G-CSF binding to the cell surface was shown by immunofluorescence staining using biotinylated G-CSF preparation and analysed by flow cytometry. Specific binding of G-CSF to the cells was shown by pretreatment with unlabelled G-CSF. In the radioreceptor assay and Scatchard plot analysis using radiolabelled ligand, MLpN cells revealed a single species of binding site with an equilibrium dissociation constant of 167 (153-182) pM and a maximal binding site per cell of 1076 (1044-1116). The G-CSF receptor mRNA transcript was exhibited in the RNA from MLpN cells by reverse transcriptase polymerase chain reaction procedure. [3H]thymidine incorporation and trypan blue exclusion showed that the G-CSF receptor was capable of transducing the growth signal to HCF-MLpN cells. A small fraction of fresh B blasts from six patients with B-cell lymphoma and leukaemia displayed G-CSF binding by two-colour immunofluorescence staining. In contrast, a panel of seven B-cell lines was negative for the binding to biotinylated G-CSF preparation. These results suggest that the phenotype of G-CSF binding may be lost during the culture. The expression of G-CSF receptor in HCF-MLpN cells appeared to be exceptional.
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PMID:Constitutive expression of granulocyte-colony stimulating factor receptor on a human B-lymphoblastoid cell line. 875 83

We describe a 44-year-old man with non-Hodgkin's lymphoma receiving granulocyte colony-stimulating factor (G-CSF) who developed an acute arterial thrombosis. The removed thrombus contained large amounts of platelet aggregation. A rapid increase of platelets and increased adenosine diphosphate (ADP)- and collagen-induced platelet aggregation were observed at the time of the thrombotic event. A challenge test of G-CSF showed an increase in the platelet count and an augmentation of ADP- and collagen-induced platelet aggregation. In the use of GCSF. patients who produce a rapid increase in platelet levels could be at greater risk for thrombotic events and need to be followed-up carefully.
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PMID:Acute arterial thrombosis due to platelet aggregation in a patient receiving granulocyte colony-stimulating factor. 875 7

Counterflow centrifugal elutriation (CCE) has been extensively employed in T cell depletion of bone marrow cells for allografting. Nevertheless very little is known about CCE properties of mobilized hematopoietic progenitors. In this study five leukapheresis products collected after chemotherapy and G-CSF from patients with non-Hodgkin's lymphoma were elutriated. Two mononuclear cell fractions were obtained containing smaller and less dense cells (lymphocyte fraction) and larger and denser cells (monocyte fraction), respectively. The presence of immature CD34+ progenitor cells, not co-expressing CD33, CD38 and HLA-DR antigens, was demonstrated in both cell fractions. CD34+ cells were isolated from each fraction and grown in various culture conditions (CFU-GM and BFU-E assay, blast cell colony assay, cytokine supplemented liquid culture). CD34+ cells isolated from the monocyte fraction showed a longer lasting expansion in liquid culture and a higher number of blast cell colonies than CD34+ cells selected from the lymphocyte fraction. Moreover a significant reduction of T cell number was obtained in the monocyte fraction. These data suggest that chemotherapy plus G-CSF-mobilized progenitor cells show a characteristic behavior when subjected to CCE, allowing an efficient T cell depletion without losing more immature progenitors.
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PMID:Separation of chemotherapy plus G-CSF-mobilized peripheral blood mononuclear cells by counterflow centrifugal elutriation: in vitro characterization of two different CD34+ cell populations. 886 56

Cytokines are involved in hematopoiesis by regulating proliferation, differentiation and cellular functions of various lineages of hematopoietic cells. There is an increasing range of clinical conditions in which cytokines are involved as therapeutic agents. One of the most advanced and successful applications is the stimulation of hematopoiesis by the colony stimulating factors (GM-CSF and G-CSF) and erythropoietin. Hematopoietic growth factors are effective in accelerating recovery from neutropenia after chemotherapy and bone marrow transplantation and in reducing incidence of infections. Interferon alpha (IFN-alpha) proved a useful therapeutic agent for chronic myelogenous and hairy cell leukemias as well as for multiple myeloma and non-Hodgkin's lymphoma. Interleukin 2 is the only cytokine apart from IFN-alpha accepted as antineoplastic agent. It may be useful as adjuvant therapy in the hematological malignancies. It may be supposed that in the near future new recombinant cytokines will be introduced in the treatment of blood diseases.
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PMID:Cytokines in the treatment of hematological disorders: recent progress and perspectives. 887 63

Twenty-eight patients with different hematological diseases (17 non-Hodgkin's lymphoma, one Hodgkin's disease and 10 multiple myeloma) underwent peripheral blood progenitor cell (PBPC) collection after cyclophosphamide 7 g/m2 and rh-G-CSF. Fifty-eight leukaphereses were carried out with a fully automated PBPC collection procedure. Progenitor cell release was monitored by standardized determination of CD34+ cells in the peripheral blood. After a profound aplasia, a continuous increase in CD34+ cells in the peripheral blood was seen for at least 3-4 days. In 82% of our patients more than 2.5 x 10(6) CD34/kg could be collected using a standard apheresis of 10 l. There was a high correlation between the CD34+ cells in the peripheral blood and CD34+ cells/kg harvested. (r2 = 0.91). A relatively constant ratio (median 14.3, range 3.2-22.6) was found between CD34+ cells/kg and CFU-GM/kg. Based on the CD34 values of the pre-apheresis blood and the body weight of an individual patient and using the mathematical model of regression analysis (y = mx + b) for the correlation between the CD34+ cells/microliter in the pre-apheresis blood and the CD34+ cells/kg, it was possible to create a formula allowing for target value tailored apheresis. Using this formula, the blood volume which needs to be processed in order to harvest a desired number of CD34+ cells/kg can be calculated. This strategy can be applied to reduce the time for and the number of aphereses. Nineteen leukaphereses were carried out applying the formula. In 18 of 19 leukaphereses the expected CD34+/kg values were correctly achieved or exceeded. The formula was most reliable when the CD34 value was higher than 15/microliter and when the WBC count was below 20 x 10(9)/l in the pre-apheresis blood. For mobilizations using hematopoietic growth factors alone our formula is not applicable, because in most cases the pre-apheresis white blood cell count is higher than 20 x 10(9)/l and the collection efficacy of lymphomonocytoid cells decreases with a high pre-apheresis white blood cell count. The formula also works with other mobilization regimens that induce a pronounced aplasia.
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PMID:Target value tailored (TVT) apheresis approach for blood progenitor cell collection after high-dose chemotherapy and rh-G-CSF. 887 26

In this article we report our initial clinical experiences in connection with immunomagnetic isolated CD34-positive cells from peripheral blood progenitor cells. Six patients, five with breast cancer and one with non-Hodgkin's lymphoma, were mobilized by chemotherapy and G-CSF (5ug/kg). CD34-positive cells were isolated by means of immunomagnetic beads (Dynalbeads) and Isolex 300 Cell Separator (Baxter, USA). Mean purity of isolated CD34-positive cells was 97% (94.7-99.7) and mean yield was 54% (35-68). Three patients were treated with high dose therapy followed by reinfusion of CD34-positive cells as stem cell support. Recovery of neutrophils (> 0.5 x 10(9) leucocytes/liter) occurred at day 8, 11 and 13 and of platelets (> 20 x 10(9) platelets/litre) at day 9,14 and 32. It is concluded that immunomagnetic isolated CD34-positive cells give high purity and yield. Although use of CD34-positive cells reduces the content of contaminating tumour cells in the graft, breast cancer cells were still detectable in two out of five CD34-positive cell products.
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PMID:[High-dose therapy of cancer with CD34 positive cells as stem cell support]. 892 21


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