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)

Recombinant human interleukin-3 (rhIL-3), granulocyte-macrophage colony-stimulating factor (rhGM-CSF), and granulocyte colony-stimulating factor (rhG-CSF) enhance neutrophil recovery following autologous bone marrow transplantation (ABMT) for malignant lymphoma. Based on findings in preclinical studies, a phase I-II trial was conducted to assess the safety and efficacy of the sequential administration of rhIL-3 and rhGM-CSF after bone marrow ablative cytotoxic therapy and ABMT for patients with malignant lymphoma. Thirty-seven patients (20 with non-Hodgkin's lymphoma and 17 with Hodgkin's disease) were treated with intensive cytotoxic therapy before ABMT. Patients were treated in one of four cohorts to receive rhIL-3 (2.5 or 5.0 microg/kg/d) administered by subcutaneous injection for either 5 or 10 days following ABMT. Twenty-four hours after the last dose of rhIL-3, rhGM-CSF (250 microg/m2/d as a 2-hour intravenous infusion) administration was initiated. Sequential cytokine therapy post-ABMT resulted in fewer days of platelet and red blood cell transfusions than seen in historic controls with rhIL-3, rhGM-CSF, or rhG-CSF monotherapy. These data suggest that the sequential administration of rhIL-3 and rhGM-CSF after ABMT results in rapid recovery of multilineage hematopoiesis.
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PMID:Recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma. 860 May 45

Granulocyte colony-stimulating factor (G-CSF) as a single agent is increasingly used for the mobilization of peripheral blood progenitor cells (PBPCs) for stem cell transplantation. In patients with perturbed hematopoiesis the mobilizing capacity of G-CSF alone may be inadequate. We have shown in rhesus monkeys that interleukin-3 (IL-3) pretreatment markedly potentiated the increase in PBPC numbers by subsequent administration of granulocyte/macrophage-CSF (GM-CSF). Here we studied the effect of IL-3 pretreatment on G-CSF-induced mobilization of PBPCs in 6 patients with Hodgkin's disease (n = 5) or non-Hodgkin's lymphoma (n = 1) who had low progenitor cell numbers because of previous chemotherapy. Patients were treated in cycle 1 with G-CSF at a dose of 5 microgram/kg/d for 5 days and, after a treatment-free interval, received cycle 2 consisting of 5 microgram/kg/d of IL-3 for 7 days followed by G-CSF again at a dose of 5 microgram/kg/d for 5 days. G-CSF alone increased the mean number of circulating colony-forming units-GM (CFU-GM) by 21-fold, the number of burst-forming units-erythroid (BFU-E) by 9-fold, and the number of CFU-mix by 24-fold over pretreatment values. Treatment with 5 microgram/kg/d of IL-3 for 7 days did not mobilize by itself but significantly potentiated G-CSF-induced mobilization of all progenitor cell types leading to a 56-, 15-, and 46-fold increase over baseline of CFU-GM, BFU-E, and CFU-mix numbers, respectively. In 2 patients in whom leukapheresis was performed after G-CSF alone the target number of 2 x 10(6)/kg CD34+ cells was not reached. However, leukapheresis after the IL-3/G-CSF combination obtained > or =2 x 10(6)/kg CD34+ cells in 3 of 6 patients, including both patients who had inadequate collection after G-CSF alone. In one patient adequate function of mobilized progenitors could be shown by the demonstration of rapid trilineage engraftment after infusion of progenitors after myeloablative chemotherapy. Seven-day pretreatment with IL-3 may be a useful mean to augment mobilization of circulating progenitors by G-CSF. The combination of IL-3 and G-CSF seems to allow the procurement of sufficient numbers of PBPCs in some patients who cannot be mobilized adequately by G-CSF alone.
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PMID:Potentiation of granulocyte colony-stimulating factor-induced mobilization of circulating progenitor cells by seven-day pretreatment with interleukin-3. 863 89

The methods of mobilization and collection of stem cells in peripheral blood stem cells transplantation (PBSCT) and the association between the number of stem cells transplanted and hematopoietic recovery were studied. The investigation was carried in 22 patients (11 acute leukemia, 6 multiple myeloma, 4 non-Hodgkin's lymphoma, 1 breast cancer). Three regimens for mobilization were carried out as follows: 1) chemotherapy + tetrahydrofolic acid + dexamethasone, 2) chemotherapy + rhGM-CSF + dexamethasone, 3) chemotherapy + rhG-CSF + dexamethasone. Besides, CD34/CD33 dual-color direct immunofluorescence flow cytometry assay was performed in 7 cases in the rhG-CSF group. The results showed: 1) The mean number of collected cells (MNC) in the rhG-CSF group was MNC (8.29 +/- 6.14) x 10(8)/kg and CFU-GM (21.35 +/- 17.24) x 10(4)/kg, being highest among the 3 groups. 2) The number of CD34+ cells correlated with MNC and CFU-GM. CD34+ cells in the peripheral blood were 0 or < 0.5% before mobilization and increased markedly 6-8 days after rhG-CSF administration. Harvesting should be started at that time and carried out every day until CD34+ cells reached 5 x 10(6)/kg. 3) The number of PBSC transplanted was the key to hematopoietic recovery.
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PMID:[A study on the peripheral blood stem cells mobilization, collection and their effects on engraftment]. 873 24

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

The survival, proliferation, differentiation and function of normal hematopoietic cells are negatively and positively controlled by various cytokines. Survival and proliferation of leukemic cells appears to be influenced, at least in vitro, by several cytokines. Among the different hematopoietic cell lineages, megakaryocytopoiesis represents a complex and unique hematopoietic system that is thought to be supported by some well-known cytokines; however, the hypothetical lineage-specific main regulator of platelet production, termed thrombopoietin (TPO) had remained elusive. Recently, characterization of the proto-oncogene c-mpl revealed structural homology with the hematopoietic cytokine receptor superfamily, specific expression on cells of the megakaryocytic lineage and functional involvement in megakaryocytopoiesis. Several groups purified and cloned the MPL ligand. Extensive in vitro and in vivo studies have shown that the MPL ligand has activity in stimulating both megakaryocytopoiesis and platelet production proving that this ligand is the long-sought growth factor TPO itself. The MPL receptor was found at the mRNA and/or protein level in 40-80% of primary acute myeloid leukemia (AML) cases in various series. MPL expression was not limited to certain morphological FAB types, although the highest percentages were seen in the M6 (erythroid) and M7 (megakaryocytic) subclasses. Among the myelodysplastic syndromes (MDS), MPL expression was detected in one third of the cases, in particular in refractory anemia with excess of blasts and chronic myelomonocytic leukemia. Lymphoid malignancies such as acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL) and myeloma were MPL-negative. Among the large panel of human leukemia-lymphoma cell lines studied, MPL expression occurred predominantly in lines with erythro-megakaryocytic phenotypes. Nearly all primary and continuously cultured non-hematopoietic solid tumor samples were negative for MPL expression. A significant portion of AML cases and of erythroid, megakaryocytic and myeloid leukemia cell lines co-expressed TPO and MPL mRNA transcripts, although no biologically active TPO appeared to be secreted by these cells. In several studies TPO induced in vitro proliferation of 14-37% of primary AML cases, predominantly of the M2 and M7 subtypes. TPO significantly enhanced the cytokine-induced growth of AML cells in a substantial fraction of cases responsive to GM-CSF, IL-3, IL-6 or SCF. While none of 30 growth factor-independent erythro-megakaryocytic leukemia cell lines responded to TPO with increased proliferation, TPO strongly augmented the growth of several constitutively cytokine-dependent cell lines (eg HU-3, M-07e, TF-1) which can be made TPO-dependent and used as bioassays. Neither in primary cells nor in cell lines did TPO appear to induce any signs of morphological, functional or immunological differentiation. Expression of the MPL receptor is not correlated with a proliferative response to TPO. In summary, extensive studies on normal human and animal cells demonstrated the specificity and function of the MPL receptor and proved that its ligand TPO is the major physiological regulator of megakaryocytopoiesis. The data reviewed here document the wide expression of the MPL receptor on AML cells and also suggest some proliferative effects on certain leukemia cells, apparently on non-megakaryocytic AML cells as well. Thus, experimental evidence supports the notion that TPO may contribute, at least in part, to leukemogenesis, especially in combination with other hematopoietic cytokines which is of clinical significance. TPO-responsive cell lines represent powerful tools for such analyses.
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PMID:Thrombopoietin: expression of its receptor MPL and proliferative effects on leukemic cells. 875 57

The T cell-mediated antineoplastic activity observed following allogeneic transplantation and the suggestion of improved therapeutic efficacy by autologous peripheral stem cell transplantation (PSCT) as compared to autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) stimulated our interest in the immunologic competence of stem cell products. We report the immune phenotype and function of normal peripheral blood (PB) cells, bone marrow (BM) cells from normal donors and cancer bearing patients, GM-CSF-mobilized and apheresed blood mononuclear cells from NHL patients, unmobilized apheresed mononuclear cells from normal volunteers and umbilical cord blood (CB). The analyses include three-color fluorescent cytometry of the major hematologic and immunologic phenotypes as well as natural killer (NK) activity, natural suppressor (NS) activity, and phytohemagglutinin (PHA) and pokeweed (PWM) mitogenesis. These studies demonstrated an increased frequency of T cells in apheresis products as compared to BM and CB products. Specifically, the mobilized PSC had significant increases in CD3+, CD4+, CD45RO+ and CD56+ cells relative to BM cells. In addition, the frequency of TCR gamma/delta + cells in all the stem cell products, with the exception of CB, were also increased compared to normal peripheral blood leukocytes (PBL). However, all the stem cell products had a significant depression in T (PHA mitogenesis) and B (PWM mitogenesis) cell function. The depression in immune cell functionality, in the PSC products was perhaps due to the high frequency of monocytes which appeared to be increased due to both mobilization and apheresis. The frequency of the NK cell phenotype (CD56) but not function was increased in the mobilized PSC products, while the NK cell function in the BM products from cancer patients but not normal donors was depressed as compared to normal PBL. In summary, there are significant differences in the cellular phenotypes and immunologic competence among the various stem cell products with potential therapeutic implications.
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PMID:Immunologic phenotype and function in human bone marrow, blood stem cells and umbilical cord blood. 883 96

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

Primary non-Hodgkin's lymphoma of the central nervous system (PCNSL) has recently increased in incidence, due primarily to an enlarging immunosuppressed patient population. The pathogenetic role of Epstein-Barr virus (EBV) is of interest due to its established role in other lymphoproliferative disorders in immunosuppressed patients. Twenty-three cases of histologically confirmed PCNSL with corresponding cytology were identified, all obtained under stereotactic guidance. Twenty patients were human immunodeficiency virus (HIV) positive, two were HIV negative, and one was of unknown status. Papanicolaou-stained slides were selected from each case and evaluated for the presence of EBV RNA via in situ hybridization (ISH) utilizing a biotinylated probe specific for EBER 1 RNA, and detected by a conventional streptavidin-peroxidase system. The cases included immunoblastic (12), large cell (10), and mixed small and large cell lymphoma (1). The predominant immunophenotype was B-cell (19), although T-cell (2) and biphenotypic (1) cases were also identified. ISH showed nuclear positivity for EBV RNA in 19 of 23 cases (83%). This study confirms the presence of EBV in PCNSL in immunosuppressed patients and implies a potential etiologic role. The ability to demonstrate EBV RNA in cytologic preparations by ISH also raises the possibility of early identification of high-risk patients through detection of EBV-infected lymphocytes in CSF specimens.
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PMID:Cytomorphology of primary CNS lymphoma: review of 23 cases and evidence for the role of EBV. 896 66

ACES (Ara-C, carboplatin, etoposide, steroids) therapy using granulocyte-colony stimulating factor (G-CSF) was designed for relapsed or refractory non-Hodgkin's lymphoma (NHL), and the therapeutic effects and adverse reactions were studied. The subjects were 40 patients, including 19 relapsed cases and 21 refractory cases, subjected to chemotherapy using anthracycline type agents. The ACES therapy consisted of carboplatin at 100 mg/m2 and etoposide at 80 mg/m2 for 4 d from the first day, Ara-C at 2 g/m2 on the fifth day, solumedrol at 500 mg for 5 d from the first day and G-CSF at 2 micrograms/kg from the seventh day. This therapy was performed every 3 weeks, in principle. The doses were reduced to 70% of the above values for patients aged 70 yr or older. Among the 40 patients, complete remission (CR) was achieved in 14 (35%) and partial remission (PR) in 14 (35%) for a response of 70%. The 50% survival period was 526 d, and the 2-yr disease-free survival rate was 58.3%. Adverse reactions of grade 3 or higher included granulocytopenia in 62.5%, anemia in 17.5% and thrombocytopenia in 50%, but there was no death related to treatment. Four patients underwent transplantation of hematopoietic stem cells and have survived for long periods. This treatment was effective against relapsed NHL and could be performed safely with few adverse reactions.
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PMID:Salvage chemotherapy for relapsed or refractory non-Hodgkin's lymphoma with a combination of ACES (high-dose Ara C, carboplatin, etoposide and steroids) therapy. 898 96

Recently various cytokines have been introduced into the clinic and have played important therapeutic roles in the treatment of hematological malignancies. Among these cytokines, I have focused on interferon (IFN) and granulocyte (G) or granulocyte-macrophage (GM) colony stimulating factor (CSF), which are currently the most useful cytokines, in this review. IFN-alpha has been approved for chronic myelogenous leukemia (CML), multiple myeloma and hairy cell leukemia. In addition, IFN-alpha has therapeutic potentials for low grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma. Thus, IFN-alpha is one of the most useful and wide-ranging antitumor agents in hematological malignancies. Most striking effects have been studied in chronic phase CML. Cytogenetic responses are seen in 30-40% of the treated patients and a complete cytogenetic response can be seen in about 10%. Long-term survival can be expected in these patients. Considering the risk of graft-versus-host disease-associated mortality in allogeneic bone marrow transplantation, the category of treatment is difficult to choose in IFN-responsive patients. Elucidation of the antitumor mechanism of IFN, as a prototype for other biological response modifiers, may revolutionize cancer treatment. G- and GM-CSF (CSFs) have reduced the duration of neutropenia, incidence of infectious episodes and days of hospitalization following cancer chemotherapy or stem cell transplantation. CSFs have also been used to mobilize peripheral blood stem cells and to increase dose intensity of chemotherapeutic agents. Leukemic cells from many patients with acute myelogenous leukemia (AML) have surface receptors for CSFs and may proliferate in response to CSFs. However, several randomized studies showed that CSFs can be used safely and effectively in augmenting neutrophil recovery in patients with AML when given after induction chemotherapy. Various trials have been made to prime leukemic cells by CSFs to make them more susceptible to chemotherapy, but no convincing evidence has been obtained.
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PMID:Cytokine therapy for hematological malignancies. 899 Jun 22


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