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)

A retrospective analysis of long-term hematopoiesis was performed in a group of 145 consecutive patients who had received high-dose therapy with peripheral blood progenitor cell (PBPC) support between May 1985 and December 1993. Twenty-two patients had acute myelogenous leukemia, nine had acute lymphoblastic leukemia, 43 had Hodgkin's disease, 57 had non-Hodgkin's lymphoma, and 14 patients had multiple myeloma. Eighty-four patients were male and 61 female, with a median age of 37 years (range, 16 to 58 years). In 46 patients, PBPC were collected after cytotoxic chemotherapy alone, while 99 patients received cytokines either during steady-state hematopoiesis or post-chemotherapy. Sixty patients were treated with dose-escalated polychemotherapy, and 85 patients had a conditioning therapy including hyperfractionated total body irradiation at a total dose of 14.4 Gy. The duration of severe pancytopenia posttransplantation was inversely related to the number of reinfused granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Threshold quantities of 2.5 x 10(6) CD34+ cells per kilogram or 12.0 x 10(4) CFU-GM per kilogram became evident and were associated with rapid neutrophil and platelet recovery within less than 18 and 14 days, respectively. These numbers were also predictive for long-term reconstitution, indicating that normal blood counts are likely to be achieved within less than 10 months after transplantation. Conversely, 12 patients were autografted with a median of 1.75 x 10(4) CFU-GM per kilogram resulting in delayed recovery to platelet counts of greater than 150 x 10(9)/L between 1 and 6 years. Our study includes bone marrow examinations in 50 patients performed at a median follow-up time of 10 months (range, 1 to 85 months) posttransplantation. A comparison with normal volunteers showed a 3.2-fold smaller proportion of bone marrow CD34+ cells, which was paralleled by an even more pronounced reduction in the plating efficiency of CFU-GM and burst-forming unit-erythroid. No secondary graft failure was observed, even in patients autografted with relatively low numbers of progenitor cells. This suggests that either the pretransplant regimens were not myeloablative, allowing autochthonous recovery, or that a small number of cells capable of perpetual self-renewal were included in the autograft products.
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PMID:Sustained long-term hematopoiesis after myeloablative therapy with peripheral blood progenitor cell support. 778 Jan 58

Peripheral blood stem cells (PBSC) from 15 patients with advanced non-Hodgkin's lymphoma (NHL), two patients with chronic lymphocytic leukemia, and two patients with myeloma were collected by continuous-flow leukapheresis after chemotherapy with MIV (mitoxantrone, ifosfamide, and etoposide, five patients) or high-dose cyclophosphamide (14 patients), followed by administration of GM-CSF. Sixteen patients (84%) had persistent marrow involvement at time of inclusion. Results were compared to those obtained in a control group of similar age and disease status in whom collection had been performed after MIV chemotherapy alone. The number of mononuclear cells, granulocyte-macrophage colony-forming units (CFU-GM), CD34+ cells were higher in GM-CSF treated patients with a lower mean number of leukapheresis (3.5 versus 6.4). Among the 19 patients harvested after chemotherapy plus GM-CSF, more progenitor cells were obtained in the cyclophosphamide group than in the MIV group. In all these patients except one, the number of mononuclear cells was sufficient to realize a transplantation. Seventeen patients received intensification with BEAM regimen (8 patients) or cyclophosphamide plus etoposide and total body irradiation (9 patients). Two patients failed to reconstitute correct hematopoiesis and three early toxic deaths occurred for a total of five procedure-related deaths. Nine of these 17 patients are in persistent complete remission with a median post-transplant follow-up of 18 months. Time to reach granulocyte and platelet recovery was not correlated with the number of mononuclear cells, CFU-GM, granulocyte-erythroid-macrophage-megakaryocyte colony-forming units (CFU-GEMM), CD34+ cells, and CD34+ CD33- cells but with the number of previous chemotherapy regimens. PBSC harvesting is achievable after chemotherapy plus GM-CSF in heavily pretreated patients with persistent marrow involvement. Moreover, these cells are able to reconstitute correct hematopoiesis after intensive treatment in these patients.
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PMID:Peripheral blood stem cells harvested after chemotherapy and GM-CSF for treatment intensification in patients with advanced lymphoproliferative diseases. 810 11

Recombinant human interleukin-3 (IL-3) is well-tolerated according to phase I studies, and produces trilineage hematologic responses in patients with normal bone marrow. In addition, promising results have been obtained in a variety of bone marrow failure states. We studied IL-3 in 7 patients with markedly delayed engraftment after autologous bone marrow transplantation (ABMT) for hematologic malignancies (acute myeloid leukemia 4, chronic myeloid leukemia 1, myeloma 1, non-Hodgkin's lymphoma 1). All patients were red blood cell- and platelet transfusion-dependent, had an absolute neutrophil count (ANC) < 0.7 x 10(9)/L and failed to achieve a sustained ANC > 1.0 x 10(9)/L after receiving granulocyte-macrophage colony stimulating factor (GM-CSF) for 28 days. IL-3 was given daily for 21 days at 2 micrograms/kg/d (2 patients) and 5 micrograms/kg/d (5 patients). Toxicity was mild and consisted mostly of low-grade fever and malaise. No changes in platelet, hemoglobin or reticulocyte levels were observed. Four patients had at least a 2-fold increase in ANC at the end of IL-3 treatment. Five patients received GM-CSF 10 micrograms/kg/d subcutaneously for 7 to 10 days immediately after IL-3 and 4 had a further increase in ANC (median 1.7-fold, range 1.6- to 5.8-fold), but no change in platelet transfusion requirements. Hematopoietic colony assays of bone marrow cells obtained before and after treatment showed that granulocyte-macrophage colony-forming cell (CFU-GM) and erythroid blast-forming cell (BFU-E) levels were severely reduced and multilineage progenitors (CFU-GEMM) absent in all patients, and remained low after IL-3 treatment for 21 days. Sequential IL-3 and GM-CSF produced a significant but transient increase in the neutrophil counts of some patients. IL-3 appears to be of limited benefit in patients who are severely aplastic after ABMT and have very low levels of bone marrow progenitors.
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PMID:Interleukin-3 followed by GM-CSF for delayed engraftment after autologous bone marrow transplantation. 844 Mar 38

Transfer of the multidrug resistance-1 (MDR1) gene to hemopoietic cells for myeloprotection against cytostatic agents is a new and rapidly developing field in "cancer gene therapy." Before clinical application, safety and efficacy criteria need to be met. The retroviral producer cell lines and the retroviral supernatant need to be tested for replication-competent retrovirus and contamination with adventitious agents. The cell source needs to contain sufficient hemopoietic cells with repopulating ability. We used CD34(+)-selected mobilized peripheral blood progenitor cells (PBPC) for MDR1 transductions in order to obtain a favorable vector to target cell ratio. An analysis of 249 patients who had undergone PBPC harvesting revealed that primarily solid tumor and non-Hodgkin's lymphoma patients are eligible for CD34+ selection. They can be expected to retain sufficient CD34+ cells for rapid and sustained engraftment after myeloablative therapy if the CD34+ cell loss (approximately 50%) during the procedure is taken into account. Clinical MDR1 gene therapy protocols focus on these two patient groups. Next we characterized MDR1 gene transfer into lineage-committed and primitive hemopoietic cells. Provirus-specific polymerase chain reactions showed a high efficiency gene transfer into colony-forming-units granulocyte-macrophage and long-term culture cells. The level of the conferred P-glycoprotein expression was estimated by fluorescence-activated cell sorting analysis to be up to 3 log above mock-transduced controls. The cobblestone area forming cell assay, which is a stroma-dependent long-term culture assay measuring frequencies of stem cell subsets in a limiting-dilution set-up, allowed demonstration of sustained expression of the MDR1 gene in the progeny of primitive hemopoietic cells. This is a favorable basis for a clinical MDR1 gene therapy trial.
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PMID:Retroviral transfer of the multidrug resistance-1 gene into lineage-committed and primitive hemopoietic cells. 874 95

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

To examine the safety and efficacy of recombinant-methionyl human stem cell factor (r-metHuSCF), 38 patients with intermediate-grade or immunoblastic high-grade non-Hodgkin's lymphoma who were eligible for autologous transplantation were randomized to receive r-metHuSCF (5, 10, 15, or 20 microg/kg/d) plus Filgrastim (10 microg/kg/d) or Filgrastim (10 microg/kg/d) alone to mobilize peripheral blood progenitor cells. Subcutaneous administration of r-metHuSCF was well tolerated in conjunction with a multi-agent pre-medication regimen; local injection site reactions were the most commonly seen adverse event. The total mononuclear cell count, CD34+ cell content, granulocyte-macrophage colony-forming cells (GM-CFC), and burst-forming units-erythroid (BFU-E) per kilogram in the apheresis product was similar when all patients were analyzed by treatment cohort and mobilization regimen (Filgrastim or r-metHuSCF in combination with Filgrastim); however, when prior chemotherapy was taken into account in a supplementary analysis, clinically important differences were observed. Extensive prior therapy was defined as the amount of exposure to specific stem cell toxic chemotherapeutic agents that patients received. These agents include procarbazine, nitrogen mustard, melphalan, nitrosoureas (> or = 2 cycles of any of these drugs) or greater than 7.5 g of cytosine arabinoside. In these patients, there was an increased number of CD34+ cells (1.76 v 0.28 x 10(6)/kg), GM-CFC (20.5 v 5.0 x 10(4)/kg), and BFU-E (36.9 v 8.9 x 10(4)/kg) in patients receiving r-metHuSCF and Filgrastim (N = 18) compared with Filgrastim alone (N = 5). These patients also had a decreased time to an untransfused platelet count of 20 x 10(9)/L that was 10.5 days shorter in the patients who received r-metHuSCF and Filgrastim (12.5 v 23 days). These differences were not found to be statistically significant, possibly because of small size, but are clinically important.
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PMID:Recombinant methionyl human stem cell factor and filgrastim for peripheral blood progenitor cell mobilization and transplantation in non-Hodgkin's lymphoma patients--results of a phase I/II trial. 912 16

The kinetic change in peripheral blood progenitor cells (PBPC) during 3 to 6 cycles of standard CHOP regimen supported with human recombinant granulocyte colony-stimulating factor (rG-CSF) was investigated in three patients with newly diagnosed intermediate grade, diffuse large cell type, non-Hodgkin's lymphoma (NHL) without bone marrow invasion. Patients were given rG-CSF subcutaneously (2 mu g/kg/day) initiated when total leukocytes was < 3.0 x 10(9)/1. When the leukocyte count remained at >3.0 x 10(9)/1, rG-CSF was started 10 days following the prior CHOP. Treatment with rG-CSF was discontinued after the leukocyte count reached >10.0 x 10(9)/1, and CHOP was started the next day (CHOP-G regimen). The number of PBPC was monitored by clonal assay in patients 1-3. No severe leukopenia with <0.5 x 10(9)/1 of neutrophils was seen in any patient. Colony-forming unit granulocyte-macrophage (CFU-GM) significantly increased after 2-3 days of consecutive administration of rG-CSF. The magnitudes of maximum amplification of CFU-GM in patients 1, 2, and 3, were 56-fold (during 3 cycles of CHOP-G), 216-fold (during 2 cycles), and 67-fold (during 4 cycles), respectively, and the absolute numbers of the maximum CFU-GM/ml blood were 983, 7,568, 9,865, respectively. In one patient who was given 6 cycles of CHOP-G, the peak values of mobilized CFU-GM in each cycle did not substantially decrease until 6 cycles of CHOP-G had been completed. Thus, the CHOP-G regimen described here seems to be very efficient increasing the circulating CFU-GM prior to harvesting PBPC.
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PMID:Mobilization of peripheral blood progenitor cells following CHOP treatment combined with delayed granulocyte colony-stimulating factor administration in patients with non-Hodgkin's lymphoma. 917 13

Cytokines play an important role in granuloma formation, but the extent that cytokine profiles are similar in different granulomatous diseases and whether differences in the histopathologic features of the granulomatous response results from differences in cytokine production have not been evaluated. To investigate these questions, we used RT-PCR to quantify the expression of mRNAs coding for 16 cytokines in granulomatous lymph nodes from patients with tuberculosis and sarcoidosis and from control tissues, and we sought correlations between the level of expression of these cytokines and the histopathologic features of the granulomas. Expression of mRNAs coding for a number of cytokines (IL-1beta, IFN-gamma, TNF-alpha, granulocyte-macrophage (GM)-CSF, IL-12 (p40), and lymphotoxin-beta) was increased in tuberculous and sarcoid granulomas compared with that of control tissues. All sarcoid granulomas were shown to express a Th1 pattern of cytokine mRNAs, while tuberculous lymph nodes expressed either a Th1 or a Th0 profile. GM-CSF and lymphotoxin-beta mRNAs were more abundant in sarcoid than in tuberculous granulomas, whereas IL-8 mRNA was strongly expressed only in tuberculous lymph nodes. Strong expression of GM-CSF, TNF-alpha, and IL-8 by granulomas was shown to be correlated, respectively, with the presence of florid granulomatous lesions, the absence of central necrosis, and the presence of neutrophil infiltration. These results demonstrate that the formation of tuberculous and sarcoid granulomas in humans is associated with the expression of characteristic cytokine profiles and indicate that the expression of certain cytokines is associated with the development of specific pathologic features in the resulting granulomas.
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PMID:Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response. 930 Jul 29

The common use of the marrow autograft mononuclear cell (MNC) count derives from positive correlative studies following allogeneic transplantation and from earlier conflicting data regarding the value of the bone marrow autograft colony-forming unit granulocyte-macrophage (CFU-GM) assay for prediction hematologic recovery after ABMT. We conducted a retrospective analysis at our institution to determine whether autograft CFU-GM levels predict engraftment of neutrophils and platelets after ABMT in heavily pretreated patients with hematologic malignancies. Between 1 January 1993 and 1 March 1995, 58 heavily pretreated patients received only marrow cells as the autograft product. Patients with Hodgkin's disease (n = 25), acute myeloid leukemia (n = 19), and non-Hodgkin's lymphoma (n = 14) underwent intensive therapy with etoposide and melphalan. Unpurged marrow containing a minimum of 1.5 x 10(8)/kg (range: 1.5-4.8) was infused. Median time to an absolute neutrophil count > or = 0.5 x 10(9)/L was 21 days (range 10-270) and median time to a platelet count > or = 20 x 10(9)/L independent of transfusions was 44 days (range 13-317). There was no correlation between autograft MNC count and neutrophil or platelet engraftment. However, a correlation between autograft CFU-GM and both platelet and neutrophil recovery was demonstrated with a threshold CFU-GM of 3 x 10(4)/kg; delayed neutrophil recovery was observed in 79% of patients below this threshold compared to only 9% in those with an autograft CFU-GM level of more than 3 x 10(4)/kg (p = 0.0001). Similarly, platelet recovery was delayed in 76% of patients below, and 20% of those above this threshold (p = 0.003). We conclude that marrow autograft CFU-GM is predictive of engraftment of both platelets and neutrophils in heavily pretreated patients after ABMT for hematological malignancies.
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PMID:Bone marrow mononuclear cell count does not predict neutrophil and platelet recovery following autologous bone marrow transplant: value of the colony-forming unit granulocyte-macrophage (CFU-GM) assay. 933

We assessed the concentration of haemopoietic progenitors in peripheral blood in six patients with de novo intermediate grade non-Hodgkin's lymphoma receiving multiple cycles of escalated dose epirubicin and cyclophosphamide on day 1 followed by 5 microg/kg of G-CSF (filgrastim) on days 2-14. Specimens were taken at days 12, 15 and 18 in cycles 1 and 2 and on day 15 for cycles 3-6. Progenitor numbers were maximal on day 15 in cycles 1 and 2. The median number of granulocyte-macrophage colony forming cells (GM-CFC) and CD34+ cells on day 15 of cycles 1 and 2 was 3.8 x 10(4)/ml and 11 x 10(4)/ml, respectively. A 600 ml venesection at this time would contain a median of 36 x 10(4) GM-CFC/kg (range 25-47) and 1.04 x 10(6) CD34+ cells/kg (range 0.73-1.4), based on individual patient weights. Day 15 progenitor numbers were maintained for the first 3 cycles but tended to fall thereafter. The viability of the progenitors collected in whole blood and stored at 4 degrees C for various time intervals was also assessed. The median percent of GM-CFC and erythroid blast forming units (BFU-e) surviving after storage for 48 hrs was 79% and 69% respectively and after 72 hrs was 48% and 63% respectively. Serum collected 2 hrs after the completion of chemotherapy had minimal inhibitory effect on progenitors collected prior to treatment. Our data demonstrate that two weeks after anthracycline-based chemotherapy and G-CSF in previously untreated patients the peripheral blood contains large numbers of progenitors. A 600 ml venesection at this time stored at 4 degrees C, and then reinfused after the next cycle of chemotherapy would contain sufficient viable progenitors to potentially hasten haematological recovery.
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PMID:Viability and quantification of progenitor cells in venesected blood from patients receiving escalated-dose epirubicin and cyclophosphamide with G-CSF for lymphoma: potential role in further increasing dose-intensity. 940 32


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