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)

Expression of the normally cryptic blood group antigen Tn has occasionally been reported in hematologic disease, but the true frequency of this change is not known. A mouse monoclonal antibody (FBT3) and immunohistochemistry were used to examine expression of the Tn antigen. Expression was not detected in 35 normal bone marrow aspirates examined, but it was detected in 5 of 725 abnormal bone marrow aspirates, including 2 (3.6%) of 55 cases of de novo acute nonlymphocytic leukemia and 2 cases that terminated in acute nonlymphocytic leukemia. In two patients, one with acute myeloblastic leukemia and the other in blast transformation of chronic myeloid leukemia, the Tn antigen was expressed on 2 percent of blast cells. In one case of non-Hodgkin's lymphoma, 4 percent of normal myeloid cells expressed the antigen. In the other two cases, one of acute myelomonocytic leukemia and the other of myelodysplasia, only 2 to 8 percent of myeloid and erythroid cells initially were Tn positive. Subsequent serial immunohistochemical studies of bone marrow aspirates and peripheral blood in these two cases showed increasing numbers of Tn-positive erythroid and myeloid cells 8 to 12 months before polyagglutination was detected serologically. Tn-positive cells increased to > 90 percent in the terminal phase in both cases of both diseases. The results suggest that Tn expression in these two patients may have conferred a growth advantage to the cells and could be related to disease progression.
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PMID:Expression of the Tn antigen in myelodysplasia, lymphoma, and leukemia. 147 Dec 47

Sequential bone marrow biopsy specimens and peripheral blood findings were evaluated from patients treated with recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for recurrent non-Hodgkin's lymphoma. Parallel increases were found in white blood cell count and marrow cellularity and in absolute neutrophil count, monocyte count, and marrow myeloid:erythroid ratio. Platelet count recovery and the reappearance of megakaryocytes occurred later than granulocyte/monocyte recovery. Elevated peripheral eosinophil counts and eosinophilic hyperplasia in the marrow were noted during recombinant human granulocyte-macrophage colony-stimulating factor administration, as was the appearance of distinctive, prominently granulated and/or vacuolated neutrophils and neutrophilic precursors in the blood and bone marrow. No detrimental effects of recombinant human granulocyte-macrophage colony-stimulating factor administration in the marrow or peripheral blood were observed.
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PMID:Bone marrow and blood findings after marrow transplantation and rhGM-CSF therapy. 157 3

The levels of peripheral progenitor cells was measured serially after cancer chemotherapy in 4 patients with non-Hodgkin's lymphoma and one patient with rhabdomyosarcoma who received recombinant human granulocyte colony-stimulating factor (rG-CSF). This study was composed of two independent phases: in the first phase, patients received a course of cytotoxic chemotherapy only, and in the second phase, they received the same chemotherapy followed by subcutaneous injection of rG-CSF (2 micrograms/kg/day) for 10-14 days. In the control phase, the levels of granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) per milliliter increased during the early recovery phase, but rG-CSF treatment increased the number of CFU-GM 3 to 18-folds, and the number of BFU-E increased 1.3 to 4.6-folds. An overshoot in the blood progenitor levels occurred at the day 8-10 of rG-CSF administration. And then, the peak of neutrophil count followed 3-5 days later. After the discontinuation of rG-CSF, the number of blood CFU-GM and BFU-E fell rapidly. This results suggest that in vivo expansion of circulating hemopoietic progenitors can be achieved by the administration of rG-CSF, and this approach might be clinically applicable to cancer patients who are a candidate of peripheral blood stem cell autotransplantation.
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PMID:[Expansion of peripheral blood progenitors by recombinant human granulocyte colony-stimulating factor]. 170

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

Sixteen patients with relapsed non-Hodgkin's lymphoma underwent autologous bone marrow transplantation and infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Treatment consisted of involved-field radiotherapy, cyclophosphamide 60 mg/kg/d intravenously (IV) for 2 days, and fractionated total body irradiation (1,200 cGy). Autologous bone marrow was thawed and infused IV, followed 3 hours later by the first infusion of IV rhGM-CSF 11 micrograms/kg/d over 4 hours. Infusions of rhGM-CSF were continued daily until either both neutrophil count exceeded 1,500/microL and platelet count exceeded 50,000/microL, or until 30 days after marrow re-infusion. Toxicities encountered were mild and included fever, chills, hypertension, alopecia, rash, diarrhea, stomatitis, myalgias, and synovial (knee) effusions. Neutrophil recovery greater than 500/microL occurred a median of 14 days (range, 9 to 30 days) after marrow infusion, significantly earlier than in a comparable group of historic controls who recovered counts at a median time of 20 days (range, 12 to 51 days) (P = .00002). Median time to self-sustaining platelet counts greater than 20,000/microL was 23.5 days (range, 12 to 100 days), comparable with the historic group (P = .38). One bacteremia (central venous catheter exit site infection with Staphylococcus epidermidis) and one local infection (Giardia lamblia in stool) occurred. Patients received a median of 11.4 (range, 4.4 to 20.2) x 10(4) colony-forming unit granulocyte-macrophage (CFU-GM) progenitors per kg. Stem cell progenitors CFU-GM, CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM), and burst-forming unit-erythroid (BFU-E) were detected in the bone marrow as early as 7 days after marrow re-infusion, and increased in proportion to peripheral blood counts, but by 30 to 60 days still remained much lower than before transplant. Neutrophils transiently decreased in 13 of 16 patients (median decrease, 42%) within 24 to 72 hours of discontinuing rhGM-CSF infusions. These data suggest that rhGM-CSF therapy enhances neutrophil recovery by forcing stem cells to produce mature elements at an enhanced rate but may not affect marrow stem cell and early progenitor population sizes.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for relapsed non-Hodgkin's lymphoma: blood and bone marrow progenitor growth studies. A phase II Eastern Cooperative Oncology Group Trial. 185 94

Despite major advances in supportive care, neutropenic infections and thrombopenic bleedings remain major lethal treatment- and disease-related complications in patients with malignancy. Moreover, complications of platelet (Plt) and erythrocyte transfusion therapy have become a cause of great concern and shortages of homologous blood products are a constant problem. Suggestions that the application of recombinant human hemopoietins may provide an alternative treatment modality in this patient population is currently being evaluated in clinical trials. Erythropoietin (EPO) has been shown to be effective in the treatment of anemia in patients with bone marrow, infiltrating low-grade non-Hodgkin's lymphoma, multiple myeloma, and in some patients with myelodysplastic syndrome. Preliminary data suggest that subcutaneous administration of EPO results in a higher slope of increasing erythropoietic parameters compared to intravenous administration. Protective effects on normal erythropoiesis have been attributed to EPO in patients receiving chemotherapy. The finding of EPO receptors on megakaryocytes supports the clinical observation of increased Plt production associated with decreased bleeding and transfusion frequencies in a substantial number of patients receiving EPO. Clinical trials with granulocyte-macrophage (GM-CSF) and granulocyte colony stimulating factor (G-CSF) have reached phase III trials. Both factors show high efficacy to shorten or improve neutropenia related to chemotherapy, bone marrow transplant, or underlying disease. Mechanisms responsible for mucosa protection and improved healing of mucositis observed with both factors remain undetermined yet phase I/II evaluation of IL-3 shows multilineage hemopoietic responses including myeloid, erythroid, and megakaryocyte lineages. Possible anti-cancer effects of hemopoietins achieved by direct action or by increased chemotherapy intensity are currently under investigation.
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PMID:Hemopoietins in clinical oncology. 204 61

A severe and persistent pancytopenia occurred in a 42-year-old woman with a non-Hodgkin's lymphoma following a 10-day course of intramuscular human leukocyte alpha interferon (IFN, 9.0 IU/day). Within 2 weeks of IFN, marrow nucleated myeloid and erythroid precursor cells and megakaryocytes were nearly absent and marrow progenitor cells (CFU-E, BFU-E, CFU-GM) were undetectable. Analysis of marrow lymphocytes revealed that nearly 50% of the cells were E-rosette+, T gamma+, OKT8+ (suppressor/cytotoxic) T-and/or Leu 7+ natural killer (NK) lymphocytes and 50% were IgM Kappa, B1+, B-lymphocytes. In vitro erythroid culture studies were consistent with T-cell-mediated suppression of erythropoiesis. After 2 months without improvement on corticosteroid/androgen therapy, a 10-day course of intravenous antithymocyte globulin (ATG) was administered. This was followed by a prompt reticulocytosis and a rise in blood neutrophils. After ATG therapy, there was a sixfold reduction in marrow suppressor cells, loss of in vitro suppressor effects on erythroid progenitor cells, and complete reversal of blood and marrow OKT4/OKT8 (helper/suppressor) ratios. These studies suggest that interferon may suppress hematopoiesis in some patients by activating marrow suppressor T- and/or NK cells. Treatment aimed at reduction of marrow suppressor cells may aid in hematologic recovery without eliminating the infiltrating lymphoma.
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PMID:Interferon-induced aplasia: evidence for T-cell-mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin. 241 Nov 29

Laser photoradiation therapy was tested in an in vitro model for its efficacy in the elimination of non-Hodgkin's lymphoma cells. Results show that at 31.2 J/cm2 of laser light in the presence of 20 micrograms/mL of merocyanine 540 (MC540) there was greater than 5 log reduction in Burkitt's lymphoma (Daudi) cells. Similar tumor cell kill was obtained for leukemia (HL-60) cells at a laser light dose of 93.6 J/cm2. However, to obtain the same efficiency of killing for histiocytic lymphoma (U-937) cells, a higher dose of MC540 (25 micrograms/mL) was required. Clonogenic tumor stem cell colony formation was reduced by greater than 5 logs after laser photoradiation therapy. Under identical conditions for each cell line the percent survival for granulocyte-macrophage colony-forming units (CFU-GM, 45.9%, 40%, 17.5%), granulocyte/erythroid/macrophage/megakaryocyte (GEMM, 40.1%, 20.1%, 11.5%), colony-forming units (CFU-C, 16.2%, 9.1%, 1.8%), and erythroid burst-forming units (BFU-E, 33.4%, 17.8%, 3.9%) was significantly higher than the tumor cells. Mixing of gamma ray-irradiated normal marrow cells with tumor cells (1:1 and 10:1 ratio) did not interfere with the elimination of tumor cells. The effect of highly purified recombinant interferon alpha (rIFN) on laser photoradiation therapy of tumor cells was also investigated. In the presence of rIFN (30 to 3,000 U/mL), the viability of leukemic cells was observed to increase from 0% to 1.5% with a concurrent decrease in membrane polarization, suggesting an increase in fluidity of cell membrane in response to rIFN. However, at higher doses of rIFN (6,000 to 12,000 U/mL) this phenomenon was not observed. The viability of lymphoma cells remained unaffected at all doses of rIFN tested. These results may have therapeutic relevance in patients undergoing interferon treatment who require bone marrow transplantation, as the complete elimination of tumor cells by marrow-purging procedures may be hampered by this increased survival in the presence of interferon.
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PMID:Elimination of clonogenic tumor cells from HL-60, Daudi, and U-937 cell lines by laser photoradiation therapy: implications for autologous bone marrow purging. 292 Feb 7

Bone marrow biopsies of patients with a myelodysplastic syndrome (MDS) may, in the absence of an increased number of blasts in the bone marrow smears, contain small clusters of immature precursors. The presence of these cell nests, previously described as "abnormal localized immature precursors" or ALIP, bears a strong prognostic value predisposing patients to early death with an increased risk to develop myeloid leukaemia. In order to describe and delineate this histological characteristic more precisely, we compared bone biopsies of patients with MDS, used in these previous studies, with bone marrow biopsies performed for staging procedures in patients with Hodgkin's disease, non-Hodgkin's lymphoma and carcinoma. From this comparison we conclude that immature precursors are readily differentiated from proerythroblasts, myeloblasts and small-sized megakaryocytes, and that they most probably represent precursors of the myelo-monocytic-erythroid series. A clearcut increase in their number, mostly resulting in the formation of small clusters, is only found in biopsies from patients with MDS.
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PMID:The histological characterization of ALIP in the myelodysplastic syndromes. 376 79

The effects of recombinant human tumor necrosis factor (rH-TNF) on the colony growth of human leukemia progenitor cells (L-CFU), granulocyte-macrophage progenitor cells (CFU-GM), and erythroid progenitor cells (BFU-E) were studied. L-CFU was assayed with leukemia cells obtained from patients with acute myelogenous leukemia. CFU-GM and BFU-E were assayed with bone marrow cells obtained from hematologically normal donors and patients with acute leukemia or non-Hodgkin's lymphoma in complete remission. A dose-dependent growth inhibition of L-CFU as well as CFU-GM and BFU-E was observed by rH-TNF at concentrations of 1 to 100 U/mL. The inhibitory effect on L-CFU was significantly greater than that on CFU-GM. No correlation was observed between the inhibitory effect on L-CFU and the number of colonies formed in the cultures without rH-TNF. Preincubation of the progenitor cells in culture medium containing 20% fetal calf serum with up to 1,000 U/mL of rH-TNF for 24 hours did not result in the inhibition of colony growth of L-CFU or CFU-GM. The inhibitory effect of rH-TNF was neutralized by an anti-rH-TNF murine monoclonal antibody.
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PMID:Effect of recombinant human tumor necrosis factor on the colony growth of human leukemia progenitor cells and normal hematopoietic progenitor cells. 380 62


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