Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Promising response rates are noted in patients with refractory Hodgkin's disease after radioimmunoglobulin therapy (RIT) with Yttrium-90 labeled polyclonal antiferritin. To explore the most efficacious selection of RIT reagents for use in humans, experimental animal data are reviewed for radiolabeled antiferritin and B72.3. Nude mice with subcutaneously implanted human malignancies provide an excellent primary screen for radiolabeled antibodies under consideration for use in humans. They provide information on the potential of a new reagent to target a human malignancy in vivo. The other determinant of the therapeutic ratio of RIT reagents--normal tissue toxicity--is best analyzed in large animals, such as dogs. Hematologic toxicity is dose limiting in all species and best predicted by a prescription of radiolabeled antibodies in mCi per kilogram body weight and the presence or absence of bone marrow targeting. Per cGy, RIT is more effective in causing BM damage in dogs than in rats. In dogs, bone marrow transplantation with autologous cryopreserved bone marrow cells or G-CSF treatment can accelerate hemopoietic recovery and granulopoiesis, respectively, after RIT. When dose escalation beyond bone marrow toxicity is performed, the liver (dog) or the intestinal tract (rat) become the next dose limiting tissue in dose escalation studies. Significant improvement in RIT results will be achieved when the normal liver uptake of chelated monoclonal antibody in dogs and in human patients can be prevented. The described animal models and continued investigations of RIT in patients with endstage Hodgkin's disease will allow for further improvement in the therapeutic ratio of RIT and the applicability of RIT in humans.
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PMID:Selection of reagents for human radioimmunotherapy. 172 28

Malignant lymphoma is classified roughly into Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) according to the biological characteristics. Malignant lymphoma in Japan has such characteristics as low incidence of HD, which is usually favorable in prognosis, and high incidence of NHLs, which have further distinctive features of less incidence of favorable follicular B cell lymphoma and of higher incidence of unfavorable diffuse T cell lymphoma including adult T cell leukemia/lymphoma (ATLL) in comparison with those in western countries. As a recent trend of progress in lymphoma study, the introduction of molecular diagnosis by means of gene rearrangement analysis of immunoglobulin and T cell antigen receptor has contributed diagnostically to a definitive determination of T and B cell lineage and cellular monoclonality in malignant lymphoma. On the other hand, remarkable progress has been made in the treatment of malignant lymphoma in recent years. After all, in HD even far advanced cases have been expected to be curable by the combination chemotherapy, for example, MOPP regimen in USA at the present time. Furthermore, in NHL even advanced cases with such aggressive lymphoma as diffuse large cell lymphoma of B cell type have also been able to survive for more than 10 years and may be curable with the frequency of more than 30% in several institutions. Nowadays, the treatment for malignant lymphoma has focussed on multidisciplinary cure-oriented therapy including chemotherapy and radiotherapy in a collaboration of surgical procedure and immunotherapeutic maneuvers. The recent chemotherapy regimen has been called "third generation" ones characterized by alternating non-cross resistant combination and frequent administration of intense drug dose. Furthermore, various biologics such as monoclonal antibodies, several BRMs including IFNs, IL-2 and TNF, and recombinant G-CSF and GM-CSF have been applied in lymphoma treatment to improve the efficacy of combination chemotherapy in new designs of clinical trials.
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PMID:[Malignant lymphoma]. 273 35

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) was purified from 3 liters of serum-free conditioned medium of the Hodgkin's tumor cell line L428 KSA. The conditioned medium contained a high specific activity of 2.5 X 10(5) units of total colony-stimulating factor per mg protein. Colony-stimulating factor activity was determined by colony formation by human fetal liver cells or mouse bone marrow cells. The latter bioassay discriminated colony-stimulating factor 1, a subclass specific for monocyte/macrophage production, and G-CSF, specific for granulopoiesis, from GM-CSF. The starting material contained predominantly GM-CSF with CSF-1 and G-CSF constituting 10% and 12%, respectively, of the total activity. A seven-stage purification scheme was employed. The first stage involved concentration by batch chromatography on calcium phosphate gel. Subsequent stages involved gel filtration on Ultrogel AcA44, affinity chromatography on concanavalin A-Sepharose, batch chromatography on calcium phosphate gel and high-performance liquid chromatography on C1 reversed-phase (TSK TMS-250), gel permeation and C8 reversed-phase columns. The purified material showed a single disperse band, having an Mr of 30,000, by silver staining on sodium dodecyl sulfate polyacrylamide gel electrophoresis. An amino-terminal sequence of 20 amino acids was determined in a gas-phase sequencer with 500 ng of purified material. The sequence was identical to that predicted from the cDNA sequence. It was active on human fetal liver cells with half-maximum colony formation at 1 X 10(-12) M, but was not active on mouse bone narrow cells.
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PMID:Human granulocyte-macrophage colony-stimulating factor purified from a Hodgkin's tumor cell line. 353 1

G-CSF and GM-CSF enhance the rate of neutrophil engraftment in autologous bone marrow transplantation (ABMT) without significantly affecting platelet engraftment. Peripheral blood progenitor cells (PBPC) may enhance rates of engraftment of both neutrophils and platelets. We treated 49 patients undergoing ABMT with a course of G-CSF to obtain PBPC and infused these cells post-transplant with G-CSF in an attempt to determine factors which might correlate with enhanced BM engraftment. Forty-nine patients with Hodgkin's disease, non-Hodgkin's lymphoma or breast cancer undergoing unpurged ABMT were studied. G-CSF priming consisted of an outpatient 8 day course of 5 micrograms/kg/day followed by three leukaphereses (on day 5, 7 and 8) to collect PBPC. Patients then received a chemotherapeutic BMT preparative regimen followed by an infusion of PBPC, autologous BM and the reinstitution of G-CSF (16 micrograms/kg/day). BM engraftment was rapid. The median time to achieve 0.5 x 10(9)/l neutrophils was 10 days compared with a historical BMT control patient population receiving the same preparative regimens of 19 days (p = 0.001). Time to achieve a platelet count of 20 x 10(9)/l was 16 days compared with a historical control of 22 days (p = 0.001). Neutrophil engraftment occurred in all patients by day +14. Marrow engraftment correlated with the total number of CD34+ cells infused as well as the total number of mononuclear cells infused but not the total number of CD34+/CD33- cells infused. The amount of total blood volume pheresed significantly correlated with yield of total mononuclear cells. Prior exposure to radiation therapy negatively correlated with progenitor cell yield.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:G-CSF primed peripheral blood progenitor cells in autologous bone marrow transplantation: parameters affecting bone marrow engraftment. 751 Oct 16

We report the preliminary results of a study exploring the possibility of collecting circulating progenitor cells (PBSC) with a protocol based on the administration of single doses (4 g/m2) of cyclophosphamide and G-CSF (5 or 10-micrograms/kg) in 9 patients with non Hodgkin's lymphoma. The peak level of CD34+ cells occurred after a median of 10 days (range 8-11), generally coinciding with the median peak level of CFU-GM, with a mean 31.27 fold increase above basal levels. 3 (range 2-5) leukaphereses were required to harvest a median number of 25.1 x 10(4)/kg (8-105) CFU-GM and of 9.4 x 10(6)/kg (1.2-25) CD34+ cells. No difference was recorded between 5 and 10 micrograms/kg of G-CSF in terms of PBSC yield. In transplanted patients, a strong correlation was found between CD34+ cells infused/kg and platelet recovery (r = -0.8, p = 0.002). No toxicity was observed and apheretic procedures were regularly performed outpatiently. Our conclusion is that this protocol is particularly suitable for an outpatient treatment/collection program.
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PMID:Cyclophosphamide 4 g/m2 plus rhG-CSF for mobilization of circulating progenitor cells in malignant lymphomas. 751 15

The hemopoietic growth factor filgrastim (r-metHu G-CSF) stimulates granulopoiesis after autologous BMT and can also be used as a peripheral blood progenitor cell (PBPC)-mobilizing agent. Rapid platelet recovery follows the addition of filgrastim-mobilized PBPC to autologous BMT. We have now studied 29 adults with malignant lymphoma, Hodgkin's disease or ALL to assess the ability of filgrastim-mobilized PBPC to rapidly and durably restore hemopoiesis without bone marrow (BM) infusion. Patients with a high yield of PBPC from three leukaphereses, defined as > 30 x 10(4)/kg GM-CFC, were eligible for PBPC transplant without BM. Patients with a low yield of GM-CFC received both PBPC and BM infusion. After filgrastim therapy 12 or 24 micrograms/kg/day by continuous sc infusion for 6 or 7 days, a high yield was obtained in 11 of 29 patients. Kinetics of recovery of both the platelet and neutrophil counts were more rapid in the high yield group than in the low yield group. The platelet count recovered to > 20 x 10(9)/l at a median of 9 days, to > 50 x 10(9)/l at 11 days and the neutrophil count to > 0.5 x 10(9)/l at 9 days in the high yield group compared with 12 days, 37 days and 10 days, respectively, in the low yield group (p = 0.028, p < 0.001 and p = 0.027). Fewer platelet transfusions were required in the high yield group (median 11 vs 29.5 units, p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II study of autologous filgrastim (G-CSF)-mobilized peripheral blood progenitor cells to restore hemopoiesis after high-dose chemotherapy for lymphoid malignancies. 752 4

Peripheral blood is becoming widely used as the only source of hematopoietic stem cells to support marrow ablative therapy in advanced lymphoma. We report data from 23 patients with high risk non-Hodgkin's (n = 19) and Hodgkin's lymphoma (n = 4) who underwent high-dose therapy with mobilized peripheral blood stem cell (PBSC) autografting. Peripheral blood progenitors were recruited using cytotoxic chemotherapy followed by administration of recombinant human G-CSF (filgrastim 5 micrograms/kg/day). Myeloablative treatment with autologous PBSC support was administrated to the 23 patients and followed by G-CSF at the same dose after cell reinjection. Hematopoietic reconstitution was compared with a control group of lymphoma patients who received chemotherapy mobilized PBSC transplantation but without G-CSF prior to leukaphereses or after high-dose therapy. The median time to neutrophil recovery > 0.5 x 10(9)/l was significantly shorter in study patients compared with the control patients (10 days and 17 days respectively) (p < 0.05). Self sustaining platelet counts of > 50 x 10(9)/l occurred at a median time of 17 days in both groups. Stable hemopoietic reconstitution was seen with a follow-up of 6 months after PBSC transplantation. In addition, a significant relationship was observed between the number of CFU-GM infused and the time to platelet recovery. We confirm the effectiveness of G-CSF given prior to PBSC harvesting in generating high numbers of progenitor cells. Hematologic recovery following high-dose therapy was improved after PBSC rescue and G-CSF.
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PMID:Comparison of autografting using mobilized peripheral blood stem cells with and without granulocyte colony-stimulating factor in malignant lymphomas. 752 7

Sixty-two patients with a variety of malignant diseases including 44 with breast cancer, seven with sarcomas, five with germ cell tumours, four with Hodgkin's disease and two with multiple myeloma received short duration, high dose chemotherapy, with non-cryporeserved peripheral blood progenitor cell rescue as treatment for malignancy. Limited, (one or two) peripheral blood precursor cell collections were performed following either cyclophosphamide, cyclophosphamide+GCSF or GCSF priming. Total nucleated cell and CD34+ cell yields were significantly higher with either of the two GCSF priming regimens as compared to cyclophosphamide only priming. Cell viability at the time or reinfusion was also enhanced by GCSF priming. Chemotherapy regimens included either high dose cyclophosphamide, mitoxantrone and VP16 (HD-CNV); high dose melphelan plus VP16; high dose BCNU, cyclophosphamide and VP16 (BCV); or high carboplatin, cyclophosphamide and VP16 (PCV) all given over 8-12 h. Non-cryopreserved blood progenitor cells, stored at 4 degrees C, were reinfused 24 h after completion of chemotherapy. Sixty-one of 62 patients showed hematologic recovery. Median time to hematologic recovery was significantly shorter for patients receiving GCSF primed cell collections. There was also significantly less hospitalization and antibiotic usage for patients receiving GCSF primed precursor cell collections. The addition of post chemotherapy GCSF did not, however, appear to enhance the rate of hematologic recovery. This study shows that simplified schedules for high dose chemotherapy administration together with simple precursor cell collection procedures provide safe and effective methods for administering myeloablative chemotherapy treatment.
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PMID:Non-cryopreserved, limited number (1 or 2) peripheral blood progenitor cell (PBPC) collections following GCSF administration provide adequate hematologic support for high dose chemotherapy. 752 46

Twenty-eight patients with poor prognosis acute myeloid leukemia (AML) received therapy with two courses of fludarabine 30 mg/m2/day + ara-C 2 g/m2/day (days 1-5) and G-CSF 5 mg/kg/day (FLAG) (from day 0 to polymorphonuclear recovery). Eighteen patients were considered 'refractory' (eight primarily resistant, five relapsing within 6 months of initial remission, or at a second relapse; five relapsing after an autologous bone marrow transplantation procedure. Ten cases were defined 'secondary' AML (diagnosis of AML made after a preexisting diagnosis of: myelodysplastic syndrome: five cases; myelodysplastic syndrome after therapy for breast cancer: one case; previously untreated, and concomitant, non-Hodgkin's lymphoma: two cases; Hodgkin's disease treated with chemoradiotherapy: one case). Overall, 15 patients (58%) achieved a complete remission (CR). Two patients died of infection during induction, and 11 had resistant disease. Analyzing the data in relation to selected host and disease characteristics, the response varied widely. The highest CR rates (89%) were obtained in secondary AML; in particular, two cases of 'second-primary' (concomitant with low-grade non-Hodgkin's lymphoma) AML obtained CR for both diseases. Refractory AML differed widely for response: high CR rate (75%), although with short mean CR duration for primary resistance AML, and very poor response (11% CR) for relapsed (early, second, after ABMT) cases. Interestingly, a slow kinetic of leukemic growth in vivo before FLAG administration was significantly related to the response and outcome (p = 0.0002). Hematological and nonhematological toxicities were acceptable. In conclusion, the FLAG regimen has significant antileukemic activity and acceptable toxicity especially in secondary AML, both with and without coexisting lymphoid malignancy.
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PMID:FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of 'poor risk' acute myeloid leukemias. 752 88

Primed peripheral blood progenitor cells (PBPC) with hematopoietic growth factors enhance marrow engraftment after autologous bone marrow transplantation (BMT). G-CSF and GM-CSF stimulate the production of PBPC; both cytokines alone also stimulate neutrophil recovery after autologous BMT. Little data exist comparing these two cytokines. We prospectively studied G-CSF and GM-CSF in autologous BMT. Forty-four consecutive patients with either Hodgkin's disease or non-Hodgkin's lymphoma underwent autologous BMT using both PBPC and autologous marrow. The autologous BMT preparative regimen was CBV (VP-16 2400 mg/m2, CY 1800 mg/m2 i.v. four times daily for 4 days, BCNU 600 mg/m2). Sixteen patients received G-CSF 5 micrograms/kg sc daily for 8 days for mobilization of PBPC and received G-CSF 16 micrograms/kg i.v. four times daily after autologous BMT. Twenty-eight patients received GM-CSF to mobilize PBPC (14 patients received 250 micrograms/m2 sc daily for 8 days; 14 patients received 125 micrograms/m2 sc twice daily for 8 days) and GM-CSF (250 micrograms/m2 i.v. four times daily) after autologous BMT. Patients underwent three to five pheresis procedures to harvest at least 3 x 10(8) nucleated cells/kg. Patients receiving G-CSF had higher peripheral WBC counts than did those receiving GM-CSF. Total numbers of mononuclear cells, total CD34+ cells and total CD34+/33-negative cells were similar in the two treatment groups. The patients receiving G-CSF after autologous BMT experienced a more rapid engraftment of both neutrophils (9 days vs 13 days, p = 0.0001) and platelets (14 days vs 18 days, p = 0.027) than did patients receiving GM-CSF after transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of G-CSF with GM-CSF for mobilizing peripheral blood progenitor cells and for enhancing marrow recovery after autologous bone marrow transplant. 753 72


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