Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of bone marrow transplantation is increasing in the management of advanced cancers. In autologous bone marrow transplantation (ABMT), many investigators have attempted to purge the graft of residual tumor cells because of concern that reinfused tumor cells might contribute to relapse. The feasibility of various methods (exposure to chemical agents, monoclonal antibodies (MoAbs), toxins, dye, magnetic microparticles ... ) has been confirmed. In allogeneic bone marrow transplantation, clinical studies have related the prevention of graft-versus-host disease reaction through the partial depletion of T lymphocytes in the donor graft limited to 1 log to maintain a graft-versus-leukemia (GVL) effect. Similarly, the feasibility of different assays (soybean agglutinin, Moabs and magnetic microparticles) have been shown. However, the clinical benefit of BM purging remains to be demonstrated. For ABMT, only recent data on B-cell lymphoma and leukemia strongly support the clinical usefulness of an ex-vivo purging. For allogeneic BMT, one question remains controversial: is T lymphocytes depletion the best method for GVHD prevention?
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PMID:[Ex-vivo treatment of a bone marrow graft]. 160 93

The potential of various photoradiation therapy for the in vitro purging of residual tumor cells from autologous bone marrow (BM) transplants is discussed in this paper. The results with fluorescent dyes, Dihematoporphyrin Ether (DHE) and Merocyanine-540 (MC-540) are detailed. Following photoradiation of cells with white light, both DHE and MC-540 showed high cytocidal activity towards lymphoid and myeloid neoplastic cells, but had significantly less effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E) and mixed colony-forming (CFU-GEMM) progenitor cells. Acute promyelocytic leukemia (HL-60), non-B, non-T, cALLa positive acute lymphoblastic leukemia (Reh), and diffuse histiocytic B-cell lymphoma (SK-DHL-2) cell lines were exposed to different drug concentrations in combination with white light at a constant illumination rate of 50,000 lux. With DHE doses varying from 2.0 to 2.5 ug/ml and MC-540 concentrations of 15 to 20 ug/ml, clonogenic tumor cells could be reduced by more than 4 logs, when treated alone or in mixtures with normal irradiated human marrow cells. However, preferential cytotoxicity towards neoplastic cells was highly dependent on the mode of light activation. MC-540 had no substantial effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells, and on normal marrow myeloid (CFU-GM) precursors, when the drug incubation was performed in the dark and followed by light exposure of washed cells. Equal doses of MC-540 (15-20 ug/ml) could preferentially eliminate tumor cells under conditions of simultaneous light and drug treatment (30 minutes at 37 degrees C). Using DHE (2.5 ug/ml), 29.3%, 46.8%, and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were spared, following sequential drug and light exposure of cells, while simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells below the limits of detection. The data from various centers is briefly discussed with special emphasis on clinical trials. Our results provide a useful model for leukemia and lymphoma cells and suggest that these phototherapy experiments can be implemented into clinical trials.
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PMID:Photoradiation methods for purging autologous bone marrow grafts. 213 34

Recurrence of the underlying malignancy remains a major cause of treatment failure after autologous bone marrow transplantation (BMT) for patients with lymphoma. In this regard, we have developed an immunotherapeutic approach designed to induce resistance against residual tumor cells persisting after BMT. Previous studies in the model system of 38C13, a lethal B-cell lymphoma of C3H origin, have shown that active immunization with purified tumor-derived surface immunoglobulin (Id), as a tumor-associated antigen, produces resistance to tumor growth. Id immunization of lethally irradiated mice at 3 or 5 weeks after reconstitution with syngeneic bone marrow resulted in significantly prolonged survival after tumor challenge compared with nonspecifically immunized controls. Low levels of idiotype-specific antibody were also demonstrated in the sera of specifically immunized mice at this early time, when other functional studies in the literature of immunocompetence after syngeneic reconstitution might have predicted incomplete recovery. Immunization of mice before lethal irradiation and syngeneic marrow reconstitution also induced significant resistance to tumor challenge, suggesting the persistence of established host antitumor immunity through total body irradiation. These studies demonstrate the feasibility of id immunization in conjunction with bone marrow transplantation.
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PMID:Combined syngeneic bone marrow transplantation and immunotherapy of a murine B-cell lymphoma: active immunization with tumor-derived idiotypic immunoglobulin. 225 10

To assess the potential of photoradiation therapy for the in vitro purging of residual tumor cells from autologous bone marrow (BM) transplants, we studied normal marrow and tumor cell clonogenicity in response to different light-activated compounds by using the fluorescent dyes dihematoporphyrin ether (DHE) and merocyanine-540 (MC-540). After photoradiation of cells with white light, both DHE and MC-540 showed high cytocidal activity toward lymphoid and myeloid neoplastic cells but had a significantly lesser effect on normal granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and mixed colony-forming (CFU-GEMM) progenitor cells. Acute promyelocytic leukemia (HL-60), non-B, non-T, CALLA-positive acute lymphoblastic leukemia (Reh), and diffuse histocytic B cell lymphoma (SK-DHL-2) cell lines were exposed to different drug concentrations in combination with white light at a constant illumination rate of 50,000 lux. With DHE doses varying from 2.0 to 2.5 micrograms/mL and MC-540 concentrations of 15 to 20 micrograms/mL, clonogenic tumor cells could be reduced by more than 4 logs when treated alone or in mixtures with normal irradiated human marrow cells. However, preferential cytotoxicity towards neoplastic cells was highly dependent on the mode of light activation. MC-540 had no substantial effect on malignant lymphoid (SK-DHL-2) and myeloid (HL-60) cells and on normal marrow myeloid (CFU-GM) precursors when drug incubation was performed in the dark and followed by light exposure of washed cells. Equal doses of MC-540 (15 to 20 micrograms/mL) could preferentially eliminate tumor cells under conditions of simultaneous light and drug treatment (30 minutes at 37 degrees C). When using DHE (2.5 micrograms/mL), 29.3%, 46.8%, and 27.5% of normal marrow CFU-GM, BFU-E, and CFU-GEMM, respectively, were spared after sequential drug and light exposure of cells, whereas simultaneous treatment reduced both normal (CFU-GM) and neoplastic cells below the limits of detection. In summary, our results indicate the usefulness of various photoradiation models for the ex vivo treatment of leukemic and lymphomatous bone marrow autografts.
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PMID:Photoradiation models for the clinical ex vivo treatment of autologous bone marrow grafts. 295 18

The surface Ig on each B-cell lymphoma has unique portions (idiotypes), which can be recognized by the immune system. In this study, we immunized patients against the Ig expressed by their tumor and observed their clinical outcomes. After standard chemotherapy, 41 patients with non-Hodgkin's B-cell lymphoma received a series of injections with a vaccine consisting of tumor Ig protein coupled to keyhole limpet hemocyanin and emulsified in an immunologic adjuvant. Subjects were observed for toxicity, immune responses, and tumor status. The median duration of follow-up of all patients is 7.3 years from diagnosis and 5.3 years from the last chemotherapy given before vaccine treatment. Twenty patients (49%) generated specific immune responses against the idiotypes of their tumor Ig. Two patients who had residual disease experienced complete tumor regression in association with the development of these immune responses. The median duration of freedom from disease progression and overall survival of all 20 patients mounting an anti-idiotype immune response are significantly prolonged compared to the patients who did not mount an immune response. Thirty-two patients were in their first remission and nine were in subsequent remissions before beginning vaccine treatments. Analysis of the 32 first remission patients also shows an improved clinical outcome for those patients who mounted a specific immune response compared to those who did not (freedom from progression, 7.9 years v 1.3 years P = .0001; median survival from time of last chemotherapy not yet reached v 7 years, P = .04). This study confirms an earlier report that patients with B-cell lymphoma can be induced to make a specific immune response against the Ig expressed by their own tumor. It further shows that the ability to make such an immune response is correlated with a more favorable clinical outcome. Prospective controlled trials will be needed to prove a causal relationship between anti-idiotype immunity and improved clinical outcome.
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PMID:Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma--long-term results of a clinical trial. 912 15

To study the incidence and clinical significance of bcl-2/JH fusion in 45 Chinese patients with non-Hodgkin's lymphoma, semi-nested polymerase chain reaction (PCR) was used to detect the fusion gene of non-Hodgkin's lymphoma. A total of 12 patients gave positive results, they include 9 of the 15 patients with follicular lymphoma and 3 of the 30 patients with diffuse B-cell lymphoma. The results were negative in 5 patients with reactive hyperplasia. The breakpoint was located within the major breakpoint region in 11 of the 12 patients, and the remaining patient had bcl-2 translocation in the minor cluster region. The results of the study show that bcl-2/JH fusion gene in non-Hodgkin's lymphomas is an important molecular biological marker and has a significant role in differentiating benign or malignant hyperplasia, determination of clonality, predicting prognosis and in the discovery of minor residual disease.
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PMID:[Detection of bcl-2/JH fusion gene in patients with non-Hodgkin's lymphoma by semi-nested polymerase chain reaction]. 927 69

A 56-year-old man was admitted complaining of throat discomfort and dyspnea. He was given a diagnosis of diffuse large B-cell lymphoma on the basis of findings from tumor biopsy specimens of his left pharynx. MRI tomograms and ultrasonic cardiograms revealed a right atrial tumor causing tricuspid stenosis. Although chemotherapy rendered the cardiac tumor indistinct on MRI and UCG images, gallium-67 scintigraphy still demonstrated abnormal cardiac uptake. After 6 courses of CHOP therapy, sick sinus syndrome with syncope suddenly developed in the patient. A cardiac pacemaker was immediately implanted, and radiotherapy was started. The patient's sinus rhythm returned to normal shortly afterward, and the gallium-67 uptake eventually disappeared. In this case gallium-67 scintigraphy was the only diagnostic procedure capable of detecting evidence of residual disease.
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PMID:[Sick sinus syndrome after chemotherapy for malignant lymphoma with right atrial tumor at initial presentation]. 1002 53

Derivatives of the Edmonston-B strain of measles virus (MV-Ed) are safe, live attenuated measles virus (MV) vaccines that have been used worldwide for more than 30 years. The cytoreductive potential of MV-Ed has been investigated in murine models of both aggressive and indolent B-cell lymphoma in severe combined immunodeficient (SCID) mice. The rationale for these studies was generated by experience with viral fusogenic membrane glycoproteins as cytotoxic genes and the recognition of the potential of replicating viruses in the treatment of human malignancy. Intratumoral injection of both unmodified MV-Ed and a strain of MV-Ed genetically modified by the addition of a beta-galactosidase reporter gene (MVlacZ) induced regression of large established human lymphoma xenografts, in contrast to control therapy with UV-inactivated virus, in which all tumors progressed. The antitumor effect still occurred in the presence of passively transferred anti-MV antibody. Intravenous administration of MV also resulted in considerable slowing of tumor progression. Analysis of sections of residual tumor confirmed replication of MV within the tumors. Thus, the vaccine strain of MV mediates regression of large, established human B-cell lymphoma xenografts in SCID mice, and proof of principle is established that MV is oncolytic for lymphomas in vivo. Attenuated MVs may have value as a novel replicating-virus therapy for this group of disorders. (Blood. 2001;97:3746-3754)
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PMID:Live attenuated measles virus induces regression of human lymphoma xenografts in immunodeficient mice. 1138 12

A 41-year-old male presented to our clinic with a 1-month history of left hemiparesis. He had marked left arm weakness. The diagnostic work-up revealed an intramedullary mass at spinal level C2-4. Laminectomies were performed at C2-3-4 and the tumor was subtotally resected. Histological examination identified the mass as a non-Hodgkin's diffuse B-cell lymphoma. The patient was treated with corticosteroids, chemotherapy, and adjuvant radiotherapy. The residual tumor tissue had completely disappeared by 6 months of follow-up; however, the patient presented with intraventricular metastasis at 11 months postsurgery.
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PMID:A case of primary spinal intramedullary lymphoma. 1151 61

Disease relapse occurs in 50% or more of patients who are autografted for relapsed or refractory lymphoma (NHL) or Hodgkin's disease (HD). The administration of non-cross-resistant therapies during the post-transplant phase could possibly control residual disease and delay or prevent its progression. To test this approach, 55 patients with relapsed/refractory or high-risk NHL or relapsed/refractory HD were enrolled in the following protocol: stem cell mobilization: cyclophosphamide (4.5 g/m(2)) + etoposide (2.0 g/m(2)) followed by GM-CSF or G-CSF; high-dose therapy: gemcitabine (1.0 g/m(2)) on day -5, BCNU (300 mg/m(2)) + gemcitabine (1.0 g/m(2)) on day -2, melphalan (140 mg/m(2)) on day -1, blood stem cell infusion on day 0; post-transplant immunotherapy (B cell NHL): rituxan (375 mg/m(2)) weekly for 4 weeks + GM-CSF (250 microg thrice weekly) (weeks 4-8); post-transplant involved-field radiotherapy (HD): 30-40 Gy to pre-transplant areas of disease (weeks 4-8); post-transplant consolidation chemotherapy (all patients): dexamethasone (40 mg daily)/cyclophosphamide (300 mg/m(2)/day)/etoposide (30 mg/m(2)/day)/cisplatin (15 mg/m(2)/day) by continuous intravenous infusion for 4 days + gemcitabine (1.0 g/m(2), day 3) (months 3 + 9) alternating with dexamethasone/paclitaxel (135 mg/m(2))/cisplatin (75 mg/m(2)) (months 6 + 12). Of the 33 patients with B cell lymphoma, 14 had primary refractory disease (42%), 12 had relapsed disease (36%) and seven had high-risk disease in first CR (21%). For the entire group, the 2-year Kaplan-Meier event-free survival (EFS) and overall survival (OS) were 30% and 35%, respectively, while six of 33 patients (18%) died before day 100 from transplant-related complications. The rituxan/GM-CSF phase was well-tolerated by the 26 patients who were treated and led to radiographic responses in seven patients; an eighth patient with a blastic variant of mantle-cell lymphoma had clearance of marrow involvement after rituxan/GM-CSF. Of the 22 patients with relapsed/refractory HD (21 patients) or high-risk T cell lymphoblastic lymphoma (one patient), the 2-year Kaplan-Meier EFS and OS were 70% and 85%, respectively, while two of 22 patients (9%) died before day 100 from transplant-related complications. Eight patients received involved field radiation and seven had radiographic responses within the treatment fields. A total of 72 courses of post-transplant consolidation chemotherapy were administered to 26 of the 55 total patients. Transient grade 3-4 myelosuppression was common and one patient died from neutropenic sepsis, but no patients required an infusion of backup stem cells. After adjustment for known prognostic factors, the EFS for the cohort of HD patients was significantly better than the EFS for an historical cohort of HD patients autografted after BEAC (BCNU/etoposide/cytarabine/cyclophosphamide) without consolidation chemotherapy (P = 0.015). In conclusion, post-transplant consolidation therapy is feasible and well-tolerated for patients autografted for aggressive NHL and HD and may be associated with improved progression-free survival particularly for patients with HD.
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PMID:Autotransplantation for advanced lymphoma and Hodgkin's disease followed by post-transplant rituxan/GM-CSF or radiotherapy and consolidation chemotherapy. 1189 27


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