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)

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

Non-Hodgkin's lymphoma is the commonest secondary cancer following bone marrow transplantation (BMT). We report the case of a 42-year-old man who developed a laryngeal high-grade B-cell lymphoma 5 years following a matched T depleted BMT for CML. Polymerase chain reaction (PCR) analysis using the microsatellite marker Cyp 19 demonstrated the donor origin of involved tissue. Epstein-Barr virus (EBV) genomic sequences were identified by PCR. Although EBV related B-cell lymphoproliferative disorders (BLPD) post BMT are difficult to treat, there was a complete remission in this patient following three courses of chemotherapy (CHOP) administered with G-CSF. This case of late-onset BLPD appears clinically distinct from the well-defined, aggressive, early post-transplant BLPD.
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PMID:Localized, late-onset, high-grade lymphoma following bone marrow transplantation: response to combination chemotherapy. 751 97

A 73-year-old woman was diagnosed with seropositive destructive rheumatoid arthritis in 1981. She was treated with cortisone, chloroquine, and cyclophosphamide (Sendoxan) in 1982 and 1984 and contracted severe neutropenia. After that she only received cortisone. During 1991, again low neutrophilic counts were registered, especially granulocytopenia. At first, B-cell lymphoma was suspected, but later Felty's syndrome was established. The patient was treated with high-dose cortisone with some success and had a few minor septic episodes. In May 1992 she contracted a traumatic wound on the back of the lower leg. Conservative treatment resulted in a worsening of the condition and an increased wound area, most likely related to the neutropenic condition. In mid July the patient was hospitalized. Bacterial isolates yielded mixed gram-negative enteric bacteria from the wound. Parenteral antibiotic treatment was started, followed by oral drugs, rhG-CSF (filgrastim) was given subcutaneously once a day, starting 3 days after admission. This resulted in increased numbers of peripheral granulocytes. The ulcer started to heal and by mid August the patient received a transplant with autologous skin grafting. In mid September the wound was completely healed. It is concluded that the combination of antibiotics, skin transplantation, and G-CSF was necessary for the successful result. Actually, the bacterial growth did not call for antibiotics, but it was considered necessary to cover for staphylococci. No worsening of the underlying arthritis was observed.
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PMID:Successful treatment of chronic wound infection in neutropenia and rheumatoid arthritis with filgrastim (rhG-GSF) 752 58

Cytokines play important roles in the pathogenesis of lymphomas via an autocrine or a paracrine mechanism, or both. The characteristic clinical and histopathological features of malignant lymphomas may be due in part to elevated serum or tissue levels of cytokines. Determination of the effects of cytokines on the growth or differentiation of lymphoma cells is often complicated by the fact that more than one cytokine is responsible, and by the failure of anti-cytokine antibodies or antisense oligonucleotides to block the proliferation in vitro of lymphoma cells. However, it appears that IL-6 and/or IL-9 may play a prominent role in the tumor cell proliferation of Hodgkin's disease (HD), anaplastic large-cell lymphoma, or immunoblastic lymphoma. IL-6 may also be responsible for the plasmacytoid differentiation of lymphoma cells in polymorphic immunocytoma. The histopathological changes as a result of paracrine effects are most noticeable in HD. The malignant (H-RS) cells of HD have been shown to express IL-1, IL-5, IL-6, IL-9, TNF-alpha, M-CSF, TGF-beta, and CD80, and, less frequently, IL-4 and G-CSF. These cytokines may be responsible for the increased cellular reaction and fibrosis observed in tissues involved by HD and for the immunosuppression found in patients with HD. In contrast to H-RS cells, most non-HD lymphoma cells do not produce cytokines in excess amounts and reveal only a minimal cellular reaction. Exceptions include T-cell-rich B-cell lymphoma, angiocentric T-cell lymphoma, and angio-immunoblastic lymphadenopathy (AILD-like T-cell lymphoma. IL-4 is responsible for the T-cell reaction in T-cell-rich B-cell lymphoma, whereas IL-6 accounts for the plasma cell reaction in AILD-type T-cell lymphoma. The authors extensively review the role of cytokines in lymphomas because this may lead to major advances in the understanding of the molecular processes involved in the histopathogenesis of lymphomas.
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PMID:Autocrine and paracrine functions of cytokines in malignant lymphomas. 785 53

The present study demonstrated that a human B-cell line derived from non-Hodgkin's lymphoma. HCF-MLpN. constitutively expressed G-CSF receptor on the cell surface. G-CSF binding to the cell surface was shown by immunofluorescence staining using biotinylated G-CSF preparation and analysed by flow cytometry. Specific binding of G-CSF to the cells was shown by pretreatment with unlabelled G-CSF. In the radioreceptor assay and Scatchard plot analysis using radiolabelled ligand, MLpN cells revealed a single species of binding site with an equilibrium dissociation constant of 167 (153-182) pM and a maximal binding site per cell of 1076 (1044-1116). The G-CSF receptor mRNA transcript was exhibited in the RNA from MLpN cells by reverse transcriptase polymerase chain reaction procedure. [3H]thymidine incorporation and trypan blue exclusion showed that the G-CSF receptor was capable of transducing the growth signal to HCF-MLpN cells. A small fraction of fresh B blasts from six patients with B-cell lymphoma and leukaemia displayed G-CSF binding by two-colour immunofluorescence staining. In contrast, a panel of seven B-cell lines was negative for the binding to biotinylated G-CSF preparation. These results suggest that the phenotype of G-CSF binding may be lost during the culture. The expression of G-CSF receptor in HCF-MLpN cells appeared to be exceptional.
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PMID:Constitutive expression of granulocyte-colony stimulating factor receptor on a human B-lymphoblastoid cell line. 875 83

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

Preliminary results indicate that inhibitors of the nuclear enzyme topoisomerase (topo) I, such as topotecan, may be active in non-Hodgkin's lymphoma (NHL). Pre-clinical studies have shown sequential administration of a topo I and II inhibitor has supra-additive anti-tumor effects in some model systems, and that greater cytotoxicity occurs if the topo I inhibitor is given first. We enrolled, 22 eligible patients with relapsed or refractory intermediate grade NHL in a phase II study ofsequential administration of topotecan 1.25 mg/m2 days 1-5 and etoposide 50 mg po b.i.d. days 6-12, every 28 days without G-CSF. Most patients had diffuse large B-cell lymphoma and all had received only one prior regimen (CHOP, 20 patients, or equivalent, 2 patients). Patients with stable or responding disease were allowed to proceed to high-dose therapy and autologous stem-cell transplant after 2 cycles of therapy. The 22 patients received a total of 62 cycles of topotecan + etoposide (median 2, range 1-6), and 4/22 completed all six planned cycles. Hematologic toxicity was significant and resulted in incomplete etoposide dosing in half of all cycles in 16/22 patients. Nineteen of twenty-two patients had grade 3/4 neutropenia, 12 had grade 3/4 thrombocytopenia, and 6 grade 3/4 anemia. Eleven patients had at least one episode of febrile neutropenia or had documented infection. Non-hematologic toxicity was mild. Four patients had a partial response (PR) (18.2%), nine had stable disease and seven progressed; three patients with stable disease went on to ABMT. The combination of topotecan and etoposide as given in this study has modest activity in relapsed/refractory aggressive histology NHL, and produces marked myelosuppression. Other doses and schedules combining topo I and II inhibitors, or topo I inhibitors with alkylating agents, should be explored with the addition of hematopoietic growth factors in this patient population.
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PMID:Phase II study of sequential topotecan and etoposide in patients with intermediate grade non-Hodgkin's lymphoma: a National Cancer Institute of Canada Clinical Trials Group study. 1240 Jun

Although high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), more than 50% of patients will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC) can intensify the conventional salvage treatment and improve the outcome of ASCT by maximal debulking of the tumor load with the use of non-cross resistant drugs, each at their maximal tolerated doses. We conducted a phase II study in 40 patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible for the protocol, consisting of three phases. Phase I consisted of cyclophosphamide (4.5 g/m2) followed by G-CSF and peripheral blood stem cell (PBSC) collection. Phase II consisted of etoposide (2 g/m2). The transplant phase consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by PBSC infusion. Eleven out of nineteen patients with B-cell lymphoma received rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and 55% were in partial remission (PR). After completion of all phases of the protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4 years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At a median follow-up of 32 months (range, 3 - 61), nine patients relapsed/progressed and eleven patients died. The estimated 4-year PFS and overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in NHL patients, respectively. Factors predicting OS were response to conventional salvage therapy and stage prior to salvage therapy. When compared to patients achieving PR, patients who attained CR prior to HDSC had a significantly higher probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups were defined according to the score determined by stage prior to initiation of salvage chemotherapy, remission duration prior to salvage (refractory/early relapse vs. late relapse) and response to salvage. Prognostic score was found to predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by ASCT is an effective salvage therapy with acceptable toxicity, allowing further consolidation of response attained by conventional salvage therapy.
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PMID:High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma. 1696 65

Liposomal daunorubicin (DaunoXome) was substituted for doxorubicin in the CHOP regimen, aiming to reduce toxicity and maintain or improve efficacy in elderly patients. Eligibility criteria included: age >or=60 years; previously untreated aggressive non-Hodgkin Lymphoma (NHL) and performance status (PS) 0-2. Treatment was cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2) (maximum 2 mg), and DaunoXome 100 mg/m(2) i.v. on day 1, prednisolone 100 mg po on days 1-5 and G-CSF 5 microg/kg/day sc, for 6-8 cycles. For the 51 patients, median age was 70 years (range 60-88), 94% had diffuse large B-cell lymphoma (DLBCL) and 55% were high-intermediate or high-risk according to the age-adjusted international prognostic index. A mean of 6 cycles was delivered, with dose reductions of DaunoXome in 8.3% of cycles. The combined CR and CRu rate was 65.2%, survival was 566 days and 5-year survival 35%. Three deaths occurred during treatment and may have been related to COP-X. Only 4 (7.8%) of the remaining patients had >or=10% reduction in LVEF. However, 35% of patients were hospitalised during treatment, mostly for febrile neutropenia. The response rate to COP-X was similar to that expected with CHOP, with low cardiac toxicity. The high rate of infectious complications suggests that the DaunoXome dose used may be too high for this patient group. These results support further investigation of this regimen in patients with aggressive NHL.
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PMID:A phase II study of liposomal daunorubicin, in combination with cyclophosphamide, vincristine and prednisolone, in elderly patients with previously untreated aggressive non-Hodgkin lymphoma. 1846 12

CHOP-like regimen combined with rituximab is a standard chemotherapy for diffuse large B-cell lymphoma (DLBCL). The relative dose intensity (RDI) was proposed as an index of the dose and administration interval of agents. Previous studies reported that the maintenance of the RDI during CHOP therapy improved the treatment results. However, few studies regarding RDI have reviewed patients receiving combination therapy with CHOP and rituximab. We investigated the influence of RDI maintenance, involving combination therapy with rituximab, on therapeutic effects in patients with DLBCL. We retrospectively examined 152 DLBCL patients who were treated with CHOP-like regimen combined with rituximab in whom the RDI could be followed up. Multivariate analysis revealed that international prognosis index (IPI) high intermediate-high (HI-H) (p = 0.005) and RDI of less than 70% (p = 0.007) were independent prognostic factors for low progression free survival. Concerning overall survival, IPI HI-H (p = 0.027) and an RDI of less than 70% (p = 0.002) were involved in an unfavorable prognosis. In addition, age over 60 years (p = 0.003), R-THPCOP (p = 0.034), or the presence of febrile neutropenia (p = 0.004) made RDI maintenance difficult, and prophylactic G-CSF therapy (p = 0.026) was useful for maintaining the RDI. Maintaining the RDI is important even in the era of rituximab-combined chemotherapy for DLBCL.
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PMID:Importance of maintaining the relative dose intensity of CHOP-like regimens combined with rituximab in patients with diffuse large B-cell lymphoma. 2041 58


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