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)

Coexistence of systemic lupus erythematosus (SLE) with low-grade non-Hodgkin's lymphoma (LGNHL) has been described occasionally in the literature with the potential pathogenetic role of monoclonal B CD5+/CD19+ cells. We report a case of LGNHL which developed 18 months after diagnosis of SLE. The monoclonal population of lymphocytes in the peripheral blood and bone marrow was CD5/CD19 negative but CD19/CD22 positive. The SLE responded well to treatment with prednisone and the course of the LGNHL was stable and cytotoxic treatment was not required.
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PMID:Low-grade non-Hodgkin's lymphoma in a patient with systemic lupus erythematosus. 1137 84

Rituximab (IDEC-C2B8, Mabthera, Rituxan), a chimeric monoclonal antibody against the B-cell specific CD20-antigen, has been demonstrated to be effective in the treatment of non-Hodgkin's B-cell lymphoma (B-NHL). Previous in vitro studies have shown that direct complement-dependent cytotoxicity (CDC), ADCC and apoptosis are important in the rituximab-induced killing of lymphoma cells. It is, however, unknown whether rituximab penetrates the blood-brain barrier. Therefore, we studied rituximab levels and complement (C) activation in blood and cerebrospinal fluid (CSF) following intravenous rituximab therapy in a patient with relapsing non-Hodgkin's lymphoma with central nervous system (CNS) involvement. Longitudinal samples from blood and CSF were taken at 13 time-points during the treatment period. The results show that the C cascade becomes activated in blood during the first mAb infusion (C3a-desArg concentration rose from 55 to 138 microg/ml during the first 2 hours). After the first infusion the proportions of lymphocytes positive for the CD19- and CD20-antigens in the peripheral blood were reduced from 41% and 35%, respectively, to a level of 2% (for both). In CSF the rituximab concentration increased after successive infusions, but remained below 0.55 microg/ml (compared to a Cmax of 400 microg/ml in peripheral blood). Although a minor and delayed C activation response was seen in the CSF the treatment did not clear CD20-positive cells away from the CNS. Thus, it appears that an intact blood-brain barrier restricts the entry of rituximab into the CNS. Possible options to circumvent this would be dose escalation or intrathecal rituximab treatment.
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PMID:Complement activation in circulation and central nervous system after rituximab (anti-CD20) treatment of B-cell lymphoma. 1169 3

Some data exist on the influence of leukapheresis volume on the number of harvested peripheral blood hematopoietic progenitor cells (HPC), but less is known about the influence on the composition of HPC. We therefore performed a prospective, randomized crossover trial to evaluate the effect of large-volume (LVL) vs. normal-volume leukapheresis (NVL) on subpopulations of CD34(+) cells in the harvest product of 15 patients with breast cancer and 8 patients with non-Hodgkin's lymphoma. Patients were randomly assigned to start either with an LVL on day 1 followed by an NVL on day 2 or vice versa. The number of HPC, the extraction efficiency defined as difference between yield in the harvest and decrease in peripheral blood, and the relative proportion as well as the absolute numbers of CD34(+) cells coexpressing CD38, CD90, HLA-DR, CD117, CD7, CD19, CD41, or CD33 were evaluated. There was no significant difference with regard to the percentages of the subsets on comparison of LVL to NVL procedures. Only the absolute median number of CD34(+)HLA-DR(-) cells was significantly (P=0.02) higher in LVL harvests compared with the corresponding NVL components, which can be explained on the basis of the higher yield and the higher extraction efficiency in LVL compared with NVL. LVL results in a higher yield of CD34(+) cells and leads to an intra-apheresis recruitment of HPC but the relative composition of the harvested CD34(+) cells is not changed significantly. In addition, the amount of early, HLA-DR(-), hematopoietic HPC seems to be increased by an LVL.
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PMID:Prospective, randomized, sequential, crossover trial of large-volume vs. normal-volume leukapheresis procedures: effects on subpopulations of CD34(+) cells. 1174 35

Monoclonal antibodies (MAbs) have been used as therapeutic agents for many years. In 1997, Rituxan (IDEC-C2B8, rituximab, MabThera) became the first MAb to be approved by the FDA for a cancer indication. Rituxan served to heighten interest in the therapeutic applications of MAbs. Herceptin (for patients with breast cancer) and Mylotarg (for patients with acute myeloid leukemia) were approved shortly thereafter. Literally dozens of antibodies are currently under investigation for a variety of malignant and non-neoplastic indications. Rituxan is effective in patients with low-grade or follicular, relapsed or refractory non-Hodgkin's lymphoma (NHL). The response rate and time to progression (responders) are in the 50% and 13 months range, respectively. It is also active in intermediate-grade NHL where a large randomized study, in combination with CHOP chemotherapy, has shown a statistically significant increase in complete response (CR) rate (75% vs. 60%), prolongation of 1 year event-free survival (69% vs. 49%) and of overall survival (83% vs. 68%) as compared to CHOP alone. This marks the first time that any agent has shown results superior to CHOP, the curative gold standard for this type of NHL. Other promising antibodies under clinical investigation include: Hu1D10; Anti CD19, 22, 52, and anti-Id antibodies. The safety profile, clinical activity, and mechanism of action of these MAbs make them ideal candidates for combination with chemotherapy or biologicals. Over the next few years, we will see very significant therapeutic advances emerge as this important research yields additional clinical results.
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PMID:Monoclonal antibodies: a new era in the treatment of non-Hodgkin's lymphoma. 1176 12

In recent years, radioimmunotherapy (RIT) with beta(-) particle emitting radionuclides targeting the CD20 antigen on B cells in the treatment of non-Hodgkin's lymphoma has provided the most compelling human clinical data for the success of RIT. CD19, like CD20, is an antigen expressed on the surface of cells of the B lineage, and CD19 may provide an alternative target for radioimmunotherapy of B cell neoplasms. CD19 has been largely overlooked as a target for conventional 131I RIT, because the antigen rapidly internalizes upon binding of antibody, resulting in catabolism and significant release of 131I. Such modulation may be an advantage to RIT with radiometals such as 90Y, 177Lu, 213Bi and 225Ac. Herein, we have compared beta(-) particle RIT with antibodies targeting either CD19 or CD20. The anti-CD19 and anti-CD20 antibodies, B4 or C2B8, respectively, were appended with the SCN-CHX-A''-DTPA bifunctional chelating agent and labeled with 90Y. In the tumor model used, there were three times as many CD20 target sites on lymphoma cells as compared to CD19 sites (62000 vs 20000 binding sites, respectively). We compared the efficacy of the 90Y-labeled antibodies to reduce lymphoma in a nude mouse xenograft solid tumor model, after measurable lymphoma appeared. Reduction in tumor size began at day 3 in all three 90Y-treated groups, but tumor began to recur in many animals 9 days after the treatments. There was one cure in each specific treatment group. In contrast, the tumor in the two control groups showed no regression. There was a significant prolongation of median survival time from xenograft (P < 0.0001) in all the 90Y-labeled antibody construct-treated groups (32 days for 0.15 mCi 90Y-B4; 26 days for 0.20 mCi 90Y-C2B8, and 23 days for 0.15 mCi 90Y-C2B8) in comparison to the two control groups (11 days for 0.02 mg of C2B8 and 9 days for untreated growth controls). Specificity of the radioimmunotherapy was also shown. In conclusion, 90Y-labeled anti-CD19 antibody has efficacy comparable to 90Y-labeled anti-CD20 antibody in the treatment of mice bearing human lymphoma xenografts. These data suggest that CD19-targeted RIT merits further study.
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PMID:Radioimmunotherapy for model B cell malignancies using 90Y-labeled anti-CD19 and anti-CD20 monoclonal antibodies. 1184 Feb 64

To target NK cells against non-Hodgkin's lymphoma, we constructed a bispecific diabody (BsDb) with reactivity against both human CD19 and FcgammaRIII (CD16). Bacterially produced CD19 x CD16 BsDb specifically interacted with both CD19(+) and CD16(+) cells and exhibited significantly higher apparent affinity and slower dissociation from the tumor cells than from effector cells. It was able to induce specific lysis of tumor cells in the presence of isolated human NK cells or nonfractionated PBLs. The combination of the CD19 x CD16 BsDb with a previously described CD19 x CD3 BsDb and CD28 costimulation significantly increased the lytic potential of human PBLs. Treatment of SCID mice bearing an established Burkitt's lymphoma (5 mm in diameter) with human PBLs, CD19 x CD16 BsDb, CD19 x CD3 BsDb, and anti-CD28 mAb resulted in the complete elimination of tumors in 80% of animals. In contrast, mice receiving human PBLs in combination with either diabody alone showed only partial tumor regression. These data clearly demonstrate the synergistic effect of small recombinant bispecific molecules recruiting different populations of human effector cells to the same tumor target.
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PMID:Synergistic antitumor effect of bispecific CD19 x CD3 and CD19 x CD16 diabodies in a preclinical model of non-Hodgkin's lymphoma. 1207 38

Contamination of hematopoietic stem cells (HSCs) with tumor cells has been associated with increased incidence of relapse in patients with non-Hodgkin's lymphoma following autologous HSC transplantation. Effective purging of tumor cells may improve the results of HSC transplantation, but current methods of purging are technically difficult to perform with large numbers of cells and do not consistently remove all detectable cells. We report a pilot clinical trial in which 10 patients with relapsed B-cell non-Hodgkin's lymphoma received high-dose chemotherapy followed by infusion of autologous HSCs depleted of B-cells by high-density microparticles (HDM) coated with anti-CD19 and anti-CD20 monoclonal antibodies (BCell-HDM). HSCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor. In 6 of the 10 patients, B-cells were detectable by immunocytochemical analysis of the apheresis products prior to treatment. Following treatment with the BCell-HDM, no B-cells were detected in the products from 5 of these patients, a result representing a median depletion of >2.2 logs (range, >0.4 to >5.1 logs). The median recovery of nontarget cells postdepletion was 73% for CD34 cells and 78% for CD3+ cells. All patients received high-dose cyclophosphamide, BCNU (carmustine), and etoposide prior to reinfusion of their B-cell-depleted autologous HSCs. The median number of CD34+ cells cryopreserved was 3.6 x 10(6) cells/kg (range, 2.2-10.1 x 10(6) cells/kg). Engraftment was rapid in all cases, with a median time to achieve an absolute neutrophil count of 0.5 x 10(9)/L of 10 days (range, 8-11 days). The median time to achieve a platelet count of 20 x 10(9)/L unsupported by platelet transfusion was 11.5 days (range, 8-17 days). This nonmagnetic negative-depletion technology is simple, rapid, and effective in depleting target cells to undetectable levels, with excellent recovery of nontarget cells.
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PMID:Effective purging of autologous hematopoietic stem cells using anti-B-cell monoclonal antibody-coated high-density microparticles prior to high-dose therapy for patients with non-Hodgkin's lymphoma. 1223 68

The anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) immunotoxins (ITs) are murine IgG(1) monoclonal antibodies (Mabs) conjugated to a deglycosylated ricin A chain (dgRTA). They are effective in killing B-lineage non-Hodgkin's lymphoma (NHL) cells in vitro, in vivo and in adult patients with B-lineage NHL. The potential of these agents for the treatment of childhood B-precursor acute lymphoblastic leukemia (ALL) is unknown. The anti-CD19 and anti-CD22 ITs should have anti-tumor activity against childhood B-lineage ALL since both target antigens are expressed on the surface of these cells. We have previously shown that, in vitro these two ITs selectively kill leukemia cells obtained from children with leukemia. To evaluate the efficacy of our ITs in an in vivo model we injected the human pre-B ALL cell line, NALM-6-UM1, into severe combined immunodeficient (SCID) mice. We tested the ability of two ITs to prolong survival or cure mice of both early and advanced tumors. In early disease, treatment with HD37-dgRTA, RFB4-dgRTA, or Combotox (an equimolar concentration of the two ITs) significantly improved their survival. In advanced disease, treatment with RFB4-dgRTA or Combotox significantly improved survival. Overall there were 10 long-term survivors who were cured, as determined by survival beyond 150 days with no evidence of disease as determined by polymerase chain reaction (PCR) analysis.
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PMID:Treatment of SCID/human B cell precursor ALL with anti-CD19 and anti-CD22 immunotoxins. 1259 32

Early absolute lymphocyte count (ALC) has been reported to be a powerful prognostic indicator of survival after autologous stem cell transplantation (ASCT). One possible source affecting ALC recovery includes the re-infused autologous graft lymphocytes (AGL). To assess if the re-infused AGL correlate with ALC recovery post-ASCT, we conducted a pilot study to identify which of the re-infused AGL subsets is most associated with day 15 ALC recovery in three patients with multiple myeloma and four patients with non-Hodgkin's lymphoma. Using the Spearman rank correlation coefficient analysis (r), we compared absolute numbers of CD3, CD4, CD8, CD19, and CD16+/CD56+ cells/kg of body weight from the apheresis product with ALC (cells/microl) at day 15 post-ASCT. The main lymphocyte subsets identified in the apheresis product were T cells and NK cells. There was no strong correlation between T or B cells from the apheresis product compared with the ALC at day 15 post-ASCT (CD3, r = 0.21; CD4, r = 0.32; CD8, r = 0.39; and CD19, r = 0.14). However, there was good correlation between NK cells from the apheresis product compared with ALC at day 15 post-ASCT (CD16+/CD56+/CD3-, r = 0.77). These data provide preliminary evidence that the number of re-infused autologous graft NK cells in the apheresis product significantly affect ALC recovery early post-ASCT. However, given the small sample size, our results are primarily hypothesis generating and subject of further research.
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PMID:Re-infused autologous graft natural killer cells correlates with absolute lymphocyte count recovery after autologous stem cell transplantation. 1285 1

A CD30+ anaplastic large cell lymphoma (ALCL) cell line was established from the mononuclear cells isolated from pleural effusion of a patient with non-Hodgkin's lymphoma. The cell line's biological characteristics were analyzed. The results showed that the established cell line could survive and proliferate in RPIM 1640 medium; the Wright-Giemsa-stained cells were exactly similar to malignant cells of CD30+ ALCL in morphology, with many diffuse virus granules in cytoplasm; the cytochemical staining of the cells showed the following reactivity pattern: positive for acid phosphatase (ACP) and periodic acid-Schiff (PAS), negative for peroxidase (POX), myeloperoxidase (MPO) and platelet peroxidase (PPO). The immunoprofile of the cells was positive for CD45, HLA-DR, CD30 and negative for EMA, CD34, CD38, CD2, CD3, CD4, CD7, CD8, CD10, CD15, CD19 and CD20. The cytogenetic analysis showed complicate d qualitative and quantitative abnormality of chromosomes, without typical t(2;5). It is concluded that the established cell line is CD30+ anaplastic large cell lymphoma cell line.
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PMID:[Establishment of a human CD30+ anaplastic large cell lymphoma cell line and its biological characteristics]. 1457 43


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