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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)

We retrospectively evaluated the use of 18F-FDG PET for assessment of residual disease in 27 patients after therapy for malignant lymphoma. The images were evaluated qualitatively and quantitatively using standardized uptake values (SUV). All findings were validated either by biopsy or by clinical follow-up and compared with corresponding CT findings. The impact of blood glucose concentration, body weight, body surface area, lesion diameter and the time between injection and imaging on the SUVs were analysed. All 15 patients with biopsy-proven residual disease or relapse during follow-up and 11 of 12 patients who remained relapse-free were correctly identified by qualitative interpretation of the PET images. A case of pneumonitis after radiotherapy/chemotherapy accounted for the only false-positive finding. Compared with CT imaging, PET had a significantly higher specificity (P < 0.01), accuracy (P < 0.05) and positive predictive value (P < 0.05). The mean and maximum SUV of the tumour lesions were positively correlated to lesion diameter (P < 0.01) and imaging time post-injection (P < 0.01). Standardized uptake values corrected for the partial volume effect and normalized to a standardized imaging time (SUVBPT) were significantly higher (P < 0.05) in high-grade than in low-grade non-Hodgkin's lymphoma. In conclusion, 18F-FDG PET may help in the identification of patients who need additional treatment after the completion of conventional therapy. Qualitative image interpretation appears sufficient for this purpose.
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PMID:Positron emission tomography with 18F-FDG to detect residual disease after therapy for malignant lymphoma. 986 22

The fine needle aspiration (FNA) cytologic diagnosis of non-Hodgkin's lymphoma (NHL) depends upon finding a relatively monotonous population of lymphoid cells in smears. Lymphomas have successfully been classified by FNA cytology following the prevalent histologic classifications. The success rate of FNA cytology ranges from 80%-90% in diagnosis of NHL and from 67.5%-86% in its subtyping. The cytodiagnosis of Hodgkin's disease (HD) depends upon demonstration of Reed-Sternberg cells or Hodgkin's cells amongst appropriate reactive cell components. The diagnostic accuracy of FNA cytology for HD has also been invariably high (>85%). Yet, the role of cytology in primary diagnosis, subclassification and management of patients with lymphoma remains controversial. The differential diagnostic problems for NHL include a group of small round cell tumors, nonlymphoid acute leukemias and HD. Reservations have been expressed regarding the efficacy of cytology in separating florid reactive hyperplasia from low-grade malignant lymphoma. The reported cytodiagnostic accuracy for follicular lymphomas and nodular sclerosis type of HD is less compared to other subtypes of NHL and HD respectively since nodular pattern and sclerosis are strict histologic criteria which can not be appreciated in cytologic preparations. Entities like atypical lymphoproliferative disorders, peripheral T-cell lymphomas and Ki-1 positive anaplastic large cell lymphomas pose diagnostic challenges to cytologists. Despite these limitations, FNA cytology remains the first line of investigations (screening test) used in cases of lymphadenopathy. Besides initial diagnosis of lymphoma, it helps in detection of residual disease, recurrences and progression of low-grade to high-grade lymphoma, and helps in staging the disease. Availability of prior FNA cytology report facilitates the histologic diagnosis and classification of NHL. Various special ancillary techniques are now being performed on lymph node aspirates to diagnose lymphoma versus other malignancies, and to decide the functional character of lymphomas and their clonal nature. Diagn. Cytopathol. 1999;21:240-249.
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PMID:Value and limitations of fine-needle aspiration cytology in diagnosis and classification of lymphomas: A review. 1049 16

The purpose of our study was to investigate the efficacy of an acute lymphoblastic leukemia (ALL)-type treatment with moderate-dose, prophylactic cranial irradiation and without local radiotherapy for childhood T-cell lymphoblastic lymphoma (T-LBL). From April 1990 to March 1995, 105 evaluable patients, 1.1 to 16.4 years of age, with T-LBL were enrolled in study NHL-BFM 90 (non-Hodgkin's lymphoma-Berlin-Frankfurt-Munster 90). They received an 8-drug induction over 9 weeks followed by an 8-week consolidation including methotrexate (MTX) 5 g/m(2) x 4. Patients with stage I (n = 2) and II (n = 2) continued with maintenance therapy (6-mercaptopurine daily and MTX weekly, both orally) until a total therapy duration of 24 months. Patients with stage III (n = 82) and IV (n = 19) received an 8-drug intensification over 7 weeks and cranial radiotherapy (12 Gy for prophylaxis) after consolidation, followed by maintenance. Residual tumor after induction had to be resected. Patients received intensified chemotherapy if tumor regression on day 33 of induction was less than 70% or when vital residual tumor was present after the complete induction phase. With a median follow-up of 4.5 years, the estimated event-free survival at 5 years is 90% (95% confidence interval, 82%-100%). Events were 1 early death, 8 tumor failures, and 1 secondary acute myeloid leukemia. A total of 101 patients were evaluable for the speed of tumor response. Two patients received intensified therapy due to less than 70% tumor regression on day 33. Of 19 patients with tumor residues after induction, 2 relapsed as compared to 4 of 80 patients with complete tumor regression. We conclude that, with intensive ALL-type chemotherapy including moderate cumulative doses of anthracyclines 240 mg/m(2) and cyclophosphamide (3 g/m(2)) and moderate-dose prophylactic cranial irradiation but no local radiotherapy, an event-free survival rate of 90% can be achieved in childhood T-LBL. (Blood. 2000;95:416-421)
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PMID:Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. 1062 44

The reduction of residual tumor cells is one of the main targets of leukapheresis product (LP) processing. Immunomagnetic enrichment/selection of CD34+ progenitor cells (Baxter Isolex 300i) can achieve a reduction of contaminating B-cells of approximately 2-3 logs in B-cell non-Hodgkin's lymphoma patients. Specific release of the enriched CD34+ cells (stem cell releasing agent PR34+; Baxter) and the use of antibody-coated immunobeads targeted against B-cell markers (CD10, CD19, CD20, CD22, CD23, and CD37) during this procedure allows the GMP-like simultaneous capture of residual B cells within a closed system. This combination of two purging techniques enhances the B-cell depletion capacity up to 4.5 logs. By performing 10 clinical-scale purging procedures, we could show that the simultaneous immunomagnetic purging method is easy to perform and highly efficient. We evaluated B-cell log depletion by flow cytometry for cases with marker-positive cells detectable before and after the purging procedure. The mean reduction of B-cells in these cases was 3.5 logs; the mean CD34+ cell yield and purity were 47 and 92%. Using three LPs, we tested the procedure on a modified Baxter Isolex 300i device with software adaptations for this procedure (software version 2.0) in direct comparison with CD34+ cell selection only, using the former version (version 1.12). The CD34+ cell yield was 49% (40-54%) for the CD34+ cell selection and 51% (19-72%) for simultaneous double selection. The mean purity was 96% for CD34+ cell selection and 98% for simultaneous double selection. B-cell depletion was 1.9 logs for CD34+ cell selection, and after simultaneous double selection, the B-cell content was decreased by 3.7 log steps (P = 0.0495). Clinical application of double-purged cells has not prolonged the hematopoietic recovery times after high-dose therapy as compared with nonpurged peripheral blood progenitor cell autotransplants. In conclusion, we could show that the simultaneous double selection protocol developed leads to a highly increased B-cell purging efficacy when compared with CD34+ cell selection without any negative effects regarding CD34+ cell yield and engraftment times after high-dose therapy.
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PMID:Simultaneous immunomagnetic CD34+ cell selection and B-cell depletion in peripheral blood progenitor cell samples of patients suffering from B-cell non-Hodgkin's lymphoma. 1120 18

Myelitis is a rare but well documented complication of therapeutic radiation exposure to the spinal cord and is characterized by delayed development of paresthesias, sensory changes and, in severe cases, progressive paresis and paralysis. Although accepted radiation tolerance limits for the spinal cord have successfully limited the incidence of this problem (45-50 Gy, in daily 1.8-2 Gy fractions), aggressive systemic therapy may render patients more susceptible to radiation-related neurotoxicity. We describe the case of a 38-year-old man with refractory non-Hodgkin's lymphoma who underwent matched sibling peripheral blood stem cell transplant following a conditioning regimen of cyclophosphamide (60 mg/kg x 2) and total body irradiation (120 cGy x 11). This was followed by delivery of 30.6 Gy involved-field radiation at 1.8 Gy/day to the mediastinum and left supraclavicular fossa for bulky residual tumor. Although maximum cumulative radiation dose to the spinal cord was less than 45 Gy, the patient subsequently developed progressive lower extremity weakness and MRI abnormalities of the spinal cord limited to the radiation field. This represents the second report in the literature of this unexpected complication, prompting a need to re-examine current guidelines for radiotherapy in the context of high-dose systemic treatment.
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PMID:Radiation myelitis following allogeneic stem cell transplantation and consolidation radiotherapy for non-Hodgkin's lymphoma. 1154 53

Lymphoproliferative disorders associated with the Epstein-Barr virus (EBV) include non-Hodgkin's lymphoma, Hodgkin's lymphoma, and "post-transplant lymphoproliferative disorders" (PTLD), which occur with immunosuppression after marrow and organ transplantation. PTLD is characterized by actively proliferating, latently infected EBV(+) B-lymphocytes, and often manifests a rapidly progressive fatal clinical course if the immunosuppression cannot be reversed. Lung transplant recipients are a subset of patients at special risk for developing PTLD. The incidence of PTLD development in these patients has been estimated at 5--10%. Whereas immunologic and antiviral therapy have been moderately effective for treating EBV-associated infections in the lytic phase, they have been less useful in the more common latent phase of the disease. One common treatment for herpesvirus infections has targeted the virus-specific enzyme thymidine kinase (TK). The lack of viral TK expression in EBV(+) tumor cells, due to viral latency, makes anti-viral therapy alone ineffective as an anti-neoplastic therapy, however. We have developed a strategy for the treatment of EBV-associated lymphomas/PTLD using pharmacologic induction of the latent viral TK gene and enzyme in the tumor cells, followed by treatment with ganciclovir. Arginine butyrate selectively activates the EBV TK gene in latently EBV-infected human lymphoid cells and tumor cells. A Phase I/II trial has been initiated, employing an intra-patient dose escalation of arginine butyrate combined with ganciclovir. In six patients with EBV-associated lymphomas or PTLD, all of which were resistant to conventional radiation and/or chemotherapy, this combination produced complete clinical responses in four of six patients, with a partial response occurring in a fifth patient. Pathologic examination in two of three patients demonstrated complete necrosis of the EBV lymphoma, with no residual disease, following a single three-week course of the combination therapy. Possible side-effects of the therapy included nausea and reversible lethargy at the highest doses. One patient suffered acute liver failure, thought to be secondary to release of FasL from the necrotic tumor. Analysis of patient-derived tumor cells in culture demonstrated that arginine butyrate produced selective induction of the EBV TK gene, which then conferred sensitivity to ganciclovir, resulting in tumor apoptosis. Additional patient accrual is sought for further evaluation of this therapy.
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PMID:Epstein--Barr virus post-transplant lymphoproliferative disease and virus-specific therapy: pharmacological re-activation of viral target genes with arginine butyrate. 1149

Contamination of stem cell harvests with residual tumor cells is a significant problem hampering the success of autologous peripheral blood stem cell transplantation in non-Hodgkin's lymphoma (NHL). Techniques have therefore been introduced to attempt to remove these cells, either in vivo, prior to harvesting, or ex vivo, before reinfusion into the patient. Rituximab is a human-mouse chimeric anti-CD20 monoclonal antibody that has been administered to patients prior to stem cell harvesting, to purge the blood of residual malignant cells. Clinical studies have shown that rituximab is safe to use during stem cell mobilization since administration did not adversely affect the yield of CD34+ stem cells or the functional capability of these progenitors. Rituximab was also effective in purging stem cell harvests of malignant cells. Translocation of the bcl-2 gene was found in a significantly smaller proportion of stem cell harvests from patients who had received a purging infusion of rituximab than controls. Rituximab may also be useful as salvage therapy following post-transplant relapse or as maintenance therapy for patients in remission. Prospective randomized trials will ultimately define the role of rituximab in the autologous transplantation setting.
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PMID:Rituximab in autologous stem cell transplantation for follicular lymphoma. 1150 33

Autologous peripheral blood stem cell mobilization is increasingly applied in the treatment of hematological malignancies. Despite the frequent clinical use in a setting of residual disease, it is not known whether mobilization of hematopoietic stem cells might facilitate tumor outgrowth in vivo. In the bone marrow, a bipotential precursor for hematopoietic and endothelial cells called hemangioblast exists. This hemangioblast, characterized by the expression of CD34 and vascular endothelial growth factor receptor (VEGFR)-2, is released from the bone marrow by mobilization and might be able to result in not only the generation of peripheral blood cells but vasculogenesis due to differentiation of the hemangioblast along the endothelial lineage [in addition to VEGFR-2 expression, angiopoietin-2 (ANG-2) expression can also be found in this stage]. New vessel formation in the tumor is critical for tumor growth. A xenotransplant model was established with 10 x 10(6) Daudi cells (non-Hodgkin's lymphoma) s.c. injected in the neck region of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, who were sublethally irradiated with 2 Gy. At day 10 after tumor inoculation, half of the mice were given 0.5 x 10(6) human CD34+ cells i.v., whereas the other half were given PBS i.v. The human CD34+ cells were obtained from leukapheresis samples of myeloma patients undergoing autologous peripheral blood stem cell mobilization. We compared tumor growth and human-specific VEGFR-2 and ANG-2 expression in the two groups. Tumor growth is enhanced 2-fold when mobilized hematopoietic human CD34+ cells are given compared with PBS controls (P = 0.004). In addition, the human-specific VEGFR-2 and ANG-2 reverse transcription-PCR was only positive in the tumors of mice i.v. injected with human CD34+ cells. This indicates that the injected human CD34+ cells home to the tumors and differentiate along the endothelial lineage. In the present study, we demonstrate that mobilized human CD34+ hematopoietic cells injected i.v. might facilitate the outgrowth of tumors in the setting of minimal residual disease. Malignant tumors are capable of incorporating human CD34+ hematopoietic cells. This study questions the safety of leukapheresis in patients with (residual) tumor and has important implications for further development of intensive chemotherapy protocols with autologous stem cell rescue.
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PMID:Mobilized human CD34+ hematopoietic stem cells enhance tumor growth in a nonobese diabetic/severe combined immunodeficient mouse model of human non-Hodgkin's lymphoma. 1160 8

Vaccination with the idiotype (Id) protein derived from B-cell malignancies can produce Id-specific immune responses that correlate with improved remission duration and survival rates in patients with follicular non-Hodgkin's lymphoma (NHL). A state of minimal or no residual disease correlates strongly with the laboratory detection of a cellular or humoral immune response. High-dose cytotoxic therapy (HDCT) with autologous stem cell support (autologous bone marrow transplantation [ABMT]) can provide profound cytoreduction of B-cell NHL, but the potential immune suppression associated with myeloablative therapy may compromise a patient's ability to mount a specific immune response. To determine whether patients with NHL could mount detectable immuneresponses following ABMT, Id vaccines were administered at 2 to 12 months following myeloablative therapy to a series of patients with relapsed or resistant B-cell NHL. Two different vaccination strategies produced robust immune responses against KLH in all patients, supporting the capacity of the reconstituted immune system following HDCT to react against a strong antigen. Combining the results from both vaccination strategies, 10 of 12 patients mounted Id-specific humoral or cellular responses. Vaccinations were consistently well tolerated. Of the 12 patients, 7 have experienced prolonged remissions with a follow-up from HDCT ranging from 3 to more than 11 years. Our experience serves to document the ability of the recovering immune system to react against both self and xenotypic antigens and supports the feasibility and safety of antigen-specific vaccination following myeloablative therapy in patients with B-cell NHL.
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PMID:Idiotype vaccination following ABMT can stimulate specific anti-idiotype immune responses in patients with B-cell lymphoma. 1166 19

Campath-1H is a humanized monoclonal antibody targeted against the CDw52 membrane antigen of lymphocytes, which causes complement and antibody-dependent cell-mediated cytotoxicity. Campath-1H has been used in B-chronic lymphocytic leukemia (B-CLL), T-prolymphocytic leukemia (T-PLL), and low-grade non-Hodgkin's lymphoma (LGNHL). Campath-1H is administered intravenously thrice weekly for up to 12 wk, at an initial dose of 3 mg, escalated to 10 and 30 mg. The responses (complete [CR] and partial [PR]) obtained in untreated B-CLL patients are of the order of 90%. In previously treated B-CLL patients, responses are of the order of approximately 40%, with 2-4% CRs. Responses are more prominent in the blood and bone marrow compared to the lymph nodes. The median duration of response is 9-12 mo. Because of the antibody's higher activity on circulating lymphocytes, it has been used for in vivo purging of residual disease in B-CLL, followed by autologous stem-cell transplantation. In heavily pretreated advanced stage LGNHL, response is achieved only in 14% of cases with B-phenotype; a 50% response rate is noted in mycosis fungoides. In T-PLL, the CR rate is approximately 60%. Promising results have been reported in a small number of patients with refractory autoimmune thrombocytopenia of lymphoproliferative disorders. The main complications of Campath-1H treatment are caused by tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 release, usually during the first intravenous infusion, and include fever, rigor, nausea, vomiting, and hypotension responsive to steroids. These side effects are usually less severe with subsequent infusions and can be prevented by paracetamol and antihistamines. Immunosupression resulting from normal B- and T-lymphocyte depletion is frequent, resulting in an increased risk for opportunistic infections. More clinical trials in a larger number of patients are necessary to determine the exact role and indications of Campath-1H in lymphoproliferative disorders.
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PMID:Campath-1H (anti-CD52) monoclonal antibody therapy in lymphoproliferative disorders. 1177 65


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