Use of a novel fibronectin receptor for liver infiltration by a mouse lymphoma cell line RL-male1. (9/6021)

The mechanism whereby some lymphomas invade liver extensively has not been fully investigated. There is no basement membrane under the sinusoidal endothelium of the liver, and hepatocytes produce fibronectin (FN); therefore, adhesion to this FN may be particularly important for liver infiltration by lymphoma cells. A mouse lymphoma cell line, RL-male1, adhered to FN. However, this cell line did not express classical FN receptors such as very late antigen (VLA)-4 and VLA-5, as estimated by immunofluorescent staining. We have generated monoclonal antibodies (mAbs) that inhibit adhesion of RL-male1 cells to FN. Western blot and immunoprecipitation analyses showed that the new mAbs recognize a protein with an approximate molecular weight of 55,000 (p55). This antigenic protein was highly purified by immunoprecipitation and processed for microsequencing. From NH2-terminal sequence results, the p55 antigen was not identical to known FN receptors. Radioisotope-labeled RL-male1 cells, when injected i.v. into mice, rapidly infiltrated the liver (30-35% of injected cells), as measured by a gamma counter. Intravenous injection of the new mAbs partially (20%) blocked the infiltration of i.v.-injected lymphoma cells into the liver, whereas control rat IgG and an anti-CD11a mAb did not. These results demonstrate that the mouse lymphoma cell line RL-male1 nses a novel FN receptor for liver infiltration.  (+info)

Splenic marginal zone lymphomas of mice. (10/6021)

Splenic marginal zone lymphomas (MZLs) have been found to occur at a high frequency in NFS.N mice congenic for high-expressing ecotropic murine leukemia virus (MuLV) genes from AKR and C58 mice. Based on morphological, immunological, and molecular studies of these mice, MZL is clearly recognizable as a distinct disease with a characteristic clinical behavior. MZL was staged according to the degree of accumulation and morphological change of cells within the splenic marginal zone, as follows: 1) a moderate increase in normal-looking MZ cells, judged to be prelymphomatous, and 2) MZL in three variants: i) distinct enlargement of MZ by normal-looking cells (MZL), ii) distinct enlargement of MZ by basophilic centroblast-like cells (MZL+), and iii) extensive splenic involvement by centroblast-like cells (MZL++). The rate of mitosis and apoptosis increases with lymphoma grade. In most cases, emergence of a dominant IgH clonal pattern in paired splenic biopsy and necropsy samples was correlated with progression. MZLs were transplantable and homed to the spleen. MZL may constitute a commonly occurring lymphoma type unrecognized, in part, because of the centroblastic morphology of high-grade MZL and possible overgrowth of lower-grade MZL by more aggressive follicular lymphomas.  (+info)

Health-related quality of life 1 year after allogeneic or autologous stem-cell transplantation: a prospective study. (11/6021)

PURPOSE: To evaluate health-related quality of life (HRQOL) in adults treated with high-dose chemotherapy followed by allogeneic (SCT) and autologous (ASCT) stem-cell transplantation 1 year after transplantation, using data from concurrent lymphoma patients receiving combination chemotherapy (CT) as a reference. MATERIALS AND METHODS: Forty-one leukemia patients (SCT group), 51 lymphoma patients (ASCT group), and 85 CT patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire at baseline and after 1 year. RESULTS: The SCT group (median age, 36 years) had better functioning scores and less symptomatology at baseline compared with the ASCT (median age, 41 years) and CT (median age, 37 years) groups. Statistically significant differences of 10 or more points on the 0 to 100 scales were found for 10 of 15 scales and items (P< or =.01) between the SCT and ASCT groups. Global quality of life (79 v 58, P<.0001), role function (83 v 65, P = .001), sleep disturbances (6 v 28, P<.0001), and fatigue (25 v 44, P = .0001) deviated most. The differences were 10 or more points for seven of 15 scales and items comparing the SCT and CT groups, with sleep disturbances (6 v 35, P<.0001) and pain (11 v 29, P<.01) deviating most. Differences across groups were smaller after 1 year; cognitive function was the only scale with a statistically significant difference (ASCT 80 v CT 89; P = .002). Patterns of change in HRQOL scores were different between groups during follow-up. A great improvement was found in the ASCT group (P<.01 for emotional and role function, fatigue, appetite, and constipation), whereas no significant changes were observed for the SCT group. CONCLUSION: Prospective studies with extended follow-up periods are necessary to separate a slow recovery process from more permanently reduced HRQOL after transplantation and to examine the late side effects from previous treatment.  (+info)

Cytokine mRNA profiles in Epstein-Barr virus-associated post-transplant lymphoproliferative disorders. (12/6021)

Cytokine mRNA patterns were analyzed in 11 post-transplant lymphoproliferative disorder (PTLD) specimens using qualitative reverse-transcriptase polymerase chain reaction (RT-PCR). In each case, a pattern of IL2-, IFN gamma-, IL4+, IL10+ was seen. A similar pattern was observed in a spleen sample from 1 patient with contemporaneous PTLD elsewhere. Semiquantitative RT-PCR for cytokine message was performed using RNA from bronchoalveolar lavage (BAL) specimens obtained from 2 patients with pulmonary PTLD. In both cases, IL4 message predominated. Reduction of message coincided with resolution of the tumors. The pattern differed from that seen in 1 patient with acute pulmonary rejection, in which RT-PCR of BAL cells showed predominance of IL6 and IFN gamma. We conclude that at least some PTLDs exist within a T-helper cell type 2 (Th2)-like cytokine microenvironment. The presence of a similar mRNA pattern in an extratumoral specimen at the time of PTLD suggests that it may reflect a systemic phenomenon. Disappearance of this pattern following PTLD resolution indicates its dynamic nature and is consistent with the hypothesis that specific cytokines contribute to the development of PTLDs.  (+info)

Spectrum of p53 gene mutations suggests a possible role for ultraviolet radiation in the pathogenesis of advanced cutaneous lymphomas. (13/6021)

There is evidence that the incidence of primary cutaneous lymphoma, like other forms of non-Hodgkin's lymphoma, is increasing, yet little is known of the pathogenetic events involved in this group of disorders. In this study we examine the frequency and spectrum of P53 gene mutations in a large series of primary cutaneous lymphomas, with particular emphasis on tumor stage mycosis fungoides, as it is in these cases that p53 overexpression has previously been reported. Sixty-six samples from 55 patients with primary cutaneous B cell and T cell lymphomas were analyzed for mutations in exons 5-9 of the P53 gene using polymerase chain reaction/single strand conformational polymorphism, and subsequent cloning and sequencing of genomic DNA. Fourteen separate P53 mutations were identified in blood, skin, and lymph node samples in 13 patients (24%). Twelve of 14 mutations occurred at dipyrimidine sites, eight resulting in C-->T transitions and one in a CC-->TT tandem base transition, a mutation spectrum strikingly similar to that reported in nonmelanoma skin cancer and characteristic of DNA damage caused by ultraviolet B radiation. In the subset of patients with mycosis fungoides, P53 mutations were identified in six of 17 patients with tumor-stage but in none of 12 patients with plaque-stage disease (Fisher's exact test p = 0.027). These data suggest a role for ultraviolet radiation in the pathogenesis of primary cutaneous lymphomas and a possible ultraviolet B-related step in the progression of mycosis fungoides from plaque to tumor-stage disease.  (+info)

Staging and monitoring of malignant lymphoma of the bone: comparison of 67Ga scintigraphy and MRI. (14/6021)

The aim of this study was two-fold: to compare 67Ga scintigraphy with MRI (a) for the staging of malignant lymphoma of the bone and (b) with regard to accuracy in detecting residual disease after first-line chemotherapy for restaging. METHODS: Twenty-one patients with 36 malignant osseous lesions were examined, including 7 patients with primary or multifocal osseous lymphoma and 14 patients with malignant lymphoma and simultaneous or secondary involvement of the bone. After first-line therapy, MRI and 67Ga scintigraphy were performed on 13 patients. The remission status based on all clinical and radiological findings during the follow-up was used as the gold standard. RESULTS: The osseous lesions were located on the axial skeleton in 64% of patients and on the appendicular skeleton in 36%. 67Ga scintigraphy detected 77% of the osseous lesions examined by MRI. For restaging after first-line therapy, MRI had a sensitivity of 90% and a specificity of 80% when dynamic MRI information was included. There were several false-positive results as a result of the pathologic increase in signal intensity ratios of reactive hematopoietic regions after chemotherapy. For 67Ga scintigraphy, a sensitivity of 70% and a specificity of 93% were calculated. CONCLUSION: These data show that monitoring malignant lymphoma of the bone still presents diagnostic problems. Given the high sensitivity of MRI and the high specificity of 67Ga scintigraphy but the limited specificity of MRI and sensitivity of 67Ga scintigraphy, both methods are valuable but should be used as complementary diagnostic tools.  (+info)

Stimulation of autologous blood lymphocytes by malignant lymphoma cells and homogenates. (15/6021)

The blastogenic response to autologous blood lymphocytes to whole-cell suspensions and to homogenates obtained from malignant lymphoma tissue has been investigated. Spleens were obtained from patients in whom laparotomy was performed for staging of malignant lymphoma. Cell suspensions prepared from tumour nodules were treated with mitomycin C and allowed to react with separated autologous blood lymphocytes for 6 days. Lymphocyte stimulation was measured by liquid scintillation counting after exposure to 3H-TdR. Cultures were also prepared in which autologous lymphocytes were treated with spleen tumour homogenate. Control experiments used spleens from staging procedures in which no tumour deposits were present, and normal spleens removed incidentally during other operations. In the controls, the uptake of TdR was never more than twice that of unstimulated lymphocytes. Greater degrees of lymphocyte stimulation were seen in 6 out of 14 patients, using whole tumour cells, and in 7 out of 16 patients, using tumour homogenates. The results indicate an antigenic difference between tumour and host cells, and suggest that lymphocytes can react to a tumour-associated antigen.  (+info)

Costs of high-dose salvage therapy and blood stem cell transplantation for resistant-relapsed malignant lymphomas in a southern Italian hospital. (16/6021)

BACKGROUND AND OBJECTIVE: Analysis of costs of high technological procedures such as peripheral blood stem cell (PBSC) autotransplantation in lymphomas are generally finalized at disclosing whether the improvement of survival in a subset of patients is cost effective and whether the cost of the procedure could be reduced. With the aim of revealing a possibility of reducing costs with respect to conditions of safety, we present our experience with PBSC autotransplantation in a particularly poor prognosis subset of patients with lymphoma. DESIGN AND METHODS: The expenses are analyzed for groups of cost and main resources necessary at unitary cost are considered separately. Groups of cost include various phases of the PBSC autotransplantation such as preparative procedures, execution of myeloablative therapy, reinfusion of CD34 cells, supportive therapy after reinfusion until discharge of the patient, general support for the management of patient. All costs are calculated according to 1997 prices and salaries and reported in dollars. The analysis was conducted on 21 patients with lymphoma resistant to other therapies treated by myeloablative therapy and PBSC autotransplantation in an hematologic unit in an open ward; the assistance was provided by staff not exclusively dedicated to bone marrow transplant procedures, with some help from a family member. RESULTS: The PBSC procedure, including all phases, costs from $17,761.9 to $18,259.9 depending on the type of myeloablative therapy employed; the mean cost was $18,092.6. The preparative phase with mobilization of CD34 cells, cryopreservation and reinfusion costed $3,538.7 (19.6% of the total cost); a major cost of this phase was cryopreservation and CD34 manipulation ($857.1). The second phase with myeloablative therapy and reinfusion of CD34 cells had a mean cost of $2,785.9 (15.4% of the total cost); a major cost of this phase was the hospitalization ($1,119.8). The third phase of patient's support after treatment had a total cost of $7,649 (42.3% of the cost of the total procedure) with the major cost being due to hospitalization ($2,571) calculated on a mean of 15 days after the reinfusion of CD-34. The last group of costs, including management support, accounted for $4,119 (22.7%) with a major cost being amortization of the structure ($1,600). The general cost for nurse's assistance to the patient was $1,355.1 (7.5%). INTERPRETATION AND CONCLUSIONS: A procedure of PBSC autotransplantation in resistant lymphoma is affordable without the strict precautions generally given in intensive care units. This provides a substantial reduction of expenses because of the low number of specifically trained staff members and the generally low cost of the necessary supplies. Before, however, proposing PBSC autotransplantation in most patients with resistant lymphoma, an evaluation of whether costs could be further reduced and whether the procedure has a cost benefit impact is needed.  (+info)