Secondary malignant neoplasms in patients with non-Hodgkin's lymphoma

In 1979-1987, 570 patients with non-Hodgkin's lymphomas (226 female and 344 male patients) were treated at the Department of Hematology of the Pomeranian Medical Academy and hematological outpatient clinic. The second malignant tumors were diagnosed in 25 (4.4%) patients. Two patients suffered from three malignant tumors. The most frequent combination of 2 tumors were: non-Hodgkin lymphoma and cancer of the lungs in 8 patients, non-Hodgkin lymphoma and cancer of the skin in 6 patients, non-Hodgkin lymphoma and cancer of the larynx in 4 patients, non-Hodgkin lymphoma combined with cancer of the stomach in 2 patients, and non-Hodgkin lymphoma together with cancer of the bladder in 2 patients. Moreover, non-Hodgkin lymphoma coexisted with cancer of the colon, cervix and prostate (one case of each). The authors stress the possibility of other malignant tumors in patients with non-Hodgkin lymphomas and occurrence of the subsequent neoplasms without preceding chemo- or radiotherapy.     

Examination of platelet aggregation and ultrastructure in patients with non-Hodgkin's lymphoma

Aggregation and secretion reaction of thrombocytes were studied in 54 patients suffering from Non-Hodgkin's++Lymphoma. Results were compared with electron-microscopic findings on thrombocytes of the same patients. Slight changes were found in stage II. In stage IV distinct therapy-resistant changes were noted in combination with storage pool disease syndrome which is to be considered as a consequence of impaired generation of thrombocytes in bone marrow.     

Megakaryocytes emperipolesis in bone marrow of the patients with non-Hodgkin's lymphoma

Emperipolesis of hematopoietic cells within the cytoplasm of the megakaryocytes was most often described in association with various pathologic conditions. The aim of the research was estimation of the incidence of emperipolesis in the bone marrow of the patients with non-Hodgkin's lymphoma (NHL). 30 patients with different histological types of NHL (chronic lymphocytic leukaemia--CLL, hairy cell leukaemia--HCL, multiple myeloma--MM) in compliance with clinical stage of the disease, patient's age and sex were analyzed. Trephine biopsies of the bone marrow were carried out in fixative solution and paraffin embedding. Hematoxylin and eosin and monoclonal antibody CD 61 were applied on thin sections. Phenomenon of megakaryocytic emperipolesis in human bone marrow was found in 6 cases: in 5 cases in CLL and in 1 case in HCL. In most of them emperipolesis was related to single megakaryocytes. We observed in the cytoplasm of the megakaryocytes single hematopietic cells-most often lymphocytes, rarely eosinophilic granulocytes. We found no correlations between histological types of NHL, clinical stage of the disease, patients' age, sex and the incidence of megakaryocytic emperipolesis.     

High-dose sodium selenite can induce apoptosis of lymphoma cells in adult patients with non-Hodgkin's lymphoma

The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the apoptosis of lymphoma cells in patients with non-Hodgkin’s lymphoma (NHL). Forty patients with newly diagnosed NHL were randomly divided into two groups. Group I received standard chemotherapy, whereas group II received adjuvant sodium selenite 0.2 mg kg⁻¹ day⁻¹ for 7 days in addition to chemotherapy. Flow cytometry was used for monitoring of lymphoma cells apoptosis at the time of diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant increase in percentage of apoptotic lymphoma cells after therapy in group II (78.9 ± 13.3% versus 58.9 ± 18.9%, p < 0.05). In addition, patients who received sodium selenite treatment demonstrated statistically significant increase in percentage of reduction of cervical and axillary lymphadenopathy, decrease in splenic size, and decreased percentage of bone marrow infiltration. Also, we found a statistically significant decrease in cardiac ejection fraction (CEF) in group I and no reduction in CEF in patients who received sodium selenite ‘group II’, denoting the cardioprotective effect of selenium. It is concluded that sodium selenite administration at the dosage and duration chosen has synergistic effect to chemotherapy in inducing apoptosis and, consequently, could improve clinical outcome.     

Hungarian experience with non-Hodgkin's lymphoma in childhood

Between 1990 and 2004, 230 children with non-Hodgkin's lymphoma (NHL) were treated according to the Berlin-Frankfurt-Münster (BFM) protocols (NHL-BFM-90 and -95) in Hungary. The aim of the present study was to summarize our experience with these protocols, to assess the survival rates and to compare the Hungarian data with the international results. The male-to-female ratio was 2.59:1, the mean age at the time of diagnosis was 10 years and 1 month. Ninety-one children had lymphoblastic/T-NHL (LB/T-NHL), 108 B-NHL and 31 anaplastic large cell lymphoma (ALCL). Twenty-eight patients had relapse after a mean time of 13 months from the time of the initial diagnosis. In the above mentioned period, 16 children underwent autologous stem-cell transplantation. Nine patients with B-NHL got anti-CD20 immunotherapy. The five-year overall survival (OS) of our patients is 77.8%+/-3%, the event-free survival (EFS) is 75.1%+/-3%. The 5-year OS and EFS rates were not statistically different in the three histology groups (OS: 71.6%+/-5%, 82.7%+/-4% and 80.3%+/-7%; EFS: 68.7%+/-5%, 81.1%+/-4% and 73.9%+/-8% in LB/T-NHL, B-NHL and ALCL, respectively). We can conclude that non-Hodgkin's lymphoma has a quite good prognosis among the malignant pediatric diseases. The cure rate is over 75%. The Hungarian results are comparable with other international data. In the last five years the mortality during induction was reduced from 10% to 2% and the OS is about 10% better than it was before. In case of relapse or residual disease, therapeutic results can be improved with stem-cell transplantation with or without immunotherapy.     

Serum and urine levels of interleukin-8 in patients with non-Hodgkin's lymphoma

Angiogenesis plays an important role in many types of cancer. Interleukin-8 (IL-8) is known to be a pro-inflammatory and pro-angiogenic cytokine, and IL-8 has been reported to be associated with tumor progression, prognosis and survival in several types of cancers. However, the role of IL-8 in non-Hodgkin's lymphoma (NHL) has not been fully determined. Here, we evaluated the usefulness of measuring serum and urine IL-8 levels in patients with NHL. We developed reference intervals for serum and urine IL-8 level in 131 control individuals. We measured serum IL-8 and urine IL-8 levels in patients with NHL, and we compared the concentrations with those of control individuals. The reference intervals for serum IL-8 and urine IL-8 corrected by creatinine (Cr) were 15.9-430.3 pg/mL and 0.0-28.4 pg/mg Cr, respectively. The concentrations of urine IL-8/Cr were significantly higher in patients than in controls (48.9+/-194.4 vs. 5.2+/-13.8 pg/mg Cr, P<0.001). However, there were no significant differences in serum IL-8 concentrations between NHL patients and controls (159.2+/-40.4 vs. 99.6+/-107.1 pg/mL; P=0.099). Receiver operating characteristic (ROC) analysis gave 0.83 and 0.43 ROC area values for urine IL-8/Cr and serum IL-8, respectively. There was no correlation between the serum and urine concentrations of IL-8 and clinical variables, the only exception being the international prognostic index (IPI), which showed a marginal correlation with urine IL-8/Cr levels (P=0.07). This study indicated that urine IL-8/Cr levels might be useful as a diagnostic marker of NHL.     

Proinflammatory chemokine gene expression influences survival of patients with non-Hodgkin's lymphoma

The migration, survival and proliferation of cells is the basis for all physiologic and pathologic processes in the human body. All these reactions are regulated by a complex chemokine network that guides lymphocytes homing, chemotaxis, adhesion and interplay between immunologic system response cells. Chemokines are also responsible for metastatic dissemination of cancers, including Hodgkin's and non-Hodgkin's lymphomas. The purpose of this study was to determine chemokine gene expression (CXCL8, CXCL10, CCL2, CCL3, CCL4 and CCL5) in lymphoma lymph nodes compared to their expression in reactive lymph nodes. We also analyzed the influence of chemokine gene expression on the survival of lymphoma patients. Chemokine gene expression was evaluated in 37 lymphoma lymph nodes and in 25 samples of reactive lymph nodes. Gene expression of chemokines CXCL8, CXCL10, CCL2, CCL3, CCL4 and CCL5 was measured using the PCR method. Statistical analysis was performed using CSS Statistica for Windows (version 7.0) software. Probability values 〈 〈 0.05 were considered statistically significant and those between 0.05 and 0.1 as indicative of a trend. We found lower CXCL8 and CXCL10 gene expression in lymphoma lymph nodes compared to reactive lymph nodes. In the cases of CCL2 and CCL3, expression in lymphomas was higher than in reactive lymph nodes. Patients with high expression of CCL2 and CXCL10 had shorter survival.     

Cutaneous manifestations in non-Hodgkin's lymphoma

OBJECTIVE: To examine and subtype cutaneous lymphoma specimens for diagnosis. STUDY DESIGN: Aspiration smears from skin lesions and lymph nodes diagnosed as non-Hodgkin's lymphoma (NHL) on cytology in 6 cases over a period of 1 year were reviewed. Two were follow-up cases of nodal lymphoma and were receiving chemotherapy, during which they developed skin lesions. In 4, the patients had cutaneous lesions as a presenting manifestation. Cytologic findings were correlated with histologic and hematologic findings and immunocytochemical markers for subtyping. RESULTS: Patients ranged from 14 to 50 years, with equal sex ratio. All presented with 0.5-5 cm multiple nodular, ulcerated and fungating skin lesions at various body sites. The aspirate was satisfactory in all cases. Cytologically, all cases were diagnosed as NHL. They were then immunocytochemistry subtyped as various lymphomas. CONCLUSION: Cutaneous lymphoma should always be considered in the presence of predominantly atypical lymphoid cells in smears from nodular and fungating skin lesions, even in the absence of a definitive clinical diagnosis.     

Rituximab induced hypoglycemia in non-Hodgkin's lymphoma

Background

Patients with aero-digestive malignancy will often require a feeding gastrostomy during their treatment to maintain their nutritional status. These are usually placed percutaneously using an endoscopic technique.

Case presentation

A fifty-six year old male underwent placement of a percutaneous gastrostomy (PEG) prior to commencement of his treatment for an oral squamous cell carcinoma. The treatment for this was locally curative. However, he developed a metastasis at the site of his PEG tube. This was excised en-bloc with the anterior gastric and abdominal walls.

Conclusion

Tumour implantation into wounds has been previously reported. In this case the direct trauma of passing the PEG tube through the oropharynx led to implantation of cells in the anterior abdominal wall. In these cases laparoscopic placement may be more beneficial to avoid this problem.     

Depressed cytotoxic T-cell responses in previously treated Hodgkin's and non-Hodgkin's lymphoma patients

Summary Peripheral blood lymphocytes from 62 previously treated Hodgkin's and non-Hodgkin's lymphoma patients were tested for their ability to generate cytotoxic T lymphocytes in response to stimulation with allogeneic cells in mixed leukocyte culture. In most patients, including some in long-term unmaintained remission, extremely low cytotoxic responses were generated. To test whether these patients have circulating cells that suppress autologous lymphocytes from responding to alloantigens, patients' responding cells were passaged over columns of sepharose beads conjugated with histamine-rabbit serum albumin (Hist-RSA). This procedure has been shown to remove mouse suppressor cells and Concanavalin A(ConA)-induced human suppressor cells. Passage of patients' cells, prior to allogeneic stimulation, over columns of sepharose beads conjugated with Hist-RSA but not over control RSA columns, resulted in the isolation of lymphocytes that generated increased cytotoxic responses to alloantigens in 18 of 22 patients with initially low cytotoxic responses. These results suggest that the impaired ability of treated Hodgkin's and non-Hodgkin's lymphoma patients' lymphocytes to differentiate into cytotoxic T lymphocytes is at least in part due to the presence of circulating suppressor cells that bear histamine receptors.Scholar of the Leukemia Society of America     

Production of interleukin-1 and tumour necrosis factor in non-Hodgkin's lymphoma patients

Summary Peripheral blood monocytes from non-Hodgkin's lymphoma (NHL) patients were assessed for the monocyte functions with respect to their ability to secrete interleukin-1 and tumour necrosis factor (TNF) and their cytotoxic potential to tumour target WEHI 164 clone 13. Our results indicate comparable levels of interleukin-1 and TNF production by NHL patients. The cytotoxic potential by monocytes was also not depressed in these patients. The data obtained suggest normal monocyte functions in NHL patients.     

Cytomorphologic characteristics of non-Hodgkin's lymphoma

The cytologic samples of 84 non-Hodgkin's lymphomas, classified according to the Rappaport system, were reviewed, with particular attention to the cell pattern, the size of the cells and other morphologic characteristics. The analysis revealed that: (1) the subgroups of malignant lymphoma in the Rappaport classification display a heterogeneous cytologic picture; (2) cytology cannot make the differentiation between nodular and diffuse non-Hodgkin's malignant lymphomas; and (3) reliable cytologic classification is possible only in certain cases of well-differentiated lymphocytic and diffuse histiocytic lymphomas. Well-differentiated lymphocytic lymphoma is characterized by a uniform cell picture consisting of mature lymphocytes, prolymphocytes or centrocytes up to 12 micron in size, by the presence of paraimmunoblasts and by the absence of reticulum cells. The diffuse histiocytic lymphoma contains over 48% centroblasts or over 8% immunoblasts or multinucleated giant blast cells.     

Management of localized non-Hodgkin's lymphoma

Non-Hodgkin''s lymphomas (NHLs) are a heterogeneous group of disorders that vary widely in response to therapy. In Canada the modified Rappaport classification is used to categorize NHL. To facilitate the reporting and comparison of treatment results all cases should also be categorized in the terminology of the National Cancer Institute''s working formulation. The choice of therapy should be guided by specific prognostic factors: stage and bulk of the disease, patient''s age, presence of systemic symptoms and histologic subtype. Of these, the last appears to be the most important. Radiotherapy (RT) is the treatment of choice in localized low-grade lymphomas with favourable prognoses, while bimodal therapy (RT and chemotherapy [CT]) is warranted in presentations with unfavourable prognoses. Regional irradiation alone is indicated in intermediate-grade lymphomas with good prognoses (i.e., pathological stage I or II or clinical stage IA or IIA localized disease of small bulk in young patients). All other patients require CT followed by RT. The results of CT alone are encouraging but remain experimental. Aggressive therapy with multidrug regimens that include central nervous system prophylaxis is the foundation for successful treatment of high-grade NHL such as lymphoblastic lymphoma and diffuse small-noncleaved-cell lymphomas. Low-dose RT should be given to sites of bulky disease.     

Chronic gamma-radiation sensitivity of skin fibroblasts from patients with non-Hodgkin's lymphoma (NHL)

Cultured skin fibroblasts from 11 patients with non-Hodgkin's lymphoma (NHL), 3 with ataxia telangiectasia (AT), 3 AT heterozygotes and 6 healthy subjects were studied for impaired colony-forming ability upon chronic exposure to gamma-radiation. A comparison of survival curves of the different cell lines revealed an AT heterozygote-like response (intermediate radiosensitivity) in 8 (73%) out of 11 NHL patients. These results suggested that the majority of the NHL patients may have an underlying abnormality of DNA repair.     

Histopathology of the spleen in non-Hodgkin's lymphoma

The human spleen has several different lymphoid compartments, which may be preferentially involved by non-Hodgkin's lymphomas. Low grade B-cell lymphomas tend to involve the compartments of the spleen where their normal physiological counterparts are found. High grade B-cell lymphomas grow more destructively without respecting lymphoid compartments. T-cell lymphomas involve mainly the T-cell areas, but may also involve follicles and the red pulp. Since non-Hodgkin's lymphomas can be regarded as clonal proliferations of lymphocytes frozen at a stage in differentiation, one possible conclusion is that low grade lymphomas are governed by normal homing mechanisms. High grade lymphomas may have lost their homing properties.     

Disordered development of macrophages in non-Hodgkin's lymphoma

Macrophage development in 20 untreated patients with non-Hodgkin's lymphoma (NHL) has been studied and compared with that in 20 normal subjects. Morphometric measurements were carried out on ultrastructural features of cell, nucleus and mitochondria during 6 days suspension culture of blood monocytes in the presence of autologous serum and lymphocytes. The results were subjected to multivariate and univariate analysis of variance. Statistically significant differences were found between the subject groups with respect to the volumes and surface areas of cell, nucleus and mitochondria, to the excess surface membrane of cell and nucleus (as compared with equivalent spheres) and to the number of mitochondrial profiles per section. It would appear that the patients' cell grew less, showed less elaboration of surface features and had reduced nuclear and mitochondrial development, the latter affecting mitochondrial numbers rather than individual size. The findings provide further evidence that mononuclear phagocytes are deranged in NHL.     

Angiogenesis measured by expression of CD34 antigen in lymph nodes of patients with non-Hodgkin's lymphoma

Angiogenesis is important in development, maintenance and progression of haematological malignancies. Some clinical observations have indicated that in non-Hodgkin's lymphoma (nHL) tumour microvessel density (MVD) may correlate with tumour staging and outcome. The aim of the study was to examine relationship between MVD as a parameter of tumour angiogenesis measured by expression of CD34 and the grade of nHL histological malignancy as determined by REAL classification. 40 lymph node samples of patients with newly diagnosed nHL (17 women, 23 men; aged 48-70 yrs, median age 64 yrs; stage III and IV) and treated at the Department of Haematology, Wroc?aw Medical University in 1999-2002 were fixed in 10% buffered formalin and embedded in paraffin. In all the studied cases, sections were incubated with antibodies against CD34. The slides were stained with hematoxylin and eosin and evaluated histopathologically. Patients were divided into two groups according to histological malignancy: indolent nHL (19 patients) and aggressive nHL (21 patients). Mean MVD measured by expression of CD34 in aggressive and indolent nHL groups amounted to 19.45 +/- 11.24 vessels/0.375 mm2 and 21.7 +/- 12.4 vessels/0.375 mm2, respectively. Statistical analysis of microvessel staining demonstrated no correlation between tumour MVD and grade of histological malignancy in lymph nodes of nHL patients. Nevertheless, angiogenesis observed in nHL provides rationale for use of angiogenesis inhibitors in lymphoma therapy.