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Background: The treatment of patients with relapsed or refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) remains challenging. Gemcitabine is a cytidine analog with a wide spectrum of antitumor activity. Gemcitabine treatment is widely used to treat patients with certain solid tumors and relapsed/refractory hematological malignancies. There are several reports indicating that this compound is active in lymphoid malignancies. In patients with relapsed or refractory HL and NHL, gemcitabine has demonstrated efficacy as a single agent and in combination with other cytostatics., Objectives: The aim of the study was to analyze the efficacy and toxicity of gemcitabine-based chemotherapy in patients with relapsed or refractory lymphomas., Material and Methods: The study evaluated 68 heavily pretreated patients with relapsed/refractory HL and NHL. The median age of the patients was 36 years. All the patients received gemcitabine-based chemotherapy (gemcitabine monotherapy or gemcitabine in combination with other cytostatics)., Results: The overall response rate was 46%. Complete response was achieved by 21% of the patients and partial response by 25%. Out of those who responded to gemcitabine treatment, 26 patients proceeded to autologous stem cell transplant. Toxicities connected with gemcitabine therapy occurred in 44% of the patients and included grade 3/4 neutropenia, thrombocytopenia and anemia., Conclusions: The results suggest that gemcitabine-based salvage chemotherapy is effective and well tolerated in patients with relapsed/refractory HL and NHL.

Background: CXCR4 chemokine receptor is constitutively expressed on normal and malignant B lymphocytes derived from patients with B-cell lymphoproliferative disorders and has a significant role in cell migration to lymph nodes and bone marrow. Non-Hodgkin's lymphomas (NHL) constitute a heterogeneous group of lymphoproliferative diseases, which can localize not only to lymph nodes, but also can migrate to peripheral blood and metastase to other organs, including bone marrow., Aim: The purpose of this study was to determine CXCR4 gene expression in peripheral blood and bone marrow of NHL patients before and after treatment., Methods: Samples of lymphoma lymph nodes, peripheral blood and bone marrow aspirates of patients with B-cell NHL were taken at diagnosis and after chemotherapy. Gene expression was determined by the reverse transcription (RT)-polymerase chain reaction method. Expression was estimated from 0 AU (no amplificate signal) to 3 AU (maximal amplificate signal)., Results: No significant difference in the level of CXCR4 expression was found in reactive lymph nodes compared to lymphoma samples We observed high level of CXCR4 expression in most patients before treatment: in bone marrow: 3 AU-10 pts, 2 AU-8 pts, 1 AU-2 pts. In peripheral blood: 3 AU-14 pts, 2 AU-4 pts, 1 AU-1 pts, 0 AU-1 pts. After chemotherapy, significant decrease in CXCR4 expression was observed. Bone marrow: 3 AU-5 pts, 2 AU-7 pts, 1 AU-5 pts, 0 AU-3 pts (p = 0.03). Peripheral blood: 3 AU-2 pts, 2 AU-6 pts, 1 AU-10 pts, 0 AU-2 pts (p = 0.0002). There was a good response to treatment in patients with significant decrease of CXCR4 expression in the bone marrow after treatment with 10-fold lower risk of death (p = 0.03)., Conclusions: Decrease in CXCR4 expression in the bone marrow of NHL patients after chemotherapy may be a good prognostic factor.

Angiogenesis and lymphangiogenesis are important in the proliferation and survival of the malignant hematopoietic neoplasms, including non-Hodgkin's lymphomas (NHLs). Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) play an important role in the initiation of angiogenesis. Both VEGF and bFGF have been reported to have prognostic significance in NHL. The present study aimed to determine an association between the VEGF and bFGF gene polymorphisms and disease susceptibility and progression. VEGF (rs3025039; 936 C>T) and bFGF (rs308395, -921 G>C) variants were determined in 78 NHL patients and 122 healthy individuals by PCR-RFLP technique. The presence of the VEGF 936T allele was found to significantly associate with worse prognosis of the disease (expressed by the highest International Prognostic Index (IPI)) (0.41 versus 0.20, P = 0.044 for IPI 4 among patients having and lacking the T allele). The VEGF 936T variant was also more frequent among patients with IPI 4 than in controls (OR = 3.37, P = 0.029). The bFGF -921G variant was more frequently detected among patients with aggressive as compared to those with indolent histological subtype (0.37 versus 0.18, P = 0.095) and healthy individuals (0.37 versus 0.19, OR = 2.51, P = 0.038). These results imply that VEGF and bFGF gene polymorphisms have prognostic significance in patients with NHL.

Background: Y-Box-binding protein-1 (YB-1) acts as a transcription factor for multiple genes and is linked to DNA replication and repair, cell proliferation and resistance to cytostatic drugs., Patients and Methods: The prognostic value of YB-1 expression in primarily untreated malignant non-Hodgkin's lymphomas (NHLs) was examined using immunohistochemistry., Results: Expression of YB-1 was detected in 48 out of 56 NHLs, and the immunohistochemical reaction was localized exclusively in the cytoplasm. Expression of YB-1 did not correlate with clinicopathological variables. Patients with higher YB-1 expression had shorter progression-free survival during the entire period of observation (p=0.0434), as well as in the course of 30 months' observation (p=0.0253). Additionally, in the course of 50 months' observation, patients with higher expression of YB-1 demonstrated a shorter overall survival time (p=0.0383) and a shorter progression-free survival (p=0.0309)., Conclusion: Elevated YB-1 expression may represent a new unfavorable prognostic factor.

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.

One of the leading causes of chemotherapy failure in non-Hodgkin's lymphomas (NHLs) is multidrug resistance (MDR). MDR can be associated with expression of members of the family of ABC-transporters. Since a correlation between expression of cyclooxygenase-2 (COX-2) and MDR in various cancer cells was described, the expression of COX-2 and the ABC-transporters MDR1/P-glycoprotein (P-gp), MRP1, MRP2 and BCRP was examined in 56 previously non-treated patients by immunohistochemistry. The data show that: i) P-gp is not expressed in non-treated NHLs; ii) MRP2 can be localized in the nuclear membranes of NHL cells; iii) expression of MRP2 in the cytoplasm membrane correlates with clinical response; iv) elevated expression of BCRP is typical for the patients, who did not respond to primary chemotherapy and for cases with shorter progression-free survival time in a 30 months follow-up; and v) there is a strong correlation between COX-2 and MRP1, MRP2 and BCRP. It can be concluded that: i) BCRP may be a crucial factor involved in primary resistance of NHLs, thus it may be useful for prediction of chemotherapeutic treatment and risk of relapse; and ii) since there is strong correlation between COX-2 expression and MDR in NHLs, the application of COX-2 inhibitors may be considered for chemosensitization.

The pathophysiology of Non-Hodgkin's lymphoma (NHL) is still unknown and clinical course is very unpredictable. Many cytokines, including interleukin-10 (IL-10), play a role in the perpetuation of this disease. The IL-10-producing capability has been found to be influenced by the IL-10 gene promoter polymorphisms. The aim of the present study was to assess whether any of IL-10 (-1082 A/G, -819 C/T and -592 A/C) genotypes prevails in Polish patients with NHL and whether IL-10 promoter polymorphisms may be associated with less or more favourable course of the disease. IL-10 gene promoter polymorphisms were assessed in 105 individuals, including 55 NHL patients and 50 ethically matched controls. The frequency of the IL-10 low-producing -1082 AA homozygous genotype was significantly higher in patients with aggressive NHL as compared with patients with indolent forms of the disease (0.57 vs 0.28, P < 0.05) and controls [0.57 vs 0.32, odds ratio (OR) = 2.69, P < 0.05]. Also, the presence of the ACC genotype was more frequently detected among patients with more aggressive disease than in those with indolent forms (0.74 vs 0.47, P < 0.05) and healthy controls (0.74 vs 0.42, OR = 3.69, P < 0.05). In multivariate analyses, the AA homozygosity (OR = 6.33, P < 0.05) and ACC genotype (OR = 3.57, P = 0.05) appeared as independent risk factors of more aggressive manifestation of NHL in addition to the elevated lactate dehydrogenase 480 level. Although no direct association was found between IL-10 promoter polymorphisms and NHL, IL-10 (-1082) AA homozygosity and IL-10 ACC genotype were found to be associated with unfavourable prognosis in patients with NHL.

Non-Hodgkin's lymphomas (NHL) constitute a heterogenous group of mainly B-cell lymphoproliferative diseases with different patterns of clinical behaviour. Biological mechanisms leading to development of NHL are not clearly understood. Transforming growth factor-beta1 (TGF-beta1) influences B cell growth and development. The present study aimed to determine whether there is an association between the polymorphic features located within the TGF-beta1 gene in NHL patients and progression of the disease. Two single nucleotide polymorphisms at positions 869 T/C (Leu10Pro) and 915 G/C (Arg25Pro) in the precursor region of the TGF-beta1 gene were determined in 55 NHL patients and 50 healthy individuals by PCR-SSP technique using commercial primers. In univariate analysis the presence of TGF-beta1 high producer genotypes (T/T G/G or T/C G/G) was found to significantly associate with an increased number of extranodal sites (11/30 vs 3/25, p=0.035 for two or more extranodal sites in patients having or lacking the TGF-beta1 high producer genotype, respectively). TGF-beta1 high producer genotype together with other clinical and biological factors (patient sex and age, stage and aggressiveness of the disease, presence of B symptoms, serum LDH level) were subjected to multivariate logistic regression analyses for the number of extranodal sites. Multivariate analysis confirmed the role of TGF-beta1 high producer genotype as a risk factor of NHL manifestation in two or more extranodal sites (OR=7.217, p=0.043) in addition to histological aggressiveness of the disease (OR=4.302, p=0.057). TGF-beta1 gene polymorphisms were found to associate with the course of the disease in NHL patients. TGF-beta1 high producer genotype appeared as an independent risk factor of extranodal manifestation of the disease.

Lymphatic vasculature in solid tumors may serve as the pathway for metastatic spread of the cancer to the regional lymph nodes and to distant organs. Controversy still exists whether tumors metastasize through existing lymphatics or through newly formed vessels (lymphangiogenesis). The role of lymphangiogenesis in lymphoma spread and proliferation is not clearly established. VEGF-C is the most potent inducer of lymphangiogenesis. LYVE-1 was shown to be a specific marker for lymphatic vessels in normal and tumor tissue. The aim of the present study was the evaluation of lymph node LYVE-1-positive lymphatic sinus density (LSD) and VEGF-C expression in patients with non-Hodgkin's lymphoma (nHL) and in reactive lymph nodes. Sixty paraffin-embedded lymph nodes from newly diagnosed patients with B-cell nHL were evaluated. Twelve lymph node biopsy specimens from adult patients with reactive lymphonodulitis were used as controls. Sections of lymph nodes were stained immunohistochemically for LYVE-1 and VEGF-C. VEGF-C expression in lymph nodes of nHL patients was low and not significantly different from that in the control (p = 0.6). Moreover, VEGF-C expression did not differ significantly between aggressive and indolent lymphomas (p = 0.53). Similarly we did not find differences in LSD in aggressive nHL and in indolent nHL (p=0.49). The mean LSD in reactive lymph nodes was higher than in nHL (p = 0.03). Only in 2 out of 12 reactive lymph nodes LYVE-1-positive vessels were absent. In all groups we demonstrated a strong positive correlation between VEGF-C and LYVE-1-expression (p = 0.0001). Higher LSD in reactive lymph nodes as compared to those of nHL patients suggests that lymphoma proliferation leads to the destruction of the existing lymphatics rather than to lymphangiogenesis within lymph nodes. NHL are not associated with increased expression of VEGF-C nor increased LYVE-1-positive lymphatic sinuses density within lymph nodes.

High serum VEGF and bFGF levels are independent prognostic factors of poor prognosis in NHL patients. There is growing evidence that both angiogenesis and haemostatic aberrancies are integral parts of the pathobiology of cancer growth and dissemination. The purpose of the study was: (a) to analyze relations of VEGF and bFGF serum levels, fibrinogen and D-dimer plasma levels with lymphoma Ann Arbor Staging System (AASS) and International Prognostic Index (IPI) and, (b) to evaluate correlations between serum levels of angiogenic cytokines and plasma levels of coagulation-fibrinolysis factors in 52 previously untreated NHL patients included to the study. The control group consisted of 23 healthy volunteers. Serum VEGF, bFGF and plasma D-dimer levels were measured by enzyme-linked immunosorbent assay (ELISA). Plasma levels of fibrinogen were determined on Behring Coagulation System (BCS) equipment. In lymphoma group serum VEGF and bFGF levels were significantly higher than in the control. Differences in concentrations of VEGF, bFGF between II, III and IV stage of disease acc. AASS were not statistically significant. Plasma levels of fibrinogen and D-dimer were elevated in lymphoma patients when compared with the control. Fibrinogen plasma levels were similar in all stages. The D-dimer level was significantly higher in patients with IV stage in comparison to stage II and III. Statistically significant differences of VEGF and bFGF serum levels were observed only between intermediate/high and high risk groups acc. IPI. Fibrinogen plasma levels were significantly higher in high risk group than in low risk group. D-dimer plasma levels were significantly higher in high risk group than in low risk group and low/intermediate group. We observed positive correlation between serum level of VEGF and plasma level of fibrinogen, and between serum level of bFGF and plasma level of fibrinogen. There was also negative correlation between serum level of VEGF and plasma level of D-dimer, and between serum level of bFGF and plasma level of D- dimer. Our study indicates that D-dimer level, but not VEGF, bFGF and fibrinogen correlates with AASS and IPI in NHL patients. Significant correlations between levels of VEGF/bFGF and fibrinogen/D-dimer suggest specific interactions between angiogenic and coagulation-fibrinolysis system.

LYVE-1 (lymphatic endothelium hyaluronan receptor) has been identified as a powerful marker for lymphatic endothelium. Apart from lymphatic endothelium, LYVE-1 is expressed in normal liver blood sinusoids, spleen endothelium and activated tissue macrophages. LYVE-1 has not been detected in blood vascular endothelium with the exception of blood vessels in the lung. High endothelial venules (HEVs) belong to the vascular compartment of lymph nodes. They are the major site of entry for circulating lymphocytes into the node. HEVs are characterized by cuboidal endothelial cells, the existence of discontinuous junctions between these endothelial cells, and the presence of large numbers of lymphocytes within their walls. 40 paraffin-embedded lymph node biopsy specimens from newly diagnosed patients with non-Hodgkin lymphoma were evaluated as well as 10 lymph node biopsy specimens from adult patients with reactive lymphadenitis, and 10 normal, non-metastatic lymph nodes obtained from adult patients during cancer surgery served as controls. Samples were fixed in 10% buffered formalin, paraffin embedded, and stained with hematoxylin and eosin for histopathological evaluation. Sections were also evaluated with mouse monoclonal antibodies against LYVE-1 and CD34, and expression of both LYVE-1 and CD34 was demonstrated in HEVs. LYVE-1 expression was also found on the endothelial cells of the lymphatic sinus and in reticular cells in the lymph nodes.

The aim of the present study was to investigate changes in spectrin and protein kinase C theta; (PKC theta;) organisation in human lymphoid and leukaemic cells undergoing chemotherapeutically induced apoptosis. An analysis of spectrin arrangement in human peripheral lymphoid (non-Hodgkin lymphoma) and leukaemic (acute lymphoblastic leukaemia) cells before and after chemotherapy revealed radical differences in the distribution of this protein. By using immunofluorescent technique, in lymphocytes isolated before chemotherapy, we found spectrin evenly distributed in the cytoplasm and the plasma membrane, while after the therapy changes in spectrin organisation occurred. Moreover, in lymphocytes after chemotherapy, extraction with buffer containing non-ionic detergent (Triton X-100) revealed presence of an insoluble fraction of spectrin. In normal or malignant cells before chemotherapy spectrin was totally soluble, however it should be mentioned that in total cell extracts and supernatants (but not in pellets) apoptotic fragments of spectrin (in addition to intact alpha and beta chains) were also found. In malignant cells after chemotherapy changes in PKC theta; organisation, similar to this observed in the case of spectrin, were shown by the immunofluorescence technique. In contrast, no differences in the distribution of other isoforms of protein kinase C: betaI and betaII, before and after chemotherapy, were found. Apoptotic phosphatidyloserine (PS) externalisation, as well as cell shrinkage, membrane protrusions and blebbing were observed in lymphocytes after chemotherapy and treatment with cytostatics in vitro. The overall results may suggest that spectrin redistribution/aggregation is the phenomenon involved in programmed cell death (PCD) of normal and neoplastic lymphocytes and lymphoblasts, however molecular basis of this phenomenon should be further investigated.

Non-Hodgkin's lymphomas (nHL) is a heterogenous group of lymphoid malignancies with different patterns of behaviour and response to treatment. International Prognostic Index (IPI) is commonly used to predict outcome of treatment in nHL. There are several reports that vascular endothelial growth factor (VEGF), the most potent inducer of angiogenesis, may have prognostic significance in nHL. The aim of the study was to evaluate the serum level of VEGF as a marker of angiogenesis in 35 patients with B-cell nHL compared with control group of 14 healthy people. Moreover, in nHL group VEGF serum level was correlated with IPI risk factors. VEGF serum level was evaluated by ChemiKine sandwich ELISA kit (Chemicon International). VEGF serum level was significantly higher in nHL group than in the control, 193.78 pg/ml +/- 6.82 SEM and 31.51 +/- 1.67 SEM respectively. In nHL group a positive correlation was found between increased VEGF serum level and serum lactate dehydrogenase level. The levels of VEGF were not significantly different in agressive or indolent nHL patients. VEGF serum level is increased in active lymphoma. This observation may have prognostic and clinical significance and provides rationale for use antiangiogenic agents in nHL therapy.

There are some reports, suggesting that infiltrating macrophages may promote tumour progression in non-Hodgkin's lymphoma (nHL). The aim of the study was an evaluation of macrophages, marked by antibody against CD68 in indolent and aggressive nHL. The study was performed in 65 patients: 50 with nHL and 15 with lymph nodes affected by reactive hyperplasia. Immunohistochemical analyses were performed on paraffin-embedded specimens with monoclonal anti-CD68 antibody. Scoring on the basis of the percentage of positive cells indicated CD68 expression in 34/50 (68%) of the patients with nHL and in only 5/15 (33%) of the patients with reactive hyperplasia. The expression of CD68 was statistically significantly higher in the aggressive nHL than in indolent nHL. An increased number of CD68 positive macrophages in clinically aggressive nHL may confirm their role in tumour progression.

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, Wrocław 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.

The bone marrow (BM) is a frequent site of involvement in non-Hodgkińs lymphomas (NHL) and evidence of an infiltrated BM may implicate different therapeutical regimens. Flow cytometric immunophenotyping of bone marrow aspirates now is included in the assessment of patients with NHL and used as an adjunct to morphologic evaluation in the staging of lymphoma. The aim of the study was to compare flow cytometric immunophenotyping of BM and paraffin section staining of BM biopsies in the marrow involvement of NHL. Cytometric immunophenotyping of bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in 53 B- and T-cell lymphoma patients were performed. We used the following fluorochrom conjugated monoclonal antibodies specific for: CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, CD22, CD23, CD79B, FMC7 and Ig kappagamma light chain. Unilateral BM trephine biopsies were obtained in all cases, fixed, decalcified and paraffin-embedded. Morphologic marrow involvement by lymphoma was found in 24 cases; flow immunophenotyping identified 26 cases with NHL: morphology-positive/flow-positive (n=21), morphology positive/flow-negative (n=3), morphology-negative/flow-positive (n=4), and morphology-negative/flow-negative (n=23). The concurrence rate of BM trephine biopsy and flow cytometric immunophenotyping in evaluation of NHL bone marrow infiltration was 88.7%. Immunophenotyping of the bone marrow of NHL patients by flow cytometry is helpful for assessment of bone marrow infiltration, especially in B-cell disorders. Both trephine biopsies and flow cytometry are better than single investigation for detection of infiltration in NHL.

Background: Monitoring of disease activity and effectiveness of treatment plays an important role in curative management of patients with non-Hodgkin's lymphomas (n-HL). In the search for markers useful for biochemical monitoring of n-HL patients, a group of proteins called adhesion molecules attracted attention. Particular attention has been devoted to sICAM-1 (intercellular adhesion molecule-1). A correlation between sICAM-1 levels and histological malignancy grades and clinical staging of n-HL, activity of the disease and tumor mass has been observed. The aim of the study was to assess the utility of determining serum levels of selected adhesion molecules in n-HL monitoring. The study was carried out in 60 patients with intermediate and high malignancy grade n-HL according to Working Formulation (anaplastic, lymphoblastic, immunoblastic, centroblastic and centroblastic-centrocytic)., Material/methods: Soluble ICAM-1 adhesion molecule (sICAM-1) and selectin E levels were determined in the sera of 31 newly diagnosed patients, 18 with complete remission, and 11 with relapse of the disease. The control group consisted of 15 healthy subjects. The results were expressed in ng/ml., Results: sICAM1 levels were similar in healthy controls and patients in the remission phase and significantly lower in patients with diagnosed active disease and relapses. Relapses were associated with slightly lower levels (on borderline of statistical significance) than of diagnosis Serum selectin E levels, however, demonstrated no differences among patient groups or as compared with controls., Conclusions: The presented results indicate the utility of serum sICAM-1 level determination in assessment of activity of intermediate and high malignancy grade non-Hodgkin's lymphomas.

Cytotoxic activity of NK cells in the peripheral blood has been determined in 30 patients with malignant non-Hodgkin lymphomas prior to and following therapy. In the whole group as well as in subgroups classified according to the criteria of Working Formulation as lymphomas of the low, moderate and high degree of malignancy, activity of NK cells has been statistically significantly lower than that in healthy individuals. Marked increase in this activity has been noted in 19 patients in the state of clinical remission after the treatment with cytotoxic agents, and sometimes radiotherapy. The value of mean cytotoxic activity reached normal limits in the lymphoma of high degree of malignancy, and exceeded these limits in the lymphomas of moderate and low malignancy.

In 20 patients with non-Hodgkin lymphoma as the first treatment and in 10 patients with the same diagnosis as the second treatment (group II) has been applied the therapeutical protocol proposed by I. Koza et al., composed of 4 monthly cycles of cyclophosphamide, vincristine, bleomycin, methotrexate and prednisone and in the other 4 cycles of doxorubicin, vincristine bleomycin, prednisone. The diagnosis in the I group was: immunoblastic lymphoma in 13 cases, other high grade lymphomas in 5 and low grade lymphoma in 2 cases. In the group II half of the patients showed low or intermediate grade lymphoma but with maximal clinical advancement and resistance to previous therapy. Complete remission (CR) has been obtained in 12 patients of the I group, partial remission (PR) in 7, 1 patient did not respond to therapy. In 3 cases relapse of the disease has been noted, including 2 patients in whom relapse occurred before finishing therapy: the patients remained resistant to alternative one. In the group II the PR and CR has been obtained in 5 and 3 cases respectively: 2 patients with immunoblastic lymphoma resistant to previous therapy did not respond either. Among undesirable effects myelosuppression, mainly granulocytopenia has been mostly noted: infection and septic shock was a cause of death in 1 patient. In 2 patients severe polyneuropathy and in 2 other mucositis of the digestive tract was noted. The treatment used gives beneficial results as induction therapy in cases of immunoblastic lymphoma and enables obtaining remission in therapy resistant cases of low grade lymphoma.