Comparative Study on Complete Remission Rate and Overall Survival in Three Groups Classified Based on the Serum Interleukin-18 Level in Non-Hodgkin’s Lymphoma Patients

2000 ◽  
Vol 104 (4) ◽  
pp. 220-222 ◽  
Author(s):  
Takayuki Takubo ◽  
Takeo Kumura ◽  
Takafumi Nakao ◽  
Hirohisa Nakamae ◽  
Yasutaka Aoyama ◽  
...  
Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3541-3550 ◽  
Author(s):  
Nozomi Niitsu ◽  
Junko Okabe-Kado ◽  
Takashi Kasukabe ◽  
Yuri Yamamoto-Yamaguchi ◽  
Masanori Umeda ◽  
...  

The outcome of patients with non-Hodgkin’s lymphoma has been improved by current approaches to treatment. Nevertheless, many patients either do not have a complete remission or ultimately relapse. To identify such patients, it is important to be able to predict the outcome. We previously found that the differentiation inhibitory factor/nm23 was correlated with the prognosis of acute myeloid leukemia. To examine the prognostic effect of nm23 on non-Hodgkin’s lymphoma, we established an enzyme-linked immunosorbent assay procedure to determine nm23-H1 protein levels in plasma and assessed the association of this protein level with the response to chemotherapy, overall survival, and progression-free survival in patients with aggressive non-Hodgkin’s lymphoma. The plasma concentration of nm23-H1 was significantly higher in patients with malignant lymphoma than in normal controls, especially in aggressive non-Hodgkin’s lymphoma. The complete remission rate in patients with higher nm23-H1 levels was significantly worse than that in patients with lower nm23-H1 levels. Overall survival and progression-free survival were also lower in patients with higher nm23-H1 levels than in those with lower levels. The 3-year survival rates in patients with low and high nm23-H1levels were 79.5% and 6.7% (P = .0001). A multivariate analysis of prognostic factors showed that the plasma nm23-H1level was independently associated with the survival and progression-free survival. An elevated plasma nm23-H1concentration predicts a poor outcome of advanced non-Hodgkin’s lymphoma. Therefore, nm23-H1 in plasma may be useful for identifying a distinct group of patients at very high risk.


2004 ◽  
Vol 22 (14) ◽  
pp. 2826-2834 ◽  
Author(s):  
N. Mounier ◽  
C. Gisselbrecht ◽  
J. Brière ◽  
C. Haioun ◽  
P. Feugier ◽  
...  

Purpose Improved survival has been observed in aggressive non-Hodgkin's lymphoma (NHL) patients with adverse prognostic factors when autotransplantation (ASCT) was performed after complete remission. However, there is no agreement on the prognostic factors for patients treated with ASCT. We aimed to estimate the prognostic effect of clinical and biologic variables on relapse and survival rates by pooling the data from two trials. Patients and Methods Of the patients treated in the LNH87 and LNH93 trials, 330 under age 60 years achieved complete remission after high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone, and received consolidative ASCT; 16% of patients had T-cell NHL. The International Prognostic Index (IPI) score was 0 for 11%, 1 for 23%, 2 for 51%, and 3 for 15%. Univariate and Cox multivariate survival analyses were retrospectively performed on this population. Results Overall survival was 75 ± 5% at 5 years and disease-free survival (DFS) 67 ± 5%. For T-cell NHL, these scores were 54% and 44%, respectively. The IPI score had no prognostic value and only the following parameters adversely affected overall survival and DFS (P < .05): marrow involvement; more than one extranodal site; histology (nonanaplastic T-cell v others); and type of anthracycline (mitoxantrone v doxorubicin, for DFS only). Conclusion These results suggest that ASCT can prevent relapse in patients with adverse IPI factors. However, patients presenting with a nonanaplastic T-cell phenotype, more than one extranodal site, or marrow involvement still have a higher risk of relapse. These factors should be taken into account when designing post-ASCT maintenance studies.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4689-4689
Author(s):  
Sonja G. Genadieva-Stavrik ◽  
Ljube G. Ivkovsi ◽  
Gorgi D. Zografski ◽  
Borce A. Georgievski ◽  
Zlate R. Stojanoski ◽  
...  

Abstract There are two subgroups of the untreated lymphomas according to the outcome of the disease: indolent and aggressive. Unlike the indolent lymphoma, aggressive lymphomas are fatal in several weeks or months if untreated. However, the therapy available nowadays makes this group of patients with aggressive Non-Hodgkin’s lymphoma curable. Autologous stem cell transplantation used as first-line therapy can improve overall survival in selected group of patients with aggressive Non-Hodgkin lymphoma. To make the right and optimal therapeutic approach we need to stratify those patients in subgroups of patients with "high" and "low" risk, which was achieved with this study. This study comprises 211 patients with histopathology diagnosis of aggressive Non-Hodgkin’s lymphoma treated at the Department of Hematology in the period 1989–2002, which gave us the observation period of 6 to 183 months. There were 88 male patients, median age 53 years and 60 female, median age 52 years. Most of the patients were in the advanced clinical stage at the disease on the initial presentation of the disease, 24% of the patients in the third stage and 43% in the fourth stage. Bone marrow infiltration was found in 29%. Bcl-2 positively was confirmed in 26 cases by imunohistochemistry and there was proliferative index Ki-67 above 60% in 32 patients. Imunophenotipisation suggested that 80% of the cases are B-cell lymphoma. The patients were treated with antracicilin included regiments, most of them being CHOP regiment. After initial chemotherapy complete remission was achieved in 60%, partial response in 4% and there was no response in 32% with early deaths in 4%. At the end of the study 32% of the patients were alive and well, 32% were deceased and the reminder had unknown status. There was relapse of the disease in 50 patients with previous complete remission. According to the univariante analysis the following parameters had significantly influence the overall survival in the patients with aggressive Non-Hodgkin’s lymphoma: initial anemia, initial LDH, the stage of the disease, ECOG score, bone marrow infiltration, number of sites of extranodal infiltration, lymphoma subgroup according to various classification systems, morphology of the lymphoma cell, imunophenotype profile, percent of Ki-67 positively, bcl-2 positively, time to complete remission. The multiply progression analysis produce mathematical model through which we can anticipate the expected survival in each patients individually based on the statistically most influential prognostic markers, those achieving stratification of the patients in risk groups. In our study 32% of the patients with "high" risk are alive and "low risk patients have 70% 5-years overall survival. With the use of this prognostic model for aggressive Non-Hodgkin’s lymphoma we achieved risk based stratification of the patients even in the fourth stage of the disease with statistical significance. This prognostic model for aggressive Non-Hodgkin’s lymphoma enables the clinical hematologist to create the optimal individual therapeutic approach for each patient with aggressive Non-Hodgkin’s lymphoma. The patients with "high" risk are group of patients where beside the standard chemotherapy, use of aggressive chemotherapy and haematopoetic stem cell transplantation as well as the new therapeutic approaches would improve therapeutic results and overall survival.


Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
O Hermine ◽  
C Haioun ◽  
E Lepage ◽  
MF d'Agay ◽  
J Briere ◽  
...  

Abstract Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.


Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
O Hermine ◽  
C Haioun ◽  
E Lepage ◽  
MF d'Agay ◽  
J Briere ◽  
...  

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T- cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.


1997 ◽  
Vol 15 (4) ◽  
pp. 1595-1600 ◽  
Author(s):  
E Vandenberghe ◽  
R Pearce ◽  
G Taghipour ◽  
L Fouillard ◽  
A H Goldstone

PURPOSE Treatment of selected patients with poor-prognosis lymphomas with high-dose chemotherapy and marrow or peripheral stem-cell rescue improves prognosis. A second course of myeloablative chemotherapy has been given to some patients, but few data are available on the indications, morbidity, and overall survival associated with this approach. This study was undertaken to evaluate morbidity and identify subgroups of patients who may benefit from a second transplant. PATIENTS AND METHODS Thirty-four patients with lymphoma given two cycles of myeloablative chemotherapy and entered onto the European Blood and Bone Marrow Transplant (EBMT) registry between 1982 and 1995 were included in this study: Hodgkin's disease (HD), n = 12; intermediate/high-grade non-Hodgkin's lymphoma (HG-NHL), n = 17; and low-grade non-Hodgkin's lymphoma (LG-NHL), n = 5. The reason for second transplant, status at transplant, conditioning regimen, morbidity, and both progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS The second procedure was performed for the following reasons: (1) elective double procedure in four patients, (2) relapse after first transplant in 20, (3) partial remission (PR) after first transplant in eight, and (4) refractory disease after first transplant in two. The OS rate at 2 years for patients who underwent two transplants (estimated from the date of second transplant) was 49%, with a median follow-up time of 44 months. The OS rate at 2 years by histologic subtype was as follows; HD, 50%; HG-NHL, 60%; and LG-NHL, 0%. Seven of 15 patients with HD or HG-NHL who relapsed after they had achieved a posttransplant complete remission (CR) remain in CR 13 to 36 months after the second transplant, compared with two of 10 patients in CR (at 6 and 19 months after second transplant) who achieved a PR or had refractory disease after the first transplant. There were eight deaths (24%) before 3 months, of which three (9%) were transplant-related and the remainder due to persistent disease. Three late toxic deaths occurred: two of cardiovascular disease and one of secondary leukemia. CONCLUSION Selected patients with HD and HG-NHL whose disease recurs after one transplant may benefit from a second transplant. Patients with refractory disease and LG-NHL did not benefit from a second transplant.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4543-4543 ◽  
Author(s):  
Naoe Goto ◽  
Hisashi Tsurumi ◽  
Masao Takemura ◽  
Takeshi Hara ◽  
Michio Sawada ◽  
...  

Abstract Interleukin-18 (IL-18), originally designated as an interferon (IFN)-gamma inducing factor, is a cytokine which induces cytotoxic NK cell activity and stimulates T cells to produce IFN-gamma, IL-2, and GM-CSF. Increased serum IL-18 levels have been found in patients with acute lymphoblastic leukemia, chronic myelocytic leukemia, multiple myeloma and non-Hodgkin’s lymphoma (NHL). The aim of the present study was to assess the prognostic significance of serum IL-18 in aggressive NHL. Consecutive 99 previously untreated patients with aggressive NHL (diffuse large B-cell lymphoma; 84 patients, peripheral T-cell lymphoma; 15 patients) prospectively participated in this study between 1997 and 2003. The patients were treated with 6–8 cycles of CHOP or THP (pirarubicin) -COP regimens. To evaluate serum levels of IL-18, venous blood samples were drawn from patients immediately before the initiation of treatment. In all patients with aggressive NHL, the mean ± SD of serum IL-18 level was 1200.8±151.5 pg/ml (range 96–6603.5) with a median of 556.75 pg/ml. Several poor prognostic features such as poor PS, multiple extranodal sites, advanced disease (clinical stage III/IV), existence of B-symptom, and high soluble interleukin-2 receptor (sIL-2R) were strongly associated with a high serum IL-18 levels. An increased LDH and gender were weakly associated with a high serum IL-18. Histology and age were not associated with serum IL-18 levels. The median serum IL-18 levels of the different IPI risk groups were; 321 pg/ml for the L risk; 442 pg/ml for the LI risk; 557 pg/ml for the HI risk; 1532 pg/ml for the H risk, respectively (P&lt;0.005). The CR rate of patients with an IL-18 level of less than 700 pg/ml was better than that of 700 pg/ml or higher (77% and 50%, P&lt;0.01). Patients with high IL-18 (700 pg/ml and over) at onset had a significantly lower survival rate (5-year: 25%) than those with low IL-18 (below 700 pg/ml) (68 %) ( p&lt;0.0001). Multivariate analysis employing IL-18 and some conventional prognostic factors demonstrated that IL-18, performance status and the number of extranodal sites were significantly poor prognostic factors for both overall survival (OS) and event free survival (EFS). The results suggest that a high serum IL-18 level predicts a poor prognosis in aggressive NHL and may be a useful biomarker for selecting appropriate treatment.


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