Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma

Abstract: Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p< 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p< 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p< 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-α, interleukin-1β, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.     

A high serum-soluble interleukin-2 receptor level is associated with a poor outcome of aggressive non-Hodgkin's lymphoma

Soluble interleukin-2 receptor (sIL-2R) is produced by activated T and B cells, and the level of this receptor is elevated in patients with non-Hodgkin's lymphoma (NHL). The present study demonstrated that the sIL-2R level was high in the following groups of patients with aggressive NHL; those aged > or = 60 yr, those with a poor PS, those in Ann Arbor stage III or IV, and those in the high intermediate or high risk group according to the International Prognostic Index (IPI). Overall survival was significantly poorer when the sIL-2R level was 2000 U/ml or more. In addition, the overall survival of patients in the low (L) and low-intermediate (L-I) risk groups with an sIL-2R level of 3000 U/ml or more was significantly poorer, suggesting that the sIL-2R level could be particularly useful for identifying patients with a poor prognosis among the L and L-I risk groups. Univariate analysis identified some significant prognostic factors, and multivariate analysis of these factors plus the five IPI prognostic factors showed that the sIL-2R level was an independent prognostic indicator. In conclusion, the present findings established that the sIL-2R level is a significant independent prognostic factor in patients with aggressive NHL.     

Serum-soluble tumor necrosis factor receptor 2 (sTNF-R2) level determines clinical outcome in patients with aggressive non-Hodgkin's lymphoma

BACKGROUND: Recently investigators have worked to identify prognostic factors in non-Hodgkin's lymphoma (NHL) so an appropriate therapeutic plan can be put in action. The aim of the present study was to assess the prognostic significance of serum soluble tumor necrosis factor receptor (sTNF-R) 2 in aggressive NHL. METHODS: One hundred and ten consecutive patients with aggressive NHL who were previously untreated (diffuse large B-cell lymphoma; 94, peripheral T-cell lymphoma; 16) were prospectively enrolled in this study between 1997 and 2002. The patients were treated with 6-8 cycles of CHOP or THP-COP regimens. RESULTS: High serum sTNF-Rs level was associated with some poor prognostic factors and low complete remission rate. Patients with high sTNF-R1 (4 ng/mL and over) and sTNF-R2 (15 ng/mL and over) at onset had significantly lower survival rates (5 yr: 19%, 19%) than those with low sTNF-R1 (under 4 ng/mL) and sTNF-R2 (under 15 ng/mL) (62% and 69%), respectively (P < 0.0005 and 0.0001). Multivariate analysis employing sTNF-R2 and some conventional prognostic factors demonstrated that a combination of sTNF-R2 and performance status, and that of sTNF-R2, sIL-2R, and LDH were significant prognostic factors for poor overall survival and for poor event-free survival, respectively. In addition, we attempted to use sTNF-R2 in combination with the international prognostic index (IPI). The patients in the high risk group and those with high sTNF-R2 in the low-intermediate (LI)/high-intermediate (HI) risk group had significantly lower survival rates than the patients in the low risk group and those with low sTNF-R2 in LI/HI risk group (P < 0.0001). CONCLUSIONS: The results suggest that a high serum sTNF-R2 level predicts a poor prognosis in aggressive NHL and may be a useful biomarker for selecting appropriate treatment when used in combination with the IPI.     

Prognostic value of soluble interleukin 2 receptor levels in Langerhans cell histiocytosis

We investigated the prognostic significance of soluble interleukin 2 receptor (sIL-2r) levels in the pre- and post-treatment serum of paediatric patients with Langerhans cell histiocytosis (LCH). Serum levels of sIL-2r from 32 LCH patients and 14 healthy controls were determined using enzyme-linked immunosorbent assay. The LCH patients were classified, evaluated and treated according to the Histiocyte Society's protocols. The following clinical stages were considered: single-system disease (A) divided into single-site (A1; n=4), multiple-site (A2; n=9), and multisystem disease (B) without organ dysfunction (B1; n=5) and with organ dysfunction (B2; n=14). Pretreatment concentrations of sIL-2r were markedly increased at diagnosis in LCH patients compared with controls [in pg/ml, median (range) 9200 (1124-40000) versus 610 (343-800)], P < 0.0001. Levels differed significantly between stages A [3250 (1124-11000)] and B [22750 (3400-40000)], P < 0.05, and between substages A2 and B2, P < 0.05. There was a significant correlation between clinical stages and sIL-2r serum levels, r=0.7996 (P < 0.0001). Patients with > or = 17500 pg/ml of sIL-2r had a 30-month survival of 0.417 (SEM: 0.142) compared with those with levels < 17500 pg/ml, who presented a 30-month survival of 0.848 (SEM: 0.100) (log-rank, P < 0.0001). In multivariate analysis, sIL-2r levels > or = 17500 pg/ml were found to have greater predictive strength than other well-known prognostic factors.     

The prognostic significance of CA 125 in patients with non-Hodgkin's lymphoma

OBJECTIVE: To assess the association of serum CA 125 in patients with non-Hodgkin's lymphoma (NHL) with prognostic parameters of the disease, response to treatment, and survival. PATIENTS AND METHODS: Sixty-eight patients [38 males, median age 56 (range 17-82) yr] with NHL were evaluated. CA 125 was measured by an enzyme immunoradiometric assay at diagnosis and at the end of first-line treatment. RESULTS: Median overall CA 125 was 49 (1-963) U mL-1, whereas 49 patients had initially abnormal (>35 U mL) CA 125 levels. High CA 125 was found to correlate with failure of treatment (P = 0.001) and relapse (P = 0.01), and to be independently associated with bulky disease, effusions, LDH, and the International Prognostic Index (IPI) score (P<0.01 for each of these four variables). An initially abnormal CA 125 value was associated with poorer 5-yr survival [median survival of patients with CA 125>35 U mL-1 33 (18-72) months compared to 58 (20-77) months for those with CA 125 = 35 U mL-1, P = 0.012]. Moreover, CA 125>35 U mL-1 (among stage III/IV and LDH>460 mU mL-1) emerged as an independent predictor of death within 5 yr from diagnosis (Relative Risk (RR) 3.1, 95% CI 1.5-12.8, P = 0.02). CONCLUSION: Measurement of serum CA 125 is useful for staging, monitoring, and estimating prognosis in patients with NHL.     

Prognostic value of the soluble interleukin-2 receptor level after patients with follicular lymphoma achieve a response to R-CHOP

Objectives: Follicular lymphoma (FL) is a clinically and biologically heterogeneous disease. Therefore, it is important to identify factors that can predict its clinical outcome.

Methods: We retrospectively evaluated the usefulness of soluble interleukin-2 receptor (sIL-2R) levels after R-CHOP (posttreatment sIL-2R) in 72 patients with newly diagnosed FL who had either a complete response (CR) or partial response. With the use of a recursive partitioning analysis, we determined the cut-off values of post- and pretreatment sIL-2R levels that were associated with disease progression, which corresponded to 486.5 and 5405?U/mL, respectively.

Results: The high posttreatment sIL-2R group showed a significantly inferior progression-free survival (PFS) compared to the low posttreatment sIL-2R group in all patients (3-year PFS 52.6% vs. 77.4%, P?=?0.003), and in patients with CR (3-year PFS 57.1% vs. 82.1%, P?=?0.034). Although a multivariate analysis showed that pretreatment sIL-2R, but not posttreatment sIL-2R, was an independently significant predictive factor for disease progression, among patients with low pretreatment sIL-2R levels, those with high posttreatment sIL-2R levels tended to have inferior PFS. There was a significant trend in PFS among the high pretreatment sIL-2R group, the low pre- and high posttreatment sIL-2R group, and the low pre- and low posttreatment sIL-2R group (P?Conclusion: Among patients with a low pretreatment sIL-2R level who exhibited a positive response to R-CHOP, the posttreatment sIL-2R level may help to identify those with a poor prognosis.     

Antiphospholipid antibodies may be a new prognostic parameter in aggressive non-Hodgkin's lymphoma

OBJECTIVES: Patients with malignancies have an increased prevalence of antiphospholipid antibodies (APA). The aim of this study was to determine the prevalence of IgG, IgM, and IgA anticardiolipin antibodies (aCL) and anti-beta-2 glycoprotein I antibodies (anti-beta2-GPI) in patients with non-Hodgkin's lymphoma (NHL), and to investigate their clinical and prognostic significance. METHODS: The study group included 86 patients with NHL. Enzyme-linked immunosorbent assay kits were used to measure the concentrations of aCL and anti-beta2-GPI, and coagulation tests, to measure lupus anticoagulant (LAC) activity. Blood was collected at diagnosis in all patients and at follow-up in 15. Median follow-up time was 1.9 yr. RESULTS: Elevated APA levels were found in 35 patients (41%) at diagnosis: one patient aCL IgG, five patients aCL IgM, five aCL IgA, one anti-beta2-GPI IgG, 14 anti-beta2-GPI IgM, and 19 anti-beta2-GPI IgA; LAC activity was found in three of 67 patients (4.5%). There was no significant correlation between elevated APA levels and patient's age or sex, disease stage or grade, bone marrow involvement, B symptoms, serum lactate dehydrogenase levels, serum beta2 microglobulin levels, International Prognostic Index (IPI) score, performance status, type of treatment, or response to treatment. There was a correlation between elevated APA and absence of extranodal disease (P = 0.045). A strong negative correlation was found between elevated APA at diagnosis and survival time. Two-year survival was 90 +/- 5% for patients without APA at diagnosis compared with 63 +/- 11% for patients with an elevated APA levels (P = 0.0025). APA added to the predictive value of IPI for event-free and overall survival. CONCLUSIONS: APA are elevated in 41% of NHL patients at diagnosis and are correlated with shortened survival. Their level may serve as an independent prognostic variable in aggressive NHL.     

血清CA125和IL-10水平测定在评估晚期非小细胞肺癌患者预后中的价值

目的探讨血清CA125和IL-10水平测定在评估晚期非小细胞肺癌(NSCLC)患者预后中的价值。方法本文对132例晚期NSCLC患者进行了治疗前后血清CA125和IL-10水平的测定,并与76例良性肺部疾病患者进行了比较性分析,采用受试者工作特征曲线(ROC曲线)分析了CA125和IL-10水平在评估晚期NSCLC患者预后中的价值。结果 132例晚期NSCLC患者(包括51例腺癌、53例鳞癌和28例腺鳞癌)血清CA125和IL-10水平较76例良性肺部疾病患者明显增高(P0.05~0.001)。Ⅳ期和低分化NSCLC患者血清CA125和IL-10增高的病例数较Ⅲa期和高分化患者明显增高(P均0.05)。47例部分缓解(part remission,PR)患者血清CA125和IL-10水平治疗后明显降低、37例疾病进展(progressive disease,PD)患者治疗后血清CA125和IL-10水平仍明显升高、且47例PR患者生存期较37例PD患者明显延长(P均0.05)。ROC曲线分析显示:CA125和IL-10水平评估晚期NSCLC患者预后价值的AUC为0.803和0.764,临界值分别为84.1U/ml和65.2ng/L,敏感度分别为81.5%和77.4%,特异度分别为87.6%和80.1%。结论血清CA125和IL-10水平是评估晚期NSCLC患者预后的有价值指标。     

Detection of membrane and soluble interleukin-6 receptor in lymphoid malignancies

Summary. We studied the membrane expression of the gp80 chain of IL-6 receptor (IL-6R) by quantitative flow cytometry in chronic lymphocytic leukaemia (CLL) and leukaemic centrocytic lymphoma using a panel of seven monoclonal antibodies. IL-6R was detected in 18/26 CLL cases and 4/7 lymphoma cases, with a mean antigen density <3000 molecules/cell. Multiple labelling experiments confirmed the IL-6R expression by neoplastic cells. Specific mRNA was found by RT-PCR in neoplastic cells. A specific ELISA test was designed using two anti-IL-6 receptor MAbs to measure the serum soluble IL-6R (sIL-6R) in CLL (n = 48), B-cell non-Hodgkin's lymphoma (NHL; n = 40), and monoclonal gammopathy (MG; n = 32). SIL-6R was higher in CLL (170±12.6ng/ml) in NHL (160 ± 12ng/ml) and MG patients (183±23ng/ml) than in age-matched controls (100 ±5.6 ng/ml; P < 0.001) and higher in high-grade than low-grade NHL. No correlation was noted with a previous treatment. Among CLL cases the patients classified as stage B according to the Binet's staging of the disease had the highest sIL-6R values, thus suggesting a link with tumour cell mass.     

Elevated serum levels of soluble CD44 variant 6 are correlated with shorter survival in aggressive non-Hodgkin's lymphoma

A variant form of CD44 that has additional amino acids in the common protein backbone (CD44-v6) seems to play a role in the metastasis of malignancies. We measured soluble CD44-v6 (sCD44-v6) by ELISA in 201 patients with malignant lymphoma. The sCD44-v6 level was significantly elevated in patients with non-Hodgkin's lymphoma (NHL) (n = 184). The sCD44-v6 level was correlated significantly with the standard sCD44 and soluble interleukin-2 receptor levels, but only weakly with serum lactate dehydrogenase (LDH). In 149 patients with aggressive NHL, the sCD44-v6 level was elevated in the subgroups with a high LDH level, stage III/IV disease, T-cell lymphoma, and high-intermediate or high risk group as identified by the International Prognostic Index (IPI). When the sCD44-v6 level was > or = 800 ng/ml the overall survival rate was significantly decreased (p = 0.0001). In the low + low-intermediate risk group (IPI) both overall survival rates (log-rank p = 0.0005, Wilcoxon p =0.002) were significantly decreased when the sCD44-v6 level was > or = 800 ng/ml. In multivariate analysis, sCD44-v6 was shown to be independent of the five prognostic factors in the IPI (age, performance status, number of extranodal sites, Ann Arbor stage and LDH level), so it may be useful for predicting the outcome of aggressive NHL.     

Plasma soluble interleukin-2 receptor levels in patients with idiopathic thrombocytopenic purpura

Soluble interleukin-2 receptor (sIL-2R) was measured in the plasma of 31 patients with idiopathic thrombocytopenic purpura (ITP) and 22 normal controls. When thrombocytopenia persisted longer than 6 months, the diagnosis of chronic ITP was made. Twenty patients had acute ITP, 11 patients had chronic ITP, and all patients received high-dose methylprednisolone (HDMP) (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days). The sIL-2R levels of the patients were determined before being giving HDMP and 14 days after the end of HDMP therapy. Platelet counts were determined before administration of HDMP, one day after the end of HDMP therapy, and once every 28 days for 7 months thereafter. There was not a significant difference between the mean pre-treatment plasma sIL-2R levels of both acute and chronic ITP groups (P > 0.05), and these were higher than that of the control group (P < 0.001). The mean post-treatment sIL-2R level of the chronic ITP group was significantly higher than those of both the control and post-treatment acute ITP groups (P < 0.001). There were negative correlations between the plasma sIL-2R levels and platelet counts of both group patients in the pre-treatment period and between post-treatment sIL-2R levels and platelet counts in chronic ITP group (P < 0.05). We think that there was a good correlation between prognosis of ITP and sIL-2R levels after HDMP therapy, and platelet counts in patients with ITP are linked to sIL-2R levels. Am. J. Hematol. 57:119–123, 1998. © 1998 Wiley-Liss, Inc.     

High levels of serum prostate-specific antigen due to PSA producing follicular non-Hodgkin's lymphoma

OBJECTIVE: Both carcinoma of the prostate and non-Hodgkin's lymphoma are common in elderly patients. Measurement of serum prostate-specific antigen (PSA) is a frequently used tool to diagnose and monitor prostate carcinoma and is generally specific for diseases of the prostate. CASE: We describe a 68-yr-old patient with voiding difficulties and high PSA levels, but without inflammatory or malignant changes upon multiple transrectal ultrasound guided prostate biopsies. Digital rectal examination was normal. Laboratory showed a strongly elevated PSA level (62 microg/L, Immulight 2000); DPC, USA). A CT-scan showed a retroperitoneal process with mass in the right pelvis and infiltration of the bladder wall, suggestive for metastatic prostate carcinoma. Surgical excision of an axillary lymph node set the diagnosis at a stage IV follicular lymphoma, Berard grade I to II in which the majority of neoplastic cells expressed PSA. After lymphoma-specific treatment, there was a positron emission tomography (PET) confirmed complete remission with normal PSA levels (6 microg/L), which still persists. CONCLUSION: Although rare, high PSA levels can be due to the presence of non-Hodgkin's lymphoma. Such a diagnosis should be considered when patients present with lymphadenopathy other than regional prostatic lymphadenopathy.     

Specific detection of Epstein-Barr virus in inflammatory pseudotumor of the spleen in a patient with a high serum level of soluble IL-2 receptor

A case of inflammatory pseudotumor of the spleen is described in a 63-year-old woman who presented with an intrasplenic tumor and an elevated serum level of soluble interleukin 2 receptor (sIL-2R). Microscopic examination after removal of the spleen revealed that the tumor was composed of mixed cellular infiltrates, mainly lymphocytes and plasma cells, and spindle-cell proliferation. Epstein-Barr virus (EBV) was specifically detected in the tumor by in situ hybridization for EBV RNA. The serum level of sIL-2R level was normalized after splenectomy. EBV infection may play a role in the development of splenic inflammatory pseudotumor and the elevation of sIL-2R level. Received: May 27, 1999 / Accepted: November 26, 1999     

Effect of granulocyte colony-stimulating factor on IL-12 p40 production during chemotherapy for B-cell lineage non-Hodgkin's lymphoma patients

Interleukin (IL)-12 is a 70-kDa cytokine comprised of two disulfide-linked proteins (p35 and p40) and is essential for the initiation of effective immune response. Granulocyte-colony stimulating factor (G-CSF) affects the balance in the production of anti-inflammatory cytokines. We investigated the serum IL-12 p40 and IL-12 Mix (p40 and p70) production in 28 patients with B-cell lineage non-Hodgkin's lymphoma (NHL) treated with chemotherapy (e.g., CHOP regimen) with or without G-CSF administration and eight healthy volunteers. We found that serum levels of IL-12 p40 (191.2 +/- 150.0 pg/mL) and IL-12 Mix (277.4 +/- 274.5 pg/mL) in the patients before chemotherapy were higher than those in the healthy volunteers (IL-12 p40: 76.4 +/- 25.3 pg/mL, IL-12 Mix: 48.5 +/- 33.4 pg/mL) (P = 0.04 and 0.02, respectively). Next, we examined the serum IL-12 p40 and IL-12 Mix levels in nine patients receiving chemotherapy with administration of G-CSF (CG group, n = 9) and without G-CSF (C group, n = 9). Serum IL-12 p40 and IL-12 Mix levels were decreased on 10 d after chemotherapy in both groups, and those in CG groups were significantly lower than those in C group. These results indicated that administration of G-CSF decreased serum IL-12 p40 and IL-12 Mix levels. Overall survival (OS) at 24 months was not significantly different in the two groups (58.3% in group C vs. 80.0% in group CG, P = 0.67). However, the survival rate of patients at clinical stages III and IV in CG group (n = 6, 66.0%) was significantly better than that of patients in C group (n = 4, 25.0%) (P = 0.02). Long-term administration of G-CSF appears to influence the survival rate by reducing immunosuppressive IL-12 p40 production.     

Simultaneous elevation of the serum concentrations of vascular endothelial growth factor and interleukin-6 as independent predictors of prognosis in aggressive non-Hodgkin's lymphoma

Therapeutic approaches for non-Hodgkin's lymphoma (NHL) are currently based on the International Prognostic Index (IPI). Research on biological prognostic factors has been actively pursued in recent years, with serum vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) being identified as prognostic factors for NHL. Here, we determined that serum VEGF and IL-6 levels are independent prognostic factors for aggressive lymphoma. Compared with normal controls, serum VEGF and IL-6 levels were significantly higher in patients with aggressive lymphoma or adult T-cell leukemia/lymphoma. Furthermore, overall and disease-free survival rates for patients with high levels of VEGF or IL-6 were significantly poorer than for patients with low levels. In addition, the prognosis for patients with high levels of both serum VEGF and IL-6 was significantly poorer than that for patients with high levels of either VEGF or IL-6 or with low levels of both VEGF and IL-6. Multivariate analyses of a variety of prognostic factors, including the five IPI factors, revealed that serum VEGF and IL-6 were both independent prognostic factors for overall survival of aggressive lymphoma. Therefore, a combination of VEGF and IL-6 represents a useful prognostic factor for aggressive lymphoma.     

Treatment results of aggressive B non-Hodgkin's lymphoma in advanced age considering comorbidity

The aim of this retrospective single institution study was to investigate the long-term outcome of sequential chemotherapy (CHT) and radiotherapy (RT) in patients >/= 70 years old, considering the International Prognostic Index (IPI) for high-grade non-Hodgkin's lymphoma (NHL) and comorbidity. The study involved 106 patients aged 70 years and above, treated between 1986 and 1998, for diffuse large B-cell NHL (DLBCL); 57% had localized disease (stage I or II) and 43% had advanced disease (stage III or IV). All patients received four to six cycles of CHOP (cyclophosphamide, hydroxy-daunorubicin, oncovin, prednisone) CHT at 14-21 d intervals, followed in 69 cases by extended-field or involved-field RT. Complete response rate was 65%; overall survival probability at 5 years was 41% in all stages. Five-year survival was 62% in patients with localized and 12% in advanced disease. There were 3% treatment-related deaths. The 5-year survival rate was 70% in patients with IPI low risk, 46% with low-intermediate risk, 28% with high-intermediate risk and 0% with high risk. Patients with cardiac problems and advanced disease were more susceptible to treatment-related toxicity. Patients with hypertension showed a high rate of vinca alkaloid-associated polyneuropathy. Most patients with localized DLBCL achieved long-term remission after CHT and RT regimens despite advanced age and frequent comorbidities. Advanced disease increased the risk for treatment-related complications and efficacy of treatment seemed limited.     

Correlation of serum IL-6, IL-8 and IL-10 levels with clinicopathological features and prognosis in patients with diffuse large B-cell lymphoma

Cytokines play important roles in the pathogenesis of lymphomas. This study aimed to determine the relationship(s) between serum levels of interleukin (IL)-6, IL-8 and IL-10, measured by enzyme-immunoassay, and the clinical characteristics and outcomes in 46 untreated patients with diffuse large B-cell lymphoma (DLBCL). Serum IL-6, IL-8 and IL-10 levels were higher in DLBCL patients than in control subjects. Elevated levels of IL-6, IL-8 and IL-10 correlated with more adverse disease features. Consequently, patients with elevated IL-6, IL-8 and IL-10 levels prior to treatment had a lower response to therapy. Furthermore, those with elevated IL-6 and IL-10 levels had poor median, 3-year and 5-year survival, while elevated serum IL-8 level did not correlate with overall survival. Worse survival was also confirmed in patients with combined elevated pretreatment serum levels of IL-6, IL-8 and IL-10 (none, one, two or three elevated). Multivariate analysis identified elevated values of IL-6 and IL-10 and response to therapy as significant predictors for overall survival. Serum levels of IL-6, IL-8 and IL-10 before treatment of patients with newly diagnosed DLBCL may give some insight into the possible prognosis and thus facilitate the decisions regarding therapeutic approaches for individual patients.     

Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma

The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the assessment of post-treatment residual masses in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphomas (NHL) was evaluated. We prospectively studied 58 patients with HD (n = 43) or NHL (n = 15) who had post-therapeutic complete remission with residual masses (CRu) indicated by computerized tomography. Analysis of 62 residual locations by FDG-PET was performed separately for HD and NHL. Patients with a PET-positive residual mass [standardized uptake value (SUV) > 3] had a recurrence rate of 62.5% (5/8 patients), whereas patients with PET-negative residual mass (SUV < or =3.0) showed a recurrence rate of 4% (2/50 patients, P = 0.004). A positive FDG-PET study correlated with a significantly poorer progression-free survival (P < 0.00001). No recurrence occurred in any of the 39 HD patients with a negative PET scan (negative predictive value, 100%). Four out of four NHL patients with a positive PET study relapsed (positive predictive value, 100%). In conclusion, FDG-PET is a suitable non-invasive method with a high degree of accuracy in the prediction of early recurrence in lymphoma patients with CRu.     

Conservative management of follicular non-Hodgkin's lymphoma in childhood

Among 447 children with non-Hodgkin's lymphoma (NHL) on the childhood U.K. registry, seven children with follicular (NHL) were identified. Four were male and their age ranged from 4.25 to 13.5 years (median 7.5); all had localized disease, Murphy's stage I ( n  = 4) and II ( n  = 3). Sites involved at presentation were cervical lymph nodes and tonsils ( n  = 5), ileum ( n  = 1) and parotid gland ( n  = 1). Three had complete surgical excision only and four had complete ( n  = 1) or incomplete excision ( n  = 3) followed by a short multi-agent chemotherapy regimen (UKCCSG 9001 protocol). With a median follow-up of 1.5 years (range 0.25–5 years) from diagnosis, six are alive in complete remission (CR) including three who had no chemotherapy.
These results confirm previous reports that follicular lymphomas in children are rare (1.5%) and tend to be localized at presentation. Their rarity makes it difficult to produce guidelines about treatment, but in localized cases a period of non-intervention may be justified.