Follicular lymphoma is an indolent lymphoma with a long median overall survival. However, a considerable number of patients die within the first 2 years after the onset of the disease. Because the ...treatment options vary with respect to antitumor effect and potential toxic adverse effects, the identification of high-risk patients would be helpful in directing therapeutic decisions in individual patients. Several histopathologic biomarkers for risk stratification have been suggested, but most markers have not been validated in patients treated in prospective trials.
We report a comprehensive approach to evaluate histopathologic biomarkers, including WHO grade, histology, and proliferation and quantitation of immune bystander cells, in 158 patients with nodal advanced-stage follicular lymphoma treated first line within a randomized trial.
Tumor sclerosis was a significant prognostic marker of poor overall survival that was independent of the Follicular Lymphoma International Prognostic Index (FLIPI). WHO grade, proliferation, and total T-cell or macrophage content were not associated with overall survival.
The presence of sclerosis within the lymphoma is a marker of poor overall survival that is independent of the FLIPI. The quantification of macrophage or absolute T-cell content, grading, and proliferation are of no help in predicting the outcome of FL. Future studies need to identify surrogate markers for the prognostic immune signatures identified by gene expression profiling. Most importantly, new prognostic markers need to be confirmed in patients treated within prospective trials.
Clinical outcome of mantle cell lymphoma (MCL) is highly heterogeneous. Tumor cell proliferation as assessed by the Ki-67 index has been shown to yield prognostic information on MCL in many studies ...using heterogeneously treated patient cohorts. The prognostic value of the Ki-67 index in patients treated with anti-CD20 therapy has not been studied so far. We analyzed the Ki-67 index at primary diagnosis in 249 advanced-stage MCL patients treated within randomized trials. Ki-67 showed high prognostic relevance for overall survival (relative risk 1.27 for 10% higher Ki-67, P < .001), also independently from clinical prognostic factors. The 3 groups with different Ki-67 index of less than 10%, 10% to less than 30%, and 30% or more showed significantly different overall survival in patients treated with CHOP (P = .001) as well as in patients treated with CHOP in combination with anti-CD20 therapy (R-CHOP, P = .013). Thus, the Ki-67 index remains an important prognostic marker in the era of anti-CD20 therapy. The Euro-pean MCL study is registered at www.ClinicalTrials.gov as #NCT00016887.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mantle cell lymphoma (MCL) has a heterogeneous clinical course and is mainly an aggressive B cell non-Hodgkin lymphoma; however, there are some indolent cases The Ki-67 index, defined by the ...percentage of Ki-67-positive lymphoma cells on histopathological slides, has been shown to be a very powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 × 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value has been shown to predict survival in prospective randomized trials of the European MCL Network
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Estimation by eyeballing and digital image analysis showed a poor concordance with the gold standard (concordance correlation coefficients CCC between 0.29 and 0.61 for eyeballing and CCC of 0.24 and 0.37 for two methods of digital image analysis, respectively). Counting a reduced number of lymphoma cells (2 × 100 cells) showed high interobserver agreement (CCC = 0.74). Pitfalls of the Ki-67 index are discussed and guidelines and recommendations for assessing the Ki-67 index in MCL are given.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We evaluated the rate and type of second malignant neoplasms (SMN) after BFM treatment of children with Non-Hodgkin lymphoma (NHL). Between January 1981 and February 2003 2451 patients (pts) <15 ...years (y) of age at diagnosis were enrolled into the subsequent trials NHL-BFM 81, 83, 86, 90, and 95. Pts with lymphoblastic lymphoma (LBL) (n=547) or non-anaplastic peripheral T-cell lymphoma (n=97) received acute lymphoblastic leukemia (ALL)-type therapy including cumulative doses of cyclophosphamide (max. 3g/m2), daunorubicine/doxorubicin (max. 280mg/m2), but, except few pts, no etoposide. Prophylactic cranial radiotherapy (CRT) was given in stage III/IV (omitted in NHL-BFM95). Pts with mature B-cell neoplasms (n=1597), or anaplastic large cell lymphoma (n=210) received B-type therapy, consisting of 2–8, 5-day courses including cumulative doses of cyclophosphamide (max. 7g/m2), ifosfamide (max. 8g/m2), doxorubicine max. 150mg/m2 (in trial 81 max. 200mg/m2), and etoposide (max. 1.4g/m2). CRT was omitted since trial NHL-BFM86. With a median follow-up of 6.9 (range 0.2–22.6) years the probability of survival at 15 y was 83+1%. By June 2005, 47 SMN were documented, including 16 acute myeloid leukemias/myelodysplastic syndromes (AML/MDS), 11 NHL, 2 ALL, 1 Hodgkin's lymphoma, 7 brain tumors, and 10 other SMN. All SMN occurred in first remission after a median time of 2.9 (range: 0.4–12.3) years from diagnosis of NHL. The cumulative incidence of SMN at 15 y was 4.0% (95% confidence interval CI: 1.9%–6.1%) for the total group. The cumulative incidence of SMN was significantly higher among pts with LBL receiving ALL-type therapy (6.3% at 15 y 95%CI: 2.4%–10.3% (13 AML/MDS, 2 NHL, 3 brain tumors, and 3 other SMN), as compared to pts with other NHL-entities receiving B-type therapy (3.4% at 15 y 95% CI: 0.5–6.4% (3 AML/MDS, 9 NHL, 2 ALL, 1 Hodgkin's lymphoma, 4 brain tumors, and 7 other SMN), p=0.002. There was no significant difference of cumulative incidence of SMN in pts who received CRT compared to pts not receiving CRT. However, 5 of 7 pts, who developed brain tumor, received CRT of 12–24 Gy. Also, there was no significant correlation between the incidence of SMN and the cumulative doses of drugs, except for anthracyclines. For pts receiving a cumulative dose of anthracyclines of >160mg/m2 (almost exclusively pts with LBL receiving ALL-type therapy) the cumulative risk for SMN at 15 y was 6.5% (95% CI: 1.5-11.5%), as compared to 2.0% (95% CI: 1.1–2.9%) for pts with lower doses, p=0.007. Exposure to etoposide was not a risk factor for secondary AML/MDS (11 of 16 pts with sec. AML/MDS did not receive etoposide). In a Cox regression analysis only diagnosis of LBL remained a significant risk factor for SMN (RR 2.5, 95% CI 1.4–4.4). Our analysis revealed a cumulative risk for SMN of 4% at 15 y after successful treatment of childhood NHL. The cumulative incidence of SMN was significantly higher in LBL-pts than in other pts. AML/MDS were the most frequent SMN following LBL while second lymphoid malignancies were the most frequent SMN following non-LBL.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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