Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI.

BACKGROUND: Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score to determine which were the most useful. PATIENTS AND METHODS: This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. RESULTS: Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. CONCLUSIONS: In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers.

A modified scoring of the NCCN-IPI is more accurate in the elderly and is improved by albumin and ß2 -microglobulin.

The International Prognostic Index (IPI) has been used for decades in diffuse large B-cell lymphoma (DLBCL). A retrospective cancer registry analysis in North America showed significantly improved results when an enhanced IPI, the National Comprehensive Cancer Network (NCCN)-IPI was applied. This novel score puts more weight on age and high levels of lactate dehydrogenase (LDH). Nevertheless, it remains unclear if these results can be extrapolated to the general population. This retrospective bi-centre analysis included 499 unselected DLBCL patients who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and 2013. In our cohort, the NCCN-IPI was more accurate in identifying patients at low or high risk, despite older age, and more patients with increased LDH. Nevertheless, a modified scoring of the risk factors was required to more accurately identify elderly patients with a very favourable diagnosis, suggesting an impaired value of the original NCCN-IPI in the elderly. Serum ß2 -microglobulin and albumin were retained as independent prognostic factors for survival in a multivariate analysis. Our data confirm, for the first time, the superior prognostic power of the NCCN-IPI in an unselected, middle-European cohort. We furthermore propose a modified NCCN-IPI for more accurate prognostication in the elderly. Albumin and ß2 -microglobulin levels are likely to add significant information to the NCCN-IPI.

Liver toxicity during temozolomide chemotherapy caused by Chinese herbs.

BACKGROUND: Complementary and alternative medicine is often used by patients with malignant glioma. Although several interactions of various alternative agents with chemotherapy are known, none has been described for temozolomide so far. CASE PRESENTATION: We report the case of severe liver toxicity with jaundice during radiochemotherapy with temozolomide likely due to interaction with a popular Chinese herbal formula after surgery for glioblastoma. After cessation of the herbal formula as well as the chemotherapy liver enzymes slowly normalized. Due to tumor progression the patient was retreated with temozolomide for 5 cycles without toxicity. Because of further progression combination treatment of bevacizumab and irinotecan was started and again no liver toxicity was observed. CONCLUSIONS: We conclude that the observed toxicity with jaundice was probably caused by an interaction of this popular Chinese formula and temozolomide. This is the first report about a relevant interaction of temozolomide and any herbal formula.

Effect of folate supplementation on N-terminal pro-brain natriuretic peptide.

BACKGROUND: Increased plasma homocysteine (HCY) has been suggested as a novel risk factor for chronic heart failure (CHF). This study investigated the effect of a HCY lowering therapy by folic acid (FA) supplementation on N-terminal pro-brain natriuretic peptide (NT-proBNP) in healthy subjects. METHODS: We treated 61 healthy individuals (median age [25th-75th percentile]: 57 [53-69] years with placebo, 0.4, 1.0 or 5.0 mg FA daily for 2 months. Fasting blood samples were taken after 0, 4 and 8 weeks. Serum HCY, folate, vitamin B12 and NT-proBNP were studied. RESULTS: Baseline HCY, folate and NT-proBNP levels were 13.6 (10.0-16.4) micromol/L, 5.0 (3.8-6.4) microg/L and 40.4 (21.8-67.3) ng/L, respectively. Serum folate increased during supplementation (4 weeks of placebo, 0.4, 1.0, 5.0 mg of FA: -9%, +131%, +150%, +314%; 8 weeks: -72%, +152%, +185%, +62%) and HCY decreased (4 weeks: +2%, -12%, -20%, -15%; 8 weeks: -2%, -9%, -17%, -15%) in the treatment groups. NT-proBNP did not change within groups. Pooling FA treated subjects, individuals with a baseline NT-proBNP above the median of 40 ng/L exhibited a 20% decrease of NT-proBNP (significant on a 10% level) while HCY decreased by 15%. CONCLUSION: FA supplementation with doses between 0.4 and 5 mg does not affect NT-proBNP in healthy subjects with an NT-proBNP concentration <40 ng/L, but possibly lowers NT-proBNP in individuals with NT-proBNP levels >40 ng/L.

Folate supplementation does not affect biochemical markers of bone turnover.

BACKGROUND: Recently, increased plasma homocysteine (HCY) has been suggested as a novel independent risk factor for osteoporotic fractures. This study aimed to analyze the effect of a HCY lowering therapy by folic acid (FA) supplementation on biochemical bone markers in healthy subjects. MATERIAL AND METHODS: We treated 61 healthy individuals (mean age: 58+/-8 years) with placebo, 0.4, 1 or 5 mg FA daily for 2 months. Fasting blood samples were taken after 0, 4 and 8 weeks. Serum HCY, folate, vitamin B12, osteocalcin (OC), procollagen type I N-terminal propeptide (PINP) and C-terminal telopeptides of human collagen type I (CTX) were studied. RESULTS: Overall baseline HCY and folate levels were 13.4 +/- 3.6 micromol/L and 5.7 +/- 3.0 microg/L, respectively. Participants exhibited normal baseline OC, PINP and CTX levels. Serum folate increased during supplementation (4 weeks of placebo, 0.4, 1 and 5 mg of FA: -7, +160, +162 and +436 %; 8 weeks: -6, +305, +340 and +216 %) and HCY decreased (4 weeks of placebo, 0.4, 1 and 5 mg of FA: +2, -14, -21 and -17 %; 8 weeks: +2, -8, -20 and -17 %) in the treatment groups, but not in the placebo group. OC (placebo: 22.8 vs. 23.0 vs. 23.6; 0.4 mg FA: 21.6 vs. 22.1 vs. 24.1; 1 mg FA: 23.7 vs. 22.6 vs. 23.4; 5 mg FA: 24.1 vs. 20.5 vs. 20.9 microg/L), PINP (placebo: 43.5 vs. 51.3 vs. 46.5; 0.4 mg FA: 34.0 vs. 34.1 vs. 39.5; 1 mg FA: 43.6 vs. 39.7 vs. 43.2; 5 mg FA: 41.1 vs. 38.7 vs. 37.4 microg/L) and CTX (placebo: 258 vs. 360 vs. 321; 0.4 mg FA: 229 vs. 290 vs. 315; 1 mg FA: 319 vs. 325 vs. 301; 5 mg FA: 293 vs. 321 vs. 304 ng/L) did not change throughout the study. CONCLUSION: Short-term FA supplementation does not affect biochemical bone markers in non-osteoporotic subjects with a low folate status.