natriuretic-peptide--brain and Lymphoma--Large-B-Cell--Diffuse

Chemoimmunotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is the standard treatment for diffuse large B-cell lymphoma (DLBCL). Doxorubicin may induce early and late cardiotoxicity. Non-pegylated liposomal (NPL) doxorubicin may reduce cardiotoxicity.. Patients with untreated CD20+ DLBCL were randomised to conventional R-CHOP chemoimmunotherapy or rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone (R-COMP) with doxorubicin substituted by NPL-doxorubicin. Left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were measured before each treatment cycle and after the end of treatment.. The mean LVEF of 178 and 158 measurements in the R-COMP and R-CHOP arms was 63.31% and 62.25%, respectively (P = 0.167). During treatment the LVEF measurements were below 50% in 10/218 (4.6%) in the R-COMP arm and 31/196 (15.8%) in the R-CHOP arm (P<0.001). Thirty-six of 40 (90%) patients in the R-COMP arm, but only 24/36 (66.7%) in the R-CHOP arm had all NT-proBNP levels below 400 pg/ml during and at the end of treatment (P = 0.013). There were more serious adverse events in the R-CHOP arm (26 versus 40, P = 0.029). Infections were more common (15 versus 28) in the R-CHOP arm.. In patients with normal cardiac function, six cycles of R-CHOP resulted in a low rate of early cardiotoxicity. NPL-doxorubicin did not reduce cardiotoxicity, although cardiac safety signals were elevated in R-CHOP compared to R-COMP.. Cephalon provided the Arbeitsgemeinschaft Medikamentöse Tumortherapie with NPL-doxorubicin and an unrestricted grant, but was not involved in the study protocol, data acquisition, data analysis or the writing of the paper.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Austria; Biomarkers; Cyclophosphamide; Disease Progression; Disease-Free Survival; Doxorubicin; Female; Heart Diseases; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polyethylene Glycols; Prednisolone; Proportional Hazards Models; Remission Induction; Risk Factors; Rituximab; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Vincristine; Young Adult

Standard treatment for elderly patients with relapsed or refractory DLBCL has not been established. CPT-11 has a broad spectrum of anticancer activities including a cytotoxic effect in a variety of malignant tumors. The results of combined treatment with CPT-11 and rituximab have not been reported. The R-CMD regimen was given to elderly patients with relapsed or refractory DLBCL. The safety and efficacy of this regimen were studied. In addition, the serum nm23-H1 level was determined to study whether or not it can serve as a prognostic factor. Thirty elderly patients with DLBCL were studied. The main non-hematological toxicities were infusion-related adverse events. Grade 3/4 hematological toxicity was seen in 19 patients. Following R-CMD treatment, the BNP and troponin T levels did not increase. The CR rate was 57%, PR rate was 17%, 2-year survival rate was 45.2%, and PFS rate was 37.2%. Patients with serum nm23-H1 levels of higher than 80 ng/mL before the treatment showed significantly poorer prognosis. The serum nm23-H1 level of the 30 subjects before the treatment was elevated at 39.4 +/- 41.3 ng/mL, but it significantly decreased only in the subset of patients who achieved CR. The R-CMD regimen was safe in elderly patients with DLBCL. No new signs of cardiotoxicity were observed with this regimen. It was also effective in patients with relapsed or refractory DLBCL who had previously used DXR.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Dexamethasone; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Irinotecan; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Mitoxantrone; Natriuretic Peptide, Brain; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Prognosis; Recurrence; Rituximab; Survival Analysis; Survival Rate; Treatment Outcome; Troponin T

To evaluate the role of N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and a cardiovascular (CV) risk score named FRESCO for predicting anthracycline-induced cardiotoxicity (AIC) in diffuse large B-cell lymphoma (DLBCL).. A total of 130 consecutive DLBCL patients treated in first-line with anthracycline-containing immunochemotherapy. Competitive risk between NT-proBNP, FRESCO, and time to AIC was considered.. Cumulative incidence of AIC was 12.2% and 17.5% at 1 and 5 years, respectively. Median time to development cardiotoxicity was 6.4 months, with half of the cases showing heart failure and the other half silent AIC. Both NT-proBNP levels and FRESCO score were independently associated with higher risk of AIC (P = 0.001 and P = 0.03, respectively). Patients with NT-proBNP ≥600 pg/mL or those with FRESCO ≥4.5% had 3.97 or 2.54 times higher risk of AIC than those with lower values (P = 0.001 and P = 0.048, respectively). According to the previous cutoffs, three groups of patients with a significantly different risk of AIC could be identified (P < 0.0001).. Doxorubicin-containing chemotherapy is associated with increased risk of silent and overt AIC. Baseline NT-proBNP levels and FRESCO CV risk score are accurate predictors of AIC and can identify groups of patients at different risk, in which personalized cardiologic evaluation should be offered.

Topics: Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cardiotoxicity; Female; Heart Diseases; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Spain

A 50-year-old woman received a diagnosis of diffuse large B-cell non-Hodgkin's lymphoma in 2000 and achieved complete remission. In April 2004, echocardiography and computed tomography examinations identified a tumor attached to the tricuspid valve and protruding within the right atrium. Bone marrow and lymph node biopsies showed a relapse of large cell lymphoma. The patient had a markedly elevated level of B-type natriuretic peptide (BNP) but a normal level of cardiac troponin I. The follow-up evaluation of the BNP level after chemotherapy showed that it had returned to within normal limits, and an echocardiogram showed regression of the tumor. Use of the BNP level as a monitor in the treatment of cardiac lymphoma has never been reported. This article is the first to report the use of BNP monitoring before and after chemotherapy to evaluate a patient with an unusual relapsed lymphoma with cardiac involvement.

Topics: Female; Heart Neoplasms; Heart Valve Diseases; Humans; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Monitoring, Physiologic; Natriuretic Peptide, Brain; Radiography; Recurrence; Tricuspid Valve