Diffuse Large B-Cell Lymphoma in Chile: The Impact of Combined CHOP Plus Rituximab in the Public Health System.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. The purpose of this study was to evaluate the clinical features, prognostic factors, and results of DLBCL that was treated in the cancer centers of the public health system in Chile and compare cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). PATIENTS AND METHODS: Patients age > 15 years who were treated in 18 cancer centers in the country between 2001 and 2017 were included. The Kaplan-Meier method was used to calculate overall survival (OS), and Cox proportional hazard regression modeling was used to evaluate the effect of the addition of rituximab to CHOP on OS. RESULTS: A total of 1,807 patients were evaluated. The median age at diagnosis was 62 (range, 15-95) years, with a female predominance (53%). Half of the patients were age ≥ 60 years. Serology for HIV infection was positive in 5% of cases (96 cases). International Prognostic Index scores were available for 90% of patients, of which 45% had low-risk, 25% low-intermediate-risk, 18% high-intermediate-risk, and 11% high-risk scores. CHOP was administered to 986 patients (55%; median follow-up, 13.2 years) and R-CHOP to 821 patients (45%; median follow-up, 8.4 years). R-CHOP was associated with superior OS compared with CHOP (5-year 66% v 48%, and 10-year 53% v 35%; P < .001). CONCLUSION: Rituximab improved the survival of patients with DLBCL diagnosed and treated in Chile. The benefit was sustained over time, with curative rates of > 50%. This intervention shows that the inclusion of this biological drug justified the expenses incurred by the Ministry of Health in the National Lymphoma Protocols in Chile.

[Adolescent and young adult Philadelphia negative B cell acute lymphoblastic leukemia: results of the Chilean protocol LLA 15-30]. / Leucemia linfoblástica aguda estirpe B Philadelphia negativa en adolescentes y adultos jóvenes: Resultados del Protocolo Terapéutico LLA 15-30, Programa Nacional de Cáncer del Adulto (PANDA), Ministerio de Salud, Chile.

BACKGROUND: Intensified treatment of Philadelphia chromosome negative acute lymphoblastic leukemia (Ph(-)ALL) in adolescents by pediatric teams, with fve years disease free survival (DFS) rate of 65%, encouraged the use of intensified protocols in patients between 15 and 30 years, improving the DFS from 45% to 60-80%. The protocol LLA 15-30 for patients between 15 and 30 years with Ph(-)ALL, based on the Children's Oncology Group (COG) protocol AALL0232 resulting in a five years DFS of 78%, was started in 2007 by the PANDA national program. AIM: To report the results of the prospective cohort study evaluating the results of this protocol four years after its implementation. PATIENTS AND METHODS: Between January 2007 and December 2010, 68 Ph(-) ALL patients, aged between 15-30 years (75% males) were incorporated. Survival was evaluated using Kaplan-Meier and log-rank tests. RESULTS: Fifty percent of patients were of high risk. A complete response was achieved in 91%, early death occurred in 6% and induction failure in 3%. Median follow-up was 23 months. Overall survival, disease free survival and relapse rates at 35 months were 61.8, 67.5% and 31% respectively. CONCLUSIONS: LLA 15-30 protocol significantly improved three-year overall survival from 31 to 62%. The 20% difference observed with AALL0232 protocol is explained by the high rate of relapse. Improving provider and patient compliance with protocols may eliminate this gap.

Leucemia linfoblástica aguda estirpe B Philadelphia negativa en adolescentes y adultos jóvenes: Resultados del Protocolo Terapéutico LLA 15-30, Programa Nacional de Cáncer del Adulto (PANDA), Ministerio de Salud, Chile / Adolescent and young adult Philadelphia negative B cell acute lymphoblastic leukemia: Results of the Chilean protocol LLA 15-30

Background: Intensified treatment of Philadelphia chromosome negative acute lymphoblastic leukemia (Ph(-)ALL) in adolescents by pediatric teams, with fve years disease free survival (DFS) rate of 65%, encouraged the use of intensified protocols in patients between 15 and 30 years, improving the DFS from 45% to 60-80%. The protocol LLA 15-30 for patients between 15 and 30 years with Ph(-)ALL, based on the Children’s Oncology Group (COG) protocol AALL0232 resulting in a five years DFS of 78%, was started in 2007 by the PANDA national program. Aim: To report the results of the prospective cohort study evaluating the results of this protocol four years after its implementation. Patients and Methods: Between January 2007 and December 2010, 68 Ph(-) ALL patients, aged between 15-30 years (75% males) were incorporated. Survival was evaluated using Kaplan-Meier and log-rank tests. Results: Fifty percent of patients were of high risk. A complete response was achieved in 91%, early death occurred in 6% and induction failure in 3%. Median follow-up was 23 months. Overall survival, disease free survival and relapse rates at 35 months were 61.8, 67.5% and 31% respectively. Conclusions: LLA 15-30 protocol significantly improved three-year overall survival from 31 to 62%. The 20% difference observed with AALL0232 protocol is explained by the high rate of relapse. Improving provider and patient compliance with protocols may eliminate this gap.

Leucemia promielocítica aguda: Resultados del protocolo terapéutico LPA2000, Programa Nacional de Cáncer del Adulto (PANDA), Ministerio de Salud, Chile / Acute promyelocytic leukemia: Results of the Chilean protocol LPA2000

Background: The current recommendations for treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) include all-trans-retinoic acid (ATRA) and anthracycline based chemotherapy. Aim: To evaluate the results of the Chilean protocol following the LPA99 regimen of the Spanish PETHEMA group, except for the replacement of Idarubicin by Daunorubicin. Patients and Methods: Induction consisted of Daunorubicin 45 mg/m² on days 2, 4, 6 and 8 plus ATRA 45 mg/m² daily until complete remission. Patients in complete remission (CR) received three monthly chemotherapy courses: Daunorubicin 45 mg/m²/d/4days i.v. and ATRA 45 mg/m²/d/15 days p.o. (course no. 1); Mitoxantrone 10 mg/m²/d/5 days i.v. and ATRA 45 mg/m²/d/15 days p.o. (course no. 2); Daunorubicin 60 mg/m²/d/ day 1 i.v. in the low risk group, and 1 and 2 in the intermediate-high risk groups and ATRA 45 mg/m²/d/15 days p.o. (course no. 3). Maintenance therapy consisted of mercaptopurine 90 mg/m²/d p.o., methotrexate 15 mg/m²/wk p.o. and, ATRA intermittently, 45 mg/m²/d p.o. for 15 days every three months. Results: Between January 2000 and December 2005, 56 patients with newly diagnosed APL from 10 centers were enrolled. A total of 46 patients achieved CR (85%), 8 (15%) died of early complications, seven patients relapsed, with a 16% relapse risk at three years. The 5-year Kaplan-Meier estimates of overall survival and relapse-free survival were 64% and 84% respectively. Conclusions: These data indicate that this protocol has a good antileukemic effect but further reduction of early death and relapse, especially in the high risk group is needed.

[Acute promyelocytic leukemia: results of the Chilean protocol LPA2000]. / Leucemia promielocítica aguda: Resultados del protocolo terapéutico LPA2000, Programa Nacional de Cáncer del Adulto (PANDA), Ministerio de Salud, Chile.

BACKGROUND: The current recommendations for treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) include all-trans-retinoic acid (ATRA) and anthracycline based chemotherapy. AIM: To evaluate the results of the Chilean protocol following the LPA99 regimen of the Spanish PETHEMA group, except for the replacement of Idarubicin by Daunorubicin. PATIENTS AND METHODS: Induction consisted of Daunorubicin 45 mg/m² on days 2, 4, 6 and 8 plus ATRA 45 mg/m² daily until complete remission. Patients in complete remission (CR) received three monthly chemotherapy courses: Daunorubicin 45 mg/m²/d/4days i.v. and ATRA 45 mg/m²/d/15 days p.o. (course no. 1); Mitoxantrone 10 mg/m²/d/5 days i.v. and ATRA 45 mg/m²/d/15 days p.o. (course no. 2); Daunorubicin 60 mg/m²/d/ day 1 i.v. in the low risk group, and 1 and 2 in the intermediate-high risk groups and ATRA 45 mg/m²/d/15 days p.o. (course no. 3). Maintenance therapy consisted of mercaptopurine 90 mg/m²/d p.o., methotrexate 15 mg/m²/wk p.o. and, ATRA intermittently, 45 mg/m²/d p.o. for 15 days every three months. RESULTS: Between January 2000 and December 2005, 56 patients with newly diagnosed APL from 10 centers were enrolled. A total of 46 patients achieved CR (85%), 8 (15%) died of early complications, seven patients relapsed, with a 16% relapse risk at three years. The 5-year Kaplan-Meier estimates of overall survival and relapse-free survival were 64% and 84% respectively. CONCLUSIONS: These data indicate that this protocol has a good antileukemic effect but further reduction of early death and relapse, especially in the high risk group is needed.

[Hodgkin lymphoma in Chile: experience of the national adult cancer program]. / Linfoma de Hodkin en Chile: experiencia de 15 años del Programa Nacional de Cáncer del Adulto.

BACKGROUND: Hodgkin lymphoma is a highly curable disease. AIM: To evaluate the clinical characteristics and the treatment results of Hodgkin lymphoma patients of the National Cancer Program in Chile. PATIENTS AND METHODS: Prospective assessment of 682 patients treated in 18 adult cancer centers. Progression free survival (PFS) and overall survival (OS) were calculated. Median follow up was 127, 95, 87, 72 and 50 months for C-MOPP, radiotherapy (RT), C-MOPP/ABV, NOVP and ABVD, respectively. RESULTS: Median age was 37 years (15-84). Nodular sclerosis and mixed cellularity were equally expressed. Advanced stages (III & IV) were present at diagnosis in 61% of cases. Age over 40 was an adverse prognostic factor (p<0.001). The rate of PFS at 5 and 10 years for early stages was 73% and 66% with RT, 80% and 74% with C-MOPP+RT, 73% and 71% with C-MOPP/ABV, 59% and 59% with NOVP+RT, and 81% with ABVD+RT, at 5 years, being significantly lower for NOVP (p=0.02). The rate of OS at 5 and 10 years for advanced stages was 82% and 70% with RT, 82% and 76% with C-MOPP+RT, 82% and 80% with C-MOPP/ABV, 68% and 60% with NOVP, and 85% with ABVD at 5 years, also significantly lower for NOVP (p=0.04). For advanced stages, the rate of PFS at 5 and 10 years was 49% and 43% with C-MOPP, 69% and 62% with C-MOPP/ABVD or C-MOPP/ABV, and 71% at 5 years with ABVD, significantly lower for C-MOPP (p=0.01). The rate of OS at 5 and 10 years was 52% and 46% with C-MOPP, 70% and 63% with C-MOPP/ABVD or C-MOPP/ABV and 76% with ABVD at 5 years, significantly lower for C-MOPP (p=0.0002). CONCLUSIONS: Age over 40 years was an adverse prognostic factor. C-MOPP/ABVD, C-MOPP/ABV and ABVD had comparable results and reached a high tumor control and overall survival in both early and advanced stages.

Antioxidant and pro-oxidant effects of red wine and its fractions on Cu(II) induced LDL oxidation evaluated by absorbance and chemiluminescence measurements.

Cu(II) mediated low density lipoprotein (LDL) oxidation has been followed by the changes in absorbance at 234 nm and the emitted low level chemiluminescence (CL). The similarity of the time profiles allows us to conclude that the emitted CL is due to the decomposition of a transient product, most likely a hydroperoxide. Red wine, as well as its fractions, afford a noticeable protection when added prior to the start of the LDL oxidation process. On the other hand, when they are added after the onset of the autocatalytic oxidation phase, red wine and its fractions behave as pro-oxidants. This is particularly evidenced by a strong burst of CL (enhancement of the light by a factor approximately 20). This burst is reduced by metal chelators (EDTA and DFO) and can be associated to a sequence of reactions such as XOH + Cu(II) --> X* + H(+) + Cu(I), Cu(I) + LOOH --> chemiluminescence where XOH is a phenolic compound and LOOH is a peroxide-like compound produced in the LDL oxidation.

Cytoprotection by neutral fraction of tannat red wine against oxidative stress-induced cell death.

Some of the beneficial effects of the Mediterranean diet on human pathologies have been attributed to red wine polyphenols. It has been postulated that the antioxidant activity of the latter would be also responsible for the cytoprotective capacity of red wine that has been reported in a few papers. Nevertheless, red wine shows a complex composition, and the active fraction is not known yet. In this context, the protective capacity of total lyophilized extracts of red wine and anthocyanin, neutral, or acidic fractions, was explored in PC12 cells in culture after a hydrogen peroxide insult. Although all fractions showed high antioxidant activity, only the neutral fraction was cytoprotective. The analysis of this active fraction showed that it was rich in the aglycons quercetin and myricetin as well as the glycosides of kaempferol, isorhamnetin, epicatechin, and catechin, some of which are known to be cytoprotective. This is the first paper to reveal the active fraction of total wine responsible of its cytoprotection.

Juice and phenolic fractions of the berry Aristotelia chilensis inhibit LDL oxidation in vitro and protect human endothelial cells against oxidative stress.

Oxidative modification of low-density lipoprotein (LDL) particles is a key event in the development of atherosclerosis. Oxidized LDL induces oxidative stress and modifies gene expression in endothelial cells. Berries constitute a rich dietary source of phenolic antioxidants. We found that the endemic Chilean berry Aristotelia chilensis (ach) has higher phenol content and scores better for total radical-trapping potential and total antioxidant reactivity in in vitro antioxidant capacity tests, when compared to different commercial berries. The juice of ach is also effective in inhibiting copper-induced LDL oxidation. In human endothelial cell cultures, the addition of ach juice significantly protects from hydrogen peroxide-induced intracellular oxidative stress and is dose-dependent. The aqueous, anthocyanin-rich fraction of ach juice accounts for most of ach's antioxidant properties. These results show that ach is a rich source of phenolics with high antioxidant capacity and suggest that it may have antiatherogenic properties.

Participación del laboratorio en el diagnóstico de mieloma múltiple: análisis de 16 casos / Participation of the laboratory in the diagnosis of multiple myeloma: analysis of 16 cases

Se analizan las características de laboratorio en 16 casos de Mieloma Múltiple, presentados en los últimos seis años. Se encontró que un 62,5% de los pacientes fueron mujeres. Un 56,3% de los casos tenían entre 51 y 70 años. Encontramos que un 75% de los casos presentó sólo anemia como alteración hematológica en sangre periférica. En un 83,3% de los pacientes, se encontró sobre un 30% de células plasmáticas en médula ósea. Un 57,1% de los Mielomas analizados, fueron IgG, y 28,6% IgA. El nivel promedio de Inmunoglobulinas, en los casos IgG, fue 8.574 mgr/dl y 5.135 mgr/dl en los IgA. Además, se presentan otras características hematológicas, inmunológicas y químicas observadas. La tasa de incidencia(1,1 al año, por cada 100 mil habts.), es baja en relación a lo descrito en la literatura. Se sugiere buscar más esta patología e implementar la técnica de Electroforesis de Proteínas en orina