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.

Epidemiological and clinical characteristics and outcome of monoclonal gammopathy of renal significance-related lesions in Latin America.

BACKGROUND: Monoclonal gammopathy of renal significance (MGRS)-related lesions are infrequent entities. There are no publications on these disorders in Latin America (LA). The aim of this study was to describe epidemiological and clinical characteristics of these patients in LA. METHODS: We performed a multicentre retrospective study. Patients with diagnosis of MGRS between 2012 and 2018 were included. Epidemiological and clinical data were collected from clinical records. RESULTS: Twenty-seven patients from Chile, Argentina, Ecuador and Uruguay were included. Half debuted with a nephrotic syndrome, and 32% required dialysis. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits was found in 33%, amyloidosis in 26% and monoclonal immunoglobulin deposition disease also in 26%. The immunoglobulin most frequently found in renal biopsies was IgG kappa. In 67% a paraprotein was found. Twenty patients received an anti-plasma cell regimen, and 3 a rituximab-based regimen (IgM-MGRS). Renal response (RR) was achieved in 56%. Early treatment (≤3 months) was associated with higher RR (75% vs 43%). Three patients relapsed within 21.5 months, and 3 progressed: 1 to multiple myeloma, 1 to systemic amyloidosis and another to systemic light-chain deposition disease. Two patients died, both due to infection during induction treatment. CONCLUSION: There was a higher than expected frequency of patients requiring dialysis. The most common MGRS-related lesion was PGNMD. Early treatment was associated with better response. As a rare disease, increasing awareness and promoting early diagnosis are necessary in LA to improve outcomes. SUMMARY AT A GLANCE A collection of 27 cases of MGRS from Latin America with information on epidemiology, clinical characteristics, treatment and outcome of patients diagnosed of MGRS-related renal lesions.

[Survival of 1,103 Chilean patients with multiple myeloma receiving different therapeutic protocols from 2000 to 2016]. / Mieloma múltiple en Chile: pasado, presente y futuro del programa nacional de drogas antineoplásicas (PANDA). Revisión de 1.103 pacientes.

BACKGROUND: Multiple myeloma (MM) is one of the most common malignancies found in hematology. AIM: To describe the features of patients with MM and perform a survival analysis according to the different treatment protocols used between 2000 and 2016. MATERIAL AND METHODS: Analysis of the database of the Chilean national anti-neoplastic drug program. Information was obtained from 1,103 patients, with a median age of 64.5 years (range 27-95) and a male to female ratio of 1:1.2. RESULTS: The mean overall survival (OS) of patients receiving or not receiving Thalidomide was 46 and 30 months, respectively (p < 0.01). The mean OS of patients treated before 2007 (treated with melphalan and prednisone) and between 2007 and 2012 (treated with thalidomide and dexamethasone) was 36 and 48 months respectively. In the group starting in 2013 (treated with cyclophosphamide, thalidomide and dexamethasone) the median survival had not been reached at 20 months of follow up (p = 0.01 for all comparisons). Autologous transplantation (AT) was carried out in only 18% of the eligible patients. The median OS of the patients who receive an AT had not been reached at 48 month compared with 36 month among those who did not received the procedure (p < 0.01). CONCLUSIONS: Even though overall survival has improved with time, new drugs must be introduced in our protocols to obtain similar results to those obtained worldwide.

Mieloma múltiple en Chile: pasado, presente y futuro del programa nacional de drogas antineoplásicas (PANDA). Revisión de 1.103 pacientes / Survival of 1, 103 Chilean patients with multiple myeloma receiving different therapeutic protocols from 2000 to 2016

Background: Multiple myeloma (MM) is one of the most common malignancies found in hematology. Aim: To describe the features of patients with MM and perform a survival analysis according to the different treatment protocols used between 2000 and 2016. Material and Methods: Analysis of the database of the Chilean national anti-neoplastic drug program. Information was obtained from 1,103 patients, with a median age of 64.5 years (range 27-95) and a male to female ratio of 1:1.2. Results: The mean overall survival (OS) of patients receiving or not receiving Thalidomide was 46 and 30 months, respectively (p < 0.01). The mean OS of patients treated before 2007 (treated with melphalan and prednisone) and between 2007 and 2012 (treated with thalidomide and dexamethasone) was 36 and 48 months respectively. In the group starting in 2013 (treated with cyclophosphamide, thalidomide and dexamethasone) the median survival had not been reached at 20 months of follow up (p = 0.01 for all comparisons). Autologous transplantation (AT) was carried out in only 18% of the eligible patients. The median OS of the patients who receive an AT had not been reached at 48 month compared with 36 month among those who did not received the procedure (p < 0.01). Conclusions: Even though overall survival has improved with time, new drugs must be introduced in our protocols to obtain similar results to those obtained worldwide.

[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.

Breakthrough bacteremia due to Clostridium tertium in a patient with neutropenic fever, and identification by MALDI-TOF mass spectrometry.

Clostridium tertium is rare in a human clinical specimen and its pathogenicity is often uncertain. However, the organism has been increasingly recognized as a cause of bacteremia and other infections in immunocompromised patients, especially those with hematologic malignancies. The diagnosis and treatment of C. tertium are difficult due to its growth pattern, micromorphology, and antibiotic resistance. The organism can easily be misidentified as Gram-positive aerobic rods such as Bacillus species, usually considered as a contaminant. Furthermore, it is not covered by empirical treatment with many broad-spectrum antibiotics. Here we report a case of breakthrough bacteremia due to C. tertium that occurred in a patient with acute leukemia and neutropenic fever, who was treated with an empirical regimen of ceftazidime and amikacin. The bacterium was rapidly identified by new mass spectrometry technology (MALDI-TOF MS) and the patient recovered under meropenem and vancomycin treatment, without complications.