Overexpression of BCL2, BCL6, VEGFR1 and TWIST1 in Circulating Tumor Cells Derived from Patients with DLBCL Decreases Event-Free Survival.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignant lymphoid neoplasm and is the most common subtype of non-Hodgkin lymphoma in adults. More than half of patients with DLBCL can achieve remission with standard R-CHOP regimes; however, approximately 30-40% of patients are still failing this standard therapy, which remains as an important cause of progression and mortality of this disease. It is necessary to have diagnostic and monitoring tools that allow us to improve the accuracy of prognosis in these patients. Circulating tumor cells (CTCs) identification through molecular biomarkers is one of the novel strategies that have been used in other types of cancer, and we aim to use this tool to analyze the potential role in DLBCL. Patients and Methods: We analyzed 138 blood samples of patients with DLBCL, of which CTCs were isolated by density gradient for subsequent detection and quantitation of molecular biomarkers using RT-qPCR with TaqMan probes. Survival analysis was performed using Kaplan-Meier curves. Results: We found overexpression of ABCB1, αSMA, BCL2, BCL6 and VEGFR1 genes, as well as the presence of CK19, EpCAM, KI67, MAGE-A4, SNAIL and TWIST1 genes. CK19 and EpCAM expression were associated with a minor OS (85.7% vs 98.1%, p = 0.002). The overexpression of BCL2, BCL6, VEGFR1 and TWIST1 was related to a minor EFS (p = 0.001). Conclusion: This study showed that in liquid biopsies analyzed, the presence of CTCs can be confirmed through molecular biomarkers, and it has an impact on OS and EFs, making this detection useful in the follow-up and prognosis of patients with DLBCL.

Experiences with health care and health-related quality of life of patients with hematologic malignancies in Mexico.

BACKGROUND: In Mexico, patients with hematologic malignancies (HMs) are characterized by being at high risk and advanced stages at diagnosis and by having a low cure rate; yet information on their experiences with health care and health-related quality of life (HRQL) is scarce. We aimed to evaluate experiences with health care and HRQL of patients with HMs and the association between these patient-reported measures. METHODS: We conducted a cross-sectional survey in two public oncology hospitals in Mexico City. The study included outpatient cancer patients aged ≥18 years with a diagnosis of leukemia, lymphoma, or multiple myeloma. We used a patient-centered quality of cancer care questionnaire to assess patient experiences with receiving 1) timely care; 2) clear information; 3) information for treatment decision-making; 4) care to address biopsychosocial needs; and 5) respectful and coordinated care. We applied the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) to measure HRQL. We performed a multiple linear regression to evaluate the association between patient-reported experiences (independent variables) and the QLQ-C30 summary score (dependent variable). RESULTS: Of the 515 participating HM patients, 46.6% had lymphoma, 34% leukemia, and 19.4% multiple myeloma; 70.9% were at advanced stages or at high risk. Additionally, 15.1% had anxiety and 12.8% had depression. Over one third (35.9%) reported receiving clear information, 28.5% timely care, 20.6% information for treatment decision-making, 23.7% care that addressed their biopsychosocial needs, and 31% respectful and coordinated care. The mean QLQ-C30 summary score was 71.9 points. Timely care, clear information, and care that addresses biopsychosocial needs were associated with higher HRQL. CONCLUSIONS: Health care services for HM patients at public oncology hospitals in Mexico need improvement. Notably, providing timely care, clear information, and care that addresses patients' biopsychosocial needs can increase the likelihood of better HRQL. Health care providers should measure and improve the experiences of HM patients with health care.

Iron Chelation in Transfusion-Dependent Patients With Low- to Intermediate-1-Risk Myelodysplastic Syndromes: A Randomized Trial.

Background: Iron chelation therapy (ICT) in patients with lower-risk myelodysplastic syndromes (MDS) has not been evaluated in randomized studies. Objective: To evaluate event-free survival (EFS) and safety of ICT in iron-overloaded patients with low- or intermediate-1-risk MDS. Design: Multicenter, randomized, double-blind, placebo-controlled trial (TELESTO). (ClinicalTrials.gov: NCT00940602). Setting: 60 centers in 16 countries. Participants: 225 patients with serum ferritin levels greater than 2247 pmol/L; prior receipt of 15 to 75 packed red blood cell units; and no severe cardiac, liver, or renal abnormalities. Intervention: Deferasirox dispersible tablets (10 to 40 mg/kg per day) (n = 149) or matching placebo (n = 76). Measurements: The primary end point was EFS, defined as time from date of randomization to first documented nonfatal event (related to cardiac or liver dysfunction and transformation to acute myeloid leukemia) or death, whichever occurred first. Results: Median time on treatment was 1.6 years (interquartile range [IQR], 0.5 to 3.1 years) in the deferasirox group and 1.0 year (IQR, 0.6 to 2.0 years) in the placebo group. Median EFS was prolonged by approximately 1 year with deferasirox versus placebo (3.9 years [95% CI, 3.2 to 4.3 years] vs. 3.0 years [CI, 2.2 to 3.7 years], respectively; hazard ratio, 0.64 [CI, 0.42 to 0.96]). Adverse events occurred in 97.3% of deferasirox recipients and 90.8% of placebo recipients. Exposure-adjusted incidence rates of adverse events (≥15 events per 100 patient treatment-years) in deferasirox versus placebo recipients, respectively, were 24.7 versus 23.9 for diarrhea, 21.8 versus 18.7 for pyrexia, 16.7 versus 22.7 for upper respiratory tract infection, and 15.9 versus 0.9 for increased serum creatinine concentration. Limitations: The protocol was amended from a phase 3 to a phase 2 study, with a reduced target sample size from 630 to 210 participants. There was differential follow-up between treatment groups. Conclusion: The findings support ICT in iron-overloaded patients with low- to intermediate-1-risk MDS, with longer EFS compared with placebo and a clinically manageable safety profile. Therefore, ICT may be considered in these patients. Primary Funding Source: Novartis Pharma AG.

Acute Leukemia Characteristics are Different Around the World: the Mexican Perspective.

BACKGROUND: The incidence of acute leukemia (AL) has increased. Its prognosis is variable and depends on several baseline characteristics with a highly heterogeneous presentation. In Mexico, large-scale descriptive studies have not yet been published; the objective of this study was to analyze the initial basic characteristics of patients diagnosed with AL in our population. PATIENTS AND METHODS: In this multicenter, retrospective study, 1018 patients ≥ 16 years of age and diagnosed with AL between 2009 and 2014, were included. We described age, gender, complete blood count, and AL subtype according to flow cytometry analysis. RESULTS: Acute lymphoblastic leukemia (ALL) was as common as acute myeloid leukemia (AML) (51% vs. 49%). The median age was 31 years. Only 9.6% of patients with ALL were positive for the Philadelphia chromosome. No gender differences were observed. The median age at presentation of AML was 43 years. Acute promyelocytic leukemia was the most frequent AML subtype (38.3%), with a median age of 37 years. CONCLUSION: ALL is equally as frequent as AML in patients ≥16 years of age. Philadelphia-positive prevalence is less frequent than that reported in literature. AML cases occur in a younger age in comparison with other countries. There is a higher rate of acute promyelocytic leukemia among our patients compared with other non-Latin American populations. This study is the largest ever performed in Mexico regarding descriptive AL data.

[Acute leukemia frequency observed in a reference hospital]. / Frecuencia de leucemias agudas en un hospital de referencia.

OBJECTIVE: to compare the frequency of acute leukemia in two periods of study in a reference Hospital at Mexico City. METHODS: it was an observational study. There were registered 250 cases with the morphology diagnostic criterion of acute leukemia. RESULTS: 63 cases versus 92 of acute lymphoid leukemia (ALL) and 16 versus 79 acute myeloid leukemia (AML) of 1990-1992 versus 2008-2009 respectively was observed; corresponding to 62 % in total of ALL in both periods and 38 % of AML. The ALL was the most frequent variant (62 % versus 38 %). The median age was 26 years, male 52 %. It showed a significant increase in the number of admissions in the period of 2008-2009 and acute promyelocytic leukemia also showed an increase (p = 0.001). CONCLUSIONS: acute leukemia is the main cause of admission, mortality and morbidity. Our study differs slightly from the literature; the leukemia that diagnostic with major frequency was the acute lymphoid leukemia increasing his number in the period of 2008-2009. The significant rise due to an increase use of new diagnostic tools such as the flow cytometry and molecular biology.