Background:Breast cancer is an important cause of cancer-related death in women worldwide and represents the second most frequent cause of brain metastases after lung cancer. The aim of this study was to determine the characteristics and outcomes of triple-negative breast cancer (TNBC) patients with brain metastasis (BM). Methods:We retrospectively reviewed a cohort of patients diagnosed with TNBC at the "Instituto Nacional de Enfermedades Neoplasicas" (period 2000-2014) to evaluate patients who developed BM. Survival rates were assessed by the Kaplan-Meier method, and prognostic factors were identified with the Cox regression analysis. Results:Of a total of 2007 TNBC patients, 193 (9.62%) developed BM. Of these, 169 stages I-III patients with a median age of 45 years (range:21-78) were included. The stage in this cohort was 4 (2.4%) clinical stage (CS) I, 23 (13.6%) with CS II and 142 (84.0%) with CS III. Most of these patients presented ECOG ≥2 (68.6%). The most common symptom was headache (74.0%), followed by nausea-vomiting (46.7%). Imaging showed that 80 patients (53.0%) had ≥1 metastatic brain lesion. Regarding the treatment of BM in this cohort, 132 patients (84.6%) received radiotherapy (RT), 2 (1.5%) surgery, and 6 (4.5%) surgery plus RT. The overall survival (OS) rate of BM was 59.8%, 37.3%, and 15.0% at 3, 6, and 12 months, respectively. A multivariate analysis showed RT to be the only factor with a positive impact on the OS of BM (hazard ratio (HR) = 0.48, 95% confidence interval (CI):0.30-0.77, and p = 0.002), while ECOG ≥2 was associated with a worse OS (HR = 1.69, 95%CI:1.15-2.48, and p = 0.007). Conclusion:Despite the poor prognosis of TNBC patients who develop BM, RT showed a benefit in OS rates, while ECOG ≥2 was the only prognostic factor associated with a worse OS. These results may be useful for multidisciplinary teams for treatment planning in patients with TNBC and BM.

Purpose: Patients with diffuse large B-cell lymphoma (DLBCL) are typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, a standard of care for managing adolescents and young adults (AYAs) with DLBCL is lacking. We examine treatment approaches and outcomes of this population. Methods: We included 90 AYAs (15-39 years) diagnosed with DLBCL between 2008 and 2018 in three tertiary centers in Peru. Overall response rates (ORR) were available for all patients. Overall survival (OS) and progression-free survival (PFS) rates were estimated using the Kaplan-Meier method. Results: The median age at diagnosis was 33 years, 57% were males, 57% had good performance status (Lansky/Karnofsky ≥90), and 61% were diagnosed with early-stage disease (Ann Arbor stages I-II). R-CHOP (n = 69, 77%) was the most frequently used first-line regimen, with an ORR of 91%. With a median follow-up of 83 months, the 5-year OS and PFS among all patients were 79% and 67%, respectively. Among the patients who received R-CHOP, the 5-year OS and PFS were 77% and 66%, respectively. Of the 29 (32%) patients with relapsed/refractory (R/R) disease, 83% received second-line treatment and only 14% underwent consolidation therapy with autologous transplantation. The 3-year OS for R/R DLBCL was 36%. Conclusion: Our data show that AYAs with DLBCL who received conventional therapy had comparable outcomes to those observed in studies conducted among the adult population. However, the prognosis for AYAs with R/R disease was dismal, indicating the unmet need for developing and increasing access to novel treatment modalities in AYAs.

Adult T-cell leukemia/lymphoma (ATLL) is a refractory blood cancer with severe immunodeficiency resulting from retroviral infection. ATLL develops in only 5 % of HTLV-1-infected individuals, but the entire mechanism of ATLL progression remains unknown. Since recent studies have reported that the gut microbiome influences the progression of various diseases, we hypothesized that ATLL is also related to the gut microbiome and aimed to investigate this relationship. We analyzed the taxonomic and functional profiles of the gut microbiota of ATLL patients (n = 28) and HTLV-1-infected individuals (n = 37). We found that the succinic semialdehyde (SSA) synthesis pathway was significantly enriched in the gut microbiome of ATLL patients (P = 0.000682), and Klebsiella, whose abundance was significantly greater in ATLL patients and high-risk HTLV-1-infected individuals (P = 0.0326), was the main contributor to this pathway. Administration of SSAs to ATLL cell lines resulted in significant cell proliferation. Herein, we propose that the gut microbiome can regulate ATLL progression via metabolites.

ABSTRACT:Epstein-Barr virus (EBV) is a potent carcinogen linked to hematologic and solid malignancies and causes significant global morbidity and mortality. Therapy using allogeneic EBV-specific lymphocytes shows promise in certain populations, but the impact of EBV genome variation on these strategies remains unexplored. To address this, we sequenced 217 EBV genomes, including hematologic malignancies from Guatemala, Peru, Malawi, and Taiwan, and analyzed them alongside 1307 publicly available EBV genomes from cancer, nonmalignant diseases, and healthy individuals across Africa, Asia, Europe, North America, and South America. These included, to our knowledge, the first natural killer (NK)/T-cell lymphoma (NKTCL) EBV genomes reported outside of East Asia. Our findings indicate that previously proposed EBV genome variants specific to certain cancer types are more closely tied to geographic origin than to cancer histology. This included variants previously reported to be specific to NKTCL but were prevalent in EBV genomes from other cancer types and healthy individuals in East Asia. After controlling for geographic region, we did identify multiple NKTCL-specific variants associated with a 7.8-fold to 21.9-fold increased risk. We also observed frequent variations in EBV genomes that affected peptide sequences previously reported to bind common major histocompatibility complex alleles. Finally, we found several nonsynonymous variants spanning the coding sequences of current vaccine targets BALF4, BKRF2, BLLF1, BXLF2, BZLF1, and BZLF2. These results highlight the need to consider geographic variation in EBV genomes when devising strategies for exploiting adaptive immune responses against EBV-related cancers, ensuring greater global effectiveness and equity in prevention and treatment.

Purpose: Outcomes of females with triple-negative breast cancer (TNBC) are rarely explored in adolescents and young adults (AYAs). We compared clinical and survival outcomes of Latin American AYAs (≤39 years) with middle-aged (40-59 years) and older (≥60 years) females with TNBC by cancer stage. Methods: We performed a single-center retrospective cohort study among treated females with cancer stages I-III diagnosed from 2000 to 2014 in Peru. We evaluated overall survival (OS) and event-free survival (EFS). Time-to-event methods were used for analyses. Results: Of 1582 females with TNBC, 350 (22%) were AYAs, 887 (56%) were middle-aged, and 345 (22%) were older women. Tumor size >5 cm, histological grade III, and brain metastasis were more common features in AYAs. AYAs were treated more frequently with neoadjuvant chemotherapy. With a median follow-up of 102 months, the 5-year OS/EFS for AYAs was 55%/53%, similar to middle-aged (54%/49%) and older females (56%/51%). AYAs were not at higher risk for decreased OS or EFS in the multivariable Cox analysis. Our findings remained consistent by cancer stage. Conclusion: Although Latin American AYAs with TNBC have more aggressive clinical features at diagnosis, survival outcomes were comparable with middle-aged and older women with TNBC, suggesting that age is not a risk factor for worse survival outcomes if treatment is given according to cancer stage. Our findings should be interpreted with caution given the lack of information on certain covariates such as comorbidities. Strategies for early detection in primary care and prompt referral for treatment initiation should be developed.

PURPOSE:Human T-lymphotropic virus type 1 (HTLV-1) is an endemic virus in Latin America that is directly linked to adult T-cell leukemia/lymphoma (ATL). Previous studies have suggested an oncogenic role of HTLV-1 in non-ATL neoplasms and have found higher mortality in HTLV-1 carriers without ATL.METHODS:In this retrospective cohort study, HTLV-1 carriers were identified through screening at a tertiary cancer center between 2006 and 2019. We compared the overall survival (OS) outcomes of patients with ATL with those with other solid or hematologic malignancies by sex stratification.RESULTS:We identified 1,934 HTLV-1 carriers diagnosed with cancer. The median age at diagnosis was 62 (range 20-114) years, 76% were female, 60% had no or elementary school education, and 50% were born in the Andean highlands. The most common non-ATL neoplasm was cervical cancer (50%) among females and non-ATL non-Hodgkin lymphoma (26%) among males. With a median follow-up of 66 months, the 5-year OS of HTLV-1 carriers with non-ATL neoplasms (26%-47% for females and 22%-34% for males) was inferior to those reported in the general population. As expected, patients with ATL had a worse prognosis (5-year OS: 10% for females and 8% for males).CONCLUSION:HTLV-1 carriers with cancer were middle age and from underprivileged settings, suggesting an undetected transmission among vulnerable populations, especially females. Survival estimates of HTLV-1 carriers with non-ATL neoplasms were lower than the regional outcomes. Future research should ascertain how the biology of HTLV-1 and health care disparities affect the outcomes of HTLV-1 carriers, as well as determine the burden of HTLV-1 infection in the cancer population to recommend screening in the outpatient setting of endemic regions.

Human T-cell leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATL). HTLV-1 carriers have a lifelong asymptomatic balance between infected cells and host antiviral immunity; however, 5–10% of carriers lose this balance and develop ATL. Coinfection with Strongyloides promotes ATL development, suggesting that the immunological status of infected individuals is a determinant of HTLV-1 pathogenicity. As CD4+ T cells play a central role in host immunity, the deregulation of their function and differentiation via HTLV-1 promotes the immune evasion of infected T cells. During ATL development, the accumulation of genetic and epigenetic alterations in key host immunity-related genes further disturbs the immunological balance. Various approaches are available for treating these abnormalities; however, hematopoietic stem cell transplantation is currently the only treatment with the potential to cure ATL. The patient’s immune state may contribute to the treatment outcome. Additionally, the activity of the anti-CC chemokine receptor 4 antibody, mogamulizumab, depends on immune function, including antibody-dependent cytotoxicity. In this comprehensive review, we summarize the immunopathogenesis of HTLV-1 infection in ATL and discuss the clinical findings that should be considered when developing treatment strategies for ATL.

The recommended first-line chemotherapy agents for managing Kaposi sarcoma (KS) in high-income countries are expensive and often unavailable in developing nations such as Peru. Limited data exist on whether management practices in these countries affect patient outcomes. We assessed the real-world treatment approaches and outcomes of patients with KS in Peru. We retrospectively reviewed the medical records of patients with acquired immunodeficiency syndrome-related KS (AIDS-related KS; n = 95) and classic KS (CKS; n = 81) diagnosed at a tertiary center between 2000 and 2014 in Lima, Peru. We used the Kaplan–Meier method to estimate overall survival (OS) rates. The median follow-up was 64 months for AIDS-related KS and 88 months for CKS. The median age of patients with AIDS-related KS was 35 years (range 20–63 years) and 70 years (range 33–91 years) for those with CKS. Most individuals had an Eastern Cooperative Oncology Group performance status of ≥ 2 (AIDS-related KS 75

Introduction: Anemia is a global public health issue that affects mainly children aged less than 5 years. In Peru, despite the reduction in the prevalence of anemia between 2010 and 2018, anemia remains a major concern, especially in high-risk zones such as rural areas. Several sociodemographic factors have been associated with anemia in children; however, components contributing to the urban-rural gap have not been previously assessed. The purpose of this study was to evaluate the determinants of the difference in anemia prevalence between urban and rural areas, and its spatial distribution in Peruvian children aged 6-59 months. Methods: A secondary data analysis was conducted using the 2019 Peruvian Demographic Health Survey. The study population included 18 846 children aged 6-59 months. A multivariate decomposition analysis for non-linear response model was performed to identify the factors contributing to the gap in the prevalence of anemia across urban and rural areas. Global Moran's I autocorrelation, Ordinary Kriging interpolation and Bernoulli-based purely spatial scan statistics were employed to assess the spatial pattern of anemia. Results: Nationwide, the prevalence of anemia in Peru was 29.47% (95%CI 28.63-30.33). In rural areas, it was 38.25%, and in urban areas 26.39%. The decomposition analysis revealed that 88.61% of the difference in the prevalence of anemia between urban and rural areas was attributed to the difference in the respondents' characteristics. Wealth index, mother's education, mother's employment status, number of living children and mother's age were key determinants contributing to the rural-urban gap. Spatial heterogeneity of anemia prevalence in childhood was observed at both inter- and intradepartmental level. The SaTScan spatial analysis identified six significant cluster areas with high prevalence of anemia in childhood. Conclusion: A considerable gap of anemia prevalence between urban and rural areas was found. Targeted interventions are necessary to reduce geographic disparities.

BackgroundThe COVID-19 pandemic has had a direct effect on patients with cancer, as reflected by the large number of COVID-19-related cancer deaths reported worldwide and the substantial decrease in cancer-related consultations during the pandemic. However, the impact of the COVID-19 pandemic on cancer mortality in Latin American countries has not been properly estimated. The aim of this study was to analyse the excess mortality related to cancer during the pandemic in Peru, including deaths directly or indirectly attributed to COVID-19.MethodsExcess mortality, which compares the number of deaths by any cause with the average number of expected deaths in typical circumstances during a specific timeframe, can be used as a simple but reliable indicator of the impact of the COVID-19 pandemic on cancer services. We carried out a descriptive study using data from the Peruvian death registration system, from which we filtered records that had registered neoplastic diseases (according to the tenth revision of WHO's International Statistical Classification of Diseases and Related Health Problems) as the cause of death between. Only data for the period of March 15 to June 30 in the years 2017–20 was included. We calculated excess mortality by subtracting the average number of deaths recorded for the indicated period between 2017 and 2019 from the same period of 2020 records (ie, the duration of lockdown measures in Peru) to obtain the percentage of excess mortality.FindingsThe percentage of changes in the number of cancer-related deaths in Peru was +13·90% from 2017 to 2018, –1·27% from 2018 to 2019, and +16·94% from 2019 to 2020. We found an excess mortality of 928 cases (corresponding to an excess mortality of +17·27%) among patients with cancer, when comparing years 2017–19 with the year 2020. During the lockdown in 2020, 3135 (58·4%) of 5372 cancer deaths happened at home (vs 5900 [44·2%] of 13 338 for the years 2017–19). The highest excess mortality percentage was observed in patients with prostate cancer (+50·43%), breast cancer (+33·62%), and leukaemia (32·78%). Although these findings appear to be in line with reports from other countries, only 184 (3·4%) of 5372 deaths were registered with COVID-19 as an additional cause of death.InterpretationOur results suggest that COVID-19 control measures (eg, lockdowns, physical distancing, and isolation of symptomatic patients), alongside the overwhelming strain on the health-care system, had a detrimental impact on cancer mortality in Peru. The pandemic has exposed flaws in the Peruvian health-care system, especially regarding cancer care. Although we recognise that the rate of COVID-19 testing in Peru is one of the lowest in Latin America, the excess of cancer deaths cannot be fully explained by COVID-19. These findings might be an indication that the alarming increase in cancer mortality in Peru could continue over the upcoming months if no action is taken. Our study also shows the importance of an adequate registry of deaths. We recommend that the national authorities should implement policies to limit the impact of the COVID-19 pandemic on patients with cancer, and that the continuous update and monitoring of deaths initiated during the COVID-19 pandemic is sustained. These measures can help to confirm the increasing trend in cancer deaths; serve as a rationale to develop strategies that can alleviate this burden (eg, by adopting models for delivering optimal cancer care while minimising transmission of COVID-19); and minimise the possibility of an increase in patients presenting with advanced-stage cancers.FundingInternational Joint Laboratories Programme of the French National Research Institute for Sustainable Development.

Abstract Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/Black or Non-Hispanic White women. An Indigenous American breast cancer–protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47–0.59], as well as the lower odds of developing hormone receptor negative (HR−) versus HR+ disease (OR, 0.77; 95% CI, 0.61–0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51–0.92), HR−HER2+ (OR, 0.63; 95% CI, 0.44–0.90) and HR−HER2− (OR, 0.77; 95% CI, 0.56–1.05) compared with HR+HER2−. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR− and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.

Objectives: Venetoclax combinations are a new standard for patients with acute myeloid leukemia (AML). We aimed to evaluate the safety and efficacy of these combinations in a period of accelerated approval in Latin-America.Methods: This observational study evaluated adults with acute myeloid leukemia who received venetoclax-based therapy in 11 public or private centers in Mexico and Peru for both newly diagnosed or relapsed and refractory AML.Results: Fifty patients were included; 28 with newly diagnosed (ND) AML and 22 with relapsed/refractory (RR) disease. ND patients were older (64 vs. 40 years; p < 0.001) with a lower functional capacity (ECOG ≥2 64.3% vs 9%; p < 0.001). Venetoclax was frequently combined with azacytidine (60%) and prophylactic azoles (82%) with a median maximum dose of 200 mg (range, 100-600 mg). Hematologic toxicities were common. Complete response rates including patients with incomplete hematopoietic recovery were 78.6% in ND and 45.5% in RR patients, with a median overall survival of 9.6 (95% CI 3.7-15.5) and 8 months (95% CI 4.8-11.2).Discussion: Our study showed a preferred use of venetoclax plus azacytidine over cyatrabine. Patients in the first-line setting were similar to those in the landmark studies, while most patients with relapsed disease had received prior intensive therapies. Responses were favorable, with a median survival in agreement to other reports, albeit shorter than that observed in the randomized phase-3 trials.Conclusion: Venetoclax-based therapy in AML was effective despite dose reductions and prophylactic antifungals in two middle-income countries outside of a clinical trial setting.

7012 Background: Acute Lymphoblastic Leukemia (ALL) in Latino countries is characterized by high incidence and worst outcomes compare to other ethnicities. However, the actual epidemiological characterization of ALL in South America remains unknown. The lack of registries, uniform treatment and prospective protocols have been pointed out for these disparities. Also, biological, and social aspects of this disease play an important role that has not been well examined. We aimed to evaluate the survival of patients with acute lymphoblastic leukemia according to demographic characteristics with emphasis in the place of residence. Methods: We performed an analytical retrospective cohort study with subjects diagnosed and treated for ALL during the period 2016-2018 at the Peruvian national cancer center (INEN, Instituto Nacional de Enfermedades Neoplasicas). INEN is currently the main center dedicated to diagnosing and treat acute leukemias for patients without social neither private insurance. Also, INEN is located at the capital city (Lima-Peru). The calculated sample size was 378 patients. Patient data were obtained from the epidemiological registry and corroborated with the national registry of mortality (RENIEC, Registro Nacional de Identificacion y Estado Civil Overall survival probabilities according to demographic characteristics were estimated using the Kaplan-Meier curve; in addition, the Log-rank test and Cox regression were used. Results: A sample of 378 patients were included during the study period (N = 588), of which 212 (56.8%) were male, 42% were between 0-10 years, 24% in 46-65 years. Regarding the characteristics at diagnosis, 80% were Ph(-) BCP-ALL and 69% corresponded to high-risk groups. At 42 months of follow-up, the median survival of the patients was 29 months (95% CI: 23.3-34.6), and the overall survival at three years was 44.8%. Overall survival in males (48.8%) was higher than in females (39.5%). According to the range of age, the highest survival was in the group of 0-10 years (70%), followed by 11-20 years (36.8%) and the lowest survival was in 46- 65 years (12.5%). Furthermore, overall survival in Lima (51.5%) was higher than in the country-side (39.7%). There was a statistically significant association (p < 0.05) between survival and sex (p = 0.042), age range (p = 0.000) and place of residence (p = 0.005); according to the Log-rank test. Conclusions: We report a lower survival among all age groups in ALL compared to international working groups. Living in a country-side region represents a significant factor for dismal survival in our cohort. Specialized health care access to diagnosis and treatment should be warranted for patients with geographical limitations and programs to ensure it must be implemented.

Abstract Background: COVID-19 is a condition caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing a systemic inflammatory response and respiratory failure. Patients with acute leukemia are presumed to be at the highest risk among all cancer patients, given their state of severe immunosuppression from both the disease and aggressive therapy. Therefore, we aimed to determine if COVID-19 increases the early-mortality risk of ALL patients during the induction phase. Methods: We conducted a retrospective cohort study by reviewing medical records of newly diagnosed ALL patients between March 2020 and September 2020 at a single Peruvian institution (INEN, Lima-Peru). We included patients older than 14 years, with the initial intent of intensive treatment. The proposed protocol was the CALGB10403 with asparaginase modification. COVID-19 was determined by a +ve nasopharyngeal SARS-CoV-2 RT-PCR or serology. The outcomes were 30-day and 60-day mortality and treatment response at the end of induction. Results: Of 63 patients with ALL in induction therapy, 22 (35%) had COVID-19, and 41 (65%) did not. Overall, the median age was 30 (IQR 21 - 42), and 59% were males. Table 1 shows that age, sex, ALL subtype, and laboratory characteristics had a similar distribution between both groups. The mortality rate of ALL patients with COVID-19 was non-statistically different from non-COVID-19 patients at 30 (23% versus 12%, p=0.466) and 60 days (32% versus 20%, p=0.434). Multivariate logistic regression did not find a significant association between COVID-19 and complete treatment response (aOR: 0.44, 95% CI: 0.02-4.54). Similarly, patients with COVID-19 did not had an increased mortality risk at 30 days (aHR: 2.37, 95% CI: 0.64-8.75) and 60 days (aHR: 1.98, 95% CI: 0.7-5.64). Conclusion: In our cohort, COVID-19 did not increase the risk of early death in newly diagnosed patients with ALL. Table 1.Characteristics of patients with ALLOverallCOVID-19 NegativeCOVID-19 positivep-value*n=63n=41n=22Age (years)**33 ±1532 ±1635 ±130.377Sex Male37 (59%)25 (61%)12 (55%)0.821 Female23 (41%)16 (39%)10 (45%)Type B-ALL56 (86%)36 (88%)18 (72%)0.787 T-ALL9 (14%)5 (12%)4 (18%)B-ALL subtype NOS42 (78%)29 (81%)13 (72%)0.873 E2A/PBX12 (4%)1 (3%)1 (6%) MLL/AF42 (4%)1 (3%)1 (6%) TEL/AML1 (2%)1 (3%)0 (0%) BCR/ABL5 (8%)3 (7%)2 (10%) Unknown2 (4%)1 (3%)1 (6%)DHL (U/L)655 ±854719 ±988536 ±5230.422D-dimer (ng/mL)4539 ±59085319 ±70293164 ±27290.184Leucocytes (x103µL)38 ±10044 ±11927 ±490.528Hemoglobin (g/dL) †9 (7-14)9 (7-11)10 (7-54)0.475CNS Infiltration11 (17%)8 (20%)3 (14%)0.812ECOG>32 (3%)1 (2%)1 (5%)Complete Response43 (68%)28 (68%)15 (68%)0.896Minimal Residual Disease29 (46%)20 (49%)9 (41%)0.8330-day mortality10 (16%)5 (12%)5 (23%)0.46660-day mortality15 (24%)8 (20%)7 (32%)0.434*Univariate Cox regression.**Mean (standard deviation)†Median (Interquartile range) Citation Format: Daniel J. Enriquez-Vera, Ali Al-kassab-Cordova, Lizbeth Lachira-Yparraguirre, Gustavo Sandival-Ampuero, Bryan Valcarcel, Cesar Samanez, Juan Haro-Varas, Shirley Quintana-Truyenque, Luis Malpica, Henry Gomez-Leonidas, Tatiana Vidaurre-Rojas. Early death in acute lymphoblastic leukemia during COVID-19 pandemic: A single institution cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 721.

Context: AML represents a broad and complex group of diseases characterized by involvement of the myeloid lineage on hematopoiesis. Objective: To explore the frequency and impact of mutated genes on clinical outcomes in a cohort of Peruvian patients. Design: In this report, we showed 32 AML cases treated at 3 medical centers in Lima (Clínica Delgado, Anglo Americana, and INEN) from January 2016 until May 2021. Setting: Information at diagnosis was clinical, karyotype, molecular PCR panel, myeloid NGS panel, therapy regimen, response to treatment, DFS, and OS Patients or Other Participants: A total of 32 cases were studied. F/M=0.6 (12/20), median age 55 years (32–87). Interventions: Among the 24 available karyotypes, the abnormal vs diploid karyotype ratio was 0.26 (5/19). Number of pathogenic mutated genes was 2.5 (range 0–10). Most common (≥15%) pathogenic mutated genes were BCOR (n=7, 21.9%), CUX1 (n=5, 15.6%), DNMT3 (n=8, 25.0%), and NRAS (n=5, 15.6%). Main Outcome Measures: Response rates were as follows: 71.9% complete (23/32), 18.8% non-response (6/32), and 9.3% non-evaluable (3/32). The estimated median OS was 26.01 months for the entire cohort, the 1- and 2-year OS were 72.1% and 51.1%, respectively. The estimated median DFS was 15.79 months for the entire cohort, the 1- and 2-year DFS were 77.6% and 31.5%, respectively. Mutated TP53 was detected in 3 cases, with no therapeutic response in 2 of them. Results: No significant difference in OS was observed in cases with ≥3 pathogenic mutated genes (log-rank 0.10, p=0.920) or ≥3 pathogenic mutated genes + TP53 cases (log-rank 0.11 p=0.739). No significant difference in DFS was observed in cases ≥3 pathogenic mutated genes + TP53 cases (log-rank 0.775 p=0.379). Conclusions: Of 53 genes, four genes were detected in ≥ 15% of cases: BCOR, CUX1, DNMT3, and NRAS. TP53 was related to a high degree of therapeutic failure response and short OS. Number of pathogenic mutated genes ≥3 or ≥4 by NGS showed no significant tendency toward shorter OS. A composite analysis of patients with 4 mutated genes with or without mutated-TP53 showed no significantly shorter OS and DFS. Further studies with mature data and more cases are warranted to propose risk stratification by NGS. AML represents a broad and complex group of diseases characterized by involvement of the myeloid lineage on hematopoiesis. To explore the frequency and impact of mutated genes on clinical outcomes in a cohort of Peruvian patients. In this report, we showed 32 AML cases treated at 3 medical centers in Lima (Clínica Delgado, Anglo Americana, and INEN) from January 2016 until May 2021. Information at diagnosis was clinical, karyotype, molecular PCR panel, myeloid NGS panel, therapy regimen, response to treatment, DFS, and OS A total of 32 cases were studied. F/M=0.6 (12/20), median age 55 years (32–87). Among the 24 available karyotypes, the abnormal vs diploid karyotype ratio was 0.26 (5/19). Number of pathogenic mutated genes was 2.5 (range 0–10). Most common (≥15%) pathogenic mutated genes were BCOR (n=7, 21.9%), CUX1 (n=5, 15.6%), DNMT3 (n=8, 25.0%), and NRAS (n=5, 15.6%). Response rates were as follows: 71.9% complete (23/32), 18.8% non-response (6/32), and 9.3% non-evaluable (3/32). The estimated median OS was 26.01 months for the entire cohort, the 1- and 2-year OS were 72.1% and 51.1%, respectively. The estimated median DFS was 15.79 months for the entire cohort, the 1- and 2-year DFS were 77.6% and 31.5%, respectively. Mutated TP53 was detected in 3 cases, with no therapeutic response in 2 of them. No significant difference in OS was observed in cases with ≥3 pathogenic mutated genes (log-rank 0.10, p=0.920) or ≥3 pathogenic mutated genes + TP53 cases (log-rank 0.11 p=0.739). No significant difference in DFS was observed in cases ≥3 pathogenic mutated genes + TP53 cases (log-rank 0.775 p=0.379). Of 53 genes, four genes were detected in ≥ 15% of cases: BCOR, CUX1, DNMT3, and NRAS. TP53 was related to a high degree of therapeutic failure response and short OS. Number of pathogenic mutated genes ≥3 or ≥4 by NGS showed no significant tendency toward shorter OS. A composite analysis of patients with 4 mutated genes with or without mutated-TP53 showed no significantly shorter OS and DFS. Further studies with mature data and more cases are warranted to propose risk stratification by NGS.

BackgroundPrevious studies have found that healthcare-associated bacteremia (HAB) by Aeromonas species is associated with mortality. However, there is limited data on this outcome in patients with hematologic malignancies. This study aimed to identify the clinical features of patients with malignant hematologic diseases diagnosed with Aeromonas sobria bacteremia and to evaluate whether the type of bacteremia, community-acquired bacteremia (CAB) or HAB, is associated with mortality.MethodsWe retrospectively reviewed the clinical records of pediatric and adult patients between January 2000 and December 2017. Clinical characteristics were compared between CAB and HAB. Additionally, we stratified based on age group. Survival outcomes were assessed with Kaplan-Meier curves and a multivariate Cox regression analysis.ResultsA total of 37 patients (median age 24 years) were identified; 23 (62%) had HAB and 14 (38%) had CAB. Overall, the most common presenting symptom was abdominal pain (41%). Acute lymphoblastic leukemia (n = 12/15, 80%) and acute myeloid leukemia (n = 8/22, 36%) were the primary hematologic malignancies in pediatric and adult patients, respectively. CAB patients had worse overall survival (OS) rates at 30 days in all (43% versus HAB 91%, p = 0.006) and adult patients (30% versus HAB 92%, p = 0.002). Cox regression analysis found that quick Sequential Organ Failure Assessment and CAB were statistically significant factors associated with mortality. Low antimicrobial-resistant was noted, except for ciprofloxacin (n = 5/37, 14%).ConclusionOur study found a worse OS among patients with hematologic malignancies and CAB by Aeromonas sobria. Our results suggest that patients with CAB present with a worse disease severity. These findings should aid clinicians to determine the survival prognosis in this population.

Objetivo. Evaluar las características clinicopatológicas del linfoma de células B grandes difuso, sin otra especificación (LCBGD, NOS), en una cohorte de pacientes peruanos. Métodos. Se estudiaron 72 casos con diagnóstico de LCBGD, NOS, en el INEN. Se evaluaron características clinicopatológicas, sobrevida global (SG) y otros parámetros clínicos de acuerdo con la célula de origen, la infección por virus Epstein-Barr (EBER) y la expresión inmunohistoquímica (IHQ) de MYC y BCL2. Resultados. Hubo 54 % de mujeres y 46 % de hombres, con edad promedio de 65 años. El 76 % fueron ganglionares, la mayoría de ubicación cervical y el 24 % extraganglionares, siendo el estómago el más afectado. Los estadios más frecuentes fueron II (35 %) y III (29 %), la mayoría con IPI medio-alto y alto. Histológicamente, casi todos los casos tuvieron morfología centroblástica e inmunoblástica. Hubo proporción similar de casos con subtipos centro germinal (GCB) y no centro germinal (no-GCB). Los GCB y EBER+ tuvieron mejor SG que los no-GCB y los EBER-, respectivamente. Asimismo, los casos con IHQ negativa para MYC y BCL2 tuvieron mejor SG y mayor porcentaje en estadios tempranos. Estos hallazgos no tuvieron significación estadística. Conclusión. Nuestros casos presentan características similares a lo descrito en la literatura, aunque con mayor porcentaje asociados al EBV y de casos no-GCB. El poco número de casos evaluados con IHQ para determinar subtipos y biomarcadores puede haber limitado el análisis estadístico en esta cohorte de casos.