Browsing by Author "Malpica, L"

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Distinctive genomic features of human T-lymphotropic virus type 1-related adult T-cell leukemia-lymphoma in Western populations
(Ferrata Storti Foundation, 2024) Myers, CS; Williams, E; Cornejo, CB; Pongas, G; Toomey, NL; Sanches, JA; Battistella, M; Mo, S; Pulitzer, M; Moskaluk, CA; Bhagat, G; Ofori, K; Davick, JJ; Servitje, O; Miyashiro, D; Climent, F; Ringbloom, K; Duenas, D; Law, C; Zambrano, SC; Malpica, L; Beltran, BE; Castro, D; Barreto, L; Brites, C; Chapman, JR; Choi, J; Gru, AA; Ramos, JC
Adult T-cell leukemia-lymphoma (ATLL) is an aggressive malignancy driven by human T-cell leukemia virus type 1 (HTLV-1). Although patients from the Western hemisphere (Afro-Caribbean and South American) face worse prognoses, our understanding of ATLL molecular drivers derives mostly from Japanese studies. We performed multi-omic analyses to elucidate the genomic landscape of ATLL in Western cohorts. Recurrent deletions and/or damaging mutations involving FOXO3, ANKRD11, DGKZ, and PTPN6 implicate these genes as potential tumor suppressors. RNA-sequencing, published functional data and in vitro assays support the roles of ANKRD11 and FOXO3 as regulators of T-cell proliferation and apoptosis in ATLL, respectively. Survival data suggest that ANKRD11 mutation may confer a worse prognosis. Japanese and Western cohorts, in addition to acute and lymphomatous subtypes, demonstrated distinct molecular patterns. GATA3 deletion was associated with chronic cases with unfavorable outcomes. IRF4 and CARD11 mutations frequently emerged in relapses after interferon therapy. Our findings reveal novel putative ATLL driver genes and clinically relevant differences between Japanese and Western ATLL patients.
Epidemiological Features and Outcomes of HTLV-1 Carriers Diagnosed with Cancer: A Retrospective Cohort Study in an Endemic Country
(Lippincott Williams and Wilkins, 2023) Valcarcel, B; Enriquez-Vera, D; De-La-Cruz-Ku, G; Chambergo-Michilot, D; Calderon-Huaycochea, H; Malpica, L
PURPOSEHuman 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.METHODSIn 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.RESULTSWe 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).CONCLUSIONHTLV-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.
Epidemiology and Risk Factors for the Development of Infectious Complications in Newly Diagnosed Multiple Myeloma: A Multicenter Prospective Cohort Study in Latin America
(Lippincott Williams and Wilkins, 2022) Bove, V; Riva, E; Vásquez-Chavez, J; Peña, C; Seehaus, C; Samanez, C; Bustos, J; Hernández, M; Fernández, J; Ríos, O; Rodríguez, Y; Figueredo, I; Fantl, D; Malpica, L
PURPOSE: Infections are a significant cause of morbidity and mortality in patients with multiple myeloma (MM). In Latin America, data on infectious complications in this patient population are lacking. METHODS: We conducted a prospective cohort study of patients with newly diagnosed MM (NDMM) in seven Latin American countries between June 2019 and May 2020. Patients with active disease, on active therapy, and with a follow-up of 6 months from the time of diagnosis were included. Our primary end point was the number of infectious events that required hospitalization for ≥ 24 hours. RESULTS: Of 248 patients with NDMM, 89 (35.9%) had infectious complications (113 infectious events), the majority (67.3%) within the first 3 months from diagnosis. The most common sites of infection were respiratory (38%) and urinary tract (31%). The microbial agent was identified in 57.5% of patients with gram-negative bacteria (73.5%) as the most common pathogen. Viral infections were infrequent, and no patients with fungal infection were reported. In the multivariable analysis, diabetes mellitus (odds ratio [OR], 2.71 95% CI, 1.23 to 6.00 P = .014), creatinine ≥ 2 mg/dL (OR, 4.87 95% CI, 2.29 to 10.35 P < .001), no use of trimethoprim-sulfamethoxazole prophylaxis (OR, 6.66 95% CI, 3.43 to 12.92 P < .001), and treatment with immunomodulatory drugs (OR, 3.02 95% CI, 1.24 to 6.29 P = .003) were independent factors associated with bacterial infections. At 6 months, 21 patients (8.5%) had died, 47.6% related to infectious complications. CONCLUSION: Bacterial infections are a substantial cause of hospital admissions and early death in patients with NDMM. Antibiotic prophylaxis should be considered to reduce infectious complications in patients with MM.
Outcomes of HTLV-1 Carriers with Diffuse Large B-Cell Lymphoma: A Single-Center Retrospective Matched Cohort Study
(Elsevier Inc., 2022) Valcarcel, B; Ampuero, GS; de la Cruz-Ku, G; Enriquez, DJ; Malpica, L
Background: The human T-cell lymphotropic virus type 1 (HTLV-1) is associated with aggressive diseases, such as adult T-cell leukemia/lymphoma (ATLL). However, less is known on the impact of HTLV-1 infection in non-ATLL hematologic malignancies. We aimed to investigate if HTLV-1 carriers with diffuse large B-cell lymphoma (DLBCL) have worse survival outcomes than non-HTLV-1 carriers. Materials and Methods: We performed a single-center retrospective cohort study by matching HTLV-1 carriers to non-carriers based on age, sex, Ann Arbor stage, and year of diagnosis. Our outcomes of interest were overall survival (OS) and progression-free survival (PFS). The Kaplan-Meier method was used to estimate OS and PFS between carriers and non-carriers. We fitted multivariate Cox regression models to assess the mortality and recurrence/disease progression risk of HTLV-1 infection. Results: A total of 188 patients, 66 with HTLV-1 infection and 122 without HTLV-1, were included in the study. HTLV-1 carriers had higher extranodal involvement than non-carriers (47% vs. 27%, P = .010). With a median follow-up of 78 months (95% CI: 41-90 months), HTLV-1 carriers had a similar 5 year OS (41% vs. 42%, P = .940) and PFS (34% vs. 32%, P = .691) compared to non-carriers. In the multivariate Cox analysis, HTLV-1 infection was not associated with worse OS (aHR: 0.98, 95% CI: 0.64-1.50) or PFS (aHR: 0.90, 95% CI: 0.60-1.34). Conclusion: HTLV-1 carriers with DLBCL did not have worse survival outcomes compared to non-carriers. Our results suggest that clinicians should follow standard guidelines for DLBCL management on HTLV-1 seropositive patients.
Real-World Outcomes of Adolescents and Young Adults with Diffuse Large B-Cell Lymphoma: A Multicenter Retrospective Cohort Study
(Mary Ann Liebert Inc., 2024) Castro-Uriol, D; Rios, L; Enriquez-Vera, D; Montoya, J; Runciman, T; Alarcón, S; Zapata, A; Hernández, E; León, E; Malpica, L; Valcarcel, B
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.