RESUMEN
Acute myeloid leukemia (AML) is an aggressive, clonally heterogeneous, myeloid malignancy, with a 5-year overall survival of approximately 27%. It constitutes the most common acute leukemia in adults, with an incidence of 3-5 cases per 100,000 in the United States. Despite great advances in understanding the molecular mechanisms underpinning leukemogenesis, the past several decades had seen little change to the backbone of therapy, comprised of an anthracycline-based induction regimen for those who are fit enough to receive it, followed by risk-stratified post-remission therapy with consolidation cytarabine or allogeneic stem cell transplantation (allo-SCT). Allo-SCT is the most fundamental form of immunotherapy in which donor cytotoxic T and NK cells recognize and eradicate residual AML in the graft-versus-leukemia (GvL) effect. Building on that, several alternative or synergistic approaches to exploit both self and foreign immunity against AML have been developed. Checkpoint inhibitors, for example, CTLA-4 inhibitors, PD-1 inhibitors, and PD-L1 inhibitors block proteins found on T cells or cancer cells that stop the immune system from attacking the cancer cells. They have been used with limited success in both the AML relapsed/refractory (R/R) and post SCT settings. AML tumor mutational burden is low compared to solid tumors and thus, it is less likely to generate neoantigens and respond to antibody-mediated checkpoint blockade that has shown unprecedented results in solid tumors. Therefore, alternative therapeutic strategies that work independently of the T cell receptor (TCR) specificity have been developed. They include bispecific antibodies, which recruit T cells through CD3 engagement, and in AML have shown an overall response rate ranging between 14 and 30% in early phase trials. Chimeric Antigen Receptor (CAR) T cell therapy is a type of treatment in which T cells are genetically engineered to produce a recombinant receptor that redirects the specificity and function of T lymphocytes. However, lack of cell surface targets exclusively expressed on AML cells including Leukemic Stem Cells (LSCs) combined with clonal heterogeneity represents the biggest challenge in developing CAR therapy for AML. Antibody-Drug Conjugates (ADC) constitute the only FDA-approved immunotherapy to treat AML with Gemtuzumab Ozogamicin, a CD33-specific ADC used in CEBPα-mutated AML. The identification of additional cell surface targets is critical for the development of other ADC's potentially useful in the induction and maintenance regimens, given the ease at which these reagents can be generated and managed. Here, we will review those immune-based therapeutic interventions and highlight active areas of research investigations toward fulfillment of the great promise of immunotherapy to AML.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Inmunoconjugados , Leucemia Mieloide Aguda , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Inmunoconjugados/uso terapéutico , Inmunoterapia/métodos , Inmunoterapia Adoptiva , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Linfocitos TRESUMEN
BACKGROUND: Cancer is the leading cause of death for Hispanics in the USA. Screening and prevention reduce cancer morbidity and mortality. METHODS: This study administered a cross-sectional web-based survey to self-identified Hispanic residents in the state of Indiana to assess their cancer-related knowledge, beliefs, and behaviors, as well as to identify what factors might be associated with cancer screening and prevention. Chi-square and Fisher's exact test were used to compare associations and logistic regression used to develop both univariate and multivariate regression models. RESULTS: A total of 1520 surveys were completed, median age of respondents was 53, 52% identified as men, 50.9% completed the survey in Spanish, and 60.4% identified the USA as their country of birth. Most were not able to accurately identify ages to begin screening for breast, colorectal, or lung cancer, and there were significant differences in cancer knowledge by education level. US-born individuals with higher income and education more often believed they were likely to develop cancer and worry about getting cancer. Sixty eight percent of respondents were up-to-date with colorectal, 44% with breast, and 61% with cervical cancer screening. Multivariate models showed that higher education, lack of fatalism, older age, lower household income, and unmarried status were associated with cervical cancer screening adherence. CONCLUSIONS: Among a Hispanic population in the state of Indiana, factors associated with cervical cancer screening adherence were similar to the general population, with the exceptions of income and marital status. Younger Hispanic individuals were more likely to be adherent with breast and colorectal cancer screening, and given the higher incidence of cancer among older individuals, these results should guide future research and targeted outreach.
Asunto(s)
Neoplasias Colorrectales , Neoplasias del Cuello Uterino , Masculino , Femenino , Humanos , Indiana/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Detección Precoz del Cáncer , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Hispánicos o Latinos , Tamizaje MasivoRESUMEN
Improving understanding of behaviors that increase or reduce cancer risk for different Hispanic groups is a public health priority; such knowledge is sparse in new gateway immigration locations such as Indiana. The aims of this study were to: 1) describe cancer beliefs and cancer preventive/risk reduction behaviors (physical activity, tobacco, and alcohol use) among Hispanic adults; 2) examine differences in cancer beliefs and preventive behaviors by country/territory of birth, socioeconomic status, and area of residence (urban vs. rural); and 3) determine predictors of engagement in cancer prevention and risk reduction behaviors in this population. A cross-sectional online survey targeted adult Indiana residents who identified as Latino, Hispanic, or Spanish recruited using Facebook-targeted advertising. Complete survey data from 1520 respondents were analyzed using descriptive, unadjusted, and adjusted models. The majority of respondents believed they were unlikely to get cancer but held many other fatalistic beliefs about cancer. Only 35.6% of respondents had received the HPV vaccine, 37.6% reported they were currently smoking cigarettes, and 64% reported occasional or frequent drinking of alcohol. Respondents spent an average of 3.55 days per week engaged in moderate exercise. Differences were observed by country/territory of birth, income, and education but not by rural residence status. Predictors of cancer risk/risk reduction behaviors were identified. The Hispanic population in Indiana is diverse and effective interventions for cancer prevention should be culturally targeted based on country/territory of birth and individually tailored based on cancer-related beliefs.
RESUMEN
CNS involvement by CLL is a rare occurrence, usually happening in the context of a transformation to a more aggressive lymphoma in what is known as Richter's transformation. We report a patient with active CLL who developed confusion and was found to have West Nile encephalitis that initially mimicked CNS involvement by CLL. The patient recovered with supportive treatment and later restarted ibrutinib therapy. This case illustrates the importance of maintaining a broad differential among cancer patients with new onset confusion as well as that of questioning malignant infiltration of CNS when there is concomitant active CNS infection.