Measurable residual disease conversion rate with consolidation chemotherapy in acute myeloid leukemia.

The rate of MRD clearance in AML with standard consolidation chemotherapy is not well defined. A multi-institution retrospective analysis was performed on 107 consecutively treated AML patients in morphologic complete remission with detectable MRD post-induction therapy who received standard chemotherapy consolidation. In response to standard intermediate/high-dose cytarabine consolidation therapy, 26 of 60 patients (43.3%) with MRD threshold of detection of at least 0.1% converted to MRD-negative status (undetectable with assay used), and 6 of 47 patients (12.8%) with MRD threshold of detection > 0.1% converted to MRD-negative status. Multivariable logistic regression for patients with MRD threshold of detection of at least 0.1% showed that, when controlling for age, ELN risk category, dose of cytarabine, and use of a combination agent, treatment with 1 cycle of consolidation cytarabine versus ≥2 cycles decreased the odds of conversion of AML to MRD-negative (OR = 0.24, 95% CI 0.07-0.85, p = 0.03).

Tobacco and Cannabis Use During and After Pregnancy in California.

OBJECTIVES: As the social and legal acceptance of cannabis use grows, health professionals must understand and mitigate the impact of cannabis use in the perinatal period. Here we compare the prevalence of tobacco and cannabis use during and after pregnancy in California, a state that recently legalized cannabis use. METHODS: Measures of tobacco and cannabis use during and after pregnancy were obtained from California's Maternal and Infant Health Assessment, an annual population-based survey of California resident women with a live birth. To allow analysis of county-level variation, we pooled data from the 35 counties with the largest numbers of births from 2017 to 2019. RESULTS: Cannabis use was more than twice as common as cigarette smoking among pregnant women (4.9% vs. 2.1%) in California. This difference was even more pronounced in some counties; for example, in Los Angeles, cannabis use was four times more prevalent than cigarette use. Either during or soon after birth, 7.3% of women in California reported cannabis use. Of those who smoked tobacco cigarettes prior to pregnancy, 73% quit before their third trimester of pregnancy, though 33.0% of these women reported a post-partum relapse in cigarette use. CONCLUSIONS: States that have legalized cannabis must attend to the increasing prevalence of perinatal cannabis use, as well as concurrent use with tobacco and other substances. Efforts to support cannabis cessation should draw from successful public health approaches in tobacco control.

Clinical Impact of Measurable Residual Disease in Acute Myeloid Leukemia.

Measurable residual disease (MRD) has emerged as a primary marker of risk severity and prognosis in acute myeloid leukemia (AML). There is, however, ongoing debate about MRD-based surveillance and treatment. A literature review was performed using the PubMed database with the keywords MRD or residual disease in recently published journals. Identified articles describe the prognostic value of pre-transplant MRD and suggest optimal timing and techniques to quantify MRD. Several studies address the implications of MRD on treatment selection and hematopoietic stem cell transplant, including patient candidacy, conditioning regimen, and transplant type. More prospective, randomized studies are needed to guide the application of MRD in the treatment of AML, particularly in transplant.

Clinical experience with frontline Hyper-CVAD-based regimens, including Hyper-CVAD plus ponatinib, in patients with acute lymphoblastic leukemia treated at a comprehensive cancer center.

BACKGROUND: Hyper-CVAD is an established regimen for adult ALL that was developed at the MD Anderson Cancer Center (MDACC). However, results can vary across different institutions given the heterogeneity of patient populations and institutional practices. Moreover, while a MDACC study demonstrated that the combination of ponatinib plus hyper-CVAD produced remarkable activity in untreated Ph+ ALL, it remains to be externally validated. We sought to validate those findings in previously untreated adult patients with Ph+ ALL. METHODS: This was a retrospective study analyzing the outcomes of previously untreated adult ALL patients treated with hyper-CVAD, with a focus on Ph+ ALL patients treated with ponatinib plus hyper-CVAD. RESULTS: 82 patients were included. The median age was 51 years. The median follow-up was 2.62 years. The 5-year overall survival (OS) and event-free survival (EFS) were 39.5 % and 28.2 %, respectively. For Ph+ ALL patients (n = 13) receiving ponatinib plus hyper-CVAD, 3-year OS and EFS were both 92.3 %. Univariate analysis showed a high WBC and poor-risk cytogenetics to be associated with inferior outcomes, while CD20 + predicted favorable outcomes in B-ALL patients. On multivariate analysis, CD20 + retained significance for Philadelphia-negative (Ph-) ALL. For Ph+ ALL, ponatinib was associated with better OS and EFS on univariate and multivariate analysis. CONCLUSION: Our data supports the use of ponatinib plus hyper-CVAD as a standard of care regimen for Ph+ ALL. Our outcomes for Ph-ALL and T-cell ALL (T-ALL) show that advances are still needed in the frontline setting, and clinical trial enrollment is recommended.

Special Considerations for Women of Reproductive Age on Anticoagulation.

Anticoagulation poses unique challenges for women of reproductive age. Clinicians prescribing anticoagulants must counsel patients on issues ranging from menstruation and the possibility of developing a hemorrhagic ovarian cyst to teratogenic risks and safety with breastfeeding. Abnormal uterine bleeding affects up to 70% of young women who are treated with anticoagulation. As such, thoughtful clinical guidance is required to avoid having young women who are troubled by their menses, dose reduce, or prematurely discontinue their anticoagulation, leaving them at increased risk of recurrent thrombosis. Informed by a review of the medical literature, we present current recommendations for assisting patients requiring anticoagulation with menstrual management, prevention of hemorrhagic ovarian cysts, and avoiding unintended pregnancy. The subdermal implant may be considered a first-line option for those requiring anticoagulation, given its superior contraceptive effectiveness and ability to reliably reduce risk of hemorrhagic ovarian cysts. All progestin-only formulations-such as the subdermal implant, intrauterine device, injection, or pills-are generally preferred over combined hormonal pills, patch, or ring. Tranexamic acid, and in rare cases endometrial ablation, may also be useful in managing menorrhagia and dysmenorrhea. During pregnancy, enoxaparin remains the preferred anticoagulant and warfarin is contraindicated. Breastfeeding women may use warfarin, but direct oral anticoagulants are not recommended given their limited safety data. This practical guide for clinicians is designed to inform discussions of risks and benefits of anticoagulation therapy for women of reproductive age.

Hospital-acquired influenza in the United States, FluSurv-NET, 2011-2012 through 2018-2019.

OBJECTIVE: To estimate population-based rates and to describe clinical characteristics of hospital-acquired (HA) influenza. DESIGN: Cross-sectional study. SETTING: US Influenza Hospitalization Surveillance Network (FluSurv-NET) during 2011-2012 through 2018-2019 seasons. METHODS: Patients were identified through provider-initiated or facility-based testing. HA influenza was defined as a positive influenza test date and respiratory symptom onset >3 days after admission. Patients with positive test date >3 days after admission but missing respiratory symptom onset date were classified as possible HA influenza. RESULTS: Among 94,158 influenza-associated hospitalizations, 353 (0.4%) had HA influenza. The overall adjusted rate of HA influenza was 0.4 per 100,000 persons. Among HA influenza cases, 50.7% were 65 years of age or older, and 52.0% of children and 95.7% of adults had underlying conditions; 44.9% overall had received influenza vaccine prior to hospitalization. Overall, 34.5% of HA cases received ICU care during hospitalization, 19.8% required mechanical ventilation, and 6.7% died. After including possible HA cases, prevalence among all influenza-associated hospitalizations increased to 1.3% and the adjusted rate increased to 1.5 per 100,000 persons. CONCLUSIONS: Over 8 seasons, rates of HA influenza were low but were likely underestimated because testing was not systematic. A high proportion of patients with HA influenza were unvaccinated and had severe outcomes. Annual influenza vaccination and implementation of robust hospital infection control measures may help to prevent HA influenza and its impacts on patient outcomes and the healthcare system.

An evaluation of venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine as therapy for acute myeloid leukemia.

INTRODUCTION: Older patients with acute myeloid leukemia (AML) ineligible for conventional chemotherapy have historically received low-intensity treatments, if any, and have had dismal outcomes. Recent phase III data have demonstrated significant efficacy of venetoclax-based combinations and have begun to address the unmet need in this patient population. As venetoclax-based combinations become increasingly used in the clinical setting, it is important to understand their development, current use, and future directions. AREAS COVERED: This review covers the clinical development of venetoclax-based combinations for the management of AML, and their current and future use. A search of PubMed and ashpublications.org using the keywords 'venetoclax', 'AML', and 'hypomethylating agents' as the search terms was undertaken to identify the most pertinent publications. EXPERT OPINION: While venetoclax-based combinations have shown excellent responses and improved survival in patients with untreated AML, further studies are required to understand how to expand on their frontline use, manage patients who fail venetoclax-based combinations, and their true efficacy in the relapsed/refractory setting. Management of AML with venetoclax-based combinations is expected to evolve over the next few years.

Venetoclax-based combinations for the treatment of newly diagnosed acute myeloid leukemia.

Elderly and/or unfit patients with acute myeloid leukemia have historically been challenging to manage as they were ineligible for what was considered standard of care treatment with induction chemotherapy. The emergence of venetoclax with hypomethylating agents or low-dose cytarabine has substantially improved outcomes in the frontline setting with manageable toxicity. However, this regimen can be challenging to deliver given its differences from standard intensive chemotherapy. In this review, we summarize the landmark trials that established venetoclax-based combinations as a new standard of care for patients with acute myeloid leukemia not suitable for intense chemotherapy, provide practical clinical pearls for managing patients on these therapies, and offer a brief overview of modifications to these regimens under development to improve their efficacy and/or applicability.

Lay abstract Older and/or unfit patients with acute myeloid leukemia (AML) have historically had bad outcomes with standard therapies and an overall dismal prognosis. The advent of venetoclax (VEN)-based regimens has led to significantly improved responses for patients with untreated AML with an acceptable safety profile. However, delivering these therapies are associated with their own unique challenges. In this review, we summarize the key trials that demonstrated the success of VEN-based combinations in this particular AML population, provide practical considerations for managing patients on these therapies, and discuss ongoing studies to further improve VEN-based therapy.

Cytomegalovirus shedding from breastmilk and mucosal sites in healthy postpartum women: A pilot study.

Mother-to-child cytomegalovirus (CMV) breastmilk transmission can occur in the postnatal period. In a pilot study, we measured daily CMV detection by polymerase chain reaction in breastmilk, vaginal, and saliva samples from nine healthy CMV-seropositive postpartum women for 28 days. CMV was found in seven of nine women and 171 of 253 breastmilk samples (67.6%). In four women, all breastmilk samples were positive. CMV was less frequently detected in the vagina (39 of 258, 15.1%) and saliva (53 of 258, 20.5%). Daily breastmilk, oral, and genital collection is feasible and demonstrates high variability between women. Further study of the dynamics of CMV in distinct anatomic compartments is warranted.

BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial.

BACKGROUND. Bacillus Calmette-Guérin (BCG) vaccine is administered at birth to protect infants against tuberculosis throughout Africa, where most perinatal HIV-1 transmission occurs. We examined whether BCG vaccination alters the levels of activated HIV target T cells in HIV-exposed South African infants. METHODS. HIV-exposed infants were randomized to receive routine (at birth) or delayed (at 8 weeks) BCG vaccination. Activated and CCR5-expressing peripheral blood CD4+ T cell, monocyte, and NK cell frequencies were evaluated by flow cytometry and immune gene expression via PCR using Biomark (Fluidigm). RESULTS. Of 149 infants randomized, 92% (n = 137) were retained at 6 weeks: 71 in the routine BCG arm and 66 in the delayed arm. Routine BCG vaccination led to a 3-fold increase in systemic activation of HIV target CD4+CCR5+ T cells (HLA-DR+CD38+) at 6 weeks (0.25% at birth versus 0.08% in delayed vaccination groups; P = 0.029), which persisted until 8 weeks of age when the delayed arm was vaccinated. Vaccination of the infants in the delayed arm at 8 weeks resulted in a similar increase in activated CD4+CCR5+ T cells. The increase in activated T cells was associated with increased levels of MHC class II transactivator (CIITA), IL12RB1, and IFN-α1 transcripts within peripheral blood mononuclear cells but minimal changes in innate cells. CONCLUSION. BCG vaccination induces immune changes in HIV-exposed infants, including an increase in the proportion of activated CCR5+CD4+ HIV target cells. These findings provide insight into optimal BCG vaccine timing to minimize the risks of HIV transmissions to exposed infants while preserving potential benefits conferred by BCG vaccination. TRIAL REGISTRATION. ClinicalTrials.gov NCT02062580. FUNDING. This trial was sponsored by the Elizabeth Glaser Pediatric AIDS Foundation (MV-00-9-900-01871-0-00) and the Thrasher Foundation (NR-0095); for details, see Acknowledgments.

Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice.

Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar.