Racial and ethnic disparities in Acute Myeloid Leukemia: 15-year experience at a safety net hospital system.

Despite recent therapeutic advances, ethnic minorities in the U.S. continue to have disproportionately poor outcomes in many hematologic malignancies including AML. We identified 162 adult AML patients treated at a non-transplant safety net hospital from 2007 to 2022 and evaluated differences in disease characteristics, treatment and clinical outcomes based on race and ethnicity. Our cohort consisted of 82 (50.6%) Hispanic, 36 (22.2%) non-Hispanic black and 44 (27.2%) non-Hispanic white and Asian patients. Median age at diagnosis was 42.5, 49.0 and 52.5 years respectively (p=0.025). Hispanics had higher rates of intermediate and high-risk disease (p=0.699) and received high intensity induction and consolidation chemotherapy at lower rates (p=0.962), although differences did not reach statistical significance. Despite this, similar remission rates were achieved. Hispanics with high-risk disease had longer overall survival (OS) than the combined non-Hispanic cohort (mOS 14 m vs 7 m, p=0.030). Multivariate regression analysis showed that OS was negatively associated with age (HR 1.023, p=0.006), intermediate (HR 3.431, p=0.0003) and high-risk disease (HR 4.689, p<0.0001) and positively associated with Hispanic ethnicity (HR 0.614, p=0.026). This report suggests that contrary to other studies, Hispanics, particularly those with high-risk AML, may have improved OS compared to other ethnic groups. These results are unique to our safety net hospital setting where common barriers to medical care and healthcare disparities are largely mitigated.

Possible role of IL-23 inhibitor in autoimmune hemolytic anemia.

Rituximab and prednisone are commonly used treatments for autoimmune hemolytic anemia (AIHA), where the body's immune system attacks and destroys its red blood cells. However, some AIHA patients may become refractory to rituximab treatment, and this can result in continued hemolysis and persistent anemia, making it challenging for affected individuals to manage their symptoms. The underlying causes of rituximab refractoriness in AIHA patients can be complex and vary from patient to patient. Herein, we present a case of newly diagnosed warm and cold AIHA that remained in remission with an interleukin-23 inhibitor.

Novel Investigational Agents and Pathways That May Influence the Future Management of Acute Myeloid Leukemia.

Acute Myeloid leukemia (AML) is a clinically heterogeneous disease with a 5-year overall survival of 32% between 2012 to 2018. The above number severely dwindles with age and adverse risk of disease, presenting opportunities for new drug development and is an area of dire unmet need. Basic science and clinical investigators across the world have been working on many new and old molecule formulations and combination strategies to improve outcomes in this disease. In this review, we discuss select promising novel agents in various stages of clinical development for patients with AML.

Paradigm Shift in the Management of Acute Myeloid Leukemia-Approved Options in 2023.

The word Leukemia was coined nearly 200 years ago by Rudolf Virchow. Once a death sentence, Acute Myeloid Leukemia (AML) is now a treatable condition. The introduction of "7 + 3" chemotherapy, originally reported from the Roswell Park Memorial institute in Buffalo, New York, in 1973, changed the treatment paradigm for AML. About twenty-seven years later, FDA approved the first targeted agent, gemtuzumab, to be added to this backbone. During the last seven years, we have had ten new drugs approved for the management of patients with AML. Work by many dedicated scientists led to AML achieving the elite status of being the first cancer to have the whole genome sequenced using next-generation sequencing. In the year 2022, we witnessed the introduction of new classification systems for AML by the international consensus classification and the world health organization, both emphasizing molecular classification of the disease. In addition, the introduction of agents such as venetoclax and targeted therapies have changed the treatment paradigm in older patients ineligible for intensive therapy. In this review, we cover the rationale and evidence behind these regimens and provide insights into the newer agents.

SARS-CoV-2 Vaccination IgG Antibody Responses in Patients with Hematologic Malignancies in a Myeloid Enriched Cohort: A Single Center Observation.

OBJECTIVE: Patients diagnosed with hematologic malignancies are at increased risk for severe SARS-CoV-2 infection. We evaluated the serological IgG response following two doses of the SARS-CoV-2 vaccine in patients with hematologic malignancies. METHODS: Patients treated at UT Southwestern Medical Center with a diagnosis of a myeloid or lymphoid neoplasm were included. SARS-CoV-2 vaccination response was defined as a positive quantifiable spike IgG antibody titer. RESULTS: Sixty patients were included in the study and 60% were diagnosed with a myeloid neoplasm. The majority (85%) of the patients with a myeloid malignancy and 50% of the patients with a lymphoid malignancy mounted a serological response after receiving two doses of the vaccine. CONCLUSION: Vaccination should be offered irrespective of ongoing treatment or active disease. Findings require validation in a larger cohort of patients.

Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for high-risk myeloid malignancies. Post-transplant cyclophosphamide (PT-Cy) has proven to be effective for graft versus host disease (GVHD) prophylaxis. Given that graft-versus-tumor (GVT) effect plays a major role in reducing the risk of disease relapse, the application of PT-Cy must balance the risk of relapse. Mixed chimerism (MC) refers to a state of concurrent presence of recipient and donor cells post allo-HSCT which may precede relapse disease. OBJECTIVE: We investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT. STUDY DESIGN: This retrospective single-center study included patients that underwent allo-HSCT between 2015 and 2021. Patient and disease characteristics were collected from the electronic health records. EMC was defined as <95% donor cells at day 90-120 post allo-HSCT. RESULTS: A total of 144 patient that received an allo-HSCT were included in the study. One hundred and eight (75%) patients received PT-Cy as part of the GVHD prophylaxis regimen. The majority underwent allo-HSCT for acute myeloid leukemia (62%) or myelodysplastic syndrome (31%). Sixty-five percent received allo-HSCT from a matched unrelated donor transplant and 65% received a myeloablative conditioning regimen. A lower rate of chronic GVHD (p = 0.03) and a higher rate of EMC (p = 0.04) were observed in patients that received PT-Cy. PT-Cy was not associated with overall survival (OS) and relapse-free survival (RFS). Multivariable analysis identified measurable residual disease status (p = 0.003), hematopoietic cell transplantation-specific comorbidity index (p = 0.012) and chronic GVHD (p = 0.006) as independent prognostic variables for OS. AML-adverse risk (p = 0.004) and EMC (p = 0.018) were independently prognostic for RFS. While EMC overall was not significantly associated with higher risk of relapse, EMC was associated with shorter RFS within adverse-risk AML patients. CONCLUSION: Our study shows that PT-Cy was associated with an increased risk of EMC. The predictive value of EMC for relapse remains unclear and may depend on the underlying disease, which should be validated in a larger cohort.

Clinical and molecular characteristics associated with Vitamin C deficiency in myeloid malignancies; real world data from a prospective cohort.

Vitamin C is an essential vitamin that acts as a co-factor for many enzymes involved in epigenetic regulation in humans. Low vitamin C levels in hematopoietic stem cells (HSC) promote self-renewal and vitamin C supplementation retards leukaemogenesis in vitamin C-deficient mouse models. Studies on vitamin C levels in patients with myeloid malignancies are limited. We thus conducted a retrospective analysis on a prospective cohort of patients with myeloid malignancies on whom plasma vitamin C levels were measured serially at diagnosis and during treatment. Baseline characteristics including hematological indices, cytogenetics, and molecular mutations are described in this cohort. Among 64 patients included in our study, 11 patients (17%) had low vitamin C levels. We noted a younger age at diagnosis for patients with myeloid malignancies who had low plasma vitamin C levels. Patients with low plasma vitamin C levels were more likely to have acute myeloid leukemia compared to other myeloid malignancies. Low vitamin C levels were associated with ASXL1 mutations. Our study calls for further multi-institutional studies to understand the relevance of low plasma vitamin C level in myeloid neoplasms, the role of vitamin C deficiency in leukemogenesis, and the potential benefit of vitamin C supplementation.

Analysis of the impact of COVID-19 pandemic on house-staff in the USA: addressing the ripple effects.

Background: The novel corona virus has changed the way individuals interact with each other and society. In the medical sector, this has affected the residents and fellows who spend the majority of their time on the front lines. Methods: We conducted a cross-sectional survey to assess the impact of the COVID-19 pandemic on the lives and training of house-staff across the USA. Respondents in our survey reported feeling significantly overwhelmed by the ongoing pandemic. Results: The majority of house-staff were significantly concerned about the lack of protective equipment, inability to safeguard themselves from infection and inability to look after their families. Concerns regarding contracting the infection and transmitting it to their loved ones were reported as a cause of mental distress among resident physicians. Increasing patient load, lack of protective equipment, and disruption of educational and academic activities during the COVID-19 pandemic have all reportedly affected the training and overall well-being of resident physicians. Conslusion: Our study adds further support for measures to safeguard house-staff with proper protective equipment and ensure adequate support for both mental and physical well-being during these challenging times.

Use of Peripheral µ-Opioid Receptor Antagonists for Treating Opioid-Induced Constipation among US Medicare Beneficiaries from 2014 to 2018.

Background: Opioid-induced constipation (OIC) remains the most common adverse event associated with opioid use. Treatment with more novel and costly agents (such as peripheral µ-opioid receptor antagonists [PAMORAs]) may be indicated in patients with laxative-refractory OIC. Three PAMORAs are U.S. Food and Drug Administration approved for managing OIC-methylnaltrexone (FDA approved in 2008), naloxegol (in 2014), and naldemedine (in 2017). These drugs are indicated only in limited scenarios. Their contemporary patterns of use and burden of spending remain unknown. Objective: To evaluate the trends in use and expenditures for the three PAMORAs approved for treating OIC. Design: Retrospective cross-sectional study using the 2014-2018 Medicare Part D Prescription Drug Event data and the 2018 Part D Prescriber Public Use File. Setting: Prescribers and beneficiaries using PAMORAs. Measurements: The annual spending, number of beneficiaries, number of claims, and spending per beneficiary and claim for each PAMORA. The distribution by prescriber specialty using PAMORA. Results: From 2014 to 2018, aggregate spending on PAMORAs increased, from $13.6 to $150.9 million, and use increased, from 4221 to 72,592 beneficiaries. After FDA approval in 2014, naloxegol overtook methylnaltrexone in the number of users in 2015 and spending in 2016. In 2018, 6989 unique prescribers used any PAMORA. Among them, the most common specialties/professions were family practice (20.2%), internal medicine (18.0%), and nurse practitioner (15.4%). Conclusions: Our findings-significant and increasing expenditure on PAMORAs, and broad use across specialties-serve as a call for defining and implementing appropriate use of PAMORAs.

BReast CAncer (BRCA) gene mutations as an emerging biomarker for the treatment of gastrointestinal malignancies.

BReast CAncer (BRCA) genes 1 and 2 were discovered in the 1990's by Hall et al. and Wooster et al. respectively. BRCA genes have been shown to be associated with an increased risk of various gastrointestinal (GI) cancers beyond known risk of breast, ovary and prostate cancers. Studies have demonstrated the role of BRCA genes in the DNA repair pathway and modalities to exploit this pathway are being currently explored. Using the concept of synthetic lethality, poly-ADP ribose polymerase inhibitors (PARPi) have significant activity in BRCA deficient cells. Targeted therapy is gaining popularity worldwide and BRCA genes have received much attention since the development and approval of PARPis. Multiple studies have also identified the predictive value of BRCA genes related to platinum and other DNA-damaging cytotoxic agents. BRCA deficient cells are about 5-fold more sensitive to platinum-based agents and almost 1,000-fold more with PARPis. Genomic instability has been established as the hallmark of BRCA deficient tumors and the specific roles of BRCA genes in DNA damage repair is increasingly clear. Herein, we discuss the risks and incidence of individual GI cancers seen with BRCA mutations, highlight tumor biology and provide a comprehensive review of the available preclinical and clinical data and upcoming trials related to this topic. The "POLO" trial in metastatic pancreas cancer establishes a "proof of principle" regarding treatment of BRCA-related cancer and PARPi. In pancreatic cancer routine germline genetic testing is now recommended in most major guidelines. Newer studies are emerging, which will expand the concept of BRCAness and ways to effectively detect this phenotype in GI cancers and impact clinical practice.

Dissemination of Information on Neutropenic Diet by Top US Cancer Centers: In-line with the Evidence?

Aim: The neutropenic diet is commonly prescribed to cancer patients with neutropenia with the goal of reducing infections. However, multiple randomized trials have proved no benefit with neutropenic diets compared to less restricted diets with regards to reducing infectious risk. We aimed to ascertain if top cancer centers recommended for or against the use of neutropenic diets on their official websites. Methods: We reviewed the websites of the top 20 hospitals in the 2017 US News Best Hospitals for Cancer©, and ascertained recommendations for neutropenic diet (for, against, equivocal, or not addressed). Results: Seven websites (35%) made recommendations for, four (20%) against, and nine (45%) did not address the neutropenic diet. Only five (25%) backed any of their recommendations with evidence (four against, one for), including two (10%) links to abstracts (both against), whereas seven mentioned the FDA safe food handling guidelines (non-exclusive). Type of recommendation made (for or against) did not depend on US News rank (top vs bottom 10; p = 1.00.). Conclusion: The neutropenic diet continues to be recommended on many (35%) websites of top US cancer centers, despite strong evidence against its use. The website content of major US cancer centers should be updated to better guide patients regarding neutropenic diets.

Trends in Outcomes of Patients With Metastatic Cancer Undergoing Intubation and Mechanical Ventilation: Results of the National Hospital Discharge Survey.

Background: There has been an overall decline in intensive care unit mortality over the past 2 decades, including in patients undergoing intubation and mechanical ventilation (MV). Whether this decline extends to patients with metastatic cancer remains unknown. We analyzed the outcomes of patients with metastatic cancer undergoing intubation/MV using the National Hospital Discharge Survey (NHDS) database from 2001 to 2010. Methods: Diagnosis and procedure codes were used to identify patients with metastatic cancer who underwent intubation/MV. Demographics, diagnoses, length of stay (LOS), and discharge information were abstracted. Multivariate linear and logistic regression models with weighted analysis were conducted to study trends in outcomes. Results: During the 10-year study period, 200,350 patients with metastatic cancer and who underwent intubation/MV were identified; the mean age was 65.3 years and 46.2% were men. There was an increase in the total number of patients with metastatic cancer who underwent intubation/MV during the study period, from 36,881 in 2001-2002 to 51,003 in 2009-2010 (P<.001). The overall inpatient mortality rate was 57.3%, discharge to a care facility (DTCF) rate was 40.9% among patients alive at discharge, and mean LOS was 11.1 days. No significant trends were seen in rates of mortality, DTCF, or LOS from 2001 to 2010. Conclusions: In this national database, there was an increase in the number of patients with metastatic cancer who underwent intubation/MV. These patients had high rates of inpatient mortality and DTCF, which did not improve during the study period. Therefore, novel solutions are required to improve outcomes for these patients.