Blast from the Past: Acute Myeloid Leukemia Presenting with Cardiac Tamponade.

Acute Myeloid Leukemia (AML) is a life-threatening illness that requires prompt diagnosis and often immediate treatment. It can present in a variety of manners but most commonly is associated with fevers, fatigue, shortness of breath, or infection. Extramedullary leukemia is a less common finding upon initial presentation, but includes dermatologic manifestations, including leukemia cutis, and rarely, large mass-like presentations known as myeloid sarcomas. While leukemic infiltration of organ systems is a well-described phenomenon, cardiac tamponade is a rare form of presentation. Herein we describe a 58-year-old man with a recent hospitalization for idiopathic cardiac tamponade who re-presented to the hospital with worsening dyspnea and fevers. He was found to have a recurrent pericardial effusion with features concerning for tamponade, as well as worsening thrombocytopenia and macrocytic anemia. Bone marrow biopsy revealed 24% myeloblasts, confirming the diagnosis of AML. Notably, his cardiac symptoms improved with treatment of his leukemia. To our knowledge, this is one of only a few cases of AML with cardiac tamponade as the initial presentation.

Progressive Multifocal Leukoencephalopathy Unmasked by Teclistamab in a Refractory Multiple Myeloma Patient.

This case report describes the development of Progressive Multifocal Leukoencephalopathy (PML) in a 72-year-old male with relapsed/refractory multiple myeloma (RRMM), following a single dose of teclistamab amidst a COVID-19 infection. Shortly after starting teclistamab treatment, the patient developed symptoms, including fever, altered mental status, and right-sided paresis. A diagnosis of PML was confirmed through the detection of JC virus PCR in the cerebrospinal fluid. Our report emphasizes the occurrence of PML after only one dose of teclistamab and highlights teclistamab's potential for severe infectious complications, despite its promise in treating RRMM.

Immune checkpoint inhibitors in advanced and relapsed/refractory Hodgkin lymphoma: current applications and future prospects.

Classic Hodgkin lymphoma (cHL) treatment paradigms are undergoing a shift with the integration of immune checkpoint inhibitors (ICIs) into both first-line and relapsed/refractory (R/R) regimens. In first-line therapy, the synergy between ICIs and chemotherapy may surpass the previous standards of ABVD and BV-AVD established by landmark trials including RATHL and ECHELON-1. In R/R disease, the combination of ICIs with chemotherapy has begun to challenge the paradigm of chemotherapy as a bridge to consolidative autologous stem cell transplantation. The clinical advances heralded by ICI offer unique challenges to management. ICI treatment and the associated inflammatory response can make the traditional timing and modalities of treatment response assessment difficult to interpret. In contrast to ABVD and BV-AVD, pembrolizumab-AVD results in PET2 positivity rates that are higher and less predictive of treatment response even when ultimate outcomes may be superior. This suggests that the predictive value of PET2 may be less reliable in the ICI era, prompting a reevaluation of response assessment strategies. Looking forward, circulating tumor DNA (ctDNA) may be a promising tool in response-adapted therapy. Its potential to complement or even supersede PET scans in predicting response to ICIs represents a critical advancement. The integration of ctDNA analysis holds the promise of refining response-adapted approaches and enhancing precision in therapeutic decision-making for patients with cHL. This review navigates the evolving landscape of cHL therapy, emphasizing the paradigmatic shift brought about by ICIs. This article explores the impact of combining ICIs with chemotherapy in both relapsed/refractory and first-line settings, scrutinizes the challenges posed to response-adapted therapy by ICIs, and highlights the potential role of ctDNA as an adjunct in refining response-adapted strategies for cHL.

Progression-free survival is a weakly predictive surrogate end-point for overall survival in follicular lymphoma: A systematic review and meta-analysis.

Although progression-free survival (PFS) is a commonly used surrogate end-point for clinical trials of follicular lymphoma (FL), no analyses have evaluated the strength of surrogacy for PFS with overall survival (OS). A systematic review was performed and 20 studies (total participants, 10 724) met final inclusion criteria. PFS was weakly associated with OS (correlation coefficient; 0.383, p < 0.001). The coefficient of determination was 0.15 (95% CI: 0.002-0.35) suggesting 15% of OS variance could be explained by changes in PFS. This challenges the role for PFS as a surrogate end-point for clinical trials and drug approvals.

Advances in Immunotherapy for the Treatment of Cutaneous T-Cell Lymphoma.

Cutaneous T-Cell Lymphoma (CTCL) is a heterogenous disease that consists of distinct clinicopathologic entities and presentations requiring a unique and expert approach to management. The most common subtype is mycosis fungoides, in which local disease has an excellent prognosis and is often managed with topical therapy alone. More extensive cutaneous involvement as well as involvement of lymph nodes and the peripheral blood (Sezary syndrome) require systemic therapies. Recent years have brought an expansion of therapeutic options, specifically with immune-based approaches that were developed using the knowledge gained regarding the biology and molecular pathology of CTCL. Previous systemic therapies such as retinoids, histone deacetylase inhibitors, and chemotherapeutic agents come with significant toxicity and only short-term response. Newer agents such as mogamulizumab and brentuximab vedotin use a targeted immune-based approach leading to longer periods of response with less systemic toxicity. While still in its infancy, the use of immune checkpoint inhibitors such as nivolumab and pembrolizumab appears promising, and while their current clinical application is limited, early data suggest possible future areas for research of immune manipulation to treat CTCL. Herein, we review these novel immune-based treatment strategies, their superiority over prior systemic options, and the ongoing need for further research and clinical trial enrollment.

Ixazomib, Oral Metronomic Cyclophosphamide, and Dexamethasone for First-Line Treatment of Multiple Myeloma: A Phase II Brown University Oncology Group Study.

BACKGROUND: Newly diagnosed multiple myeloma patients have many available treatment options. While lenalidomide, bortezomib, and dexamethasone (RVD) is the preferred initial treatment for many patients, several other agents may provide similar efficacy with less toxicity and improved ease of administration. METHODS: We evaluated the safety and efficacy of the all-oral regimen of ixazomib, cyclophosphamide, and dexamethasone with the use of metronomic cyclophosphamide dosing in the treatment of patients with newly diagnosed multiple myeloma. RESULTS: The study was stopped prior to planned enrollment due to slow recruitment, with 12 patients available for final analysis. The overall response rate was 58.3% with 2 patients achieving a very good partial response (16.7%) and 5 patients achieving a partial response (41.7%). Median progression-free survival was 16 months, and median overall survival was 43 months. There were no episodes of grade 3 or greater peripheral neuropathy. Grade 3 or greater dermatologic toxicity was experienced in 50% of patients. CONCLUSION: Although limited enrollment prevented full efficacy evaluation, our data do not support further study of metronomic cyclophosphamide in combination with ixazomib and dexamethasone in the treatment of newly diagnosed multiple myeloma. The activity of this regimen in the relapsed/refractory setting requires further study (ClinicalTrials.gov Identifier: NCT02412228).

Impact of Early Palliative Care on End-of-Life Outcomes in Hematologic Malignancies.

Background: Patients with hematologic malignancies (HMs) receive more disease directed care at the end of life (EOL) and often die in the hospital. The impact of early palliative care (PC) consultation on EOL quality outcomes in HMs has not been well described. Objectives: In 2017 we embedded a PC specialist within our inpatient malignant hematology team at our hospital in Providence, Rhode Island to facilitate the use of early PC. We sought to determine if this practice was accompanied by a shift in EOL outcomes. Design/Setting: We conducted a retrospective review of patients diagnosed with acute myeloid leukemia (AML) at our institution in the two years before (Cohort A) and after (Cohort B) insertion of a PC specialist. We identified patients who received a PC consultation and whether it was early or late. We then examined EOL quality outcomes: hospitalizations and intensive care unit (ICU) admissions in the last 30 days of life, chemotherapy use in the last 14 days of life, use of hospice, and death out of hospital. Results: Among 139 AML patients, 46 in Cohort A and 93 in Cohort B, we identified 34 and 47 decedents in each cohort, respectively. There was no significant improvement in EOL outcomes between Cohort A and B or among patients receiving early PC (p > 0.05); however, PC in general across all cohorts was associated with significant increase in hospice use and fewer ICU admissions (p = 0.016 and 0.0043, respectively). Conclusion: Earlier PC consultation in AML was not significantly associated with improvement in EOL quality outcomes; however, PC use in general was with improvement in use of hospice and ICU utilization. Further studies are needed to more definitively examine the relationship between early PC and EOL outcomes in patients with HMs and to examine non EOL outcomes such as patient experience and quality-of-life measures.

Factor XIII Deficiency: A Review of Clinical Presentation and Management.

Factor XIII (FXIII) deficiency is a rare autosomal recessive disorder that can result in life-threatening bleeding and early fetal loss. FXIII not only is responsible for cross-linking fibrinogen to stabilize and strengthen clot formation but also facilitates wound healing and angiogenesis and plays an important role in fetal vitality. Modern therapeutics allow for prophylactic treatment that can prevent most major bleeding and increasing fetal viability. Early diagnosis is paramount due to the high risk of intracranial bleeding.

Tumor lysis syndrome risk in outpatient versus inpatient administration of venetoclax and hypomethlators for acute myeloid leukemia.

INTRODUCTION: Venetoclax along with hypomethylating agents (HMAs) is the new standard therapy for older patients with acute myeloid leukemia (AML) not fit for intensive frontline induction chemotherapy. Venetoclax is associated with fatal episodes of tumor lysis syndrome (TLS) in chronic lymphocytic leukemia (CLL), and recommendations are for its initiation for CLL and AML in the inpatient setting with close monitoring. Herein, we evaluated the safety of outpatient venetoclax ramp up when given in addition to HMAs for the treatment of AML. METHODS: We conducted a retrospective review of patients diagnosed with AML at our institution from 12/1/2016 until 7/1/2020. We identified patients who received HMAs and venetoclax for AML, either as frontline or relapsed/refractory therapy. Records were reviewed for evidence of laboratory or clinical tumor lysis episodes in all patients. RESULTS: Between 12/1/2016 and 7/1/2020 43, patients at our institution received venetoclax/HMA for the treatment of AML. Thirty-nine patients (91%) had venetoclax initiation and ramp up in the outpatient setting. One episode of laboratory TLS (2.5%) was identified. This patient required admission to the hospital for rasburicase and IV fluids with resolution of the laboratory effects without resultant clinical TLS. There were no episodes of clinical TLS in either group. Thirty-day mortality from venetoclax initiation was 0% in both groups. CONCLUSION: Our experience with HMAs and venetoclax showed that outpatient ramp up of venetoclax is safe with a very low risk of laboratory TLS (2.5%) and no evidence of clinical TLS within our cohort.

Locoregional gastric cancer: a narrative review of multidisciplinary management.

Gastric cancer is one of the most common cancers worldwide. While relatively uncommon in the United States, worldwide it is the 5th most common cancer diagnosed. Almost half of patients present with locoregional disease. Even with advanced surgical techniques and adjuvant perioperative treatment the prognosis for patients in this cohort is still dismal. Perioperative chemotherapy and/or radiation have been used in the last several decades in an attempt to improve outcomes in locally advanced resectable gastric cancer. In this article, we will review the development of these multimodal treatment strategies over the past two to three decades. We will compare these treatment modalities and their impact on survival outcomes. We will review the evidence for perioperative chemotherapy and radiotherapy, used in isolation and in combination. We will evaluate the evidence for these various treatment strategies and discuss how this impacts the current guidelines and recommendations. While advanced locoregional gastric cancer continues to carry significant mortality, several recent studies have added to the armament of treatment options and have seen significant improvement in progression free and overall survival in this patient population. Ongoing studies into perioperative management continue to investigate alternative treatment options and best practice for locally advanced resectable gastric cancer.

Acute Myeloid Leukemia: A Review.

Acute myeloid leukemia (AML) is a malignancy of the stem cell precursors of the myeloid lineage (red blood cells, platelets, and white blood cells other than B and T cells). Like other malignancies, it is due to genetic variations that lead to neoplastic changes and clonal proliferation. AML remains a rare malignancy, accounting for only 1.2% of all new cancer diagnoses in the United States per year, but it accounts for close to one third of all leukemias diagnosed.* For much of the 20th and early 21st century treatment paradigms were unchanged with survival curves remaining stagnant for many decades. Recent changes in our understanding of the genetic variations in the disease have led to some promising new therapies with hopes for improved outcomes in the future. Below we review the definitions, diagnosis and classification of AML and how this affects the evolving treatment paradigm of AML.

Optic neuritis, encephalitis and leptomeningeal enhancement in a patient with anti-MOG antibodies: A case study.

A subset of patients with neuromyelitis optica spectrum disorders are positive for myelin-oligodendrocyte glycoprotein (MOG) antibodies. These patients present with distinct clinical demyelinating syndrome often confused for multiple sclerosis. We describe the case of a patient who initially presented with 10-day history of right-sided retro-orbital headache worse with lateral gaze, photophobia, and subjective decreased visual acuity. After successful treatment on a steroid regimen, this patient represented two weeks following discharge with seizure and was found to have unilateral meningeal T2-FLAIR MRI hyperintensity with associated cortical swelling, a rare finding. CSF studies showed negative anti-AQP4 antibodies and positive anti-MOG antibodies. This case demonstrates that patients presenting with symptoms concerning for NMOSD who are AQP4-Ab-negative should be tested for anti-MOG antibodies for optimized disease management and important prognostic implications.

Simultaneous onset of Alzheimer's disease in a husband and wife in their mid-fifties: what do we really know about environmental factors?

INTRODUCTION: Environmental factors can play a role in the pathogenesis of Alzheimer's disease. We present a case of the simultaneous onset of Alzheimer's disease in two middle aged adults. CASE PRESENTATION: A married couple ages 54 year and 51-year-old female cohabiting together were diagnosed with Alzheimer's disease within the same year. The patient's both developed cognitive decline shortly after a major renovation of their property and followed a similar disease course. The diagnosis was supported by clinical presentation and tissue pathology on autopsy. CONCLUSION: Environmental factors may play a role in the pathogenesis of Alzheimer's disease. Further understanding of the disease cascade is required.

Alzheimer Disease Pathology in Middle Age Reveals a Spatial-Temporal Disconnect Between Amyloid-ß and Phosphorylated Tau.

We studied the brain distribution of amyloid-ß (Aß) and phosphorylated tau (τ) in 20 consecutive autopsy cases between the ages of 51 and 65, with no history of neurologic disease during life. We note that early accumulations of Aß and τ occur in distinct neuroanatomical distributions. In the locus ceruleus and medial temporal lobe allocortex τ often occurs in the absence of diffuse Aß and that Aß occurs in the neocortex in the absence of τ. In those cases with both Aß and τ were present in the sections, there was no overlap at the microanatomical or cellular level. APOE genotype was also assessed, showing no specific relationship with the presence or distribution of Aß and τ, although the numbers of cases were limited. These findings indicate that the early appearances of hallmark proteins of Alzheimer's disease are disconnected both in time and in space, suggesting that both are reactive phenomena with no mechanistic relationship in aging or preclinical disease.