Shared Local Oncology Care After Allogeneic Hematopoietic Cell Transplantation: A Randomized Clinical Trial.

Importance: Although sharing care with local oncologists after allogeneic hematopoietic cell transplantation (HCT) has been proposed for patients living far from HCT centers, it is not known whether a shared strategy is safe or improves patient quality of life (QOL).

Objective: To determine the efficacy and safety of sharing follow-up care after HCT between the HCT specialty center and local oncologists.

Design, Setting, And Participants: This was a multicenter collaborative randomized clinical trial of patients undergoing HCT at Dana-Farber Cancer Institute (DFCI)-a high volume HCT center in Boston (Massachusetts)-and 8 local oncology practices.

Acquired von Willebrand's Syndrome in a Patient with Concomitant Chronic Lymphocytic Lymphoma and Smoldering Multiple Myeloma.

An African-American female in her sixties presented to the hospital with intermittent gum bleeding for the past two years along with severe anemia. This case details the differential and workup that lead to the diagnosis of acquired von Willebrand's syndrome (AvWS). A thorough investigation in the possible etiologies of AvWS revealed that the patient had concomitant chronic lymphocytic lymphoma (CLL) and smoldering multiple myeloma (SMM).

Immunotherapy in Acute Leukemias: Past Success Paves the Way for Future Progress.

Immunotherapy as a cancer treatment modality has undergone recent widespread proliferation across all cancer types, especially amongst patients with solid tumors. However, the longest tenured immunotherapy approach to cancer is allogeneic stem cell transplantation (allo-SCT) for two hematologic malignancies: acute myeloid and acute lymphoid leukemia (AML and ALL, respectively). While allo-SCT remains a standard of care for eligible patients, recent advances/applications of monoclonal antibodies, immune checkpoint inhibitors, bispecific T-cell engagers (BiTEs), and CAR T-cell therapy are changing the treatment landscape for these acute leukemias by either direct to tumor immune targeting or through decreased toxicities that expand patient eligibility.

The Direct Support Workforce: An Examination of Direct Support Professionals and Frontline Supervisors During COVID-19.

Direct support professionals (DSPs) and frontline supervisors (FLSs) have critical roles in home and community-based services for people with intellectual and developmental disabilities. Low wages and high levels of responsibility created a long-term crisis in recruitment and retention and are exacerbated by the COVID-19 pandemic. A national sample of DSPs and FLSs were compared on demographics and work-related circumstances using data from the third Direct Support Workforce COVID-19 Survey.

Choice of anticoagulation in patients with low risk antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an acquired hypercoagulable state necessitating long-term anticoagulation for secondary thrombosis prevention. Anticoagulation guidelines are predominantly based on data in high risk, triple positive patients, and favor Vitamin K antagonists over other forms of anticoagulation. The efficacy of alternative anticoagulants for secondary thrombosis prevention in low risk, single and double positive APS remains uncertain.

Expert consensus on microtransplant for acute myeloid leukemia in elderly patients -report from the international microtransplant interest group.

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4).

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.

Transcriptomics of acute myeloid leukaemia core bone marrow biopsies reveals distinct therapy response-specific osteo-mesenchymal profiles.

While the bone marrow (BM) microenvironment is significantly remodelled in acute myeloid leukaemia (AML), molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma. We assessed the effect of anthracycline- and cytarabine-based induction chemotherapy on both haematopoietic and non-haematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis. We compared matched human core BM biopsies at diagnosis and 2 weeks after cytarabine- and anthracycline-based induction therapy in responders (<5% blasts present after treatment) and non-responders (≥5% blasts present after treatment).

Tumor Derived Extracellular Vesicles Modulate Gene Expression in T cells.

Extracellular vesicles (EVs) are excreted from all cells in the human body and are heterogeneous lipid bilayer particles containing proteins, RNA, DNA, and other cargo. T cells are primary players of the adaptive immune system and have a significant role in anti-cancer immunotherapies. Tumor derived EVs have diverse effects on host cells including modulating the immune response.

Direct Oral Anticoagulants Versus Vitamin K Antagonists in Cerebral Venous Thrombosis: A Systematic Review and Meta-Analysis.

Background: High level evidence for direct oral anticoagulants (DOACs) in patients with cerebral venous thrombosis is lacking. We performed a systematic review and meta-analysis to assess the efficacy and safety of DOACs versus vitamin K antagonists in patients with cerebral venous thrombosis.

Methods: This systematic review was registered in PROSPERO (CRD42021228800).

Seroconversion and outcomes after initial and booster COVID-19 vaccination in adults with hematologic malignancies.

Background: Patients with hematologic malignancies have impaired humoral immunity secondary to their malignancy and its treatment, placing them at risk of severe coronavirus disease-19 (COVID-19) infection and reduced response to vaccination.

Methods: The authors retrospectively analyzed serologic responses to initial and booster COVID-19 vaccination in 378 patients with hematologic malignancy and subsequently tracked COVID-19-related outcomes.

Results: Seroconversion occurred in 181 patients (48%) after initial vaccination; patients who had active malignancy or those who were recently treated with a B-cell-depleting monoclonal antibody had the lowest rates of seroconversion.

Vincristine Sulfate Liposome Injection with Bendamustine and Rituximab as First-Line Therapy for B-Cell Lymphomas: A Phase I Study.

Background: We conducted an investigator-initiated, phase I trial of vincristine sulfate liposomal injection (VSLI) in combination with bendamustine and rituximab (BR) for indolent B-cell (BCL) or mantle cell lymphoma.

Methods: Participants received 6 cycles of standard BR with VSLI at patient-specific dose determined by the Escalation with Overdose Control (EWOC) model targeting 33% probability of dose-limiting toxicity (DLT). Maximum tolerated dose (MTD) was the primary endpoint; secondary endpoints included rates of adverse events (AEs), overall response rate (ORR), and complete response (CR).

Detection of clonotypic DNA in the cerebrospinal fluid as a marker of central nervous system invasion in lymphoma.

The diagnosis of parenchymal central nervous system (CNS) invasion and prediction of risk for future CNS recurrence are major challenges in the management of aggressive lymphomas, and accurate biomarkers are needed to supplement clinical risk predictors. For this purpose, we studied the results of a next-generation sequencing (NGS)-based assay that detects tumor-derived DNA for clonotypic immunoglobulin gene rearrangements in the cerebrospinal fluid (CSF) of patients with lymphomas. Used as a diagnostic tool, the NGS-minimal residual disease (NGS-MRD) assay detected clonotypic DNA in 100% of CSF samples from 13 patients with known CNS involvement.

Phase 1 study of oral azacitidine (CC-486) plus R-CHOP in previously untreated intermediate- to high-risk DLBCL.

Resistance to standard immunochemotherapy remains an unmet challenge in diffuse large B-cell lymphoma (DLBCL), and aberrant DNA methylation may contribute to chemoresistance. Promising early-phase results were reported with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus subcutaneous azacitidine, a hypomethylating agent. In this phase 1 study, we evaluated CC-486 (oral azacitidine) plus 6 cycles of R-CHOP in patients with previously untreated intermediate- to high-risk DLBCL or grade 3B/transformed follicular lymphoma.

Thrombosis in COVID-19: A Narrative Review of Current Literature and Inpatient Management.

COVID-19 infection has been associated with an increased incidence of thrombotic events leading to poor patient outcomes. Given the rapid rise of the COVID-19 pandemic, the ability to conduct prospective trials has been limited and data regarding the use of standard-dose versus intermediate-dose thromboprophylaxis, use of empiric therapeutic anticoagulation, and use of extended-duration thromboprophylaxis after discharge has been largely based upon observational data without any high-quality prospective data guiding their use. In this article, we will review the incidence and frequency of arterial and venous thrombotic events along with the current literature surrounding the use of intermediate-dose thromboprophylaxis, empiric therapeutic anticoagulation, and use of extended-duration thromboprophylaxis for patients hospitalized with COVID-19.

Murine Leukemia-Derived Extracellular Vesicles Elicit Antitumor Immune Response.

Background: Extracellular vesicles (EVs) are heterogeneous lipid bilayer particles secreted by cells. EVs contain proteins, RNA, DNA and other cargo that can have immunomodulatory effects. Cancer-derived EVs have been described as having immunomodulating effects in vivo with immunosuppressive and pro-tumor growth capabilities.

3D tissue engineered plasma cultures support leukemic proliferation and induces drug resistance.

Chronic myeloid leukemia (CML), acute myeloid leukemia (AML), and chronic lymphocytic leukemia (CLL) are hematological malignancies that remain incurable despite novel treatments. In order to improve current treatments and clinical efficacy, there remains a need for more complex models that mimic the intricate human leukemic microenvironment. This study aimed to use 3D tissue engineered plasma cultures (3DTEPC) derived from CML, AML and CLL patients to promote proliferation of leukemic cells for use as a drug screening tool for treatment.

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.

Enforcing the "4T": An In-Line Calculator for HIT Antibody Ordering in the Electronic Medical Record.

Heparin-induced thrombocytopenia (HIT) remains a difficult clinical diagnosis, even with the under-utilized standardized scoring systems, like the '4T' score, to aid in clinical decision-making. Our quality improvement study sought to assess the use of '4T' score, improve the use of HIT antibody (HITA) testing and improvement management of possible HIT by implementing an in-line calculator with guidance within our electronic medical record (EMR) at our institution. We retrospectively reviewed patient charts between October 2017 and October 2018, assessing practices before and after implementation of the '4T' in-line calculator in April 2018.

Intensity of anticoagulation and survival in patients hospitalized with COVID-19 pneumonia.

Background: SARS-CoV-2 infection has noted derangements in coagulation markers along with significant thrombotic complications. Post-mortem examinations show severe endothelial injury and widespread thrombotic microangiopathy in the pulmonary vasculature. Early reports describing the use of prophylactic anticoagulation demonstrated improved survival, leading to the adoption of prophylactic and therapeutic anticoagulation guided by D-dimer levels.

Preliminary findings regarding the use of direct oral anticoagulants in cerebral venous thrombosis.

Background: Direct oral anticoagulants (DOACs) have entered the treatment paradigms of various conditions based upon large randomized controlled trials. However, use of DOACs for thrombosis at unusual sites, such as cerebral venous thrombosis (CVT), is less clear as the ability to conduct large randomized controlled trials is limited by its rarity. Furthermore, its use in the setting of malignancy or in the elderly remains an area of ongoing research.

Outcomes of lenalidomide- or bortezomib-based regimens in older patients with plasma cell myeloma.

The "triplet" regimen of lenalidomide, bortezomib, and dexamethasone (RVD) showed survival advantage over lenalidomide-dexamethasone (RD) in clinical trials, but older patients with myeloma often receive doublet regimens (RD or bortezomib-dexamethasone, VD), or VD plus cyclophosphamide (VCD). We compared these first-line regimens using real-world data from Medicare beneficiaries receiving therapy between 2007 and 2015. In each comparative analysis, we balanced confounding characteristics using a propensity score.