Characterisation of infections in patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent.

We investigated the incidence of invasive fungal infections (IFIs) and other infectious complications in patients receiving venetoclax and hypomethylating agent therapy for acute myeloid leukaemia (AML). This retrospective, multicentre cohort study included adult patients with AML who received at least one cycle of venetoclax and either azacitidine or decitabine between January 2016 and August 2020. The primary outcome was the incidence of probable or confirmed IFI. Secondary outcomes included antifungal prophylaxis prescribing patterns, incidence of bacterial infections, and incidence of neutropenic fever hospital admissions. Among 235 patients, the incidence of probable or confirmed IFI was 5.1%. IFI incidence did not differ significantly according to age, antifungal prophylaxis use, or disease status. In the subgroup of patients with probable or confirmed IFIs, six (50%) were receiving antifungal prophylaxis at the time of infection. The overall incidence of developing at least one bacterial infection was 33.6% and 127 (54%) patients had at least one hospital admission for febrile neutropenia. This study demonstrated an overall low risk of developing probable or confirmed IFI as well as a notable percentage of documented bacterial infections and hospital admissions due to neutropenic fever.

Modified Hyper-CVAD With Proteasome Inhibition for Multiple Myeloma: A Single-Center Retrospective Analysis.

BACKGROUND: Although novel agents have changed the treatment landscape of multiple myeloma (MM), cytotoxic chemotherapy regimens continue to have a role in aggressive or rapidly progressive disease. In such cases, our institution has utilized a hyperfractionated cyclophosphamide regimen (termed mCAD), similar to hyper-CVAD, in which vincristine is omitted or replaced with a proteasome inhibitor (PI), either bortezomib or carfilzomib. On occasion, doxorubicin is also omitted because of patient history and provider preference. PATIENTS AND METHODS: We retrospectively reviewed the charts of adult patients with MM receiving mCAD regimens at our institution between 2012 and 2016 and analyzed utilization patterns, toxicity profiles, and clinical outcomes. RESULTS: A total of 131 patients received mCAD, including 9% for newly diagnosed MM (NDMM), 18% attempting to optimize response to frontline therapy (OPT-MM), and 73% for treatment of relapsed/refractory MM (RRMM). Renal dysfunction was common; 31% had estimated glomerular filtration rate < 50 mL/min and 14% were dialysis dependent. The overall response rate was 83%, 63%, and 67% with a median progression-free survival of 17.4, 23.7, and 4.2 months, respectively, for NDMM, OPT-MM, and RRMM. Median overall survival was not reached for NDMM or OPT-MM, and was 15.2 months for RRMM. Most patients (90%) bridged to subsequent therapy, including 32% who proceeded to autologous transplantation. Hematologic, infectious, and cardiac toxicities were common and were similar to those expected for cytotoxic chemotherapy. CONCLUSION: mCAD regimens were safe and active across patient groups, including patients with renal dysfunction. Most patients were able to bridge to subsequent therapy.

Long-term Follow-up of Hematopoietic Stem Cell Transplant Survivors: A Focus on Screening, Monitoring, and Therapeutics.

Annually, ~50,000 patients undergo hematopoietic stem cell transplantation (HCT) worldwide with almost 22,000 of these patients receiving HCT in the United States. HCT is a curative option for a wide range of hematologic malignancies, and advances in transplantation medicine have resulted in an increase in HCT survivors. It is anticipated that the number of HCT survivors will more than double from 242,000 in 2020 to ~500,000 in 2030. Survivors of HCT are at an increased risk of developing late complications due to exposure to chemotherapy and/or radiation in the pre-, peri-, and post-HCT phases and these cumulative exposures have the potential to damage normal tissue. This tissue damage leads to the early onset of chronic health conditions resulting in premature mortality in HCT survivors, who have a 15-year cumulative incidence of severe or life-threatening chronic health conditions exceeding 40%. Due to the significant burden of morbidity in HCT survivors and the delay in the development of long-term complications, this delicate patient population requires life-long monitoring due to the risk for neuropsychological, cardiac, pulmonary, renal, hepatic, ocular, skeletal, cardiac, endocrine, fertility, and sexual health complications, as well as secondary neoplasms. This review will focus on recent advances in screening, monitoring, and therapeutics for late-occurring or long-term complications in HCT survivors.

Zoledronic acid-induced orbital inflammation in a patient with multiple myeloma.

Multiple myeloma is a cancer of malignant plasma cells which stimulates osteoclasts and is associated with increased bone turnover and osteolysis. Bisphosphonates including zolendronic acid are used to prevent skeletal complications in patients with multiple myeloma. Orbital inflammation is a rare but serious complication following use of bisphosphonates. The diagnosis is made by excluding other possible causes in patients with myeloma and rapid initiation of therapy is required. Corticosteroids are the mainstay of therapy but the ideal treatment course has not been delineated. This report describes a case of this rare complication and provides a review of the literature.

Lenalidomide and secondary acute lymphoblastic leukemia: a case series.

Lenalidomide is often used in the maintenance setting for multiple myeloma and has been linked to the development of secondary primary malignancies. The mechanism of lenalidomide causing secondary malignancies has not been fully elucidated, but case reports and phase 3 trials have captured this uncommon occurrence. A case series describing development of secondary acute lymphoblastic leukemia in patients receiving lenalidomide maintenance therapy is presented. Based on data published in the literature thus far and commonalities among patients in this case series, secondary acute lymphoblastic leukemia is likely duration related rather than dose related. Increased cognizance of this secondary malignancy will allow for a more accurate characterization of its true incidence. Regimens for acute lymphoblastic leukemia can be used for management of secondary acute lymphoblastic leukemia with plan for stem cell transplantation. Further studies are needed to identify risk factors for development of secondary malignancy and the best management approach for these patients. Copyright © 2015 John Wiley & Sons, Ltd.

Ethanol locks in the prevention and treatment of catheter-related bloodstream infections.

OBJECTIVE: To evaluate the evidence regarding the use of ethanol lock therapy (ELT) for catheter-related bloodstream infection (CRBSI) prophylaxis and treatment. DATA SOURCES: A literature search was conducted using PubMed (August 2003-January 2013) with search terms: ethanol lock, ethanol locks, ethanol lock therapy, prophylaxis, prevention, catheter-related bloodstream infection, and catheter-related infection. Additional sources were identified through a subsequent review of relevant articles. STUDY SELECTION AND DATA EXTRACTION: All English-language studies with >1 patient and a primary outcome of rates of infection, clinical cure, catheter removal or line salvage were evaluated. Studies where ELT was not used for CRBSI prophylaxis or treatment, review articles, and in vitro studies were excluded. Data were abstracted through an independent review of all articles by 2 authors. Discrepancies were discussed and resolved. DATA SYNTHESIS: 13 prophylaxis studies evaluated 617 patients; all studies reported decreased rates of infection and catheter removal with ELT. The ELT regimen associated with the most consistent benefit was 70% ethanol, a 2- to 4-hour dwell time, and daily exchange for ≥1 month. 9 treatment studies evaluated 213 catheters, with 90% (192/213) cure and 84% (179/213) line salvage. ELT was always used in combination with systemic antibiotics. The most common ELT treatment regimen was 70% ethanol, a 12- to 24-hour dwell time, and a duration of 1-5 days. No serious adverse events were reported. CONCLUSION: The current literature suggests that prophylactic ELT decreases the rates of infection and catheter removal, and ELT treatment appears efficacious in combination with systemic antibiotics.

Interactions between traditional Chinese medicines and Western therapeutics.

Traditional Chinese medicine (TCM) is a holistic approach to health that attempts to bring the body, mind and spirit into harmony. TCM is an essential part of the healthcare system in several Asian countries, and is considered a complementary or alternative medical system in most Western countries. An integration of the traditional Chinese and Western systems of medicine has begun in multiple medical centers internationally, and there is increasing evidence that several herbs and combinations of herbs used in TCM impart important pharmacological effects. The number of databases and compilations of herbs, herbal formulations, phytochemical constituents and molecular targets is increasing, primarily because of the widespread use of TCM in combination with Western drugs. The continued popularity of herbal remedies worldwide suggests that evidence-based research in this field, as well as information regarding the potential efficacy and safety of phytochemical constituents in herbs and TCM formulations, are essential, particularly when TCM is used in combination with other drugs. Herb-drug interactions are similar to drug-drug interactions in terms of their effects on ADME properties. Improvements in the knowledge of the molecular targets and metabolic pathways, as well as of the synergistic and inhibitory effects associated with important phytochemicals from herbs and herbal formulations, will lead to the development of rational approaches for the safe combination of healthcare systems from different cultures.