scholarly journals A Remarkable Remission: Treating HMA Refractory Transforming MDS with Single-Agent Low-Dose Cytarabine Leading to an Ongoing Six-Year OS

2020 ◽  
Vol 2020 ◽  
pp. 1-3 ◽  
Author(s):  
David Palmer ◽  
Lydia Jones
Keyword(s):  
High Risk ◽  
Low Dose ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Intensive Therapy ◽  
Single Agent ◽  
Standard Of Care ◽  
Cell Transplant ◽  
Investigational Agents ◽  
Low Dose Cytarabine

Hypomethylating agents (HMA) are the standard of care for patients ≥65 years with intermediate-high risk myelodysplastic syndrome (MDS) unsuitable for intensive therapy or stem cell transplant (SCT). However, many patients will develop relapse/refractory disease, at which point limited treatment options remain. There has been a lot of research into investigational agents following HMA failure, especially now into targeted therapy, but there is no final consensus or convincing data to guide clinicians. Low-dose cytarabine (LDAC) has been in the armamentarium for some time, but the value of LDAC is judged differently by various guidelines. Nevertheless, in a subgroup of patients who fail on a HMA and wish to continue treatment, LDAC may still have the potential to improve overall survival (OS). In this case report, we present an 85-year-old gentleman with HMA refractory high-risk/transforming MDS (with a noncomplex karyotype) achieving an ongoing six-year OS with single-agent second-line LDAC. LDAC may therefore still be considered by clinicians as a therapeutic option, but when available, patients should be enrolled on a clinical trial.

Complete Hematological Remission after Decitabine Treatment in a Patient with Congenital Agammaglobulinemia, FLT3- and TP53-Mutated Acute Myeloid Leukemia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Vigna E ◽  
◽  
Caracciolo D ◽  
Martino E ◽  
Mendicino F ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Treatment Options ◽  
Single Agent ◽  
Response Duration ◽  
Hypomethylating Agents ◽  
Unfit Patients ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Older and unfit patients with Acute Myeloid Leukemia (AML), which are uneligible for standard induction therapy, have limited treatment options. The therapeutic approach in these cases is based on the use of hypomethylating agents, either decitabine or azacitidine, or Low-Dose Cytarabine (LDAC). However, despite the extensive use of these agents, there is no consensus regarding the extent of their efficacy, and clinical benefit deriving from their use is very modest. We present a case of FLT3- and TP53-mutated AML in an unfit patient with congenital agammaglobulinemia, responsive to single agent decitabine, with a response duration of over 20 months.

scholarly journals 789. Evaluation of Bezlotoxumab for Prevention of Recurrent Clostridioides difficile Infection in Patients at High Risk for Recurrence

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S438-S439
Author(s):  
Tanner M Johnson ◽  
Amanda Howard ◽  
Kerry Schwarz ◽  
Lorna Allen ◽  
Misha Huang ◽  
...  
Keyword(s):  
High Risk ◽  
Fecal Microbiota Transplantation ◽  
Therapeutic Option ◽  
Treatment Options ◽  
High Risk Patient ◽  
Recurrent Infection ◽  
Control Group ◽  
Clostridioides Difficile ◽  
All Cause Mortality ◽  
Clostridioides Difficile Infection

Abstract Background Recurrent Clostridioides difficile infection (rCDI) within 180 days of the index episode is associated with a 33% increase in mortality and, to-date, few treatment options exist to prevent recurrent infection. Bezlotoxumab (BEZ) is a novel therapeutic option for the prevention of rCDI, yet limited data exist regarding its effectiveness in patients at high-risk for recurrence outside of controlled trials. This study aimed to compare BEZ to a historical standard of care (SoC) cohort for the prevention of rCDI in patients at high risk for recurrence. Methods A multi-center retrospective cohort study of patients within an academic health-system with one or more risk factors for rCDI. Patients received SoC with oral vancomycin (VAN) or fidaxomicin (FDX) from January 2015 to December 2017 or BEZ, in addition to oral SoC, from September 2017 to September 2019. The primary outcome was rCDI within 90 days of completion of oral VAN or FDX. Secondary outcomes included all-cause readmission, all-cause mortality, and safety events at 90 days. Results One-hundred twenty patients received BEZ in addition to SoC (n=47) or SoC alone (n=73). Mean (SD) age was 55 (16) years, mean (SD) number of lifetime CDI was 3 (2) episodes, and 30.8% of patients had severe CDI. Six (12.8%) patients in the BEZ cohort and thirty-one (42.5%) in the SoC cohort experienced rCDI at 90 days [OR (95% CI) = 0.20 (0.07-0.53), p=< 0.01]. Incidence of all-cause mortality (2.1% vs 5.5%, p=0.67) and all-cause readmission (42.6% vs 56.2%, p=0.20) within 90 days were not statistically different between groups. Patient body weight, timing of BEZ administration, CDI severity, nor prior receipt of fecal microbiota transplantation significantly affected BEZ effectiveness. BEZ was well tolerated with one infusion-related reaction. There were no heart failure exacerbations among BEZ recipients and two exacerbations identified from control group. Conclusion In patients with at least one risk factor for rCDI, BEZ in addition to SoC was associated with lower rates of recurrent infection than SoC alone and may be a reasonable adjunct therapy in high risk patient populations. Disclosures matthew miller, PharmD, Allergan (Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

scholarly journals Approaches to Enhance Natural Killer Cell-Based Immunotherapy for Pediatric Solid Tumors

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2796
Author(s):  
Aicha E. Quamine ◽  
Mallery R. Olsen ◽  
Monica M. Cho ◽  
Christian M. Capitini
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Solid Tumors ◽  
Nk Cell ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Intensive Therapy ◽  
Killer Cell ◽  
Cell Therapies ◽  
Pediatric Solid Tumors

Treatment of metastatic pediatric solid tumors remain a significant challenge, particularly in relapsed and refractory settings. Standard treatment has included surgical resection, radiation, chemotherapy, and, in the case of neuroblastoma, immunotherapy. Despite such intensive therapy, cancer recurrence is common, and most tumors become refractory to prior therapy, leaving patients with few conventional treatment options. Natural killer (NK) cells are non-major histocompatibility complex (MHC)-restricted lymphocytes that boast several complex killing mechanisms but at an added advantage of not causing graft-versus-host disease, making use of allogeneic NK cells a potential therapeutic option. On top of their killing capacity, NK cells also produce several cytokines and growth factors that act as key regulators of the adaptive immune system, positioning themselves as ideal effector cells for stimulating heavily pretreated immune systems. Despite this promise, clinical efficacy of adoptive NK cell therapy to date has been inconsistent, prompting a detailed understanding of the biological pathways within NK cells that can be leveraged to develop “next generation” NK cell therapies. Here, we review advances in current approaches to optimizing the NK cell antitumor response including combination with other immunotherapies, cytokines, checkpoint inhibition, and engineering NK cells with chimeric antigen receptors (CARs) for the treatment of pediatric solid tumors.

scholarly journals Catheter-directed low-dose fibrinolysis infusion for treat acute intermediate-high risk pulmonary embolism

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
MM Martin Cabeza ◽  
MJ Garcia Gonzalez ◽  
P Jorge Perez ◽  
A Sanchez-Grande Flecha ◽  
R Munoz Rodriguez ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Pulmonary Hypertension ◽  
High Risk ◽  
Low Dose ◽  
Therapeutic Option ◽  
Bleeding Complications ◽  
Common Disease ◽  
Effective Treatment Option ◽  
Femoral Access ◽  
Rv Function

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND  Intermediate-high risk  (IHR) Pulmonary Embolism (PE) are a common disease witch could have a high mortality. Anticoagulation remains the first therapeutic option, but Catheter-directed therapies are being investigated as a safe and effective treatment option. PURPOSE To evaluate the safety and efficacy of Catheter-directed low-dose fibrinolysis infusion to treat IHR-PE. METHODS Retrospective analysis of 16 patients IHR-PE treated. After performing Right catheterization (RC) and angiogram, Pigtail catheters were located for intrapulmonary infusion of Alteplase 1mg/h/catheter for 24 h (25-30mg/day). Baseline and clinical characteristics, inicial and evolutive echocardiography, also clinical evaluation and echocardiography 6 months after discharge were evaluated.   RESULTS The majority were women (11) and obese (93.8%), aged 22-74 years with cardiovascular risk factors: 5 hypertension, 3 Dyslipidemia, 2 smokers and 3 severe CKD . At admission 11 patients consulted for dyspnea and 5 for syncope; all were hemodynamic stable. 68.8% presented respiratory failure. All had bilateral PE (angiography) and elevation of Nt-proBNP and troponins. The echocardiographic at admission, and its evolution are shown in Table 1.  The invasive measurement of pulmonary hypertension (PH) reflected greater severity than the estimated by echo:  5 (31.3%) Severe PH, 5 (31.3%) Moderate PH and 2 (12.5%) mild PH. At discharge all presented a decrease in PH and 15 (93.8%) improved RV function. 2 patients suffered bleeding complications (relation with femoral access): 1 not severe, 1 severe without mortality; none suffered intracranial hemorrhage. In the evaluation at 6-months: 13 patients (81.3%) where on functional Class I and without PH, 3 patients (18.8%) where in Class II and with mild-PH. CONCLUSION In short-term follow-up, intrapulmonary low-dose fibrinolysis reduces PA pressures and improves RV function, without an increased bleeding complications, especially if femoral access is avoided. However impact on long-term remains unclear. Table 1: Echocardiography evolution.RV function admissionNormal Function1 (6.3%)Mild Dysfunction9 (56.3%)Moderate Dysfunction6 (37.5%)RV Dilatation admissionDilatation 16 (100%)Not dilatation 0 (0%)PH Degree admissionMild PH6 (37.5%)Moderate PH5 (31.3%)Severe PH5 (31.3%)PH Degree 24h-postNot PH1 (6.3%)Mild PH10 (62.5%)Moderate/severe PH5 (31.3%)Improvement RV 24h-postYes14 (87.5%)Not2 (12.5%)RV function dischargeNormal Function16 (100%)Mild Dysfunction0 (0%)Moderate Dysfunction0 (0%)RV Dilatation dischargeDilatation 5 (31.3%)Not dilatation 11 (68.8%)PH Degree dischargeNot PH 9 (56.3%)Mild PH7 (43.8%)Moderate/severe PH0 (0%)RV Right Ventricular; PH: Pulmonary Hypertension,

scholarly journals Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome

Leukemia ◽  
2018 ◽  
Vol 33 (2) ◽  
pp. 379-389 ◽  
Author(s):  
Jorge E. Cortes ◽  
Florian H. Heidel ◽  
Andrzej Hellmann ◽  
Walter Fiedler ◽  
B. Douglas Smith ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Newly Diagnosed ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

scholarly journals Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2887
Author(s):  
Timothy J Voorhees ◽  
Anne W Beaven
Keyword(s):  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Standard Of Care ◽  
The United States ◽  
Autologous Stem Cell Transplant ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Novel Agents ◽  
Cell Transplant ◽  
T Cell Therapy

Hodgkin lymphoma (HL) is a B-cell malignancy representing approximately one in ten lymphomas diagnosed in the United States annually. The majority of patients with HL can be cured with chemotherapy; however, 5–10% will have refractory disease to front-line therapy and 10–30% will relapse. For those with relapsed or refractory (r/r) HL, salvage chemotherapy followed by autologous stem cell transplant (ASCT) is standard of care, but half of patients will subsequently have disease progression. Relapse following ASCT has been associated with exceedingly poor prognosis with a median survival of only 26 months. However, in recent years, novel agents including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab) have been shown to extend overall survival in r/r HL. With the success of novel agents in relapsed disease after ASCT, these therapies are beginning to show clinically meaningful response rates prior to ASCT. Finally, a new investigation in r/r HL continues to produce promising treatment options even after ASCT including CD30 directed chimeric antigen receptor T-cell therapy. In this review, we will discuss the recent advances of BV and anti-PD-1 therapy prior to ASCT, novel approaches in r/r HL after ASCT, and review active clinical trials.

scholarly journals The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1411 ◽  
Author(s):  
Brianna M. Naumchik ◽  
Ashish Gupta ◽  
Heather Flanagan-Steet ◽  
Richard A. Steet ◽  
Sara S. Cathey ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Treatment Options ◽  
Lysosomal Storage Diseases ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Lysosomal Storage ◽  
Hematopoietic Cell Transplant ◽  
Psychomotor Delay ◽  
Enzyme Replacement ◽  
Enzyme Defects

The glycoprotein disorders are a group of lysosomal storage diseases (α-mannosidosis, aspartylglucosaminuria, β-mannosidosis, fucosidosis, galactosialidosis, sialidosis, mucolipidosis II, mucolipidosis III, and Schindler Disease) characterized by specific lysosomal enzyme defects and resultant buildup of undegraded glycoprotein substrates. This buildup causes a multitude of abnormalities in patients including skeletal dysplasia, inflammation, ocular abnormalities, liver and spleen enlargement, myoclonus, ataxia, psychomotor delay, and mild to severe neurodegeneration. Pharmacological treatment options exist through enzyme replacement therapy (ERT) for a few, but therapies for this group of disorders is largely lacking. Hematopoietic cell transplant (HCT) has been explored as a potential therapeutic option for many of these disorders, as HCT introduces functional enzyme-producing cells into the bone marrow and blood along with the engraftment of healthy donor cells in the central nervous system (presumably as brain macrophages or a type of microglial cell). The outcome of HCT varies widely by disease type. We report our institutional experience with HCT as well as a review of the literature to better understand HCT and outcomes for the glycoprotein disorders.

scholarly journals Glasdegib plus low-dose cytarabine for acute myeloid leukemia: Practical considerations from advanced practitioners and pharmacists

2020 ◽  
pp. 107815522097373
Author(s):  
Valerie Relias ◽  
Ali McBride ◽  
Matthew J Newman ◽  
Shilpa Paul ◽  
Seyyedeh Saneeymehri ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Treatment Options ◽  
Treatment Delivery ◽  
Need For Treatment ◽  
Proactive Management ◽  
The Individual ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Objective Acute myeloid leukemia (AML) is primarily a disease of older adults. These patients may not be candidates for intensive treatment, and there has been an ongoing need for treatment options for this group. We review the use of glasdegib, a hedgehog-pathway inhibitor available for use in combination with low-dose cytarabine (LDAC). Data Sources: PubMed and relevant congress abstracts were searched using the term “glasdegib”. In addition, based on our experience with glasdegib, we considered treatment aspects of particular relevance to pharmacists and advanced practitioners. Data Summary: In a randomized phase II study, the combination of glasdegib plus LDAC demonstrated superior overall survival versus LDAC alone (hazard ratio 0.51, 80% confidence interval 0.39–0.67, p = 0.0004). The trial reported adverse events (AEs) of special relevance for older patients, such as hematologic events, gastrointestinal toxicity, and fatigue, as well as AEs associated with Hh-pathway inhibitors (alopecia, muscle spasms, dysgeusia). Educating patients about typical AEs can facilitate adherence as well as early AE identification and proactive management. For LDAC, which is a long-established therapy in AML, various stages of delivery need consideration, with attention to individual circumstances. Practical measures such as dispensing a longer supply can reduce the number of return clinic visits, providing a meaningful difference for many patients. Conclusions Pharmacists and advanced practitioners play important roles in treatment with glasdegib plus LDAC. Ultimately, framing plans for treatment delivery within the individual circumstances of each patient may enable them to stay on therapy longer, giving them the greatest potential to achieve benefit.

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