Should we screen patients with hematologic malignancies for COVID-19?

The coronavirus disease (COVID-19) pandemic has posed several challenges to the hematology community to re-organize the medical care of patients with hematologic malignancies. Whereas the oncology societies favored a more or less conservative approach which considered the possibility of delaying treatment administration on a case-by-case basis, the hematology community guidelines were less stringent and recommended adequate individualized regimens. As countries are de-escalating the lockdown and the medical community is unable to foresee the end of the current outbreak will and whether the pandemic would eventually come back as a seasonal infection, there is interest in screening of patients with hematology malignancies with COVID-19 instead of limiting access to curative treatments. The rapidly accumulating knowledge about COVID-19 allows a better understanding of the diagnostic tools that may be potentially used in screening. Herein, we briefly review the pathophysiology of COVID-19, the rationale of screening of patients with hematologic malignancies, tools for screening, and available guidelines.

Seguridad y efectividad del Hebervital en la prevención o tratamiento de la Neutropenia. Hospital Celia Sánchez Manduley, 2017 / Safety and effectiveness of the Hebervital in the prevention or treatment of Neutropenia. Hospital Celia Sánchez Manduley. Year: 2017

La Neutropenia es un trastorno hematológico mundialmente frecuente, que conduce a una mayor susceptibilidad a infecciones bacterianas y fúngicas. El objetivo de este trabajo es evaluar la efectividad y la seguridad de la administración del Hebervital en los pacientes incluidos en el ensayo clínico. Se realizó un estudio descriptivo, en el desarrollo y ejecución del ensayo clínico en el año 2017 en el hospital Celia Sánchez Manduley. El universo y muestra estuvo formado por un total de 87 pacientes, mediante los Cuadernos de Recogida de Datos se obtuvo la información. Las variables que se exploraron fueron la edad, el sexo, los criterios de indicación, la respuesta clínica: antes y después de iniciado el tratamiento con Hebervital y la evaluación de los posibles eventos adversos. Predominó el sexo masculino, las edades más afectadas fueron de 18 a 25 años, la causa más frecuente estuvo representada por la administración de quimioterapia, el 95,4 por ciento obtuvo una respuesta positiva, además en la totalidad de los casos no se presentaron eventos adversos graves. Se cumplió el criterio de éxito de la terapéutica propuesto en la investigación, demostrando que el Hebervital ser un fármaco de apoyo esencial en el tratamiento antineoplásico(AU)

Neutropenia is a globally frequent hematological disorder, which leads to an increased susceptibility to bacterial and fungal infections. The objective of this work is to evaluate the effectiveness and safety of Hebervital administration in patients included in the clinical trial. A descriptive study as carried out in the development and execution of the clinical trial in 2017 at the Celia Sánchez Manduley hospital. The universe and sample consisted of a total of 87 patients, through the Data Collection Notebooks the information was obtained. The variables that were explored were age, sex, criteria of indication, clinical response: before and after the start of treatment with Hebervital and the evaluation of possible adverse events. The male sex predominated, the most affected ages were 18 to 25 years, the most frequent cause was represented by the administration of chemotherapy, 95.4 percent obtained a positive response, in addition in all cases there were no adverse events serious. The criterion of success of the therapeutics proposed in the research was fulfilled, demonstrating that the Hebervital is an essential support drug in the antineoplastic treatment(EU)

Real-World Impact of a Decision Support Tool on Colony-Stimulating Factor Use and Chemotherapy-Induced Febrile Neutropenia Among Patients With Breast Cancer.

Background: White blood cell colony-stimulating factors (CSFs) decrease the incidence of chemotherapy-induced febrile neutropenia (FN). Widespread use of CSFs that is not guideline-concordant has been reported. Among patients with breast cancer receiving chemotherapy, the ability of evidence-based decision support tools to promote risk-appropriate reductions in CSF use without increased incidence of FN has not been examined. Methods: A retrospective cohort design and US commercial claims data were used. The impact of CSF decision support was analyzed among women with breast cancer receiving first-cycle chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented as part of a prior authorization process in 9 states starting July 1, 2014. Patients were assigned to intervention (ie, states where the decision support tool had been implemented) or nonintervention states (ie, 39 states where the tool had not been implemented). CSF use and subsequent incidence of FN were compared using difference-in-difference (DID) regressions adjusting for baseline differences in FN risk factors such as comorbidities and various infections. Results: The study sample of 7,224 patients (intervention states: pre-implementation, 1,991 and post-implementation, 2,010; nonintervention states: pre-implementation, 1,569 and post-implementation, 1,654) showed no significant difference in risk factors. Before and after implementation, a significant decrease in the proportion of patients with CSF use was observed in the intervention states (75% to 69%) compared with no significant change in the nonintervention (72% to 71%) states (DID, -5.4%; 95% CI, -6.0% to -4.7%; P=.006). No significance increase in FN incidence occurred in intervention (5.0% to 5.5%) and nonintervention (5.4% to 4.8%) states (DID, 0.2%; 95% CI, -0.20 to 0.30; P=.78). Similar results were obtained in subgroups by comorbidities and in sensitivity analyses by claims-based FN definitions. Conclusions: CSF use decreased modestly after implementation of the decision support tool, with no observed changes in FN rates. Such tools can reduce practice variation to improve care standards.

Assurance of Myeloid Growth Factor Administration in an Infusion Center: Pilot Quality Improvement Initiative.

PURPOSE: Four incident reports involving missed doses of myeloid growth factors (MGFs) triggered the need for an outcome-driven initiative. From March 1, 2015, to February 29, 2016, at University of California Irvine Health Chao Infusion Center, 116 of 3,300 MGF doses were missed (3.52%), including pegfilgrastim, filgrastim, and sargramostim. We hypothesized that with the application of Lean Six Sigma methodology, we would achieve our primary objective of reducing the number of missed MGF doses to < 0.5%. METHODS: This quality improvement initiative was conducted at Chao Infusion Center as part of a Lean Six Sigma Green Belt Certification Program. Therefore, Lean Six Sigma principles and tools were used throughout each phase of the project. Retrospective and prospective medical record reviews and data analyses were performed to evaluate the extent of the identified problem and impact of the process changes. Improvements included systems applications, practice changes, process modifications, and safety-net procedures. RESULTS: Preintervention, 24 missed doses (20.7%) required patient supportive care measures, resulting in increased hospital costs and decreased quality of care. Postintervention, from June 8, 2016, to August 7, 2016, zero of 489 MGF doses were missed after 2 months of intervention ( P < .001). Chao Infusion Center reduced missed doses from 3.52% to 0%, reaching the goal of < 0.5%. CONCLUSION: The establishment of simplified and standardized processes with safety checks for error prevention increased quality of care. Lean Six Sigma methodology can be applied by other institutions to produce positive outcomes and implement similar practice changes.

Reducing Overuse of Colony-Stimulating Factors in Patients With Lung Cancer Receiving Chemotherapy: Evidence From a Decision Support-Enabled Program.

PURPOSE: Colony-stimulating factors (CSFs) are frequently overused for the primary prevention of febrile neutropenia (FN) in patients receiving chemotherapy. METHODS: A retrospective cohort study design was used to analyze commercial claims data in adults with lung cancer initiated on chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented at oncology practices in phases across 14 US states. Patients were assigned to intervention and nonintervention states according to whether they resided in service areas where the tool had been implemented. Patients were followed up to 6 months after initiating chemotherapy. Difference in pre- and postimplementation CSF use and FN incidence rates were compared with the use of difference-in-differences (DID) models that were adjusted for baseline FN risk factors. RESULTS: The study population of 3,467 patients (intervention states: pre, 707; post, 1,150; nonintervention states: pre, 636; post, 974) showed no significant differences in FN risk factors at baseline. In adjusted results before and after implementation, CSF use decreased from 48.4% to 35.6% in the intervention states versus 43.2% to 44.4% in the nonintervention states (DID, -8.7%; 95% CI, -14.65% to -2.67%; P ≤ .001). The rates of FN were consistent for both groups in both periods, with no statistical difference in trend for the intervention (2.8% to 4.3%) versus the nonintervention (3.1% to 5.1%) states (DID, -0.13; 95% CI, -0.35 to 0.10; P = .927). CONCLUSION: These findings demonstrate that a decision support-enabled utilization management tool can improve risk-appropriate, guideline-adherent CSF use in patients with lung cancer.

Patterns of growth factor usage and febrile neutropenia among older patients with diffuse large B-cell non-Hodgkin lymphoma treated with CHOP or R-CHOP: the Intergroup experience (CALGB 9793; ECOG-SWOG 4494).

Patterns of myeloid growth factor (GF) usage and febrile neutropenia (FN) were examined in patients >60 years of age with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) enrolled on CALGB 9793/ECOG-SWOG 4494, receiving initial therapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or rituximab + CHOP (R-CHOP). Myeloid GFs were administered to 256/520 (49%) patients. Indications for use were: prevent dose reduction/dose delay (81%, 207/256); treat FN or non-febrile neutropenia (NFN) (19%, 48/256). One or more FN episodes occurred in 41% (212/520) of patients, with FN most often in cycle 1 (38% of episodes). In multivariate analysis, risk factors for FN included age >65 years (odds ratio (OR) = 2.6, 95% CI: [1.4, 4.9]) and anemia (hemoglobin <12 g/dl) (OR =2.2, 95% confidence intervals (CI): [1.4, 3.5]. Myeloid GF use was common in this older DLBCL population receiving CHOP-based therapy, as was FN, especially during cycle one. Risk factors predictive for FN should be used prospectively to identify patients for whom myeloid GFs are best utilized.

Burden of Chemotherapy-Induced Febrile Neutropenia Hospitalizations in US Clinical Practice, by Use and Patterns of Prophylaxis with Colony-Stimulating Factor.

INTRODUCTION: Evidence suggests that many cancer chemotherapy patients who are candidates for colony-stimulating factor (CSF) prophylaxis do not receive it or receive it inconsistent with guidelines, and that such patients have a higher risk of febrile neutropenia hospitalization (FNH). Little is known about the number and consequences of FNH by use/patterns of CSF prophylaxis in US clinical practice. METHODS: A retrospective cohort design and private healthcare claims data were employed. Study population comprised adults who received a chemotherapy course with a high-risk regimen, or an intermediate-risk regimen (if ≥1 FN risk factor present), for non-metastatic breast cancer or non-Hodgkin's lymphoma (NHL); each chemotherapy cycle within the course and each FNH episode within the cycles were identified. Consequences included mortality, inpatient days, and costs (US$2013) during FNH. Use (yes/no) and patterns (agent, administration day/duration) of CSF prophylaxis were evaluated within cycles in which FNH episodes occurred. RESULTS: Among all FNH episodes (n=6,355; 109 episodes per 1,000 patients), 41.3% (95% CI: 40.1-42.5) occurred among patients who did not receive CSF prophylaxis in that cycle, and 8.8% (8.1-9.5) occurred among those who received CSF prophylaxis on the same day as chemotherapy. Among FNH episodes occurring in patients who received daily CSF agents (2% of CSF use), 56.1% (44.1-68.0) received prophylaxis <7 days during the cycle. Results for FNH consequences were comparable. CONCLUSIONS: In this retrospective evaluation, one-half of FNH episodes, outcomes, and costs among cancer chemotherapy patients who were candidates for CSF prophylaxis occurred in those who either did not receive it or received it inconsistent with guidelines.

Chemotherapy options for previously untreated acute myeloid leukemia.

INTRODUCTION: Intensive chemotherapy with cytarabine and an anthracycline for untreated acute myeloid leukemia (AML) has remained largely unchanged over the past 40 years, despite many large trials examining the choice and dosing of these agents. AREAS COVERED: We will review the major published clinical trials for untreated AML that have established the dosing choice and schedule for intensive therapy, as well as trials for patients not eligible for more intensive therapy. We will also discuss treatment considerations for subgroups of patients. EXPERT OPINION: While one or two cycles of anthracycline and cytarabine-based combination regimens remain the standard of care for younger and older patients with AML deemed fit to receive induction chemotherapy, controversy remains regarding the optimal selection and dosing schedule for anthracyclines. Low-intensity regimens, such as low-dose cytarabine and hypomethylating agents, can achieve a complete response even with adverse risk features, and can be used in a fit subset of older patients not eligible for clinical trial or transplant. Incorporation of new targeted agents, such as tyrosine kinase and small-molecule inhibitors, combined with better selection of drugs for unique patient cohorts, will likely be necessary to substantially improve outcomes in AML.

Myeloid growth factors.

Febrile neutropenia, a common side effect of myelosuppressive chemotherapy in patients with cancer, can result in prolonged hospitalization and broad-spectrum antibiotic use, often prompting treatment delays or dose reductions of drug regimens. Prophylactic use of myeloid growth factors (mainly the colony-stimulating factors filgrastim and pegfilgrastim) in patients of heightened risk can reduce the severity and duration of febrile neutropenia. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid Growth Factors provide recommendations on the use of these agents mainly in the oncology setting based on clinical evidence and expert consensus. This version includes revisions surrounding the issue of timing of pegfilgrastim administration. It also includes new sections on tbo-filgrastim, a recently approved agent that is biologically similar to filgrastim, and the role of myeloid growth factors in the hematopoietic cell transplant setting.

Factores estimuladores de colonias. Consejos para la autoadministración / Self-administration of colony stimulating factors (CSF'S): basic advice

Como profesionales de enfermería conocemos la importancia de impartir una buena educación sanitaria para conseguir la máxima autonomía en nuestros pacientes. Como enfermeras de una Unidad de Hospital de día médico, en el que tratamos pacientes oncológicos y oncohematológicos que necesitan tratamiento con factores de estimulación de colonias, hemos creído oportuno la elaboración de un díptico informativo sobre la autoadministración de los mismos. Es cierto que los pacientes, gracias a los diferentes medios de comunicación, reciben mucha información pero, desgraciadamente, puede llegar de manera distorsionada, poco comprensible y -en ocasiones- de forma no del todo lícita. Nuestro objetivo es reforzar la autoadministración de este medicamento o, en su defecto, la aplicación por el cuidador principal o familiar. Tras varias pruebas, hemos optado por un díptico más visual que escrito porque creemos que una imagen vale más que mil palabras(AU)

As nurses we all know the importance of good health education to achieve the highest level of autonomy in our patients. In the Medical Day Unit of Palamós Hospital we treat cancer patients who need CSF's (Colony Stimulating Factors) medication. We thought it would be appropriate, therefore, to draw up an information leaflet on self-administration of CSF's. These kind of patients receive a lot of information through the different media but, unfortunately, it can get distorted, unclear, and often, not at all lawful. Our goal is that the patient or, in his absence, the main career can improve the self-administration of the drug. After several tests we have opted for a visual leaflet instead of a written one because we believe that «a picture is worth a thousand words»(AU)

Uptake and economic impact of first-cycle colony-stimulating factor use during adjuvant treatment of breast cancer.

PURPOSE: In 2002, pegfilgrastim was approved by the US Food and Drug Administration and the benefits of dose-dense breast cancer chemotherapy, especially for hormone receptor (HR) -negative tumors, were reported. We examined first-cycle colony-stimulating factor use (FC-CSF) before and after 2002 and estimated US expenditures for dose-dense chemotherapy. METHODS: We identified patients in Surveillance, Epidemiology, and End Results-Medicare greater than 65 years old with stages I to III breast cancer who had greater than one chemotherapy claim within 6 months of diagnosis(1998 to 2005) and classified patients with an average cycle length less than 21 days as having received dose-dense chemotherapy. The associations of patient, tumor, and physician-related factors with the receipt of any colony-stimulating factor (CSF) and FC-CSF use were analyzed by using generalized estimating equations. CSF costs were estimated for patients who were undergoing dose-dense chemotherapy. RESULTS: Among the 10,773 patients identified, 5,266 patients (48.9%) had a CSF claim. CSF use was stable between 1998 and 2002 and increased from 36.8% to 73.7% between 2002 and 2005, FC-CSF use increased from 13.2% to 67.9%, and pegfilgrastim use increased from 4.1% to 83.6%. In a multivariable analysis, CSF use was associated with age and chemotherapy type and negatively associated with black/Hispanic race, rural residence, and shorter chemotherapy duration. FC-CSF use was associated with high socioeconomic status but not with age or race/ethnicity. The US annual CSF expenditure for women with HR-positive tumors treated with dose-dense chemotherapy is estimated to be $38.8 million. CONCLUSION: A rapid increase in FC-CSF use occurred over a short period of time, which was likely a result of the reported benefits of dose-dense chemotherapy and the ease of pegfilgrastim administration. Because of the increasing evidence that elderly HR-positive patients do not benefit from dose-dense chemotherapy, limiting pegfilgrastim use would combat the increasing costs of cancer care.

Hematopoietic growth factors in myelodysplastic syndromes.

Hematopoietic growth factors (HGFs) continue to be the most widely prescribed class of medications for patients with myelodysplastic syndromes (MDS), despite the advent of disease-modifying therapies for MDS (eg, azacitidine, decitabine, and lenalidomide) and the current absence of an MDS-specific US Food and Drug Administration (FDA)-approved indication for any of the HGFs. Erythropoiesis-stimulating agents (ESAs: epoetin alfa, darbepoetin alfa), myeloid growth factors (MGFs: filgrastim, pegfilgrastim, sargramostim), and the newest group of HGFs, thrombopoiesis-stimulating agents (TSAs: romiplostim, eltrombopag), can increase peripheral blood counts in some patients, and may ameliorate some of the signs and symptoms of MDS-associated bone marrow failure. Although HGFs are generally considered "supportive care" measures, recent data suggest that HGFs may alter the natural history of disease in MDS, either for better or worse. This review examines data on the safety and effectiveness of HGFs for patients with MDS.

Use of colony-stimulating factors with chemotherapy: opportunities for cost savings and improved outcomes.

Myeloid colony-stimulating factors (CSFs) decrease the risk of febrile neutropenia (FN) from high-risk chemotherapy regimens administered to patients at 20% or greater risk of FN, but little is known about their use in clinical practice. We evaluated CSF use in a multiregional population-based cohort of lung and colorectal cancer patients (N = 1849). Only 17% (95% confidence interval [CI] = 8% to 26%) patients treated with high-risk chemotherapy regimens received CSFs, compared with 18% (95% CI = 16% to 20%) and 10% (95% CI = 8% to 12%) of patients treated with intermediate- (10%-20% risk of FN) and low-risk (<10% risk of FN) chemotherapy regimens, respectively. Using a generalized estimating equation model, we found that enrollment in a health maintenance organization (HMO) was strongly associated with a lower adjusted odds of discretionary CSF use, compared with non-HMO patients (odds ratio = 0.44, 95% CI = 0.32 to 0.60, P < .001). All statistical tests were two-sided. Overall, 96% (95% CI = 93% to 98%) of CSFs were administered in scenarios where CSF therapy is not recommended by evidence-based guidelines. This finding suggests that policies to decrease CSF use in patients at lower or intermediate risk of FN may yield substantial cost savings without compromising patient outcomes.

Prolonged 18FDG-PET negative complete remission in a heavily pretreated, elderly patient with diffuse large B cell lymphoma treated with lenalidomide, low dose dexamethasone, and colony stimulating factor (Rd-G).

Diffuse large B-cell lymphoma (DLBCL) is a common lymphoid malignancy among adults in the developed world and accounts for about a third of all patients newly diagnosed with non-Hodgkin lymphoma each year. The prognosis of patients with DLBCL has improved over the past 10 years since the advent of chemoimmunotherapy regimens such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). However, a significant number of patients still experience disease relapse or progression after first or second line therapy, and ~40% of patients will die within 5 years. In particular, elderly patients and those ineligible for high-dose chemotherapy due to comorbidities require effective salvage treatment options with favorable toxicity profile. Several novel therapeutic approaches have been proposed for these patients including monoclonal antibodies, radioimmunotherapy, proteasome inhibitors, mTOR inhibitors, and the immunomodulatory drugs such as thalidomide and lenalidomide.

Myeloid growth factors in acute myeloid leukemia: systematic review of randomized controlled trials.

Randomized controlled trials (RCT) investigating administration of colony-stimulating factors (CSF) during or after chemotherapy in acute myeloid leukemia (AML) patients have not been systematically reviewed. We performed a meta-analysis of all reported RCTs comparing prophylactic or concurrent use of CSFs in adult AML patients. Two reviewers extracted data independently. Summary estimates with 95% confidence intervals (CIs) were calculated using a fixed effects model. Fourteen RCTs (n = 4,069 patients) were identified investigating prophylactic CSF administration. Time to neutrophil recovery (>500/µl) was significantly reduced in the CSF group (-4.13 days; 95% CI, -4.23 to -4.04) as was the length of hospitalization (-2.06 days; 95% CI, -2.36 to -1.76). However, no significant reduction in infection-related mortality was observed in CSF-treated compared with control patients (odds ratio (OR) 0.94; 95% CI, 0.8 to 1.1). Prophylactic CSF administration did not impact complete remission (CR) rate or survival. Fourteen RCTs (n = 4,518 patients) were identified investigating administration of CSFs during chemotherapy. Summary estimates of CR, disease/event-free, or overall survival were not significantly different for CSF versus control patients. Prophylactic CSF administration reduces the time to neutrophil recovery and length of hospitalization, but has no impact on documented infections or outcome. Economic analyses of prophylactic CSF administration in AML patients are warranted.