Kraut, Eric H.

The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the appropriate use of growth factors in the clinical management of febrile neutropenia (FN), chemotherapy-induced thrombocytopenia (CIT), and chemotherapy-induced anemia (CIA). Management and prevention of these sequelae are an integral part of supportive care for many patients undergoing cancer treatment. The purpose of these guidelines is to operationalize the evaluation, prevention, and treatment of FN, CIT, and CIA in adult patients with nonmyeloid malignancies and to enable the patient and clinician to assess management options for FN, CIT, and CIA in the context of an individual patient’s condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for Hematopoietic Growth Factors, with particular emphasis on the incorporation of a newly developed section on CIT.

Abstract Introduction It is well established that von Willebrand factor (VWF) levels increase with age among healthy adults. Recently, there is emerging research demonstrating this may also occur in patients with von Willebrand disease (VWD), particularly type 1 VWD, and may be related to comorbidities. Despite increasing VWF levels, it remains unclear as to whether or not this alters bleeding phenotype. It is also unclear why this occurs most commonly in patients with type 1 VWD, but VWF mutation status may play a role. Older patients commonly undergo invasive procedures, and all VWD patients require periprocedural VWD-specific therapy to ensure appropriate hemostasis. If older type 1 VWD patients have experienced normalization of VWF levels, and no longer have an increased risk of bleeding, VWD-specific therapy may increase thrombosis risk, especially among patients with underlying cardiovascular disease or related risk factors, subject the patient to other adverse reactions such as hyponatremia, and is unnecessarily costly. For these reasons, investigation into the effect of age on VWF levels and bleeding risk in type 1 VWD patients is sorely needed. Methods This is an NHLBI-funded K23 multicenter, cross-sectional study to determine the effect of age on VWF levels and bleeding risk in patients with type 1 VWD, and to determine if pathogenic VWF mutations alter this effect.Individuals with a new or historical diagnosis of type 1 VWD (defined as clinical symptoms consistent with VWD and VWF antigen level or ristocetin cofactor activity <0.50 IU/mL) and age 18 or older are enrolled during routine clinic visits at participating Hemophilia Treatment Centers (HTCs). Following enrollment, pertinent medical history is obtained; the condensed MCMDM-1 VWD Bleeding Assessment Tool is administered, with bleeding history based on bleeding symptoms during the past 5 years; and blood samples are collected for the following: VWF antigen (VWF:Ag) level, VWF ristocetin cofactor activity, factor VIII activity, blood type, and VWF gene sequencing. We hypothesize age is associated with increased VWF:Ag levels and lower condensed MCMDM-1 VWD bleeding scores in patients with type 1 VWD, and this association is weaker among those with a pathogenic VWF mutation. In addition, we hypothesize multimorbidity partially explains the association between age and VWF:Ag levels, and VWF:Ag levels partially explain the association between age and condensed MCMDM-1 VWD bleeding scores in patients with type 1 VWD. A sample size of 250 participants provides 90% power to detect an effect size of Beta=±0.032 points per year of age, which is much smaller than the observed effect size, Beta=-0.080, from preliminary data. The primary analyses will be based on multivariable linear regression models with adjustment for blood type O, exogenous estrogen therapy, multimorbidity (defined as 2 or more of the core set of 20 chronic conditions, i.e., cancer, hypertension, stroke, etc., as selected by the United States Department of Health and Human Services), and medications (aspirin, nonsteroidal antiinflammatory drugs, and anticoagulants). In the regression models, two-sided t-tests will be used with an alpha=0.05. Results This multicenter, cross-sectional study consists of seven HTCs: Hemophilia Center of Western Pennsylvania, Children's Hospital of Pennsylvania, Mary M. Gooley Hemophilia Center, Ohio State University, Bleeding & Clotting Disorders Institute, Mayo Clinic, and University of California, San Diego. During the first year of the study, site initiation visits were conducted, regulatory approval obtained, and contracts executed. Delays in these activities occurred in large part due to the COVID-19 pandemic. As the first year of the study concludes, all sites are now active and enrolling participants. Thus far, 43 participants have been enrolled (Table 1). No barriers to enrollment have been encountered and very few patients have declined study participation. Discussion In conclusion, this ongoing multicenter, cross-section study seeks to determine the effect age has on VWF levels and bleeding risk in patients with type 1 VWD while exploring the role of VWF mutations and multimorbidity in this process. The results will be used to justify a longitudinal study, which is the ideal approach to research the effects of aging in this population. Figure 1 Figure 1. Disclosures Seaman: Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; HEMA Biologics: Consultancy, Honoraria. Ragni: Bioverativ (Sanofi): Membership on an entity's Board of Directors or advisory committees; Spark Therapeutics: Membership on an entity's Board of Directors or advisory committees; Takeda Therapeutics: Membership on an entity's Board of Directors or advisory committees; Alnylam (Sanofi): Membership on an entity's Board of Directors or advisory committees; University of Pittsburgh: Research Funding; BioMarin Pharmaceutical: Membership on an entity's Board of Directors or advisory committees. Kraut: Uniqure: Consultancy. Pruthi: CSL Behring: Honoraria; Bayer Healthcare AG: Honoraria; Instrumentation Laboratory: Honoraria; Genentech: Honoraria; HEMA Biologics: Honoraria; Merck: Honoraria. Raffini: CSL Behring: Consultancy; HEMA Biologics: Consultancy; Genentech: Consultancy; Bayer: Consultancy; XaTek: Consultancy. Roberts: Takeda; Speakers Bureau: Novo Nordisk, Octapharma, Sanofi, Takeda.: Research Funding; Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda, uniQure: Consultancy. von Drygalski: Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; uniQure: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Biomarin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hematherix, Inc: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Super FVa.

Hematopoietic growth factors, including erythrocyte stimulating agents (ESAs), granulocyte colony-stimulating factors, and thrombopoietin mimetics, can mitigate anemia, neutropenia, and thrombocytopenia resulting from chemotherapy for the treatment of cancer. In the context of pandemic SARS-CoV-2 infection, patients with cancer have been identified as a group at high risk of morbidity and mortality from this infection. Our subcommittee of the NCCN Hematopoietic Growth Factors Panel convened a voluntary group to review the potential value of expanded use of such growth factors in the current high-risk environment. Although recommendations are available on the NCCN website in the COVID-19 Resources Section (https://www.nccn.org/covid-19/), these suggestions are provided without substantial context or reference. Herein we review the rationale and data underlying the suggested alterations to the use of hematopoietic growth factors for patients with cancer in the COVID-19 era.

Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.

Abstract BACKGROUND: The study of rare diseases is limited by the uncommon nature of the conditions as well as the widely dispersed patient populations. Current rare disease registries such as the National Organization of Rare Diseases utilize centralized platforms for data collection; however because of their broad nature, these do not always capture unique, disease specific elements. Hairy Cell Leukemia (HCL) is a rare leukemia globally with approximately 900 new cases diagnosed in the US each year. The HCL Foundation undertook creation of a Patient Data Registry that collects data from multiple HCL Centers of Excellence (COE) around the globe to better understand the complications, treatment outcomes, disease subtypes, comorbid conditions, epidemiology, and quality of life of patients with HCL. METHODS: Investigators at The Ohio State University Department of Biomedical Informatics and Division of Hematology in collaboration with the HCL Foundation developed a Patient Data Registry (PDR) for the longitudinal capture of high quality research data. This system differs from other registries in that it uses a federated( rather than centralized) architecture, wherein data is queried and integrated in an on-demand manner from local registry databases at each participating site. Further, the data collected for use in the registry combines both automated exports from existing electronic health records (EHRs) as well as additional data entered via a set of web-based forms. All manually entered data comes from source documents, and data provenance spanning electronic and manually entered data is maintained via multiple technical measures. Patients may be enrolled at HCL COE, or, if they do not have access to a COE they may enroll via a web-based portal (www.hairycellleukemia.org). At this time due to regulatory requirements the web-based portal is available to US patients only. All data are de-identified (see Figure 1: De-Identification Workflow) which reduces regulatory burden and increases opportunities for data access and re-use. End users have access to data via a project-specific query portal. RESULTS: The Patient Data Registry has been deployed at The Ohio State University, Royal Marsden Hospital, and MD Anderson Cancer Center, and is undergoing deployment at the University of Rochester. Up to 25 international HCL COE may participate. In addition, US patients are actively entering the registry via the web-based portal. To date, 227 patients have been consented to the registry with 119 of these being via the web-based entry point. CONCLUSION: We created an international and web-based patient data registry which will enable researchers to study outcomes in HCL in ways not previously possible given the rarity of the disease. This work was made possible by research funding from the Hairy Cell Leukemia Foundation. Figure De-Identification Workflow Figure. De-Identification Workflow Disclosures Andritsos: Hairy Cell Leukemia Foundation: Research Funding. Anghelina:Hairy Cell Leukemia Foundation: Research Funding. Lele:Hairy Cell Leukemia Foundation: Research Funding. Burger:Pharmacyclics: Research Funding. Delgado:Gilead: Consultancy, Honoraria; Novartis/GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Infinity: Research Funding. Jones:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lozanski:Beckman Coulter: Research Funding; Genentech: Research Funding; Stemline Therapeutics Inc.: Research Funding; Boehringer Ingelheim: Research Funding. Montserrat:Morphosys: Other: Expert Testimony; Vivia Biotech: Equity Ownership; Gilead: Consultancy, Other: Expert Testimony; Pharmacyclics: Consultancy; Janssen: Honoraria, Other: travel, accommodations, expenses. Parikh:Pharmacyclics: Honoraria, Research Funding. Park:Genentech/Roche: Research Funding; Amgen: Consultancy; Juno Therapeutics: Consultancy, Research Funding. Robak:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Tam:janssen: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Heckler:Hairy Cell Leukemia Foundation: Research Funding. Payne:Hairy Cell Leukemia Foundation: Research Funding.

AbstractHairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.