Pine, Alexander B.

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.

Abstract Background. Gene mutation profiling is increasingly employed for diagnosis, risk stratification, and clinical management in patients with MDS. However, current World Health Organization MDS classification is still based on histologic findings (with the exception of SF3B1 for MDS-RS), and guidelines generally suggest that clinical decisions be guided by clinico-pathologic risk stratification tools such as Revised International Prognostic Scoring System (IPSS-R). We sought to study beliefs and patterns of practice with respect to gene mutation profiling among health care providers who manage patients with MDS. Methods. A link to a 23-question web-based survey was emailed to members of the Eastern Cooperative Oncology Group (ECOG)-ACRIN Cancer Research Group, Alliance for Clinical Trials in Oncology (Alliance), and the Southwest Oncology Group (SWOG), and the Cancer Trials Support Unit (CTSU) on 5/1/2018 with 6 subsequent weekly reminders. The Qualtrics survey platform was used to record anonymous responses. We used descriptive statistics to analyze the data. No incentive was provided for responses. Results. Of 371 received responses, 262 were received from providers who did not manage MDS patients or lacked analyzable data and therefore were excluded. Of 109 eligible responses, 108 responders were from institutions representing 31 US states (one respondent was from South America). Median age of respondents was 48 years (range, 33-75); 43 (39%) were women. A third of responders (32%) worked at a university hospital, while 25%, 17%, and 5% worked at a community hospital, private practice, or other settings, respectively. While 37% of participants worked at institutions with guidelines for clinical care of MDS patients, 28% reported that their institutional guidelines recommended MDS-specific gene mutation profiling. Such testing was performed at institutions of 13% participants; institutions of 26% of responders tested a general AML panel that included MDS-specific genes. The total number of respondents whose institutions sent out either an MDS-specific gene panel or a general AML gene panel with MDS-specific genes was similar, 25% and 12%, respectively (Fig. 1). Of those who routinely perform molecular testing, 94% do so at diagnosis, 56% at relapse, 33% during preparation for stem cell transplant, 31% after the failure of hypomethylating agents (HMA), 24% during screening for a clinical trial, and 15% at initial treatment (Fig. 2). MDS gene mutation profiling was felt to be most helpful in diagnosis (rarely 11%; sometimes 49%; often 30%; always 9%), risk stratification (sometimes 31%; often 51%; always 15%), and prognosis (sometimes 31%; often 51%; always 14%); its role was more limited in response assessment (never 12%; rarely 25%; sometimes 44%; often 14%) and to predict responses to HMAs (never 5%; rarely 28%; sometimes 52%, often 14%) (Fig. 3). Various types of evidence were used to stratify MDS risk and prognosis: genetic mutations were used by nearly everyone (95%); 70% relied on morphologic findings, while gene expression/transcriptome profiling was used by 40%. Eighty-four percent of responders reported relying on conventional prognostic models like IPSS-R to identify high-risk patients for whom they would consider intensive treatment options. For this purpose, 62% would also rely on mutation profiling, and 32% would also consider higher frequency of gene mutations. While mutations in the p53 pathway were felt to be helpful in terms of risk stratification and treatment decisions by 70% of responders, 43%, 39%, 31%, 26% 23%, 20%, and 3% considered mutations in spliceosome, DNA methylation, transcription factors, histone modification, signaling, RAS pathway, and cohesin genes, respectively, to be useful as well. Approximately 31% of responders were not certain as to which mutations would affect risk stratification and management choices and said they needed to review literature. The respondents also cited multiple limitations to wider clinical use of MDS gene mutation profiling (Fig. 4). Conclusions. Our survey demonstrates widespread use of gene mutation profiling in the management of patients with MDS, but also reveals substantial variability in beliefs, practices, testing logistics, and interpretation of molecular profiling. Our findings emphasize the need for high-quality data to develop consensus evidence-based guidelines for gene profiling of MDS patients. Disclosures Sekeres: Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Bejar:AbbVie/Genentech: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Foundation Medicine: Consultancy; Astex/Otsuka: Consultancy, Honoraria; Modus Outcomes: Consultancy; Takeda: Research Funding; Genoptix: Consultancy. Gore:Celgene: Consultancy, Research Funding. Zeidan:Ariad: Consultancy, Speakers Bureau; Gilead: Consultancy; Incyte: Employment; Celgene: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Novartis: Consultancy; Pfizer: Consultancy.

Abstract Background. Transfusion of blood products is an integral component of the management of patients with acute leukemias. However, high-quality evidence and clinical trial data to support specific practices of blood product transfusion in this population are limited. We hypothesized that there is wide variation in blood product transfusion practices among providers in North America who manage patients with acute leukemia. Methods. A 30-question web-based survey about transfusion practices was emailed to members of the Eastern Cooperative Oncology Group (ECOG)-ACRIN Cancer Research Group, Alliance for Clinical Trials in Oncology (Alliance), and the Southwest Oncology Group (SWOG), and the Cancer Trials Support Unit (CTSU) on 7/6/2015 with 4 subsequent weekly reminders. The distribution list included 9,859 recipients, of whom at least 741 were providers who treated patients with acute leukemia. Responses were anonymous, and the survey distribution was approved by the respective cooperative group chairs. Descriptive statistics were used to analyze the data. Results. Of 254 responses received, 113 were excluded as they were returned by recipients not directly treating patients with acute leukemia. Another 30 responses were excluded due to incomplete data, leaving 111 responses (43.7%) eligible for the primary analysis. Of those, 109 responders were from North America representing 83 institutions in 33 states and the province of Ontario. Eighty-four of the included responders (75.7%) were physicians, and 44 (39.6%) were females. Median age of responders was 44 years (range, 26-76). A hemoglobin (Hb) level of ≤7 g/dL was the most commonly used threshold (44%) for red blood cell (RBCs) transfusions to asymptomatic stable hospitalized patients, followed closely by 8 g/dL (38%) (Figure 1). In the outpatient setting, the most commonly reported threshold was 8 gm/dL (49%) (Figure 1). Most providers reported that they "always" use leukocyte-reduced (93%) and irradiated (79%) RBCs. A platelet level of 10,000/µL was the threshold for platelet transfusions in the stable non-bleeding hospitalized patients cited by the majority of responders (76%) (Figure 2). This platelet level remained the most common threshold for platelet transfusions for non-bleeding patients in the outpatient setting (49%), although 31% of responders reported a higher threshold of 20,000/µL. A preference for single-donor apheresis platelets was reported by 81% respondents, and 57% use these products exclusively. Most providers (70%) reported always using irradiated platelets. With respect to cryoprecipitate and plasma infusions, nearly half of the respondents reported a threshold fibrinogen level of 100 mg/dL as a trigger for administering a product to a stable non-bleeding patient (Figure 3). The most commonly reported platelet threshold for performing a bone marrow biopsy (BMB) was 10,000/μL (69% of responders), followed by 20,000 (21%), 50,000 (6%), and 30,000 (4%). Therapeutic anticoagulation was held by most responders (80%) before performing a BMB. Most responders (73%) reported a platelet level of 50,000/µL as the lowest level for performing a lumbar puncture (LP) without prophylactic platelet transfusion. Conclusions. This survey demonstrates wide variability in blood product transfusion patterns among providers who treat patients with acute leukemias. A platelet level of 10,000/µL is the most common trigger for platelet transfusions for stable non-bleeding patients in both inpatient and outpatient settings. This, along with a platelet threshold of 50,000/µL for performing an LP, appear to be most widely accepted practices. Our findings emphasize the need to obtain high-quality data to develop consensus evidence-based guidelines for transfusion practices in acute leukemia with the goal of limiting unnecessary transfusions without compromising patient outcomes. Figure 1. The most common reported hemoglobin level thresholds for red blood cell transfusions in the inpatient and outpatient settings. Figure 1. The most common reported hemoglobin level thresholds for red blood cell transfusions in the inpatient and outpatient settings. Figure 2. The most common reported platelet level thresholds for platelet transfusions in the inpatient and outpatient settings. Figure 2. The most common reported platelet level thresholds for platelet transfusions in the inpatient and outpatient settings. Figure 3. The most common reported fibrinogen level thresholds for cryoprecipitate or plasma transfusions in the inpatient and outpatient settings. Figure 3. The most common reported fibrinogen level thresholds for cryoprecipitate or plasma transfusions in the inpatient and outpatient settings. Disclosures Sekeres: TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Steensma:Onconova: Consultancy; Incyte: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Prebet:CELGENE: Research Funding. Komrokji:Celgene: Consultancy, Research Funding; Incite: Consultancy; Novartis: Speakers Bureau; GSK: Research Funding. Stone:Merck: Consultancy; AROG: Consultancy; Celgene: Consultancy; Sunesis: Consultancy, Other: DSMB for clinical trial; Abbvie: Consultancy; Novartis: Research Funding; Juno: Consultancy; Amgen: Consultancy; Roche/Genetech: Consultancy; Celator: Consultancy; Agios: Consultancy; Karyopharm: Consultancy; Pfizer: Consultancy. Erba:GlycoMimetics; Janssen: Other: Data Safety & Monitoring Committees; Sunesis; Pfizer; Daiichi Sankyo; Ariad: Consultancy; Millennium/Takeda; Celator; Astellas: Research Funding; Seattle Genetics; Amgen: Consultancy, Research Funding; Novartis; Incyte; Celgene: Consultancy, Patents & Royalties. Barbarotta:Celgene, BMS, Novartis: Speakers Bureau. Gore:Celgene: Consultancy, Honoraria, Research Funding.

BACKGROUNDTransfusion of blood products is a key component of the supportive management in patients with acute leukemia (AL). However high‐quality trial evidence and clinical outcome data to support specific transfusion goals for blood products for patients with AL remain limited leading to diverse transfusion practices. The primary objective of this study was to determine the spectrum of transfusion patterns in a variety of care settings among providers who treat AL patients.STUDY DESIGN AND METHODSA 31‐question survey queried providers caring for AL patients about the existence of institutional guidelines for transfusion of blood products, transfusion triggers for hemoglobin (Hb), platelets (PLTs), and fibrinogen in various settings including inpatient and outpatient and before procedures.RESULTSWe analyzed 130 responses and identified divergent transfusion Hb goals in hospitalized and ambulatory patients, fibrinogen goals for cryoprecipitate transfusions, and variation in practice for use of certain PLTs and red blood cell products. The least variable transfusion patterns were reported for PLT goals in thrombocytopenia and in the setting of invasive procedures such as bone marrow biopsy and lumbar punctures.CONCLUSIONSThis survey confirmed wide variations in blood product transfusion practices across several clinical scenarios in patients with AL. The findings emphasized the need for large prospective randomized trials to develop standardized evidence‐based guidelines for blood product transfusions in patients with AL with the goal of limiting unnecessary transfusions without compromising outcomes.