Ratio of stemness to interferon signalling as a biomarker and therapeutic target of myeloproliferative neoplasm progression to acute myeloid leukaemia.

Progression to aggressive secondary acute myeloid leukaemia (sAML) poses a significant challenge in the management of myeloproliferative neoplasms (MPNs). Since the physiopathology of MPN is closely linked to the activation of interferon (IFN) signalling and that AML initiation and aggressiveness is driven by leukaemia stem cells (LSCs), we investigated these pathways in MPN to sAML progression. We found that high IFN signalling correlated with low LSC signalling in MPN and AML samples, while MPN progression and AML transformation were characterized by decreased IFN signalling and increased LSC signature. A high LSC to IFN expression ratio in MPN patients was associated with adverse clinical prognosis and higher colony forming potential. Moreover, treatment with hypomethylating agents (HMAs) activates the IFN signalling pathway in MPN cells by inducing a viral mimicry response. This response is characterized by double-stranded RNA (dsRNA) formation and MDA5/RIG-I activation. The HMA-induced IFN response leads to a reduction in LSC signature, resulting in decreased stemness. These findings reveal the frequent evasion of viral mimicry during MPN-to-sAML progression, establish the LSC-to-IFN expression ratio as a progression biomarker, and suggests that HMAs treatment can lead to haematological response in murine models by re-activating dsRNA-associated IFN signalling.

Shared-care model for complex chronic haematological malignancies.

Myeloproliferative neoplasms (MPNs) are a group of rare Philadelphia-negative chronic leukemias. Disease rarity has resulted in limited expertise concentrated in specialist centres. Patients are often referred to such expert centres for diagnostic issues, complex decision-making, access to novel drugs through clinical trials, and supportive care. Attending such appointments may increase financial and travel burden, increase caregiver stress, and negatively impact quality of life. To address this, the MPN program at Princess Margaret (PM) Cancer Centre has implemented a shared-care model, working with local healthcare providers to provide ongoing management, and supportive care for MPN patients closer to home. This decreases patient travel burden, while maintaining high-quality patient-centered care. In this article we share our experience implementing the shared-care model. This model is potentially applicable to other chronic hematological malignancies and rare chronic diseases. The ultimate goal of shared-care is not to centralize care, but instead to build a community of accessible care for the patient.

Implementation of the Standards for adult immunization practice: A survey of U.S. Health care providers.

The revised Standards for Adult Immunization Practice ("Standards"), published in 2014, recommend routine vaccination assessment, strong provider recommendation, vaccine administration or referral, and documentation of vaccines administered into immunization information systems (IIS). We assessed clinician and pharmacist implementation of the Standards in the United States from 2016 to 2018. Participating clinicians (family and internal medicine physicians, obstetricians-gynecologists, specialty physicians, physician assistants, and nurse practitioners) and pharmacists responded using an internet panel survey. Weighted proportion of clinicians and pharmacists reporting full implementation of each component of the Standards were calculated. Adjusted prevalence ratio (APR) estimates of practice characteristics associated with self-reported implementation of the Standards are also presented. Across all medical specialties, the percentages of clinicians and pharmacists implementing the vaccine assessment and recommendation components of the Standards were >80.0%. However, due to low IIS documentation, full implementation of the Standards was low overall, ranging from 30.4% for specialty medicine to 45.8% in family medicine clinicians. The presence of an immunization champion (APR, 1.40 [95% confidence interval {CI}, 1.26 to 1.54]), use of standing orders (APR, 1.41 [95% CI, 1.27 to 1.57]), and use of a patient reminder-recall system (APR, 1.39 [95% CI, 1.26 to 1.54]) were positively associated with adherence to the Standards by clinicians. Similar results were observed for pharmacists. Nonetheless, vaccination improvement strategies, i.e., having standing orders in place, empowering an immunization champion, and using patient recall-reminder systems were underutilized in clinical settings; full implementation of the Standards was inconsistent across all health care provider practices.

Survival following allogeneic transplant in patients with myelofibrosis.

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.

Patterns of Ruxolitinib Therapy Failure and Its Management in Myelofibrosis: Perspectives of the Canadian Myeloproliferative Neoplasm Group.

Ruxolitinib improves splenomegaly and other disease-related symptoms in patients with myelofibrosis, but over time, many patients lose this benefit. It is difficult to determine whether this is due to resistance or intolerance to the drug; thus, we have used the more inclusive term of ruxolitinib failure. The survival of patients with myelofibrosis after ruxolitinib failure is poor but varies significantly by the pattern of the failure, underlining the need for a clinically appropriate classification. In this review, we propose diagnostic guidance for early recognition of the pattern of ruxolitinib failure and we recommend treatment options. The most frequent patterns of ruxolitinib failure are loss or failure to obtain a significant reduction in splenomegaly or symptom response, and the development or persistence of clinically significant cytopenias. Ruxolitinib dose modification and other ancillary therapies are sometimes helpful, and splenectomy is a palliative option in selected cases. Stem-cell transplantation is the only curative option for these patterns of failure, but its restricted applicability due to toxicity highlights the importance of ongoing clinical trials in this area. Recent approval of fedratinib by the US Food and Drug Administration provides an alternative option for patients with suboptimal or loss of spleen response. The transformation of myelofibrosis to accelerated or blast phase is an infrequent form of failure with an extremely poor prognosis, whereby patients who are ineligible for transplantation have limited treatment options.

Tetanus, Diphtheria, and Acellular Pertussis and Influenza Vaccinations among Women With a Live Birth, Internet Panel Survey, 2017-2018.

OBJECTIVES: Pregnant women are at increased risk of complications from influenza, and infants are at increased risk of pertussis. Maternal influenza and Tdap (tetanus, diphtheria, and acellular pertussis) vaccination can reduce risk of these infections and related complications. Our objective was to estimate vaccination coverage with influenza and Tdap vaccines during pregnancy among women with a recent live birth. METHODS: An opt-in Internet panel survey was conducted from March 28 to April 10, 2018 among pregnant and recently pregnant women. Respondents with a live birth from August 1, 2017 through the date in which the participant completed the survey were included in the analysis. Receipt of influenza vaccination since July 1, 2017 and Tdap vaccination during pregnancy were assessed by sociodemographic characteristics, receipt of a health care provider (HCP) recommendation and/or offer of vaccination, and vaccination-related knowledge, attitudes, and beliefs. RESULTS: Less than a third (30.3%) of women with a live birth were unvaccinated during their pregnancy with both Tdap and influenza vaccines. Almost a third (32.8%) of the women reported being vaccinated with both vaccines. The majority (73.0%) of women reported receiving an HCP recommendation for both vaccines, and 54.2% of women were offered both vaccines by an HCP. Reasons for nonvaccination included negative attitudes toward influenza vaccine and lack of awareness about Tdap vaccination during pregnancy. CONCLUSIONS: Maternal Tdap and influenza vaccinations can prevent morbidity and mortality among infants and their mothers, yet many pregnant women are unvaccinated with either Tdap or influenza vaccines. Clinic-based education, along with interventions, such as standing orders and provider reminders, are strategies to increase maternal vaccination.

The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes.

There is a paucity of data regarding the impact of mutations on outcomes in accelerated-phase (AP) and blast-phase (BP) myeloproliferative neoplasms (MPNs). Moreover, it is unknown whether mutational status affects survival, as seen in chronic-phase MPNs. Therefore, we performed a retrospective analysis of all patients treated at our institution with AP/BP MPNs (N = 122; AP = 14; BP = 108) to comprehensively describe the mutational profile and correlate with clinical outcomes. Targeted sequencing with a 54-gene panel was performed. Forty-four patients were treated with intensive therapy, 27 with nonintensive therapy, and 51 with best supportive care (BSC). The most common mutation was JAK2V617F, occurring in 55% of subjects; CALR was found in 13% of patients and MPL in 6%. Thirty-two (26%) patients were triple negative. Other frequently mutated genes were ASXL1 (30%), TET2 (25%), SRSF2 (22%), RUNX1 (20%), and TP53 (17%). Mutations in 1, 2, 3, and ≥4 genes were seen in 15%, 13%, 25%, and 46% of patients, respectively. There was no difference in survival between patients treated with intensive vs nonintensive therapy, and the benefit of intensive therapy was limited to patients who were able to undergo transplantation. TP53 was the only individual mutation to correlate with shorter overall survival (hazard ratio, 1.89; P = .03). In the multivariate analysis, mutated TP53, ≥4 mutations, low albumin, increased peripheral blood blasts, ≥3 cytogenetic abnormalities, and BSC were associated with shorter survival. In conclusion, mutational data enhance the understanding of patients with AP/BP MPN who are likely to benefit from current therapeutic options.

Influenza Vaccination Coverage Among Health Care Personnel - United States, 2017-18 Influenza Season.

The Advisory Committee on Immunization Practices (ACIP) recommends that all health care personnel receive an annual influenza vaccination to reduce influenza-related morbidity and mortality among health care personnel and their patients and to reduce absenteeism among health care personnel (1-4). CDC conducted an opt-in Internet panel survey of 2,265 U.S. health care personnel to estimate influenza vaccination coverage among these persons during the 2017-18 influenza season. Overall, 78.4% of health care personnel reported receiving influenza vaccination during the 2017-18 season, similar to reported coverage in the previous four influenza seasons (5). As in previous seasons, coverage was highest among personnel who were required by their employer to be vaccinated (94.8%) and lowest among those working in settings where vaccination was not required, promoted, or offered on-site (47.6%). Health care personnel working in long-term care settings, the majority of whom work as assistants or aides, have lower influenza vaccination coverage than do health care personnel working in all other health care settings, which puts the elderly in long-term settings at increased risk for severe complications for influenza. Implementing workplace strategies shown to improve vaccination coverage among health care personnel, including vaccination requirements and active promotion of on-site vaccinations at no cost, can help ensure health care personnel and patients are protected against influenza (6). CDC's long-term care web-based toolkit* provides resources, strategies, and educational materials for increasing influenza vaccination among health care personnel in long-term care settings.

Influenza and Tdap Vaccination Coverage Among Pregnant Women - United States, April 2018.

Vaccinating pregnant women with influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines can reduce the risk for influenza and pertussis for themselves and their infants. The Advisory Committee on Immunization Practices (ACIP) recommends that all women who are or might be pregnant during the influenza season receive influenza vaccine, which can be administered any time during pregnancy (1). The ACIP also recommends that women receive Tdap during each pregnancy, preferably from 27 through 36 weeks' gestation (2). To assess influenza and Tdap vaccination coverage among women pregnant during the 2017-18 influenza season, CDC analyzed data from an Internet panel survey conducted during March 28-April 10, 2018. Among 1,771 survey respondents pregnant during the peak influenza vaccination period (October 2017-January 2018), 49.1% reported receiving influenza vaccine before or during their pregnancy. Among 700 respondents who had a live birth, 54.4% reported receiving Tdap during their pregnancy. Women who reported receiving a provider offer of vaccination had higher vaccination coverage than did women who received a recommendation but no offer and women who did not receive a recommendation. Reasons for nonvaccination included concern about effectiveness of the influenza vaccine and lack of knowledge regarding the need for Tdap vaccination during every pregnancy. Provider offers or referrals for vaccination in combination with patient education could reduce missed opportunities for vaccination and increase vaccination coverage among pregnant women.

U.S. clinicians' and pharmacists' reported barriers to implementation of the Standards for Adult Immunization Practice.

BACKGROUND: The Standards for Adult Immunization Practice (Standards), revised in 2014, emphasize that adult-care providers assess vaccination status of adult patients at every visit, recommend vaccination, administer needed vaccines or refer to a vaccinating provider, and document vaccinations administered in state/local immunization information systems (IIS). Providers report numerous systems- and provider-level barriers to vaccinating adults, such as billing, payment issues, lower prioritization of vaccines due to competing demands, and lack of information about the use and utility of IIS. Barriers to vaccination result in missed opportunities to vaccinate adults and contribute to low vaccination coverage. Clinicians' (physicians, physician assistants, nurse practitioners) and pharmacists' reported barriers to assessment, recommendation, administration, referral, and documentation, provider vaccination practices, and perceptions regarding their adult patients' attitudes toward vaccines were evaluated. METHODS: Data from non-probability-based Internet panel surveys of U.S. clinicians (n = 1714) and pharmacists (n = 261) conducted in February-March 2017 were analyzed using SUDAAN. Weighted proportion of reported barriers to assessment, recommendation, administration, referral, and documentation in IIS were calculated. RESULTS: High percentages (70.0%-97.4%) of clinicians and pharmacists reported they routinely assessed, recommended, administered, and/or referred adults for vaccination. Among those who administered vaccines, 31.6% clinicians' and 38.4% pharmacists' submitted records to IIS. Reported barriers included: (a) assessment barriers: vaccination of adults is not within their scope of practice, inadequate reimbursement for vaccinations; (b) administration barriers: lack of staff to manage/administer vaccines, absence of necessary vaccine storage and handling equipment and provisions; and (c) documentation barriers: unaware if state/city has IIS that includes adults or not sure how their electronic system would link to IIS. CONCLUSION: Although many clinicians and pharmacists reported implementing most of the individual components of the Standards, with the exception of IIS use, there are discrepancies in providers' reported actual practices and their beliefs/perceptions, and barriers to vaccinating adults remain.

Clinicians' and Pharmacists' Reported Implementation of Vaccination Practices for Adults.

INTRODUCTION: Despite the proven effectiveness of immunization in preventing morbidity and mortality, adult vaccines remain underutilized. The objective of this study was to describe clinicians' and pharmacists' self-reported implementation of the Standards for Adult Immunization Practice ("the Standards"; i.e., routine assessment, recommendation, and administration/referral for needed vaccines, and documentation of administered vaccines, including in immunization information systems). METHODS: Two Internet panel surveys (one among clinicians and one among pharmacists) were conducted during February-March 2017 and asked respondents about their practice's implementation of the Standards. T-tests assessed associations between clinician medical specialty, vaccine type, and each component of the Standards (March-August 2017). RESULTS: Implementation of the Standards varied substantially by vaccine and provider type. For example, >80.0% of providers, including obstetrician/gynecologists and subspecialists, assessed for and recommended influenza vaccine. However, 24.3% of obstetrician/gynecologists and 48.9% of subspecialists did not stock influenza vaccine for administration. Although zoster vaccine was recommended by >89.0% of primary care providers, <58.0% stocked the vaccine; by contrast, 91.6% of pharmacists stocked zoster vaccine. Vaccine needs assessments, recommendations, and stocking/referrals also varied by provider type for pneumococcal; tetanus, diphtheria, acellular pertussis; tetanus diphtheria; human papillomavirus; and hepatitis B vaccines. CONCLUSIONS: This report highlights gaps in access to vaccines recommended for adults across the spectrum of provider specialties. Greater implementation of the Standards by all providers could improve adult vaccination rates in the U.S. by reducing missed opportunities to recommend vaccinations and either vaccinate or refer patients to vaccine providers.

Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience.

Although next-generation sequencing (NGS) has helped characterize the complex genomic landscape of myeloid malignancies, its clinical utility remains undefined. This has resulted in variable funding for NGS testing, limiting its accessibility. At our center, targeted sequencing (TAR-SEQ) using a 54-gene NGS myeloid panel is offered to all new patients referred for myeloid malignancies, as part of a prospective observational study. Here, we evaluated the diagnostic, prognostic, and potential therapeutic utility of clinical grade TAR-SEQ in the routine workflow of 179 patients with myeloproliferative neoplasms (MPN). Of 13 patients with triple negative (TN) MPN, who lacked driver mutations in JAK2, CALR, and MPL, TAR-SEQ confirmed clonal hematopoiesis in 8 patients. In patients with intermediate-risk myelofibrosis (MF), TAR-SEQ helped optimize clinical decisions in hematopoietic cell transplant (HCT)-eligible patients through identifying a high molecular risk (HMR) mutation profile. The presence of an HMR profile favored HCT in 9 patients with intermediate-1 risk MF. Absence of an HMR profile resulted in a delayed HCT strategy in 10 patients with intermediate-2 risk MF, 7 of which were stable at the last follow-up. Finally, TAR-SEQ identified patients with various targetable mutations in IDH1/2 (4%), spliceosome genes (28%), and EZH2 (7%). Some of these patients can be potential candidates for future targeted therapy trials. In conclusion, we have demonstrated that TAR-SEQ improves the characterization of TN MPN, can be integrated in clinical practice as an additional tool to refine decision making in HCT, and has the potential to identify candidates for future targeted therapy trials.

Influenza Vaccination Coverage Among Health Care Personnel - United States, 2016-17 Influenza Season.

The Advisory Committee on Immunization Practices (ACIP) recommends that all health care personnel (HCP) receive an annual influenza vaccination to reduce influenza-related morbidity and mortality among HCP and their patients and to reduce absenteeism among HCP (1-4). To estimate influenza vaccination coverage among HCP in the United States during the 2016-17 influenza season, CDC conducted an opt-in Internet panel survey of 2,438 HCP. Overall, 78.6% of survey respondents reported receiving vaccination during the 2016-17 season, similar to reported coverage in the previous three influenza seasons (5). Vaccination coverage continued to be higher among HCP working in hospitals (92.3%) and lower among HCP working in ambulatory (76.1%) and long-term care (LTC) (68.0%) settings. As in previous seasons, coverage was highest among HCP who were required by their employer to be vaccinated (96.7%) and lowest among HCP working in settings where vaccination was not required, promoted, or offered on-site (45.8%). Implementing workplace strategies found to improve vaccination coverage among HCP, including vaccination requirements or active promotion of on-site vaccinations at no cost, can help ensure that HCP and patients are protected against influenza (6).

Influenza Vaccination Coverage Among Pregnant Women - United States, 2016-17 Influenza Season.

Pregnant women and their infants are at increased risk for severe influenza-associated illness (1), and since 2004, the Advisory Committee on Immunization Practices (ACIP) has recommended influenza vaccination for all women who are or might be pregnant during the influenza season, regardless of the trimester of the pregnancy (2). To assess influenza vaccination coverage among pregnant women during the 2016-17 influenza season, CDC analyzed data from an Internet panel survey conducted during March 28-April 7, 2017. Among 1,893 survey respondents pregnant at any time during October 2016-January 2017, 53.6% reported having received influenza vaccination before (16.2%) or during (37.4%) pregnancy, similar to coverage during the preceding four influenza seasons. Also similar to the preceding influenza season, 67.3% of women reported receiving a provider offer for influenza vaccination, 11.9% reported receiving a recommendation but no offer, and 20.7% reported receiving no recommendation; among these women, reported influenza vaccination coverage was 70.5%, 43.7%, and 14.8%, respectively. Among women who received a provider offer for vaccination, vaccination coverage differed by race/ethnicity, education, insurance type, and other sociodemographic factors. Use of evidence-based practices such as provider reminders and standing orders could reduce missed opportunities for vaccination and increase vaccination coverage among pregnant women.

Distribution and Impact of Comorbidities on Survival and Leukemic Transformation in Myeloproliferative Neoplasm-Associated Myelofibrosis: A Retrospective Cohort Study.

BACKGROUND: We sought to describe the distribution and impact of comorbidities on outcomes in patients with myelofibrosis, a disease characterized by aberrant bone marrow function with eventual fibrosis. Comorbidities were scored using the Adult Comorbidity Evaluation-27 (ACE-27) and the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), in which a score ≥ 3 indicates severe comorbidities. PATIENTS AND METHODS: We conducted a retrospective study of 306 patients with a confirmed diagnosis of myelofibrosis. Patients were seen from 1999 to 2014 with a median follow-up of 2 years. Multivariable Cox proportional hazards models were constructed to assess the impact of comorbidities on overall survival and leukemic transformation from the date of presentation to our center. A series of descriptive analyses were performed examining the distribution of comorbidities captured by the scales. RESULTS: On multivariable survival analysis, an ACE-27 score of 3 was associated with an almost twofold increase in the risk of all-cause death (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.06-3.58; P = .03) compared with a lower score of 0 to 1. An HCT-CI score ≥ 3 was marginally significantly associated with an increased risk of all-cause death (HR 1.60; 95% CI 0.96-2.68; P = .07). ACE-27 captured a greater spectrum of cardiovascular and venous thrombotic disease. No impact of comorbidities on leukemic transformation was observed. CONCLUSIONS: Although the presence of severe comorbidities was lower when assessed by ACE-27 (13%) compared with HCT-CI (23%), and the spectrums of comorbidities captured were different, the overall impact of severe comorbidities as assessed by both scales appears to be similar and associated with a survival disadvantage.

Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy.

In myelofibrosis (MF), driver mutations in JAK2, MPL, or CALR impact survival and progression to blast phase, with the greatest risk conferred by triple-negative status. Subclonal mutations, including mutations in high-molecular risk (HMR) genes, such as ASXL1, EZH2, IDH1/2, and SRSF2 have also been associated with inferior prognosis. However, data evaluating the impact of next-generation sequencing in MF patients treated with JAK1/2 inhibitors are lacking. Using a 54-gene myeloid panel, we performed targeted sequencing on 100 MF patients treated with ruxolitinib (n = 77) or momelotinib (n = 23) and correlated mutational profiles with treatment outcomes. Ninety-nine patients had at least 1 mutation identified, 46 (46%) had 2 mutations, and 34 (34%) patients had ≥3 mutations. Seventy-nine patients carried a mutation in JAK2V617F, 14 patients had mutations in CALR, 6 patients had an MPL mutation, and 2 patients were triple negative. No mutation was significantly associated with spleen or anemia response. A high Dynamic International Prognostic Scoring System score and pretreatment transfusion dependence were associated with a shorter time to treatment failure (TTF), and this association retained significance on multivariable analysis. Patients with ASXL1 (hazard ratio [HR], 1.86; P = .03) and EZH2 mutations (HR, 2.94; P = .009) and an HMR profile (HR, 2.06; P = .01) had shorter TTF. On multivariate analysis, ASXL1 or EZH2 mutations were independently associated with shorter TTF and overall survival. These findings help identify patients unlikely to have a durable response with current JAK1/2 inhibitors and provide a framework for future studies.

Does DNA replication direct locus-specific recombination during host immune evasion by antigenic variation in the African trypanosome?

All pathogens must survive host immune attack and, amongst the survival strategies that have evolved, antigenic variation is a particularly widespread reaction to thwart adaptive immunity. Though the reactions that underlie antigenic variation are highly varied, recombination by gene conversion is a widespread approach to immune survival in bacterial and eukaryotic pathogens. In the African trypanosome, antigenic variation involves gene conversion-catalysed movement of a huge number of variant surface glycoprotein (VSG) genes into a few telomeric sites for VSG expression, amongst which only a single site is actively transcribed at one time. Genetic evidence indicates VSG gene conversion has co-opted the general genome maintenance reaction of homologous recombination, aligning the reaction strategy with targeted rearrangements found in many organisms. What is less clear is how gene conversion might be initiated within the locality of the VSG expression sites. Here, we discuss three emerging models for VSG switching initiation and ask how these compare with processes for adaptive genome change found in other organisms.

Myelofibrosis: to transplant or not to transplant?

Hematopoietic cell transplantation (HCT) is the only curative therapeutic modality for myelofibrosis (MF) at present. The optimal timing of HCT is not known in the presence of wider availability of less risky nontransplant therapies such as JAK 1/2 inhibitors. Careful review of patient, disease, and transplant-related factors is required in the appropriate selection of HCT vs the best available nontransplant therapies. We highlight some of the relevant issues and positioning of HCT in light of evolving data on JAK 1/2 inhibitors. The goal of this study is to provide the reader with updated evidence of HCT for MF, recognizing that knowledge in this area is limited by the absence of comparative studies between HCT and nontransplant therapies. Prospective studies are needed for better information on: the determination of optimal timing and conditioning regimens, the best way to integrate JAK inhibitors in the HCT protocols, and the impact of JAK inhibitors on graft-versus-host disease.

Influenza Vaccination Coverage Among Health Care Personnel - United States, 2015-16 Influenza Season.

The Advisory Committee on Immunization Practices recommends annual influenza vaccination for all health care personnel to reduce influenza-related morbidity and mortality among both health care personnel and their patients (1-4). To estimate influenza vaccination coverage among U.S. health care personnel for the 2015-16 influenza season, CDC conducted an opt-in Internet panel survey of 2,258 health care personnel during March 28-April 14, 2016. Overall, 79.0% of survey participants reported receiving an influenza vaccination during the 2015-16 season, similar to the 77.3% coverage reported for the 2014-15 season (5). Coverage in long-term care settings increased by 5.3 percentage points compared with the previous season. Vaccination coverage continued to be higher among health care personnel working in hospitals (91.2%) and lower among health care personnel working in ambulatory (79.8%) and long-term care settings (69.2%). Coverage continued to be highest among physicians (95.6%) and lowest among assistants and aides (64.1%), and highest overall among health care personnel who were required by their employer to be vaccinated (96.5%). Among health care personnel working in settings where vaccination was neither required, promoted, nor offered onsite, vaccination coverage continued to be low (44.9%). An increased percentage of health care personnel reporting a vaccination requirement or onsite vaccination availability compared with earlier influenza seasons might have contributed to the overall increase in vaccination coverage during the past 6 influenza seasons.