The new landscape of therapy for myelofibrosis.

The landscape of therapy for myelofibrosis (MF) is evolving at a pace not previously seen for this clonal myeloproliferative neoplasm. The discovery of the JAK2 V617F mutation in 2005 has led to the rapid development of therapy specifically developed for afflicted MF patients. Indeed, the successful phase III studies of ruxolitinib demonstrating improved symptomatic burden, splenomegaly and survival led to the first approved myelofibrosis drug in the United States and Europe. Multiple additional JAK2 inhibitors are currently in or nearing phase III testing, including SAR302503 (fedratinib), SB1518 (pacritinib) and CYT387 (momelotinib), seeking to offer incremental benefits to ruxolitinib in regards to cytopenias or other disease features. In parallel, phase III testing of pomalidomide is ongoing, with the goal of solidifying the role of immunomodulatory therapy in MF-associated anemia. Multiple single agents strategies are ongoing with histone deacetylase inhibitors, hedgehog inhibitors and hypomethylation agents. Incremental advances are further sought, either in additive or synergistic fashion, from combination strategies of ruxolitinib with multiple different approaches ranging from allogeneic stem cell transplant to current therapies mitigating anemia and further impacting the bone marrow microenvironment or histology. Transitioning from a pre-2011 era devoid of approved MF therapies to one of multiple agents that target not only disease course but symptomatic burden has indeed changed the platform from which MF providers are able to launch individualized treatment plans. In this article, we discuss the diagnostic and therapeutic milestones achieved through MF research and review the emerging pharmacologic agents on the treatment horizon.

Cognitive enhancement drug use among future physicians: findings from a multi-institutional census of medical students.

BACKGROUND: Nonmedical use of prescription psychostimulants such as methylphenidate and amphetamine salts for the purpose of cognitive enhancement is a growing trend, particularly in educational environments. To our knowledge, no recent studies have evaluated the use of these psychostimulants in a medical academic setting. OBJECTIVE: To conduct an online census of psychostimulant use among medical students. DESIGN: In 2011, we conducted a multi-institutional census using a 31-48 item online survey regarding use of prescription psychostimulants. PARTICIPANTS: 2,732 actively enrolled medical students at four private and public medical schools in the greater Chicago area. MAIN MEASURES: Prevalence and correlates of psychostimulant use KEY RESULTS: 1,115 (41 %) of students responded to the web-based questionnaire (range 26-47 % among schools). On average, students were 25.1 years of age (SD = 2.7, range 20-49), and single (70 %). Overall, 18 % (198/1,115) of this medical student sample had used prescription psychostimulants at least once in their lifetime, with first use most often in college. Of these, 11 % (117/1,115) of students reported use during medical school (range 7-16 % among schools). Psychostimulant use was significantly correlated with use of barbiturates, ecstasy, and tranquilizers (Pearson's correlation r > 0.5, Student's t-test p < 0.01); male gender (21 % male versus 15 % female, Chi squared p = 0.007); and training at a medical school which by student self-report determined class rank (68 % versus 51 %, Chi-squared p = 0.018). Non-users were more likely to be first year students (Chi-squared p = 0.048) or to have grown up outside of the United States (Chi-squared p = 0.013). CONCLUSIONS: Use of psychostimulants, including use without a prescription, is common among medical students. Further study of the side effects, medical implications, and use during post-graduate medical training and medical practice is needed to inform evidence-based policy.

Patients with polycythemia vera have worst impairment of quality of life among patients with newly diagnosed myeloproliferative neoplasms.

The quality of life (QoL) at the time of diagnosis of myeloproliferative neoplasm (MPN) has, to date, not been studied. One hundred and seventy-nine patients with MPN: 80 with essential thrombocythemia (ET), 73 with polycythemia vera (PV), 22 with primary myelofibrosis (PMF) and four with MPN undifferentiated, were included in this study. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQC30) and the MPN-Symptom Assessment Form (MPN-SAF) were used to evaluate QoL. Fatigue was the most reported symptom in these patients. Patients with PV reported significantly higher mean scores for inactivity, dizziness, cough, itching, depression and lower total QoL compared to patients with ET. Patients with PV had significantly more headache and itching compared to patients with PMF. When the newly diagnosed patients with MPN were compared with a cohort of patients with MPN with mean disease duration of 7.8 years, the differences were most striking for patients with PMF, with significantly more fatigue, abdominal discomfort, concentration problems, insomnia, fever, weight loss and lower overall QoL developed over time.

Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs.

PURPOSE: Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy. PATIENTS AND METHODS: The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. RESULTS: MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P<.001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) for patients with essential thrombocythemia, polycythemia vera, and myelofibrosis, respectively. The MPN-SAF TSS strongly correlated with overall quality of life (QOL; r=0.59; P<.001) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) functional scales (all P<.001 and absolute r≥0.50 except social functioning r=0.48). No significant trends were present when comparing therapy subgroups. The MPN-SAF TSS had excellent internal consistency (Cronbach's α=.83). Factor analysis identified a single underlying construct, indicating that the MPN-SAF TSS is an appropriate, unified scoring method. CONCLUSION: The MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptom study to date. This new prospective scoring method may be used to assess MPN symptom burden in both clinical practice and trial settings.