scholarly journals Managing BCR-ABL 1 Negative Myeloproliferative Neoplasms in an Emerging Economic Environment

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5489-5489
Author(s):  
Amma A. Benneh ◽  
Eugenia Vicky Naa Kwarley Asare ◽  
Edeghonghon Olayemi
Keyword(s):  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Medical Center ◽  
Treatment Options ◽  
Polycythaemia Vera ◽  
Research Fund ◽  
Diagnosis And Management ◽  
University Of Ghana ◽  
Vanderbilt University ◽  
Fund Research

Abstract Background: Myeloproliferative neoplasms (MPN) are a group of diseases characterized by clonal disorders of the pluripotent stem cell. The annual incidence of all subtypes of MPN is 6-10/100,000 population. MPN without Philadelphia chromosome or BCR-ABL1 fusion gene such as Polycythaemia Vera(PV), Essential Thrombocythaemia (ET) and Myelofibrosis (MF) are known as BCR-ABL1 negative MPN. Diagnosis and management of these conditions in a limited resource environment can be challenging. Some successes have however been chalked when diagnostic and therapeutic difficulties have been overcome. Methodology: A retrospective patient chart review of patients who attended Hematology clinic at the Department of Hematology, Korle-Bu Teaching Hospital was conducted between January 2005 and December 2015.This review included all adult patients diagnosed with PV, ET and MF over the period. Diagnosis of MPN was made mainly by film comment, bone marrow aspirate, trephine biopsy and JAK 2 mutation analysis if patient could afford. Patients records were analyzed for demographic characteristics, clinical signs, hematological parameters, treatment options and outcomes. Results: The annual incidence of MPN over the period under study was 2.4 per year. The median age was 46 (range 24 - 75) years. There was male predominance of 1.9: 1. Splenomegaly was the commonest organomegaly seen. Polycythaemia Vera was the commonest (10; 38.5%) BCR-ABL1 negative MPN to be diagnosed at the hospital within the period. Treatment options available for patients with PV was venesection and hydroxycarbamide. For ET and MF it was hydroxycarbamide and supportive treatment. The longest survivor within the period of study has lived with Polycythaemia Vera for the past 10 years. Conclusion: The diagnosis and management of BCR-ABL1 negative MPN in emerging economic environments can be challenging as resources are limited. Certain conditions such as Hyperreactive malarial splenomegaly (HMS) can also mimic MPN and as such a high index of suspicion coupled with appropriate diagnostic facilities are required for early diagnosis and prompt management. Despite these odds, the disease is controlled reasonably well in our environment giving the patients more years of quality life than they would have had without any intervention. Disclosures Asare: Intramural University of Ghana Research fund: Research Funding; Vanderbilt University Medical Center Gift Funds: Research Funding. Olayemi:Intramural University of Ghana Research fund: Research Funding; Vanderbilt University Medical Center Gift Funds: Research Funding.

Prospective Implementation of Multi-Disciplinary Obstetric Team Decreases the Mortality Rate of Pregnant Women with Sickle Cell Disease in Ghana

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1017-1017 ◽  
Author(s):  
Eugenia Vicky Naa Kwarley Asare ◽  
Yvonne Adomakoh ◽  
Edeghonghon Olayemi ◽  
Enoch Mensah ◽  
Harriet Ghansah ◽  
...  
Keyword(s):  
Maternal Mortality ◽  
Pregnant Women ◽  
Research Funding ◽  
Medical Center ◽  
Research Fund ◽  
Intervention Period ◽  
Post Intervention ◽  
Post Intervention Period ◽  
University Of Ghana ◽  
Fund Research

Abstract Introduction: Pregnant women with sickle cell disease (SCD) are at increased risk for both pregnancy and SCD related morbidity and mortality. At the Korle-Bu Teaching Hospital (KBTH), a national referral center in Accra, Ghana, the estimated maternal mortality ratio of women with and without SCD is 8,300 and 690 per 100,000 live births respectively (US, general population, maternal mortality ratio 14 per 100, 000 live births). In 2015, a multi-disciplinary obstetric SCD team was formed comprising obstetricians, hematologists, pulmonologists and nurses. In a before and after study design, we tested the hypothesis that implementing a multi-disciplinary team for care of pregnant women with SCD would significantly decrease maternal mortality. Methodology: The study received ethical approval from the Ethical and Protocol Review Committee, College of Health Sciences, University of Ghana Institutional Review Board and Vanderbilt University Medical Center (Data Coordinating Center (DCC). The pre-intervention period was from January 2014 to April 2015, and the post intervention period was May 2015 to May 2016. During the intervention period, members of the multi-disciplinary team evaluated participants at enrollment, during outpatient visits and during acute illnesses (inpatient and outpatient). Simple protocols were implemented for preventing and treating Acute Chest Syndrome (ACS). Balloons were purchased (substituted for incentive spirometry devices) and used routinely during management of acute pain episodes and after surgery. Multiple pulse oximetry machines were integrated into routine clinical practice for monitoring of oxygen desaturation. Close maternal and fetal monitoring were implemented. During the pre-intervention period, pregnant women were admitted to multiple wards throughout the hospital. Post-intervention, pregnant women were primarily admitted to two designated wards at the Obstetrics Department, for better coordinated care. All participants in the post-intervention period were followed from enrollment until six weeks postpartum. Members of the clinical research team and DCC adjudicated every vaso-occlusive pain episode, ACS episode, and acute event requiring hospitalization. Pain was defined as an acute episode, unrelated to labor and requiring hospitalization. ACS was defined based on the presence of at least 2 of the following criteria: fever, increased respiratory rate, chest pain, pulmonary auscultatory findings, increased O2 requirement or new radiodensity on chest roentgenogram. Results: A total of 154 and 91 deliveries by women with SCD were evaluated in the pre- and post-intervention period, respectively. The median age for cases in the pre-intervention period was 29 (range 18- 43) years. The median age for cases in post-intervention period was 29 (range 18-41) years and 35 participants had hemoglobin SSand 56had HbSC. Among the 91 participants, rates of pain and ACS were 194.6 (64/32.89) and 42.6 (14/32.89) events per 100 patient-years, respectively. Median gestational age at enrollment was 24 (range 7 - 40) weeks. Median gestational age at delivery was 38 (range 26 - 41) weeks. Perinatal mortality rates pre- and post-intervention were 74.3 per 1000 total births (11/ 148 X 1000) and 54.9 per 1000 total births (5/91 X 1000) respectively. Maternal mortality pre- and post-intervention were 9.7% (15 of 154) and 1.1% (1 of 91) of total deliveries respectively. The maternal mortality ratio pre- and post-intervention were 10,949 (15/137) and 1,163 (1/86) per 100,000 live births respectively. Cause of death pre-intervention period included: cardiopulmonary disease-60.0%, preeclampsia-6.67%, acute kidney injury-6.67%, severe anemia-20.0%, hypovolemic shock-6.67%. During the post-intervention period, the only death was an autopsy confirmed massive pulmonary embolism four days postpartum. Conclusion: In a low and middle income setting, a multidisciplinary team approach to care of pregnant women with SCD can dramatically decrease maternal mortality, as well as perinatal mortality. Further strategies must be employed to decrease the SCD related maternal mortality and perinatal mortality rates to levels expected in the non-SCD population and to implement multi-disciplinary SCD obstetric teams in other regions. Disclosures Asare: Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. Adomakoh:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. Olayemi:Intramural University of Ghana Research fund: Research Funding; Vanderbilt University Medical Center Gift Funds: Research Funding. Mensah:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. Ghansah:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. Osei- Bonsu:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. Crabbe:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. Musah:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. Hayfron- Benjamin:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. Boafor:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. Kassim:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding. James:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research Fund: Research Funding. Oppong:Vanderbilt University Medical Center Gift Funds: Research Funding; Intramural University of Ghana Research fund: Research Funding.

scholarly journals Targeted Exome Sequencing Identifies Novel Mutations in Familial Myeloproliferative Neoplasms Patients in the State of Qatar

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5570-5570 ◽  
Author(s):  
Nader I Al-Dewik ◽  
Bruno Cassinat ◽  
Jean-Jacques Kiladjian ◽  
Alexander Knuth ◽  
Mohamed A. Yassin
Keyword(s):  
Exome Sequencing ◽  
Research Funding ◽  
Germ Line ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Genetic Alterations ◽  
Molecular Techniques ◽  
Research Fund ◽  
Healthy Individuals ◽  
Targeted Exome Sequencing

Abstract Background: Myeloproliferative Neoplasms (MPNs) are clonal hematopoietic disorders characterized by excessive proliferation of one or more myeloid cell lineages. Philadelphia negative MPNs include Polycythemia Vera (PV), Essential Thrombocytosis (ET) & Primary Myelofibrosis (PMF). MPNs are associated with the presence JAK2 V617F mutation in 95% of PV & 50% of ET & PMF patients. Several molecular techniques such as RQ-PCR, HRM & Sequencing are currently used to detect common mutations. However, there are still significant numbers of MPNs that are negative to the most common genetic anomalies & many mutations are still unknown. The advent of Next Generation Sequencing (NGS) gives the opportunity to study relevant mutations in several genes. Aim: Utilizing NGS to identify potential genetic anomalies causing familial MPNs patients in Qatar. Methods: 6 MPNs patients from consanguineous families & 5 healthy individuals were consented into the study & peripheral blood samples were collected. gDNA was extracted & used for multiplex PCR amplification of amplicons targeting cancer associated mutations in 28 key genes (JAK2, MPL, THPO, CBL, LNK, SH2B3, NF1, SOCS1/2/3, TP53, NRAS/KRAS, NF1, IDH1/2, EZH2, ASXL1, TET2, ATM, KIT, RB, TP53, IKZF1, RUNX1, PDGFRB, TERT & CALR) using the Ion AmpliSeq Kit. NGS was performed via the Ion Torrent using the 318 chip & data was analyzed with the Torrent Suite Software. Mutation details were obtained from COSMIC database. A hg 19 sequence was used as reference. The confirmation of NGS data was performed using RQ-PCR or Sequencing. Results: 11 samples were successfully sequenced, with a mean depth of 1500 reads & the FASTQC plugin indicated good quality sequencing metrics. JAK2 V617F, JAK2 exon 12-15 & MPL (S505N, W515 L/K) negative samples tested before via RQ-PCR, HRM & sequencing were called negative by NGS. NGS identified novel deleterious mutations in MPNs patients. Out of 6 familial cases, 5 patients (P1- P5) were ET & 1 patient (P6) was PV. P1 had JAK2 V617F, ASXL1 T600P, CBFB G180S, THPO S184R &ITGA2R76Q, P2 had JAK2 V617F, MPL A554G & ATM F582L, the other three Patients (P3, P4 & P5) had CLAR K385fs*47 & one PV patient (P6) had TYK2 E1163G, ASXL1 P808H, PDGFRB P4L & TERT G300fs. Among the patients & healthy individuals, mutations/SNVs such as MPL P106L, K553N, SH2B3 L476F, ATM F1036F KIT N564S & TET2 T730R were also found Discussion & conclusion: Initial screening of known common genes (JAK2 V617F, JAK2 exon 12-15 & MPL W515 L/K) mutations did not reveal the causative mutations in 3% of 180 PV patients, 52% of 200 ET patients & 77% of 20 PMF patients. In this study, several deleterious somatic & germ-line mutations & SNVs were identified using Targeted Exome Sequencing approach. A complex combination of mutations in JAK2, THPO, ITGA2 & MPL genes occurred in ET patients & coexistence of several oncogenic events in TYK2, ASXL1, PDGFRB & TERT occurred in PV patient. This finding may also suggest that the MPNs phenotype may depend on presence of other mutations. It is worth mentioning that the presence of ATM variant in P2 is associated with increased risk of CLL. Somatic CALR type-2 mutation was identified in 3 ET (nonmutated JAK2 or MPL) patients. This mutation is 5-bp TTGTC insertion in exon 9 that generates a mutant protein with a novel C-terminal (p.K385fs*47). In patients & healthy individuals, a heterozygous germ-line mutation in exon 3 of the MPL gene (MPL P106L) has been observed. it has previously been described as a rare autosomal-dominant disorder. However, this mutation is considered to be frequent in Arabic populations, leading to severe thrombocytosis in homozygotes & occasionally to mild thrombocytosis in heterozygotes. In addition, several unreported variants of uncertain significance were identified. Our preliminary results suggested that MPNs patients in Qatar have several potential disease- associated variants & mutations. Evidences show that there exists a possibility of the disease arising out of the accumulation of genetic alterations & not as the consequence of a single genetic-hit event. This could possibly be due to the high rate of consanguineous marriages in Qatar i.e. the "Founder Effect". Our results recommended carrying out WES to explore & identify mutations which will be crucial to characterize many cases of MPNs with unknown molecular causes, gain a deep understanding of genotype-phenotype correlations & MPNs pathogenesis. Disclosures Al-Dewik: Qatar National Research Fund: Patents & Royalties, Research Funding. Yassin:Qatar National research fund: Patents & Royalties, Research Funding.

scholarly journals Advancing Personalized Care for Patients with Myeloproliferative Neoplasms (MPNs): Findings from a Phase 2 Scale-up Quality Initiative across Two Large U.S. Oncology Systems

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1911-1911
Author(s):  
Srdan Verstovsek ◽  
Ruben A. Mesa ◽  
Shelby Sullivan ◽  
Jeffrey D Carter ◽  
Cherilyn Heggen
Keyword(s):  
Decision Making ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Treatment Options ◽  
Treatment Decision ◽  
Patient Centered Care ◽  
Patient Centered ◽  
Treatment Decision Making ◽  
Black Patients ◽  
Centered Care

Abstract Background Myeloproliferative neoplasms (MPNs), a group of rare hematologic malignancies comprised of myelofibrosis, polycythemia vera and essential thrombocythemia, significantly impact the lives of patients with historically few effective treatment options. In this quality improvement (QI) initiative we assessed barriers to patient-centered MPN care in 2 large U.S. hospital systems. Methods Between 3/2021 and 5/2021, 24 hematology/oncology healthcare professionals (HCPs) from 2 large hospital systems completed surveys designed to characterize self-reported practice patterns, challenges, and barriers to collaborative MPN care. Additionally, 26 Black patients and 25 non-Black patients with MPNs completed surveys regarding their goals for treatment, barriers to care, and communication with providers. Findings from all surveys paired with patient chart data was presented to 18 HCPs from the systems in AF sessions to reflect on their own practice patterns and prioritize areas for improvement in MPN care. Participants developed team-based action plans to overcome identified challenges, including barriers in risk stratification, care coordination, and shared decision-making (SDM) for patients with MPNs. Surveys conducted before and after the small-group AF sessions evaluated changes in participants' knowledge and confidence in delivering collaborative, patient-centered MPN care. Results Team-Based Surveys: HCPs identified difficulty managing their symptoms (35%) and difficulty choosing therapy that best meets their treatment preferences and goals (25%) as the most pressing challenges their patient's face in their MPN care. The most challenging issue encountered by HCPs in selecting therapies for patients with MPNs is identifying when patients are undergoing disease progression/transformation (48%). HCPs reported effects on quality of life (75%) and treatment effectiveness (65%) as the most important factors for treatment decision-making among patients with MPNs. Teams were underutilizing SDM to provide patient-centered care, citing not enough time to engage in SDM (55%) and patients' low health literacy (50%) as the largest barriers. Patient Surveys: In contrast to HCP responses, the biggest challenge faced in their MPN care reported by Black patients was lack of reliable transportation or long distance to and from my care center (46%) difficulty managing my symptoms (36%) for non-Black patients. Furthermore, Black patients with MPN identified cost of treatment (56%) and advice from loved ones (40%) as the top factors for treatment decision-making, whereas, non-Black patients cited how the treatment is taken (52%) and how well the treatment will control my symptoms (50%). All patients identified they wish they had more time to discuss goals and preferences for treatment (62% Black, 64% non-Black ) with their provider. Black patients reported their MPN care team could improve most in education about MPNs and treatment options (73%), while non-Black patients felt improvements in empathy throughout the emotional journey of managing my MPN (68%) would be most beneficial. Small-Group AF Sessions: Across the 2 oncology centers, teams participating in the AF sessions (Table 1) shared a self-reported caseload of 219 patients with MPNs per month. HCPs reported meaningful shifts in confidence in their ability to provide optimal, patient-centered care (Figure 1) and knowledge of treatment options for MPNs (Figure 2). The aspects of patient-centered care HCPs will routinely discuss in more detail with patients are patients' goal and preferences (81%), results of genetic testing (63%), and risks and benefits of treatment options (56%). To achieve these goals, 63% of HCPs committed to improve team skills in appropriate risk stratification and differentiation of therapy based on patient-centered factors followed by sharing action plans with additional clinical team members (56%). Conclusions Participation in this QI initiative resulted in increased confidence in hematology/oncology HCPs ability to deliver patient-centered MPN care and improve commitment to team-based collaboration. Remaining practice gaps and challenges can inform future QI programs. Study Sponsor Statement The study reported in this abstract was funded by an independent educational grant from Incyte Corporation. The grantors had no role in the study design, execution, analysis, or reporting. Figure 1 Figure 1. Disclosures Verstovsek: CTI BioPharma: Research Funding; NS Pharma: Research Funding; Ital Pharma: Research Funding; Celgene: Consultancy, Research Funding; Roche: Research Funding; Protagonist Therapeutics: Research Funding; Promedior: Research Funding; PharmaEssentia: Research Funding; Gilead: Research Funding; Incyte Corporation: Consultancy, Research Funding; Genentech: Research Funding; Blueprint Medicines Corp: Research Funding; AstraZeneca: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; Constellation: Consultancy; Pragmatist: Consultancy. Mesa: Sierra Oncology: Consultancy, Research Funding; Gilead: Research Funding; Novartis: Consultancy; Celgene: Research Funding; Genentech: Research Funding; CTI: Research Funding; Abbvie: Research Funding; CTI: Research Funding; Incyte Corporation: Consultancy, Research Funding; Promedior: Research Funding; Samus: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding; Pharma: Consultancy; AOP: Consultancy; La Jolla Pharma: Consultancy.

Myeloproliferative Neoplasms: An in-Depth Case-Control (MOSAICC) Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1621-1621
Author(s):  
Mary Frances McMullin ◽  
Andrew Duncombe ◽  
Glen J. Titmarsh ◽  
Frank de Vocht ◽  
Lin Fritschi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Conflict Of Interest ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Case Control ◽  
Research Network ◽  
Polycythaemia Vera ◽  
Solvent Exposure ◽  
High Exposure ◽  
Occupational Risk Factors

Abstract Introduction The Classic Myeloproliferative Neoplasms (MPNs), characterised by an over production of one or more cells of the myeloid lineage, are classified into polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF). Despite the identification of numerous genetic mutations, a paucity of information relating to medical and lifestyle factors contributing to the aetiology of these diseases remains. Methods The MOSAICC Study was an exploratory case-control study of MPNs. MPN patients were recruited between two sites, Belfast and Southampton, in preparation for a planned UK-wide investigation. Population controls (identified by General Practitioners) and non-blood relative/friend controls were also recruited. Participants completed a telephone-based questionnaire seeking information on a range of medical, environmental, lifestyle and occupational risk factors. Risk factors were assessed using unconditional logistic regression with adjustment for potential confounders. Results Risk factors identified included smoking [≥25 pack years vs. never: odds ratio (OR) 3.14, 95% confidence interval (CI) 1.26-7.87], increasing childhood household density [>2 vs <1 Child(ren)/room: OR 3.29, 95% CI 1.31-8.30], history of heart disease (OR 3.31, 95% CI 1.23-8.87), CT scans (≥3 vs. none: OR 4.92, 95% CI 1.55-15.67), having an implant (OR 10.77, 95% CI 1.01-3.10), and pig ownership (OR 5.92, 95% CI 1.17-29.92). Alcohol was associated with a reduced risk of MPNs (OR 0.49, 95% CI 0.28-0.88) as was home working on car exhausts (OR 0.33, 95% CI 0.12-0.88), painting at home (OR 0.49, 95% CI 0.28-0.86) and short haul air travel (p for trend 0.012). Participants working in occupations with high exposure to environmental tobacco smoke had an excess risk of MPN (OR 2.45, 95% CI 1.12-5.37). Work-based radiation and solvent exposure also appeared to increase risk of MPNs (p<0.05). Conclusions This exploratory study has confirmed a reported association between cigarette smoking and MPNs. It has identified some potential novel risk factors including work-based radiation and solvent exposure. The findings of this study need to be replicated in a larger, adequately powered, study in order to identify important risk factors for the classic MPNs. Conflict of Interest The authors declare no conflict of interest. Acknowledgments: The MOSAICC Study team acknowledges the support of the National Institute for Health Research, through the Northern Ireland Cancer Research Network (NICRN) and for Southampton the Central South Coast Cancer Network (CSCCN). The team thank those who have participated in the MOSAICC study and the personnel who assisted in the recruitment of patients. Disclosures Mesa: CTI Biopharma: Research Funding; Promedior: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Incyte Corporation: Research Funding; Pfizer: Research Funding; NS Pharma: Research Funding; Genentech: Research Funding; Gilead: Research Funding.

Using Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) to Evaluate Quality of Life for MPN Patients in Qatar

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5069-5069
Author(s):  
Mohamed A. Yassin ◽  
Hanadi Rafii El-Ayoubi ◽  
Nader Al-Dewik
Keyword(s):  
Weight Loss ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Symptom Assessment ◽  
Research Fund ◽  
Eortc Qlq C30 ◽  
Night Sweats ◽  
Eortc Qlq ◽  
Pearson Correlations

Abstract Abstract 5069 Background: Myeloproliferative neoplasms (MPNs), that is, essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are a group of MPNs that can lead to significant rates of morbidity and mortality among affected patients. Specifically, patients in the early stages of these illnesses (ET, PV, and early MF) can be predisposed to thrombohemorrhagic events and vascular complications. Long-term complications of MPNs (either primary MF or MF arising from an antecedent ET or PV) can include progressive cytopenias, constitutional symptoms, cachexia and weight loss, moderate to massive splenomegaly, and risk of blastic transformation. Symptomatic burden in myeloproliferative neoplasms (MPNs) is present in most of MPN patients We sought to use broadly applicable instrument (MPN-SAF) to assess symptoms in myelofibrosis (MF), essential thrombocythemia (ET) and polycythemia vera (PV) among populations of Qatar. Methods: Using the MF-SAF as a base instrument, we added several key additional symptoms previously identified as present in all subtypes of MPNs including headaches, concentration, dizziness, extremity tingling, insomnia, sexual problems and mood changes on a 0 (absent) to 10 (worst-imaginable) scale. The MPN-SAF was administered jointly with the EORTC-QLQ-C30 as the co-validation instrument using prospective cohorts in Qatar (Patients referred to National Centre for Cancer Care and Research). Results: MPN-SAF Patient data: 123 MPN-SAF surveys were administered (English (45%), Arabic (55%) in 45 ET patients (36. 5 %%), 35 PV patients (28. 5%), and 15 MF patients (12. 2%), 28 MPN unclassified (22. 7%) an average of 7. 8 years (range 0 – 43 years) from their MPN diagnosis. Participants were of, age range (26 – 58 years) and gender (52% female) characteristic of disease. Prior hemorrhage (10%) and thrombosis (25%) were frequent. 78% of patients currently received cytoreductive therapy and 87% received cytoreductive therapy in the past. Patients and Symptomatic Burden: 19 items assessed in the MPN-SAF demonstrated consistently that the most common symptoms were decreased quality of life (93%), fatigue (84%), insomnia (65%), sad mood (65%), and sexuality problems (62%). The least common symptoms (<50% prevalence) were fevers (15%), weight loss (10%), abdominal pain (23%), cough (34%), headache (50%), and bone pain (48%). Symptoms were most severe in MF, followed by ET, then PV patients. Although symptoms are present in all 3 MPN subgroups, itching is notably more burdensome in PV patients (65%, median score of 2. 8 out of 10). Interestingly, night sweats (present in 58%). The majority found the MPN-SAF easy to understand (92%) and “addressed most of my MPN symptoms” (95%). Comparison to EORTC-QLQ-C30: Strong correlations existed between individual items represented on both the MPN-SAF and the EORTC-QLQC30 including pain, fatigue, appetite and insomnia (all p<0. 001). Additionally key symptomatic elements were highly correlated with the EORTC QLQ-C30 functional subscales. Comparison to Physician Perceptions: Comparison of the results of the MPN-SAF to enrolling physicians' blinded opinion of patients symptoms (8 assessed - night sweats, fevers, fatigue, weight loss, bone pain, and pruritus) showed excellent correlation with corresponding patients' responses (all p<0. 001). Serial MPN-SAF Results: Pearson correlations indicate that most MPN-SAF items are well correlated (r >0. 5, p<. 001) upon repeat survey administration. Items characteristic of advanced disease, including weight loss, fever, and cough displayed lower Pearson correlations (r=0. 46, −0. 08, and 0. 38 respectively). Conclusions: The MPN-SAF is comprehensive and reliable instrument which is available in multiple languages (including Arabic and English) to evaluate MPN-associated symptoms. The MPN-SAF is recommended as a uniform symptom assessment tool for MPN patient. Disclosures: Yassin: Qatar National Research Fund: Patents & Royalties, Research Funding. Off Label Use: use of pegelated interferon alfa 2a in treatment of patients with ET. Rafii El-Ayoubi:Qatar National Research Fund: Patents & Royalties, Research Funding. Al-Dewik:Qatar National Research Fund: Patents & Royalties, Research Funding.

scholarly journals Patterns of Survival Among Patients With Myeloproliferative Neoplasms Diagnosed in Sweden From 1973 to 2008: A Population-Based Study

2012 ◽  
Vol 30 (24) ◽  
pp. 2995-3001 ◽  
Author(s):  
Malin Hultcrantz ◽  
Sigurdur Yngvi Kristinsson ◽  
Therese M.-L. Andersson ◽  
Ola Landgren ◽  
Sandra Eloranta ◽  
...  
Keyword(s):  
General Population ◽  
Life Expectancy ◽  
Excess Mortality ◽  
Myeloproliferative Neoplasms ◽  
Treatment Options ◽  
Large Population ◽  
Relative Survival ◽  
Population Based ◽  
Population Based Study ◽  
Over Time

PurposeReported survival in patients with myeloproliferative neoplasms (MPNs) shows great variation. Patients with primary myelofibrosis (PMF) have substantially reduced life expectancy, whereas patients with polycythemia vera (PV) and essential thrombocythemia (ET) have moderately reduced survival in most, but not all, studies. We conducted a large population-based study to establish patterns of survival in more than 9,000 patients with MPNs.Patients and MethodsWe identified 9,384 patients with MPNs (from the Swedish Cancer Register) diagnosed from 1973 to 2008 (divided into four calendar periods) with follow-up to 2009. Relative survival ratios (RSRs) and excess mortality rate ratios were computed as measures of survival.ResultsPatient survival was considerably lower in all MPN subtypes compared with expected survival in the general population, reflected in 10-year RSRs of 0.64 (95% CI, 0.62 to 0.67) in patients with PV, 0.68 (95% CI, 0.64 to 0.71) in those with ET, and 0.21 (95% CI, 0.18 to 0.25) in those with PMF. Excess mortality was observed in patients with any MPN subtype during all four calendar periods (P < .001). Survival improved significantly over time (P < .001); however, the improvement was less pronounced after the year 2000 and was confined to patients with PV and ET.ConclusionWe found patients with any MPN subtype to have significantly reduced life expectancy compared with the general population. The improvement over time is most likely explained by better overall clinical management of patients with MPN. The decreased life expectancy even in the most recent calendar period emphasizes the need for new treatment options for these patients.

NEWS AND ANNOUNCEMENTS

PEDIATRICS ◽  
1959 ◽  
Vol 23 (1) ◽  
pp. 179-183
Keyword(s):  
Medical Center ◽  
Ohio State University ◽  
City Hospital ◽  
State University ◽  
University Of Michigan ◽  
Contagious Diseases ◽  
Ann Arbor ◽  
The University ◽  
Vanderbilt University ◽  
Michigan Medical

Postgraduate Courses—AAP The first two of a series of postgraduate courses being sponsored by the American Academy of Pediatrics will be held at the University of Michigan Medical Center, Ann Arbor, Michigan, March 2, 3, 4, and 5, 1959; and at Vanderbilt University Medical Center, Nashville, Tennessee, on March 17, 18, and 19, 1959. Tuition for these courses is $50 and $40, respectively, for Academy members. Fees for nonmembers will be $70 and $60, respectively. These courses will both be organized so that each day will be devoted to papers and discussions on a different pediatric problem. At the University of Michigan, Dr. James Wilson and the pediatric staff will be hosts, as well as part of the faculty for the course. Other speakers will include members of other departments and the guest speakers, Dr. Warren Wheeler, Professor of Pediatrics and Bacteriology, Ohio State University Medical School, and Dr. Frederick C. Robbins, Director, Department of Pediatrics and Contagious Diseases, Cleveland City Hospital.

News and Announcements

PEDIATRICS ◽  
1974 ◽  
Vol 53 (6) ◽  
pp. 955-955
Keyword(s):  
Annual Meeting ◽  
International Society ◽  
Medical Center ◽  
Pediatric Gastroenterology ◽  
University Of Minnesota ◽  
School Of Medicine ◽  
Common Problems ◽  
Sick Children ◽  
Nutrition Diagnosis ◽  
Vanderbilt University

PAEDIATIC NEUROSURGERY: The International Society for Paediatric Neurosurgery, annual meeting, London, England, September 13-14. For information write Kenneth Till, The Hospital for Sick Children, Great Ormond Street, London WC IN 3JH, England. PEDIATRIC GASTROENTEROLOCY AND NUTRITION: The Children's Hospital of Vanderbilt University, Fifth Annual Autumn Pediatric Symposium on Pediatric Gastroenterology and Nutrition-Diagnosis and Management of Common Problems, September 20-21. Guest faculty: Dr. William Schubert, Department of Pediatrics, University of Cincinnati School of Medicine; Dr. Phil Sunshine, Department of Pediatrics, Stanford University Medical Center; and Dr. Harvey Sharp, Department of Pediatrics, University of Minnesota Medical Center. For information write Harry L. Greene, M.D., Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.

scholarly journals Predictors and Outcomes of Flares in Chronic Graft-Versus-Host Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-48
Author(s):  
Grigori Okoev ◽  
Daniel J. Weisdorf ◽  
John E Wagner ◽  
Bruce R. Blazar ◽  
Margaret L. MacMillan ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Board Of Directors ◽  
Graft Versus Host Disease ◽  
Research Funding ◽  
Time Dependent ◽  
Advisory Committees ◽  
Graft Versus Host ◽  
Day Range ◽  
Similar Risk ◽  
Fund Research

Introduction: Chronic Graft-versus-Host Disease (cGvHD) frequently requires prolonged immune suppressive therapy (IST) with &gt; 50% still on IST at 5 years. The IST typically involves a slow taper of steroids often with flare of cGvHD, necessitating augmentation of previous therapy or addition of new IST. Studies describing cGvHD flares are limited. We analyzed patients with cGvHD who flared during the treatment with systemic IST, their overall survival (OS) and non-relapse mortality (NRM). Methods: This study included all adult patients with cGvHD (n=145) following an allogeneic transplant (2010 - 2017) from a matched sibling donor peripheral blood stem cell transplant (MSD, n=104 (72%) or double/single umbilical cord blood transplant (UCBT, n=41 (28%). The 2014 NIH Consensus Criteria were used to classify organ/overall cGvHD severity. Flare of cGvHD was defined as progression in cGvHD manifestations (after initial response), which was less severe than at diagnosis. Multivariate regression of flares was based on the Prentice, Williams and Peterson model for ordered multiple events (flares). Time-dependent effects on OS and NRM were analyzed by Cox and Fine and Gray regression with propensity scoring to control for confounding. Results: Flares occurred in 87 patients; the cumulative incidence of flares was 60% (95% CI: 51-70%) at a median of 188 days (range 16-751) after diagnosis of cGvHD. The median dose of prednisone was 1 mg/kg/day (range 0-4.2) at diagnosis of cGvHD. At the diagnosis of flare, 36 (41%) of the patients were off prednisone, 50 (57%) were receiving 0.1-0.5 mg/kg /day, and 2 patients &gt; 0.5 mg/kg /day. Thirty two of the 87 (36%) patients experienced multiple flares (2 to 4). The most common organs involved at cGvHD flare were skin (n=45; 51%), mouth (n=27; 31%), GI tract (n=22; 25%) and liver (n=12; 14%); often in combinations of skin/mouth in 11 cases (13%), skin/GI in 6 (7%) and liver/mouth in 4 (5%) cases. Treatment for flare was mostly increase in dose of prednisone to 0.5 mg/kg/day (range 0.3-1.0) in 77 patients (88%) plus the addition of another line of IST in 48 patients (55%). In multiple regression analysis, only donor type was significant predictor of flare in cGvHD. UCBT was associated with 2-fold lower probability of flaring (HR 0.5; 95% CI: 0.3-0.9; p=0.03) compared to MSD. cGvHD severity, organ involvement, platelet count at diagnosis and type of onset were not significant predictors of cGvHD flares. At 2 years after the initial flare, the OS was 77% (95% CI: 66-84%) and NRM 19% (95% CI: 11-28%). Multiple regression analysis evaluating OS and NRM from onset of cGvHD comparing flare to non-flare were performed using flare as a time dependent variable. Compared to cGvHD patients without flare at 2 years, those with flare of cGvHD had a similar risk of NRM (HR 1.2; 95% CI: 0.2-6.1, p=0.86) and OS (HR 0.9; 95% CI: 0.4-2.3, p=0.85). At 2 years from cGvHD onset, the cumulative incidence of resolved cGvHD (durable discontinuation of steroids for ≥ 6 consecutive months) was 31% (95% CI: 21-41%) in those who flared vs. 86% (95% CI: 75-96%) in those without flare. Conclusions: Though cGvHD patients with flare had similar risk of NRM and OS as those without a flare, patients with flare required extended steroids, along with clinical monitoring and intensified IST. cGvHD after UCBT was associated with significantly lower risk of flaring compared to MSD. The ongoing burden of IST, risk of infection and morbidity of cGvHD is substantial and needs better approaches than chronic slow taper of steroids. Disclosures Weisdorf: Incyte: Research Funding; FATE Therapeutics: Consultancy. Wagner:Novartis: Research Funding; Rocket Pharmaceuticals, Inc.: Consultancy, Current equity holder in publicly-traded company; Magenta Therapeutics: Consultancy, Research Funding; BlueRock: Research Funding; Gadeta: Membership on an entity's Board of Directors or advisory committees. Blazar:Fate Therapeutics Inc.: Research Funding; Childrens' Cancer Research Fund: Research Funding; BlueRock Therapeutics: Research Funding; BlueRock Therapeuetic: Consultancy; Magenta Therapeutics: Consultancy; KidsFirst Fund: Research Funding; Tmunity: Other: Co-founder. MacMillan:Mesoblast: Consultancy; Angiocrine Biosciences, Inc.: Consultancy; Equillium, Inc.: Consultancy; Talaris Therapeutics, Inc: Consultancy; Fate Therapeutics, Inc.: Consultancy. Holtan:Generon: Consultancy; BMS: Consultancy; CSL Behring: Other: Clinical trial data adjudication; Incyte: Consultancy. Brunstein:AlloVir: Other: Advisory board; Gamida: Research Funding; Astex: Research Funding; Magenta: Research Funding. Betts:Patent Pending: Patents & Royalties: Dr. Betts has a pending patent WO2017058950A1: Methods of treating transplant rejection. This includes the use of JAK inhibitors. Neither he nor his institution have received payment related to claims described in the patent.. Bachanova:FATE: Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding. Rashidi:Synthetic Biologics: Other: DSMC member (1 trial) and related honorarium. Arora:Fate Therapeutics: Consultancy; Kadmon: Research Funding; Pharmacyclics: Research Funding; Syndax: Research Funding.

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