Development of a symptom assessment in patients with myelofibrosis: qualitative study findings.

BACKGROUND: The goal of the research reported here was to understand the patient experience of living with myelofibrosis (MF) and establish content validity of the Modified Myeloproliferative Neoplasm Symptom Assessment Diary (MPN-SD). METHODS: Qualitative interviews were performed in patients with MF, including both concept elicitation and cognitive debriefing. Patients with MF were asked to spontaneously report on their signs, symptoms, and impacts of MF, as well as their understanding of the MPN-SD content, and use of the tool on an electronic platform. A supplementary literature review and meetings with MF experts were also performed. RESULTS: Twenty-three patients with MF participated in qualitative interviews. Signs and symptoms most commonly reported by ruxolitinib-experienced patients (n = 16) were: fatigue and/or tiredness (n = 16, 100%), shortness of breath (n = 11, 69%), pain below the ribs on the left side and/or stomach pain and/or abdominal pain (n = 9, 56%), and enlarged spleen (n = 9, 56%) and for ruxolitinib-naïve patients (n = 7) were: fatigue and/or tiredness (n = 6, 86%), pain below the ribs on the left side (n = 6, 86%), enlarged spleen (n = 4, 57%), full quickly/filling up quickly (n = 4, 57%), night sweats and/or general sweats (n = 4, 57%), and itching (n = 4, 57%). Patients demonstrated that they were able to read, understand, and provide meaningful responses to the MPN-SD. The final version of the MPN-SD includes the 10 most commonly reported concepts from the MF patient interviews. CONCLUSIONS: The findings demonstrate the comprehensiveness of the MPN-SD in assessing MF symptoms in both ruxolitinib-experienced and ruxolitinib-naïve patients, while remaining easy for patients to understand and complete.

EVALUATION OF BURDENSOME SYMPTOMS IN PATIENTS WITH RADIATION6ASSOCIATED AND SPONTANEOUS MYELOPROILIFERATIVE NEOPLASMS WITH THE USE OF OPTIMIZED SELF-ASSESSMENT MPN-SAF TSS. / OTsINKA OBTIaZhLYVYKh SYMPTOMIV U KhVORYKh NA RADIATsIINO-ASOTsIIOVANI TA SPONTANNI MIIeLOPROLIFERATYVNI NEOPLAZIÏ Z VYKORYSTANNIaM ADAPTOVANOÏ ShKALY SAMOOTsINKY MPN-SAF TSS.

OBJECTIVE: To investigate the intensity of burdensome symptoms using self-assessment MPN-SAF TSS in patientswith radiation-associated and spontaneous myeloproiliferative neoplasms (MPNs). MATERIALS AND METHODS: The study included 89 patients with radiation-associated and spontaneous MPNs, the bur-densome symptoms of MPN were determined using MPN-SAF TSS. RESULTS: The average score for complaints in patients with radiation-associated MPNs was significantly higher thanin patients with spontaneous MPNs - 43.46 and 25.04 points, respectively (p = 0.003). MPN patients classified bysubtypes also showed differences regarding intensity of burdensome MPN symptoms, demonstrating significantlyhigher average score of complaints among primary myelofibrosis patients (35.60), compared to polycythemia vera(29.60) and essential thrombocythemia (18.05) patients, (p = 0.005). Our study did not reveal any influence of theJAK2 V617F mutation on MPN burdensome symptoms intensity in MPN patients. CONCLUSIONS: We demonstrated a higher intensity of the MPN burdensome symptoms determined by the optimizedself-assessment MPN-SAF TSS in patients with radiation-associated, and in primary myelofibrosis patients, indicat-ing increased severity of patient's general conditions at the stage of diagnosis verification. It is advisable to usethe optimized MPN-SAF TSS at the moment of molecular genetic testing during the diagnosis of MPN for selectionor modifying treatment strategies in order to achieve better quality of life for patients.

Life for patients with myelofibrosis: the physical, emotional and financial impact, collected using narrative medicine-Results from the Italian 'Back to Life' project.

PURPOSE: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterised by an aggressive clinical course, with disabling symptoms and reduced survival. Patients experience a severely impaired quality of life and their families face the upheaval of daily routines and high disease-related financial costs. The aim of this study was to investigate the perceptions of Italian patients and their caregivers about living with MF and the burden of illness associated with MF. METHODS: A quali-quantitative questionnaire and a prompted written narrative survey were administered to patients affected by primary or post-essential thrombocythemia/post-polycythaemia vera MF and their primary caregiver in 35 Italian haematological centres. RESULTS: In total, 287 questionnaires were returned by patients and 98 by caregivers, with 215 and 62, respectively, including the narrative. At the time of diagnosis, the most commonly expressed emotional states of patients were fear, distress and anger, confirming the difficulty of this phase. A high level of emotional distress was also reported by caregivers. Along the pathway of care, the ability to cope with the disease differed according to the quality of care received. The mean cost to each patient attributable to MF was estimated as €12,466 per year, with an estimated average annual cost of loss of income of €7774 per patient and €4692 per caregiver. CONCLUSIONS: Better understanding of the personal life of MF patients and their families could improve the relationships between health workers and patients, resulting in better focused healthcare pathways and more effective financial support to maintain patients in their social roles.

Treatment of patients with primary myelofibrosis using dasatinib.

OBJECTIVE: Primary myelofibrosis (PMF) is a chronic clonal myeloproliferative neoplasm. It is associated with a poor prognosis, with a median survival time of approximately five years. Thus far, there are no specific targeted drugs for PMF. In this study, we evaluated the efficacy and safety of dasatinib, a second-generation tyrosine kinase inhibitor, in six PMF patients. PATIENTS AND METHODS: From June 1, 2015 to February 29, 2016, six patients with PMF in our department were enrolled into this trial. The efficacy and safety of 100 mg/d (50 mg twice daily) dasatinib were investigated in these patients. RESULTS: For patients who experienced adverse drug events, the dose was reduced to 70 or 50 mg/d, whereas for those who tolerated the drug well, the dosage was increased to 140 mg/d (70 mg twice a day). Of the six patients, two achieved bone marrow histologic remission, five showed symptomatic improvement, and one reached a stable condition. No severe hematological or non-hematological adverse events were observed thus far. CONCLUSIONS: Dasatinib treatment may be beneficial to patients with PMF and resulted in significant improvements in splenomegaly, clinical symptoms, physical condition, and quality of life. Therefore, we regard it as an effective therapy for PMF.

Psychological Symptoms Among Patients With BCR-ABL-Negative Myeloproliferative Neoplasms.

BACKGROUND: BCR-ABL-negative myeloproliferative neoplasms (MPNs) represent a heterogeneous group of diseases, including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Psychological manifestations among these diseases have not been adequately described. METHODS: Cross-sectional surveys measuring distress, anxiety, and depression were collected from patients with BCR-ABL-negative MPNs from May 2015 to October 2015. Participants provided demographic information and completed the Distress Thermometer and Problem List (DT&PL) to assess distress and the Hospital Anxiety and Depression Scale (HADS) to assess distress, anxiety, and depression. They provided information on how their MPN affected their lives. RESULTS: Of the 117 participants, 31.2% had PV, 28.4% had ET, 28.4% had MF, and 11.9% had another type of MPN. Time with MPN varied from less than 1 year (7.5%), 1 to 3 years (19.8%), 3 to 5 years (23.6%), 5 to 10 years (19.8%), and more than 10 years (29.2%). Distress averaged 3.14 (SD, 2.83; DT&PL), with 40.4% meeting NCCN criteria for distress, and averaged 8.97 (SD, 7.44; HADS), with 38.5% meeting HADS criteria for distress. Anxiety averaged 5.54 (SD, 4.37), with 31.3% meeting HADS criteria for anxiety. Depression averaged 3.4 (SD, 3.4), with 12.5% meeting HADS criteria for depression. Distress was higher for PV (3.86), MF (3.12), and "other" MPN (4.33) than it was for ET (1.81; P=.016). Distress was more common in non-white patients (P=.015) and those with either PV or MF but not ET (DT&PL ≥4; P=.038). Patients' comments described coping strategies or symptom burden. CONCLUSIONS: Distress and anxiety are highly prevalent with BCR-ABL-negative MPNs and may correspond to disease-related symptom burden. These findings deserve further study.

The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and quality of life: An analysis by the MPN QOL International Study Group.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality-related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms. METHODS: A total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age-matched, healthy control population. RESULTS: Overall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN-SAF score of 3.6 vs 2.0; P<.001), with 64% of patients with MPN describing some degree of sexual dysfunction and 43% experiencing severe symptoms. The presence of sexual symptoms correlated closely with all domains of patient functionality (physical, social, cognitive, emotional, and role functioning) and were associated with a reduced quality of life. Sexual problems also were found to be associated with other MPN symptoms, particularly depression and nocturnal and microvascular-related symptoms. Sexual dysfunction was more severe in patients aged >65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids. CONCLUSIONS: The results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016;122:1888-96. © 2016 American Cancer Society.

Quality of life and mood predict posttraumatic stress disorder after hematopoietic stem cell transplantation.

BACKGROUND: During hospitalization for hematopoietic stem cell transplantation (HCT), patients experience a steep deterioration in quality of life (QOL) and mood. To our knowledge, the impact of this deterioration on patients' QOL and posttraumatic stress disorder (PTSD) symptoms after HCT is unknown. METHODS: We conducted a prospective longitudinal study of patients hospitalized for HCT. They assessed QOL using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) and depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) at the time of admission for HCT, during hospitalization, and 6 months after HCT. We also used the Hospital Anxiety and Depression Scale (HADS) to measure patients' anxiety and depression symptoms at baseline and during HCT hospitalization. The PTSD Checklist was used to assess for PTSD symptoms. Multivariable linear regression models were used to identify predictors of QOL and PTSD symptoms at 6 months. RESULTS: We enrolled 90 of 93 consecutively eligible patients (97%) undergoing autologous and allogeneic HCT. Data at 6 months were available for 67 participants. At 6 months, 28.4% of participants met the criteria for PTSD and 43.3% had clinically significant depression. On multivariable regression analyses adjusting for significant covariates, changes in QOL and depression scores from week 2 of HCT hospitalization to baseline predicted worse QOL (changes in scores between week 2 and baseline [Δ] QOL: ß, 0.94 [P<.0001] and Δ PHQ-9: ß, -2.59 [P = 0.001]) and PTSD symptoms (Δ QOL: ß, -0.40 [P<.0001] and Δ PHQ-9: ß, 1.26 [P<.0001]) at 6 months after HCT. CONCLUSIONS: Six months after HCT, a significant percentage of patients met the criteria for PTSD and depression. A decline in QOL and an increase in depressive symptoms during hospitalization for HCT were found to be the most important predictors of 6-month QOL impairment and PTSD symptoms. Therefore, managing symptoms of depression and QOL deterioration during HCT hospitalization may be critical to improving QOL at 6 months and reducing the risk of PTSD. Cancer 2016;122:806-812. © 2015 American Cancer Society.

Deriving a Preference-Based Measure for Myelofibrosis from the EORTC QLQ-C30 and the MF-SAF.

BACKGROUND: Utility values are required for economic evaluation using cost-utility analyses. Often, generic measures such as the EuroQol five-dimensional questionnaire are used, but this may not appropriately reflect the health-related quality of life of patients with cancer including myelofibrosis. OBJECTIVE: To derive a condition-specific preference-based measure for myelofibrosis using appropriate existing measures, the Myelofibrosis-Symptom Assessment Form and the European Organisation for Research and Treatment of Cancer Quality of Life 30 Questionnaire. METHODS: Data from the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment trial (n = 309) were used to derive the health state classification system. Psychometric and factor analyses were used to determine the dimensions of the classification system. Psychometric and Rasch analyses were then used to select an item to represent each dimension. Item selection was validated with experts. A selection of health states was valued by members of the general population using time trade-off. Finally, health state values were modeled using regression analysis to produce utility values for every state. RESULTS: The Myelofibrosis 8 dimensions has eight dimensions: physical functioning, emotional functioning, fatigue, itchiness, pain under ribs on the left side, abdominal discomfort, bone or muscle pain, and night sweats. Regression models were estimated using time trade-off data from 246 members of the general population valuing a total of 33 states. The best performing model was a random effects maximum likelihood model producing utility values ranging from 0.089 to 1. CONCLUSIONS: The Myelofibrosis 8 dimensions is a condition-specific preference-based measure for myelofibrosis. This measure can be used to generate utility values for myelofibrosis for any data set containing the Myelofibrosis-Symptom Assessment Form and the European Organisation for Research and Treatment of Cancer Quality of Life 30 Questionnaire data.

Indirect and non-medical economic burden, quality-of-life, and disabilities of the myelofibrosis disease in Spain.

INTRODUCTION: Myelofibrosis is a non-frequent chronic myeloproliferative Philadelphia-negative chromosome neoplasm. It is a heavy incapacitating orphan disease and associated with high morbidity and mortality. In this context, indirect and non-medical costs are expected to be high. The main objective of this project is to estimate the economic burden of this disease in Spain. METHODS: Thirty-three patients with a diagnosis of myelofibrosis for at least 1 year participated in a questionnaire in three Spanish centers. The study consisted of analyzing in various aspects the cost and impact of the disease; indeed, daily life time limitations with a need of informal care, symtomatology. Additionally, information concerning the clinical management of the disease was collected through a focus group of eight experts. RESULTS: The mean age was 65 years. 15 of 33 patients were at their productive stage. Six had difficulties at work and eight have received informal care. Bone and muscular pain were the main symptoms of patients (72%). The estimated global indirect and non-medical costs of the disease were 86,315€ per patient (20% working and 80% informal care), which reached 104,153€ at productive stage patients (45%) and 168,459€ for more symptomatic patients. CONCLUSIONS: The economic burden of indirect and non-medical costs of myelofibrosis are important (15,142€/annual) as a result, and should be considered in economic evaluation, as well as in preventive plans for patients and caregivers, despite the fact that studies with larger numbers of patients should be done.

Psychological stress and psychosomatic treatment: major impact on serious blood disorders?

OBJECTIVE: To demonstrate evidence of possible major impacts of psychological stress and psychosomatic interventions on myeloproliferative blood disorders and develop new approaches for the unification and quantified analysis of stress and psychosomatic treatments. METHODS: This 3.5- year longitudinal study was based upon the regular blood tests of a person with myelofibrosis who experienced severe and repeated work-related psychological stress and was subjected to psychosomatic treatment in the form of regular (approximately 4 h per day) self-hypnosis sessions. Statistical data analysis was conducted on the basis of an introduced concept of generalized stress that mathematically unifies psychological stress and psychosomatic treatment. RESULTS: Severe stress and psychosomatic treatment were statistically shown to have a major (dominant) impact on blood platelet counts well described by an exponential dependence on cumulative levels of generalized stress. The typical relaxation time for the impacts of both stress and treatment was shown to be approximately 2 months. Only approximately 12% of the total variation in platelet counts could be attributed to factors other than psychological stress and psychosomatic treatment. The psychosomatic intervention resulted in a consistent reduction of high platelet counts from approximately 1,400 x 109 l⁻¹ to approximately the middle of the normal range, with other blood parameters being either approximately stable or showing indications of a strengthening immune system. CONCLUSIONS: Our findings give hope for a possible development of psychosomatic treatments of at least some blood disorders. They also indicate a highly instrumental role of platelets in the quantified analysis of stress, psychosomatic interventions, and their neuroimmunological pathways.

Merleau-Ponty and me: some phenomenological reflections upon my recent bone marrow transplant.

OBJECTIVE: During my illness and transplant I experienced an overwhelming existential crisis involving a complex intertwining of meaning and body which was often ignored, rejected, or misunderstood by others and at times by myself, which led to painful feelings of alienation. My treatment and my own conceptualizations seemed founded on assumptions of a separation of body and mind that were not true to what I was experiencing. I searched for a more accurate understanding, which I eventually found in the writings of the French existential philosopher Merleau-Ponty. CONCLUSIONS: Merleau-Ponty's extensive elaboration of the deep ambiguity of our existence as body-subjects provides an alternative model to those of the mind/body dichotomy currently in vogue in medicine and psychiatry. I found his writings a useful framework within which to comprehend my experiences. I wanted to write about these experiences and how they relate to Merleau-Ponty's insights because I found that those individuals who were able to relate to me at this level of existential ambiguity were invaluable to my recovery.

Safety and efficacy of thalidomide in patients with myelofibrosis with myeloid metaplasia.

We administered the anti-angiogenic drug thalidomide to 21 patients (12 men) with myelofibrosis with myeloid metaplasia (MMM), who were not responsive to standard treatment. Patients received thalidomide at an escalating dose from 100 to 400 mg/d. Administration of the drug was discontinued before the planned 6 months of treatment in 19 patients (90.5%), mainly because of somnolence and/or fatigue, neurological symptoms or neutropenia. Of the 13 evaluable patients (who received more than 30 d of therapy), anaemia improved in three out of seven (43%) who were treated because of anaemia; thrombocytopenia improved in two out of three (66.6%) who were treated because of thrombocytopenia; splenomegaly was reduced in four (30.8%). Undesired increases in white blood cell and platelet counts were observed in three (23.1%) and five (38.5%) patients respectively. A severity score, indexed on haematological and clinical parameters, improved in two patients (15.4%), but worsened in five (38.5%). In conclusion, standard-dose thalidomide in MMM patients is burdened with a high rate of side-effects, which prevent prolonged treatment. Because the drug is effective in improving anaemia and thrombocytopenia and in reducing splenomegaly, low-dose therapy warrants evaluation. The unexpected observation of leucocytosis and thrombocytosis suggests biological studies and better criteria for selection of patients for treatment.