Strand, Jacob J.

Evidence for massage therapy (MT) in hospice patients remains limited. We conducted a prospective pilot study on MTs impact on quality of life of hospice patients and caregivers. Patient-caregiver dyads were enrolled if patients scored ≥5 on pain, depression, anxiety, or well-being using the revised Edmonton Symptom Assessment System Revised (ESAS-r). The patient received MT weekly for up to 3 massages with assessments completed at baseline, after each massage, and 1 week after the final massage for patients and at baseline and 1 week after final massage for caregivers. A satisfaction survey was completed at study completion. A pro-rated area under the curve (AUC) was utilized to assess the primary endpoints of change in ESAS-r for patient ratings of pain, depression and anxiety as well as the Linear Analogue Self-Assessment (LASA). Median difference scores (end of study value)-(baseline value) for each participant and caregiver were calculated. Of 27 patients and caregivers enrolled, 25 patients received MT. Fifteen patients completed all 3 MT sessions and were given the final symptom assessment and satisfaction survey and their caregivers completed final assessments. The proportion of patients considered success (AUC > baseline) in the primary endpoints were the following: pain 40.9%, depression 40.9%, anxiety 54.5%, LASA 54.5%. Median difference scores were largely zero indicating no significant temporal change in symptoms. Patients were highly satisfied with MT. This pilot study indicated that MT was a feasible and well-received intervention in our population of patients with inadequately controlled symptoms.

Abstract Background: One of the utilities of molecular markers in hematological malignancies is their potential to predict response to drug therapy. Accordingly, we inquired about the effect of both cytogenetic profile and JAK2V617F mutational status on drug therapy response in myelofibrosis with myeloid metaplasia (MMM). Methods: Mutation analysis for JAK2V617 was performed in DNA derived from peripheral blood mononuclear cells, granulocytes, or both. Genomic DNA was amplified by PCR and fluorescent dye chemistry sequencing was performed using the same primers used for amplification (Levin et al. Cancer Cell2005;7:387). Abnormal cytogenetic findings were considered to be either favorable (sole 13q- or 20q- abnormalities) or unfavorable (other abnormalities) (Tefferi et al. BJH2001;113:763). Results: i. Patients and treatment: A total of 69 patients with MMM (median age 62 years, range 38–75; 47 males) received the following drugs as first-line therapy for either anemia or symptomatic splenomegaly; erythropoietin (Epo) alone or in combination with hydroxyurea (n=25), hydroxyurea alone (HU; n=17), interferon alpha (IFN; n=11), combination of thalidomide and prednisone (ThalPred; n=7), androgen preparations (Andro; n=5), and etanercept (n=4). ii. Results of cytogenetic studies and JAK2 mutation screening: Cytogenetic findings were abnormal in 35 patients (51%); favorable in 9 and unfavorable in 26. JAK2V617 mutation analysis revealed wild-type allele in 31 patients (45%) and either heterozygous (n=31) or homozygous (n=7) mutation in the remaining 38 patients (55%). iii. Correlation of response to cytogenetic/molecular markers: Overall, 17 patients (25%) achieved either a major (n=8) or minor (n=9) response in anemia from treatment with one of the aforementioned drugs. Regardless of either JAK2V617 mutational status or cytogenetic profile, treatment-induced responses in anemia were poor for IFN (0%) and HU (12%). In contrast, the best anemia responses were documented for ThalPred (57%), Andro (40%), and Epo-based therapy (32%). Among the 25 patients that received Epo-based therapy, all 3 patients with favorable cytogenetic abnormalities achieved major responses in anemia whereas such responses were seen in none of the 9 patients with unfavorable cytogenetic abnormalities and only 1 of 13 patients with normal cytogenetics (p=0.004). Furthermore, 3 of the 4 major responders were heterozygous for JAK2V617 and one carried the wild-type allele. In contrast, none of the 3 JAK2V617 homozygotes showed any type of response but all 3 also displayed unfavorable cytogenetics. None of the 7 ThalPred-treated patients carried favorable cytogenetics and yet 3 achieved major responses including one with unfavorable cytogenetics. JAK2V617 mutational status was heterozygous in 1 and wild-type in the other two. There were no major responses among the 5 Andro-treated patients despite the presence of favorable cytogenetic abnormalities in 2 patients. In order to investigate the relationship between cytogenetic profile and JAK2V617 mutational status further, we referred to an expanded database of 116 patients and found the incidence of unfavorable cytogenetics to be higher in JAK2V617 homozygotes compared to non-homozygotes (57% vs. 31%; p=0.16) Conclusion: The current study suggests clustering of favorable cytogenetic abnormalities in MMM with anemia response to Epo therapy and unfavorable cytogenetic abnormalities with homozygosity for JAK2V617 mutation.

Abstract Background: Previous cytogenetic studies in polycythemia vera (PV) have included a relatively small number of patients (“n” ranging 10–64). In the current study (n=137), we describe cytogenetic findings at presentation and examine their relationship to clinical and laboratory features, including bone marrow JAK2V617F allele burden. Methods: The study consisted of a consecutive group of patients with PV who fulfilled the World Health Organization (WHO) diagnostic criteria and in whom bone marrow biopsy and cytogenetic studies were performed at diagnosis. Results I: cytogenetic details At diagnosis: A total of 137 patients (median age, 64 years; 49% females) were studied at diagnosis and had adequate metaphases for interpretation. Cytogenetics were normal in 117 patients (85%) and displayed either a sole -Y abnormality in 5 patients (7% of the male patients), and other chromosomal abnormalities in 15 (11%). The latter included trisomy 8 in five patients, trisomy 9 in three patients, two patients each with del(13q), del(20q), and abnormalities of chromosome 1, and one patient each with del(3)(p13p21), dup(13)(q12q14), and del(11)(q21). At follow-up: Repeat cytogenetic studies while still in the chronic phase of the disease were performed in 19 patients at a median of 60 months (range, 8–198) from diagnosis. Of these, 4 had aquired new cytogenetic clones including 3 with normal cytogenetics at time of initial PV diagnosis. The new abnormalities included del(20q), del(5q), del(1p), chromosome 1 abnormality, and inv(3)(q21q26.2). At time of disease transformation: Leukemic transformation was documented in 3 patients of whom cytogenetic information at the time was available in 2 patients; both patients had normal results at time of initial PV diagnosis and complex cytogenetic abnormalities at time of leukemic transformation. In contrast, among 6 patients with available cytogenetic information at time of fibrotic transformation, the results were unchanged from those obtained at time of diagnosis in 5 patients. ii) Correlation between cytogenetics at diagnosis and JAK2V617F allele burden: Allele-specific, quantitative PCR analysis for JAK2V617F was performed in 71 patients using genomic DNA from archived bone marrow obtained at the time of the initial cytogenetic studies. JAK2V617F mutation was detected in 64 of the 71 (90%) patients; median mutant allele burden was 16% (range 3–80%) without significant difference among the different cytogenetic groups: normal vs. –Y vs. other cytogenetic abnormalities (p=0.72). iii) Clinical correlates and prognostic relevance of cytogenetic findings at diagnosis: Among several parameters studied for significant correlations with cytogenetic findings at diagnosis, an association was evident only for age (p=0.02); all –Y abnormalities (n=5) as well as 13 of the 15 (87%) other cytogenetic abnormalities occurred in patients ≥ 60 years of age. Stated another way, the incidence of abnormal cytogenetics (other than -Y) was 4% for patients younger than age 60 years and 15% otherwise. The presence of abnormal cytogenetics at diagnosis had no significant impact on either overall or leukemia-free survival. Conclusions: Abnormal cytogenetic findings at diagnosis are infrequent in PV, especially in patients below age 60 years. Furthermore, their clinical relevance is limited and there is not significant correlation with bone marrow JAK2V617F allele burden.

Abstract Background: Pruritus in polycythemia vera (PV) has been associated with a high JAK2V617F allele burden (Tefferi et al. Cancer. 2006;106:631, Vannucchi et al, Leukemia2007, in press). However, there is limited information regarding clinical correlates of pruritus per se in PV. Accordingly, we conducted a large (n=418) retrospective study in PV to accurately assess the prevalence and severity of pruritus as well as its relationship with presenting clinical features, bone marrow JAK2V617F allele burden, and prognosis. Methods: The study cohort consisted of a consecutive group of patients with PV who fulfilled the World Health Organization (WHO) diagnostic criteria and in whom information regarding the presence or absence of pruritus at diagnosis was fully documented. Pruritus was graded as being mild, moderate, or severe based on careful review of patient history. Results: Prevalence and severity of pruritus: A total of 418 patients fulfilled the above stipulated criteria for study inclusion (median age of 60 years; 56% males; median follow-up of 73 months). Of these, 131 (31%) experienced pruritus at time of initial diagnosis: mild in 97 patients (74%), moderate in 22 (17%), and severe in 12 (9%). Most patients with mild pruritus (n=92) received no specific therapy for pruritus whereas all 12 patients with severe pruritus required treatment; all 7 patients who received treatment with paroxetine responded. Pruritus and JAK2V617F allele burden: Quantitative measurement of JAK2V617F was performed in 64 patients using genomic DNA from archived bone marrow obtained at the time of PV diagnosis. Mutational frequency was 97%; median mutant allele burden was 25.4% (range 0.2 - 93.3%). Among the 62 V617F-positive patients, 24 (39%) had pruritus; the proportion of patients in the upper and lower quartile allele burden ranges were 50% and 0% in the presence of pruritus and 18% and 34% in its absence (p=0.002). Clinical correlates of pruritus: Pruritus was more prevalent in non-smokers (35% vs. 19%; p=0.004) and non-diabetics (33% vs. 16%; p=0.04) and was associated with a lower rate of arterial thrombosis at diagnosis (8% vs. 17%; p=0.01) as well as during follow-up (16% vs. 30%; p=0.003). These significant associations remained intact during multivariable analysis. Pruritus did not have an impact on the rate of leukemic or fibrotic transformation. Conclusions: Pruritus in PV is independently associated with a lower risk of arterial thrombosis despite high JAK2V617F allele burden and is also more prevalent in non-smokers. These observations suggest that pruritus might be a surrogate for an underlying platelet pathology with functional relevance.

11514 Background: Cancer pain is a significant problem that impairs patient quality of life and increases healthcare utilization. ePAL is a smartphone application that utilizes patient-reported outcomes (PROs) and artificial intelligence (AI) to optimize cancer pain management. This randomized controlled trial examined the impact of ePAL on cancer pain severity, attitudes toward cancer pain, and healthcare utilization. Methods: Patients with pain from metastatic solid tumors (n = 112) undergoing treatment in a palliative care clinic were randomized to either a control group (n = 56) that received usual care or an intervention group (n = 56) that received ePAL in addition to usual care for 8 weeks. Measures of pain severity (Brief Pain Inventory), attitudes towards cancer treatment (Barriers Questionnaire II) and anxiety (General Anxiety Disorder-7) were assessed. We used repeated measures mixed modeling to assess change in outcome measures over time. We also conducted a chart review to identify pain-related hospital admissions and emergency department (ED) visits and compared risk between study groups. Results: Pain severity (BPI) and negative attitudes toward cancer treatment (BQ-II) decreased significantly for those assigned to ePAL compared to controls (ß = -0.09, p = 0.034 and ß = -0.037, p = 0.042, respectively). Patients assigned to ePAL reported higher anxiety scores compared to controls (ß = 0.21, p = 0.015). Patients assigned to ePAL had significantly fewer pain-related hospital admissions (n = 4 vs. n = 20, per patient risk ratio 0.31, p = 0.018) and fewer pain-related admissions through the ED (n = 2 vs. n = 14, per patient risk ratio 0.18, p = 0.008) compared to control group. Conclusions: To our knowledge, this is the first mobile app to utilize patient reported outcomes and artificial intelligence to significantly decrease pain scores and pain-related hospitalizations in patients with cancer-related pain. Future directions include examining the efficacy of ePAL in settings with limited access to palliative care.

7029 Background: A leukocyte count of > 15 ×109/L has recently been associated with myocardial infarction in polycythemia vera (PV). In the current study, we examine the impact of such degree of leukocytosis on survival, leukemic transformation (LT), and thrombosis in a large cohort of PV patients from a single institution Methods: Data was abstracted from the medical records of a consecutive cohort of patients with PV defined by the World Health Organization criteria. Results: i. Patient characteristics The study cohort included 459 patients (median age, 60 years). Median follow-up was 64 months. ii. Survival In a multivariable analysis, advanced age, leukocyte count of = 15 × 109/L, and arterial thrombosis at diagnosis were significantly associated with inferior survival. A prognostic model based on age = 60 years and leukocyte count = 15 × 109/L separated low-risk, intermediate-risk, and high-risk patient groups with respective median survivals of 272, 162, and 108 months (p<0.0001). iii. Leukemic transformation In a multivariable analysis, only leukocyte count was significantly associated with LT; median leukemia-free survival for patients with leukocyte count = 15 × 109/L was 273 months vs. not reached for those with lower leukocyte count (p<0.0001). iv. Thrombosis at diagnosis In multivariable analysis, arterial thrombosis at diagnosis was significantly associated with previous history of arterial thrombosis, hypertension, and tobacco use; venous thrombosis at diagnosis was significantly associated with previous venous event and splenomegaly. v. Thrombosis during follow- up In multivariable analysis, arterial thrombosis during follow-up was significantly associated with previous arterial event, hypertension, and tobacco use; venous thrombosis during follow-up was significantly associated with previous venous event, diabetes mellitus, advanced age, and leukocyte count = 1,500 × 109/L. Conclusions: The current study for the first time identifies leukocytosis as a risk factor for inferior survival, LT risk, and venous thrombosis in PV. No significant financial relationships to disclose.

Abstract Background: Palliative care specialists provide supportive care for patients with hematologic diseases. However, the degree of engagement by palliative care physicians may be limited by the views of both palliative care physicians and hematologists. Prior studies have surveyed hematologists to identify barriers to delivery of palliative care, however palliative care physician views are unclear. This study aimed to examine views of palliative care physicians toward hematology. Methods: A survey was mailed to a random sample of the AAHPM physician contact list in 2017. Items focused on perceptions of their understanding of hematologic diseases, comfort providing care, opinions regarding palliative care and hospice involvement, and beliefs about hematologists. Anonymized responses were assessed on a Likert scale. Statistical testing was based on logistic regression models with generalized estimating equations to account for correlated data within respondents. Results: 538 of 1000 surveys were completed. 51.9% of respondents were male. Community (37.2%), academic (36.7%) and hospice (26.2%) physicians were represented. Respondents were likelier to believe they understand the trajectories of lymphoma and myeloma than leukemia or patients undergoing hematopoietic stem cell transplantation (HSCT) (p < 0.001). They were more comfortable discussing prognosis (p =< 0.001) and managing symptoms (p < 0.001) in lymphoma and myeloma than leukemia and HSCT. They were likelier to believe that hematologists' perceptions of palliative care physicians limit collaboration rather than their own views of hematologists (p < 0.001). 80.2% agreed that hospice referrals are not made early enough. Conclusions: Palliative care physicians' understanding of trajectories and comfort caring for patients varies by hematologic disease. They perceive that hematologists' perceptions are a larger barrier than their own and hospice referrals are delayed. These results provide insights into opportunities for better collaboration with hematologists. Disclosures No relevant conflicts of interest to declare.

Pain is one of the most commonly experienced and feared symptoms faced by patients with a serious illness. For these patients, intrathecal drug delivery systems (IDDSs) provide greater potency and/or few systemic side effects. However, despite these benefits, the integration and management of IDDS for patients receiving hospice care has not been previous studied. An electronic, 18-question survey was sent to 200 hospice practitioners (physicians, nurse practitioners and nurses) in the state of Minnesota to explore their experience, confidence, and the perceived barriers to caring for patients with IDDS while being cared for on hospice. Providers were identified though mailing lists from the Minnesota Network of Hospice and Palliative Care organization. The survey was administered by the Mayo Clinic Survey Research Center with institutional review board approval. Slightly more than 50% of respondents have ever cared for a patient with an intrathecal pump. If a patient had a pump in place, only 28% of providers expressed confidence in managing their pain. Additionally, only 3 of 10 respondents felt that adjusting an intrathecal pump should be the first option when a patient with an IDDS in place had increased pain. Indeed, the vast majority (over 80%) of respondents preferred the use of systemic therapies for primary pain management. Access to IDDS vendors for changes/refills in the home is identified as another barrier with over 50% of respondents either unaware of an available vendor or reporting no vendor available. There are numerous self-reported barriers to ongoing use of IDDS with patients receiving hospice care.

Pain is one of the most feared symptoms that concern cancer patients and their families. Despite well-established guidelines set forth by the World Health Organization (WHO) on the treatment of cancer pain, nearly half of cancer patients report poorly controlled pain. One of the most serious side effects of systemic oral opioid use is neurotoxicity, which is characterized by altered mental status and systemic neurologic impairments. Treatment strategies are supportive in nature and focused on reducing or changing the offending opioid and correcting any metabolic deficiencies. Herein, we discuss a case of opioid-induced neurotoxicity treated with intrathecal targeted drug delivery (TDD). The timing and implementation of advanced therapies such as intrathecal TDD is not well delineated. More importantly, patients and their oncologic providers are often unaware of this useful tool in treating challenging cancer-associated pain and significantly minimizing systemic opioid side effects. To ensure that patients have comprehensive oncologic care, best-practice guidelines suggest involvement of an interdisciplinary team and coordinated care. Early referral to a pain and palliative specialist may allow for improved patient outcomes and removal of unnecessary barriers to optimal patient care.