Reading Chekhov on the Cancer Ward.

Background: Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness. Burnout and other psychosocial distress are common among health care professionals, necessitating additional measures to promote well-being. The field of narrative medicine is one proposed solution. Observations: We added small narrative medicine group discussions of nonmedical fiction to our hematology oncology clinical program to promote physician resilience and decrease risk for burnout. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted 7 different ways by which reading and reflecting together can increase well-being. We describe how stories led us to increase bonding, improve empathy, and promote meaning in medicine. Conclusions: Our small group discussions showed that the intervention was feasible, improved empathy and fulfillment at work, and resulted in greater appreciation for the human dimensions of health care.

The Impact of Donor Type on Outcomes and Cost of Allogeneic Hematopoietic Cell Transplantation for Pediatric Leukemia: A Merged Center for International Blood and Marrow Transplant Research and Pediatric Health Information System Analysis.

Allogeneic hematopoietic stem cell transplantation (alloHCT) may be associated with significant morbidity and mortality, resulting in increased healthcare utilization (HCU). To date, no multicenter comparative cost analyses have specifically evaluated alloHCT in children with acute leukemia. In this retrospective cohort study, we examined the relationship between survival and HCU while investigating the hypothesis that matched sibling donor (MSD) alloHCT has significantly lower inpatient HCU with unrelated donor (URD) alloHCT, and that among URDs, umbilical cord blood (UCB) alloHCT will have higher initial utilization but lower long-term utilization. Clinical and transplantation outcomes data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were merged with inpatient cost data from the Pediatric Health Information System (PHIS) database using a probabilistic merge methodology. The merged dataset comprised US patients age 1 to 21 years who underwent alloHCT for acute leukemia between 2004 and 2011 with comprehensive CIBMTR data at a PHIS hospital. AlloHCT was analyzed by donor type, with specific analysis of utilization and costs using PHIS claims data. The primary outcomes of overall survival (OS), leukemia-free survival (LFS), and inpatient costs were evaluated using Kaplan-Meier curves and Cox and Poisson models. A total of 632 patients were identified in both the CIBMTR and PHIS data. The 5-year LFS was 60% for MSD alloHCT, 47% for well-matched matched unrelated donor bone marrow (MUD) alloHCT, 48% for mismatched unrelated donor alloHCT, and 45% for UCB alloHCT (P = .09). Total adjusted costs were significantly lower for MSD alloHCT versus MUD alloHCT by day 100 (adjusted cost ratio [ACR], .73; 95% confidence interval [CI], .62 to .86; P < .001), and higher for UCB alloHCT versus MUD alloHCT (ACR, 1.27; 95% CI, 1.11 to 1.45; P < .001). By 2 years, total adjusted costs remained significantly lower for MSD alloHCT compared with MUD alloHCT (ACR, .67; 95% CI, .56 to .81; P < .001) and higher for UCB alloHCT compared with MUD alloHCT (ACR, 1.25; 95% CI, 1.02 to 1.52; P = .0280). Our data show that UCB and MUD alloHCT provide similar survival outcomes; however, MUD alloHCT has a significant advantage in cost by day 100 and 2 years. More research is needed to determine whether the cost difference among URD alloHCT approaches remains significant with a larger sample size and/or beyond 2 years post-alloHCT.

Integrating Collaborative Learning and Competition in a Hematology/Oncology Training Program.

New educational methods and structures to improve medical education are needed to face the challenge of an exponential increase and complexity of medical knowledge. Collaborative learning has been increasingly used in education, but its use in medical training programs is in its infancy, and its impact is still unknown; the role of competition in education is more controversial. We introduced these pedagogical methods to the hematology/oncology fellowship program at the University of Arkansas for Medical Sciences to improve attendance and performance at didactic activities and different educational outcomes. One year after the adoption of these methods, the fellowship program has reached many of the expected goals from this intervention without the negative consequences of competition observed in younger learners. The most important conclusion of this project is that collaboration and cross-generational team work provide a healthy and effective learning environment and competition may not add further benefit. Analysis, interpretation, and discussion of our experience are provided. This study was approved by the University of Arkansas for Medical Sciences IRB as a low risk educational intervention not requiring a consent form.

Systemic Anaplastic Lymphoma Kinase-positive Anaplastic Large Cell Lymphoma: A Population-based Analysis of Incidence and Survival.

INTRODUCTION: Systemic ALK-positive anaplastic large cell lymphoma (ALK-positive ALCL) is a T-cell lymphoma. Owing to its rarity, variations in incidence and survival at the population level are not clearly known. MATERIALS AND METHODS: Using the Surveillance Epidemiology and End Results database (SEER 18), we selected patients aged ≥ 20 years with ALK-positive ALCL, diagnosed between 2001 and 2013. Incidence rate, overall survival (OS), and its determinants were analyzed with a significance level of P < .05. RESULTS: We identified 1604 patients with a median age of 54 years. The disease incidence increased significantly with advancing age, with higher incidence in Blacks and lower incidence in American Indians and Asian/Pacific Islanders as compared with Whites. The 5-year OS significantly declined as the age advanced (age 20-40 years, 68.7%; age 41-60 years, 53.8%; age 61-80 years, 28.9%; age > 80 years, 15.2%; P < .01) and varied with race (Whites, 49.7% vs. Blacks, 37.7% vs. Asian/Pacific Islander, 42.8% vs. American Indian, 35.8%; P = .03). On multivariate analysis, treatment with radiation (hazard ratio [HR], 0.72; 95% confidence interval [95% CI], 0.59-0.87; P < .01) and year of diagnosis from 2009 through 2013 (HR, 0.77; 95% CI, 0.65-0.93; P < .01) were associated with lower mortality. Advanced age, Black race (HR, 1.37; 95% CI, 1.14-1.65; P < .01), and advanced disease stage (HR, 1.74; 95% CI, 1.51-2.02; P < .01) were associated with higher mortality. CONCLUSION: Incidence and survival of ALK-positive ALCL varies significantly with patients' demographic characteristics as identified in our study. Treatment strategies need to be tailored accordingly to address these variations and ensure uniform access to care.

Addressing Opioid-Associated Constipation Using Quality Oncology Practice Initiative Scores and Plan-Do-Study-Act Cycles.

Using the Quality Oncology Practice Initiative, an affiliate program of ASCO, we outlined opioid-associated constipation (OAC) as a subject in need of quality improvement (QI) in our fellowship program at the University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System. We initiated a fellow-led QI project to advance the quality of patient care and provide a valuable avenue for QI training of young physicians. Fellows organized meetings with all stakeholders, addressed the scope of the problem, and devised strategies for OAC management. Monthly meetings were organized using Plan-Do-Study-Act principles. Mandatory check boxes were inserted into our electronic medical record templates to remind all physicians to identify patients on opioid medications and assess and address OAC. Final chart audit and patient satisfaction surveys were performed 6 months after project initiation. Assessment of OAC improved from 52% at baseline to 92% ( P < .003). This improvement corresponded with high patient satisfaction scores, with 90% of surveyed patients reporting adequate management of their constipation. In this QI initiative, we showed that participation in ASCO's Quality Oncology Practice Initiative helps identify areas in need of QI, and such fellow-led QI projects can serve as models for QI training of young physicians.

Acute Leukemia of Ambiguous Lineage in Elderly Patients - Analysis of Survival Using Surveillance Epidemiology and End Results-Medicare Database.

BACKGROUND: Acute leukemia of ambiguous lineage (ALAL) is a rare leukemia with sparse data availability about the survival and management strategies in elderly patients. METHODS: We used the Surveillance Epidemiology and End Results (SEER)-Medicare database to describe the overall survival (OS) and treatment pattern of elderly patients (age > 65 years) with ALAL. OS analysis was done using the Kaplan-Meier method, and its determinants were analyzed using the Cox proportional hazard regression method with a significant P < .05. RESULTS: We included 705 patients with ALAL and a median age of 80 years. The 2-year OS was 16.4% for patients aged 66 to 70 years, 8.1% for patients aged 71 to 75 years, 5.5% for patients aged 76 to 80 years, and 3.7% for patients aged > 80 years (P < .01). Two-year OS did not significantly vary by race or gender. Among the study cohort, 151 patients received chemotherapy. Two-year OS was 17% in the chemotherapy group and 3% in the no-chemotherapy group (P < .001). On multivariate analysis, age less than 80 years (Age 66-70 years: hazard ratio [HR]; 0.66, 95% confidence interval [CI], 0.52-0.85; age 71-75 years: HR, 0.80; 95% CI, 0.65-0.99; age 76-80 years: HR, 0.80; 95% CI, 0.66-0.98; P = .004) and chemotherapy (HR, 0.51; 95% CI, 0.42-0.62; P = .001) significantly reduced the hazard for mortality. CONCLUSION: Our study suggests that the OS of elderly patients with ALAL remains poor. Although treatment improved the OS, only 21.5% of patients received therapy. The optimal choice of therapy needs to be determined by prospective studies.

Incidence and survival outcomes of chronic myelomonocytic leukemia in the United States.

Chronic myelomonocytic leukemia (CMML) is an aggressive neoplasm with sparse data on outcomes at a population level. Using Surveillance Epidemiology and End Results (SEER) database, we identified 2238 patients with CMML diagnosed in the period 2003-2013. We found that the disease incidence was significantly higher with advancing age and lower in females, Blacks, and Asian/pacific islanders. Median OS declined significantly with increasing age (age 20-39 - 25 months, age 40-59 - 20 months, age 60-79 - 18 months, and age ≥80 - 11 months, p < .01), but did not vary by gender or race. Median OS has improved in the period 2007-2013 as compared with 2003-2006 (17 months vs. 14 months, p < .01). In spite of advances in CMML biology and therapeutics, in general, the survival of CMML patients remains dismal. More effective therapies are needed to improve the outcomes of CMML.

Improving Communication on Intent of Chemotherapy Using QOPI Scores and PDSA Cycles.

Using the standardized ASCO Quality Oncology Practice Initiative (QOPI) guidelines for assessing quality cancer care, we identified communication about intent of chemotherapy as an area needing improvement in our program at the University of Arkansas for Medical Sciences (UAMS) and the Central Arkansas Veterans Healthcare System (CAVHS). We organized training in communications on intent of treatment (palliative vs curative) and added optional checkboxes to our electronic templates for progress notes. Afterwards, we conducted a retrospective review of electronic medical records of initially often randomly selected patient charts. The first 10 patient charts after 1 month of implementation showed intent of treatment in 80 % of charts compared to 74 % at baseline. We then changed checkboxes from mandatory to optional and reviewed 30 randomly selected patient charts. Intent of treatment was documented in 96.7 % of cases compared to 74 % at baseline. We also assessed patient satisfaction through surveys distributed in clinic. Patient satisfaction scores were close to 100 % for receiving clear information, understanding the reason for which they were receiving chemotherapy, and willingness of oncologists to listen carefully, to take time to answer questions, to explain things clearly, and to spend adequate time with them. In this study, we showed that training in communication of intent of chemotherapy and use of checkboxes in progress note templates could improve competency in communication of intent of therapy in cancer patients.

MYC amplification in multiple marker chromosomes and EZH2 microdeletion in a man with acute myeloid leukemia.

The role of MYC and EZH2 in acute myeloid leukemia (AML) pathogenesis is poorly understood. Herein we present a case of AML with MYC amplification in marker chromosomes and a microdeletion of chromosome 7 below cytogenetic resolution. The karyotype of the patient's bone marrow aspirate showed three to five marker chromosomes in all dividing cells without other structural or numerical chromosomal abnormalities. Analysis by fluorescence in situ hybridization (FISH) with a probe specific for the human MYC gene revealed amplification of the oncogene localized to the marker chromosomes. Using whole genome single nucleotide polymorphism (SNP) microarray analysis, an approximately 4.4 Mb amplicon containing the MYC gene was identified with an estimated amplification of about 30 copies per leukemic cell and, thus, an average of about 8 copies per marker chromosome. A 6.4 Mb hemizygous microdeletion of chromosome 7 within band q36.1 was also found by SNP microarray analysis in a cellular-equivalent dosage of 50%. The microdeletion spans multiple genes, including EZH2, a gene with well-known cancer association. No mutation was found in the remaining EZH2 allele by next generation gene sequencing. The combination of MYC amplification and EZH2 deletion, which has not been described previously in AML, may suggest a synergistic role of the two oncogenes in the pathogenesis of the patient's acute leukemia.

New cancers after autotransplantations for multiple myeloma.

We describe baseline incidence and risk factors for new cancers in 4161 persons receiving autotransplants for multiple myeloma in the United States from 1990 to 2010. Observed incidence of invasive new cancers was compared with expected incidence relative to the US population. The cohort represented 13,387 person-years at-risk. In total, 163 new cancers were observed, for a crude incidence rate of 1.2 new cancers per 100 person-years and cumulative incidences of 2.6% (95% confidence interval [CI], 2.09 to 3.17), 4.2% (95% CI, 3.49 to 5.00), and 6.1% (95% CI, 5.08 to 7.24) at 3, 5, and 7 years, respectively. The incidence of new cancers in the autotransplantation cohort was similar to age-, race-, and gender-adjusted comparison subjects with an observed/expected (O/E) ratio of 1.00 (99% CI, .81 to 1.22). However, acute myeloid leukemia and melanoma were observed at higher than expected rates with O/E ratios of 5.19 (99% CI, 1.67 to 12.04; P = .0004), and 3.58 (99% CI, 1.82 to 6.29; P < .0001), respectively. Obesity, older age, and male gender were associated with increased risks of new cancers in multivariate analyses. This large data set provides a baseline for comparison and defines the histologic type specific risk for new cancers in patients with MM receiving postautotransplantation therapies, such as maintenance.

A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation.

Once-weekly administration of bortezomib has reduced bortezomib-induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three- and four- drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m(2) intravenously was given once-weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co-morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 1·3 months (range, 0·25-2·4 months). The progression-free and overall survivals were 8 months and 46·5 months, respectively. Twenty-four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921).

Castleman Disease.

An understanding of the disease pathogenesis has led to the discovery of therapuetic agents that target human herpesvirus-8 replication, CD20, and IL-6 and IL-6R antibodies.

Multiple Myeloma: Updates on Diagnosis and Management.

Two- and 3-drug treatment regimens and autologous stem cell transplants provide opportunities for longer term disease remission, though most patients will still develop relapsed multiple myeloma.

Updates on Cancer Survivorship Care Planning.

Cancer organizations have developed guides and tools to help build cancer survivorship programs and survivorship care plans.

Long-term survival and late effects among one-year survivors of second allogeneic hematopoietic cell transplantation for relapsed acute leukemia and myelodysplastic syndromes.

We analyzed the outcomes of patients who survived disease-free for 1 year or more after a second allogeneic hematopoietic cell transplantation (HCT) for relapsed acute leukemia or myelodysplastic syndromes between 1980 and 2009. A total of 1285 patients received a second allogeneic transplant after disease relapse; among these, 325 were relapse free at 1 year after the second HCT. The median time from first to second HCT was 17 and 24 months for children and adults, respectively. A myeloablative preparative regimen was used in the second transplantation in 62% of children and 45% of adult patients. The overall 10-year conditional survival rates after second transplantation in this cohort of patients who had survived disease-free for at least 1 year was 55% in children and 39% in adults. Relapse was the leading cause of mortality (77% and 54% of deaths in children and adults, respectively). In multivariate analyses, only disease status before second HCT was significantly associated with higher risk for overall mortality (hazard ratio, 1.71 for patients with disease not in complete remission before second HCT, P < .01). Chronic graft-versus-host disease (GVHD) developed in 43% and 75% of children and adults after second transplantation. Chronic GVHD was the leading cause of nonrelapse mortality, followed by organ failure and infection. The cumulative incidence of developing at least 1 of the studied late effects within 10 years after second HCT was 63% in children and 55% in adults. The most frequent late effects in children were growth disturbance (10-year cumulative incidence, 22%) and cataracts (20%); in adults they were cataracts (20%) and avascular necrosis (13%). Among patients with acute leukemia and myelodysplastic syndromes who receive a second allogeneic HCT for relapse and survive disease free for at least 1 year, many can be expected to survive long term. However, they continue to be at risk for relapse and nonrelapse morbidity and mortality. Novel approaches are needed to minimize relapse risk and long-term transplantation morbidity in this population.

Trends in survival outcomes of B-lineage acute lymphoblastic leukemia in elderly patients: analysis of Surveillance, Epidemiology, and End Results database.

B-lineage acute lymphoblastic leukemia (B-ALL) in the elderly population is generally considered to have a poor prognosis. It is unclear whether their survival has improved in the current era. Using the Surveillance, Epidemiology, and End Results database, we selected 717 elderly patients (age≥60) with B-ALL diagnosed between 1992 and 2011. Overall survival (OS) was compared based on their period of diagnosis and age. Patients in the age group 60-69 had an improvement in OS over time, both 1-year OS (49.4% in 2002-2011 vs. 33.1% in 1992-2001) and 5-year OS (20.4% in 2002-2011 vs. 8.1% in 1992-2001, p=0.002). Patients≥70 years had no significant improvement in 1-year OS or 5-year OS (5-year OS 5.5% in 1992-2001 vs. 9.7% in 2002-2011, p=0.326). Hence, there are discrepancies in the improvement of OS among elderly patients with B-ALL. Further focus of research in elderly patients with B-ALL is needed to improve their outcome.

Natural history of chronic myelomonocytic leukemia: gene sequencing identifies multiple clonal molecular abnormalities associated with rapid progression to acute myeloid leukemia.

KEY CLINICAL MESSAGE: Gene panel sequencing in a CMML patient without any detectable genetic abnormality by conventional genetic studies identified four concurrent somatic mutations in three genes. Gene panel mutation analysis is a rapidly emerging clinical tool to demonstrate the clonality in hematologic malignancies, and to identify the potential targets for therapy.

Effect of radiotherapy on the survival of patients with stage I and stage II mantle cell lymphoma: analysis of the Surveillance, Epidemiology and End Results database.

BACKGROUND: Radiotherapy is a treatment option for stage I and stage II MCL. However, data demonstrating the role of RT in a larger patient population and its real world effects are unknown. MATERIALS AND METHODS: To demonstrate the role of RT in the OS of patients with stage I and stage II MCL, we performed a retrospective analysis of the SEER database. Included patients were adults with age > 40 years who had MCL stages I and II, and diagnosis between 1992 and 2010. We excluded patients lacking information on demographic characteristics, survival, and RT. Patients were analyzed in 2 groups, those treated with initial RT (RT group) and those not treated with initial RT (no-RT group). RESULTS: A total of 657 patients were eligible for analysis with 178 patients in the RT group and 479 patients in the no-RT group. The median age of the study group was 68 years. The RT group had a significantly greater proportion of patients with age < 60, male sex, and extranodal disease. Median OS was 103 months in the RT group versus 66 months in the no-RT group (P = .002). On Multivariate analysis, treatment with initial RT was associated with a lower hazard for mortality (hazard ratio, 0.767; 95% confidence interval, 0.602-0.979; P = .033). Age < 60, stage I disease, and extranodal disease were independently associated with a significantly decreased hazard for mortality on Multivariate analysis. CONCLUSION: Although stage I and stage II MCL constitute only a small proportion of this disease, our study demonstrates that upfront RT improves the OS of these patients.