A Retrospective Analysis of Incident Cardiac and Neurological Co-Morbidity Following Treatment of Acute Promyelocytic Leukemia

Background Depending on the risk of disease, the use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) and/or anthracyclines is the current standard for therapy of acute promyelocytic leukemia (APL). Despite the high rates of remission and overall survival (OS) that approach 100%, the extent and characterization of long-term morbidity following treatment in these patients is unknown. We performed a retrospective study to investigate the long-term clinical course of these patients. Methods We performed a retrospective analysis of adult patients with newly diagnosed APL from 2004 through 2014. Therapeutic regimens were ATRA+ATO-based (LoCoco et al. NEJM 2013;369:2), ATRA+anthracycline+ATO-based per CALBG 9710 (Powell et al. Blood 2010;116:19), ATRA+anthracycline+mitoxantrone-based per PATHEMA (Sanz et al. Blood 2004;103), and ATO+ATRA+gemtuzumab per SWOG S0535 (ASCO 2015). Co-morbidities were documented at diagnosis and extracted from the medical record, including the date of incident event. Long-term comorbidities were defined as those occurring mostly > 6 months after complete remission (CR). Patients were followed from the time of presentation to death or censored at last known follow-up. The cumulative incidence of co-morbid conditions after diagnosis was calculated by the Fine and Gray method, with relapse and death as competing risks. OS and progression-free survival (PFS) were calculated by the Kaplan and Meier method. Results We identified 116 patients with a new diagnosis of APL. Of the 116 patients, 102 (88%) achieved CR. 54 patients were treated per CALBG 9710, 17 were treated per LoCoco et al., 24 were treated per PATHEMA, and 6 were treated per SWOG S0535. 5 patients relapsed during follow up, and underwent hematopoietic stem cell transplantation. OS for all groups was 91.3%, 89.5%, 88.5% at 1, 12, and 24 months, respectively. PFS was 91.3%, 88.6%, 85.6% at 1, 12, and 24 months, respectively. Each of the 102 patients achieving CR had an echocardiogram after completion of chemotherapy; of these, 13 (12.7%) had newly depressed ejection fraction < 50% consistent with systolic heart failure with a cumulative incidence of 6.0% at 3 years from diagnosis (CI95 1.3-6.0%) (Figure 1A). However, there was no difference in subsequent development of systolic heart failure between the regimens with and without anthracycline (chi-squared, p=0.65). Neurological co-morbidities were common following therapy, with a cumulative incidence at 3 years, which included peripheral neuropathy 13.6% (CI95 6.9-20.4%), vision change 10.5% (CI95 4.6-16.5%), and memory or cognitive change 6.5% (CI95 1.8-11.1%) (Figure 1B). Conclusions APL is a highly curable form of leukemia but patients undergoing treatment may face significant long-term cardiac and neurologic co-morbidities regardless of the treatment regimens. It is critical that future care strategies incorporate treatments to improve and prevent comorbid effects of anti-leukemic treatment, potentially incorporating cardiac and neurological care into survivorship guidelines. Figure A. Cumulative incidence of systolic heart failure plotted against relapse and death as competing risks. B. Cumulative incidence of neurological complications including vision change, peripheral neuropathy, memory or cognitive change plotted against relapse and death as competing risks. Figure. A. Cumulative incidence of systolic heart failure plotted against relapse and death as competing risks. B. Cumulative incidence of neurological complications including vision change, peripheral neuropathy, memory or cognitive change plotted against relapse and death as competing risks. Disclosures Fathi: Bexalata: Other: Advisory Board participation; Merck: Other: Advisory Board participation; Seattle Genetics: Consultancy, Other: Advisory Board participation, Research Funding; Celgene: Consultancy, Research Funding; Agios Pharmaceuticals: Other: Advisory Board participation.

The PULSE Vision & Change Rubrics, Version 1.0: A Valid and Equitable Tool to Measure Transformation of Life Sciences Departments at All Institution Types

The PULSE Vision & Change Rubrics, version 1.0, assess life sciences departments’ progress toward implementation of the principles of the Vision and Change report. This paper reports on the development of the rubrics, their validation, and their reliability in measuring departmental change aligned with the Vision and Change recommendations. The rubrics assess 66 different criteria across five areas: Curriculum Alignment, Assessment, Faculty Practice/Faculty Support, Infrastructure, and Climate for Change. The results from this work demonstrate the rubrics can be used to evaluate departmental transformation equitably across institution types and represent baseline data about the adoption of the Vision and Change recommendations by life sciences programs across the United States. While all institution types have made progress, liberal arts institutions are farther along in implementing these recommendations. Generally, institutions earned the highest scores on the Curriculum Alignment rubric and the lowest scores on the Assessment rubric. The results of this study clearly indicate that the Vision & Change Rubrics, version 1.0, are valid and equitable and can track long-term progress of the transformation of life sciences departments. In addition, four of the five rubrics have broad applicability and can be used to evaluate departmental transformation by other science, technology, engineering, and mathematics disciplines.

Vision & Change: Why It Matters

The AAAS “Vision and Change” report (2011) has been inspiring undergraduate biology educators nationwide to rethink their educational approach, favoring active-learning strategies to better prepare today's students for a complex, data-rich future. Here, we consider the history of the movement, its place in the greater arena of STEM education, and the reasons why this new approach has never been more critical. We encourage all biology educators to consider becoming agents of change, and we focus on helpful resources and practical suggestions to help ABT readers take the plunge into (or at least get their feet wet in) the welcoming waters of Vision and Change.