Germline GATA1s-generating mutations predispose to leukemia with acquired trisomy 21 and Down syndrome-like phenotype.

Individuals with Down syndrome are at increased risk of myeloid leukemia in early childhood, which is associated with acquisition of GATA1 mutations that generate a short GATA1 isoform called GATA1s. Germline GATA1s-generating mutations result in congenital anemia in males. We report on 2 unrelated families that harbor germline GATA1s-generating mutations in which several members developed acute megakaryoblastic leukemia in early childhood. All evaluable leukemias had acquired trisomy 21 or tetrasomy 21. The leukemia characteristics overlapped with those of myeloid leukemia associated with Down syndrome, including age of onset at younger than 4 years, unique immunophenotype, complex karyotype, gene expression patterns, and drug sensitivity. These findings demonstrate that the combination of trisomy 21 and GATA1s-generating mutations results in a unique myeloid leukemia independent of whether the GATA1 mutation or trisomy 21 is the primary or secondary event and suggest that there is a unique functional cooperation between GATA1s and trisomy 21 in leukemogenesis. The family histories also indicate that germline GATA1s-generating mutations should be included among those associated with familial predisposition for myelodysplastic syndrome and leukemia.

Secret Sauce-How Diverse Practices Succeed in Centers for Medicare & Medicaid Services Oncology Care Model.

PURPOSE: CMS' Oncology Care Model (OCM) is an episode-based alternative payment model designed to incent high-value care through the use of monthly payments for enhanced services and performance-based payments on the basis of decreases in spending compared with risk-adjusted historical benchmarks. Transitioning from a fee-for-service model to a value-based, alternative payment model in oncology can be difficult; some practices will perform better than others. We present detailed experiences of four successful OCM practices, each operating under diverse business models and in different geographic areas. METHODS: Practices that achieved success in OCM, on the basis of financial metrics, describe pathways to success. The practices represent distinct business models: a medium-sized community oncology practice, a large statewide community oncology practice, a hospital-affiliated practice, and a large academic medical center. RESULTS: Practices describe effective changes in practice culture such as new administrative flexibilities, physician champions, improved communication, changes in physician compensation, and increased physician-level transparency. New or improved clinical services include acute care clinics, care coordination, phone triage, end-of-life care programs, and adoption of treatment pathways that identify high-value drug use, including better use of supportive care drugs. CONCLUSION: There is no one thing that will ensure success in OCM. Success requires whole practice transformation, encompassing both administrative and clinical changes. Communication between administrative and clinical teams is vital, along with improved data sharing and transparency. Clinical support services must expand to manage problems and symptoms in a timely way to prevent costly emergency department visits and hospitalizations, while constant attention must be paid to making high-value therapeutic choices in both oncolytic and supportive drug categories.

Implementing Quality Colon Cancer Survivorship Care: A Practical Proposal for a Path Forward.

There are currently close to 17 million survivors of cancer in the United States. This number is expected to grow as both an aging population and improved treatment increase the number of survivors. Consequently, the importance of quality survivorship care has been recognized, but implementing, measuring, and paying for this care in a highly fragmented health care system, across a broad spectrum of diseases, is difficult. Quality measurement tied to payment is one approach that has commonly been used to improve the quality of care in the US health care system, but the complexity of applying quality measurement metrics across the spectrum of cancer survivorship care had led to stalemate. In this article, we draw on prior work to develop a quality cancer survivorship framework and propose a practical path forward with a focus on the provision of colon cancer survivorship care within integrated health care delivery networks. With this narrowly defined approach, we hope that we can promote a practical solution that can be extended to other diseases and payment systems over time.

Patient Navigation in Cancer: The Business Case to Support Clinical Needs.

PURPOSE: Patient navigation (PN) is an increasingly recognized element of high-quality, patient-centered cancer care, yet PN in many cancer programs is absent or limited, often because of concerns of extra cost without tangible financial benefits. METHODS: Five real-world examples of PN programs are used to demonstrate that in the pure fee-for-service and the alternative payment model worlds of reimbursement, strong cases can be made to support the benefits of PN. RESULTS: In three large programs, PN resulted in increased patient retention and increased physician loyalty within the cancer programs, leading to increased revenue. In addition, in two programs, PN was associated with a reduction in unnecessary resource utilization, such as emergency department visits and hospitalizations. PN also reduces burdens on oncology providers, potentially reducing burnout, errors, and costly staff turnover. CONCLUSION: PN has resulted in improved patient outcomes and patient satisfaction and has important financial benefits for cancer programs in the fee-for-service and the alternative payment model worlds, lending support for more robust staffing of PN programs.

The Centers for Medicare & Medicaid Services Oncology Care Model Halfway Through: Perspectives from Diverse Participants.

The Oncology Care Model (OCM) is a 5-year model developed and tested by the Centers for Medicare & Medicaid Services that uses an episode-based payment model triggered by the receipt of chemotherapy to test if changing payment mechanisms, in conjunction with a requirement for enhanced patient services, can generate clinical transformation that will orient practices toward more patient-centered, high-value care to reduce expenditures and preserve or enhance quality of care for beneficiaries. The model is geographically diverse with practices in 34 states and encompasses practices ranging in size from 1 to more than 400 practitioners, with a multitude of business structures. Given these varied clinical and business environments, we believe that OCM-participating practices will have different opportunities and challenges as they work toward practice transformation, but they will likely share similarities with other practices in similar clinical and business settings. This commentary shares the experiences of four diverse groups participating in OCM-three practices and one network of practices-halfway through the model's projected 5-year life cycle in the expectation that these experiences will be of value to other practices embarking toward patient-centered, high-value practice transformation.

Long-Term Survivorship Care After Cancer Treatment - Summary of a 2017 National Cancer Policy Forum Workshop.

The National Cancer Policy Forum of the National Academies of Sciences, Engineering and Medicine sponsored a workshop on July 24 and 25, 2017 on Long-Term Survivorship after Cancer Treatment. The workshop brought together diverse stakeholders (patients, advocates, academicians, clinicians, research funders, and policymakers) to review progress and ongoing challenges since the Institute of Medicine (IOM)'s seminal report on the subject of adult cancer survivors published in 2006. This commentary profiles the content of the meeting sessions and concludes with recommendations that stem from the workshop discussions. Although there has been progress over the past decade, many of the recommendations from the 2006 report have not been fully implemented. Obstacles related to the routine delivery of standardized physical and psychosocial care services to cancer survivors are substantial, with important gaps in care for patients and caregivers. Innovative care models for cancer survivors have emerged, and changes in accreditation requirements such as the Commission on Cancer's (CoC) requirement for survivorship care planning have put cancer survivorship on the radar. The Center for Medicare & Medicaid Innovation's Oncology Care Model (OCM), which requires psychosocial services and the creation of survivorship care plans for its beneficiary participants, has placed increased emphasis on this service. The OCM, in conjunction with the CoC requirement, is encouraging electronic health record vendors to incorporate survivorship care planning functionality into updated versions of their products. As new models of care emerge, coordination and communication among survivors and their clinicians will be required to implement patient- and community-centered strategies.

Design Challenges of an Episode-Based Payment Model in Oncology: The Centers for Medicare & Medicaid Services Oncology Care Model.

The Centers for Medicare & Medicaid Services developed the Oncology Care Model as an episode-based payment model to encourage participating practitioners to provide higher-quality, better-coordinated care at a lower cost to the nearly three-quarter million fee-for-service Medicare beneficiaries with cancer who receive chemotherapy each year. Episode payment models can be complex. They combine into a single benchmark price all payments for services during an episode of illness, many of which may be delivered at different times by different providers in different locations. Policy and technical decisions include the definition of the episode, including its initiation, duration, and included services; the identification of beneficiaries included in the model; and beneficiary attribution to practitioners with overall responsibility for managing their care. In addition, the calculation and risk adjustment of benchmark episode prices for the bundle of services must reflect geographic cost variations and diverse patient populations, including varying disease subtypes, medical comorbidities, changes in standards of care over time, the adoption of expensive new drugs (especially in oncology), as well as diverse practice patterns. Other steps include timely monitoring and intervention as needed to avoid shifting the attribution of beneficiaries on the basis of their expected episode expenditures as well as to ensure the provision of necessary medical services and the development of a meaningful link to quality measurement and improvement through the episode-based payment methodology. The complex and diverse nature of oncology business relationships and the specific rules and requirements of Medicare payment systems for different types of providers intensify these issues. The Centers for Medicare & Medicaid Services believes that by sharing its approach to addressing these decisions and challenges, it may facilitate greater understanding of the model within the oncology community and provide insight to others considering the development of episode-based payment models in the commercial or government sectors.

Centers for medicare and medicaid services: using an episode-based payment model to improve oncology care.

PURPOSE: Cancer is a medically complex and expensive disease with costs projected to rise further as new treatment options increase and the United States population ages. Studies showing significant regional variation in oncology quality and costs and model tests demonstrating cost savings without adverse outcomes suggest there are opportunities to create a system of oncology care in the US that delivers higher quality care at lower cost. DESIGN: The Centers for Medicare and Medicaid Services (CMS) have designed an episode-based payment model centered around 6 month periods of chemotherapy treatment. Monthly per-patient care management payments will be made to practices to support practice transformation, including additional patient services and specific infrastructure enhancements. Quarterly reporting of quality metrics will drive continuous quality improvement and the adoption of best practices among participants. Practices achieving cost savings will also be eligible for performance-based payments. Savings are expected through improved care coordination and appropriately aligned payment incentives, resulting in decreased avoidable emergency department visits and hospitalizations and more efficient and evidence-based use of imaging, laboratory tests, and therapeutic agents, as well as improved end of life care. CONCLUSION: New therapies and better supportive care have significantly improved cancer survival in recent decades. This has come at a high cost, with cancer therapy consuming $124 billion in 2010. CMS has designed an episode-based model of oncology care that incorporates elements from several successful model tests. By providing care management and performance based payments in conjunction with quality metrics and a rapid learning environment, it is hoped that this model will demonstrate how oncology care in the US can transform into a high value, high quality system.

Tumor Lysis Syndrome: An Unreported Complication of Intrathecal Ara-C.

Intrathecal (IT) chemotherapy is an established method of preventing and treating CNS leukemia. Although this intervention is beneficial and necessary, understanding the potential adverse effects of IT chemotherapy is important so that these potential effects can be anticipated and prevented. Tumor lysis syndrome is a known complication of systemic chemotherapy and has also been reported as a rare complication after IT chemotherapy in patients with CNS disease. We report the first case of tumor lysis syndrome occurring in a patient with T-cell acute lymphoblastic leukemia without CNS disease. The systemic effects of the IT chemotherapy were confirmed by the decreased size of the presenting mediastinal mass.

Bevacizumab treatment in multifocal lymphangioendotheliomatosis with thrombocytopenia.

Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a rare disorder characterized by a proliferation of cutaneous and gastrointestinal (GI) lesions that have characteristics of both lymphatic and vascular lesions. Thrombocytopenia is associated with this syndrome and is thought to represent platelet destruction within the lesions. The natural history is one of multiple, life-threatening episodes of GI bleeding. We report the successful use of bevacizumab in this disease, an antibody to the vascular endothelial growth factor.

Correction of celiac disease after allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia.

Allogeneic hematopoietic stem cell transplantation has been shown to correct or improve a variety of autoimmune disorders. This has not been reported for celiac disease, but transmission to a hematopoietic stem cell transplantation recipient from a donor with celiac disease has been reported. We report a 12-year-old girl with celiac disease who was diagnosed with acute leukemia and received an allogeneic hematopoietic stem cell transplant. Her celiac disease resolved after the hematopoietic stem cell transplant.

Ruptured Meckel diverticulum mimicking mucositis in a patient receiving induction therapy for high-risk acute lymphoblastic leukemia.

A Meckel diverticulum is an embryonic remnant of the vitellointestinal duct. It is present in approximately 2% of the population and is estimated to cause symptoms<5% of the time. It generally results in painless bleeding or abdominal pain. Rarely, it can rupture, resulting in peritonitis and gram-negative sepsis. We present the case of a 17-year-old male who ruptured his Meckel diverticulum 23 days after the beginning of induction chemotherapy for high-risk acute lymphoblastic leukemia. We postulate that gastritis caused by dexamethasone, mucositis caused by doxorubicin, and the unique anatomic nature of a Meckel diverticulum may have contributed to this extremely unlikely and previously unreported event.

Treatment of pediatric febrile neutropenia in the era of vancomycin-resistant microbes.

PURPOSE: The increasing frequency of Gm(+) infections in febrile neutropenic (FN) patients has resulted in increased use of vancomycin (VN). Likely as a result, VN-resistant Enterococcus (VRE) has become a significant concern in FN patients. We sought to understand how the emergence of VN resistant microbes has changed the antibiotic management of pediatric FN. METHODS: A questionnaire was distributed by e-mail to responsible investigators of the Children's Oncology Group. RESULTS: One hundred and thirty responses were analyzed. Forty-four percent initially used monotherapy, with 82% of those using ceftazidime. Twenty-seven used VN with another agent, generally ceftazidime. After the emergence of VRE and VN-resistant staphylococcus (VRS), monotherapy increased to 58%. Ceftazidime continued to be most frequently used. There was a 57% reduction in the use of VN with 88% of centers not currently using VN in their initial treatment of FN. Forty-seven percent of the centers that continue to use VN have VRE, while 90% that have discontinued its use have VRE/VRS. CONCLUSIONS: Ours is the first study to survey current practices in the treatment of pediatric FN and to document changes in practice patterns due to emerging antibiotic resistance patterns. We demonstrate increased use of monotherapy for FN, and a 57% decrease in the use of VN. Local considerations influence antibiotic choices with a significant difference in VRE prevalence between those centers that continue to use VN as compared to those that have discontinued it.