Abstract: The Levine Cancer Institute (LCI) of the Carolinas HealthCare System was established in Charlotte, NC, in 2010 as a primary through quaternary referral center. The Department of Hematologic Oncology and Blood Disorders was established as part of the LCI in an effort to bring subspecialized care in malignant and nonmalignant hematology to the region. Charlotte, NC, is the second-largest city in the southeastern United States; however, prior to the department’s establishment, the Charlotte metro area lacked a subspecialized hematologic oncology facility, and had no direct access to a hematopoietic cell transplant (HCT) program. The department has grown rapidly since its establishment, with patient volume growing six-fold. The rapid growth in each disease section has led to a rapidly expanding HCT program, with more than 100 transplants performed in the second full year of operation. The HCT program received accreditation from the Foundation for the Accreditation of Cellular Therapy in 2016, shortly after its second full year of operation. Transplant outcomes have been excellent and reflect the high quality of care provided by the new department.
Limited access to excellent health care close to home is a national and global problem. Many patients must travel long distances to receive specialized care and complex therapies. The extensive variation in hematopoietic cell transplant (HCT) rates, coupled with the geographic density of HCT centers,1 is illustrative of the geographic disparities of care.
Disease-specific specialization is associated with improved outcomes in hematologic malignancies;2 yet, such specialized care is unavailable in many areas of the United States. Charlotte, NC, is the second-largest city in the southeastern United States and one of the largest cities in the nation, with a metro-area population exceeding 2.3 million. However, subspecialized care in hematology, including a leukemia unit and HCT program, did not exist in the Charlotte area in 2012. The closest HCT program was a 90-minute drive, and patients lacking the willingness or the resources to travel did not have access to specialized treatments.
Carolinas HealthCare System (CHS) is one of the leading health care organizations, and one of the most comprehensive non-for-profit systems, in the United States. The system includes more than 2600 licensed beds, employs nearly 60,000 people, and accounts for almost 12 million patient interactions annually in the United States. It serves as a safety net for the region. In 2010, CHS decided to develop the LCI as a primary through quaternary referral center, integrated through more than 12 sites throughout North and South Carolina.
The Department of Hematologic Oncology and Blood Disorders was established in September 2012, with a goal of providing subspecialty care in malignant and nonmalignant hematology, including HCT. The department was created through a belief that developing specialized care units in leukemia, lymphoma, plasma cell disorders, sickle cell anemia, and bleeding disorders would improve the quality of care for patients in the Charlotte area as well as patients throughout North Carolina and parts of South Carolina.
It was also understood that most newly established HCT programs over the last 20 years have failed or had limited impact, due to difficulties changing established referral patterns and attracting a significant number of patients. Because HCT programs require a significant initial investment, a significant number of transplants is required to justify the expense. Additionally, centers in which physicians perform a larger number of transplants appear to have lower mortality rates compared with centers performing fewer procedures.3 It was thought that the provision of subspecialty care would attract substantial numbers of patients early in their disease course and provide a large number of candidates for appropriately timed transplantations.
Hct Program Development and Implementation
Faculty and Disease Sections
The Department of Hematologic Oncology and Blood Disorders was established with four general hematologists, and has since grown to include 24 physicians. Fifteen faculty members provide subspecialized care in hematologic malignancies and HCT (Figure 1), working with 16 midlevel providers. Interdisciplinary sections in plasma cell disorders, lymphoma, leukemia, nonmalignant hematology, and HCT convene weekly or monthly to review clinical care and pathways, progress in the disease area, clinical trials, and translational work at all stages of development.
A computer-based system of clinical pathways (EAPathways) has been established through each section and is followed within each disease specialty by physicians throughout the LCI. The tool contains care pathways on specific medical conditions and can be edited quickly; regular updates are made. The pathways include standardized orders, patient education material, and suggested time points for referral, as well as available clinical trials that patients may enter. Pathway data are accessible through the electronic medical records system.
Patients
Patient volume has grown more than six-fold since the department’s establishment (Figure 2). Patients referred from outlying sites are referred back to those sites for routine care, often including the administration of chemotherapy.
HCT Program
The HCT Program performed its first transplant in March 2014; a total of 60 transplants were performed that year. Transplant numbers increased to 81 in 2015, the first full year of transplantation services, and to 104 in 2016 (Figure 3). The program received accreditation from the Foundation for the Accreditation for Cellular Therapy in 2016, just over 2 years after the first performed transplant. The ages of transplant patients range from 22 years to 76 years, with a median age of 58 years. Sixty-nine percent of transplants have been autologous and 31% have been allogeneic, of which 65% were from haploidentical related donors. More than 90% of patients who have undergone transplantation were referred for HCT through a disease-specific section at LCI.
A unique feature of the program is that all of our malignant disease specialists follow their patients pretransplantation and posttransplantation, and rotate through the inpatient services where transplantation is performed. Cumulative nonrelapse mortality (NRM) at 1 year is 1.9% for autologous transplants and 7% for allogeneic transplants (Table 1), with 1-year survival rates of 93.5% and 79.7%, respectively (Figure 4). The use of high-dose cyclophosphamide following haploidentical family donor transplantation4 has facilitated transplantation of patients lacking HLA-identical siblings. Notably, there is no difference in NRM (P = .86), relapse-free survival (P = .85), or overall survival (P = .47) between HLA-identical and haploidentical transplant recipients.
Academic Work
In addition to patient care, the department has made significant contributions to basic and clinical research. The Hematology Oncology Translational Laboratory and Pharmacology Research Program conduct projects in several areas, including leukemogenesis and the role of CSF3R mutations in its pathogenesis; acute myeloid leukemia stem cells; and the use of pharmacogenomics to dose several transplant-related drugs. The lab is in close proximity to core facilities in genomics, flow cytometry, biostatistics, and bioinformatics.
Since its inception, the department has brought innovative clinical trials in all phases to the Charlotte area. Sixteen new trials have been opened, including two first-in-human trials. The early phase hematology trials have screened 75 patients and enrolled 63 patients. The department has published more than 120 basic and clinical articles in the last 3 years—including basic, translational, and clinical work—in Blood, Journal of Clinical Oncology, and The New England Journal of Medicine.5-8
Discussion
The LCI established the Department of Hematologic Oncology and Blood Disorders in 2012, with the specific purpose of providing access to high-quality specialized medical care to a community in which it was lacking. Because research has shown that treatment provided by specialized physicians improves outcomes in patients with benign and malignant blood diseases,1 it was our belief that improving access to disease-specific treatment that did not require the burden of travel would improve the quality of care for patients in the Charlotte metro area. Our HCT was founded in 2014, and by 2016—its second full year of operation—performed more than 100 stem cell transplantations. The department can and will continue to expand in the coming years.
We believe that several factors have contributed to the success of our department in the short time period of its existence. Disease-specific expertise has attracted a large number of patients who otherwise might have traveled out of district or out of state for care. Because disease specialists follow patients throughout their entire care experience, there is a continuity of care from highly trained physicians that was previously not available. The LCI has cultivated excellent relationships with referring physicians in the Charlotte area, and electronic pathway programs have fostered easy communication among providers within and outside of our institution. Excellent communication and collaboration among CHS providers, as well as external physicians, has been critical to our growth. We have also fostered a research community that has made the LCI a desirable work environment for skilled physicians, which has led our faculty to grow exponentially since the department’s inception.
Conclusion
As recently as 3 years ago, access to subspecialized care in hematologic malignancies, complex benign blood disorders, and HCT required significant travel for patients residing in the Charlotte metro area. The development and growth of a program that provides disease-specific care in hematologic malignancies has overcome this barrier, and provided a base for the growth of a newly established program in HCT. Disease specialists follow patients before, during, and after transplantation. Electronic pathway programs promote superb and consistent care throughout the system. These programs foster excellent communication and collaboration among providers within CHS, as well as with external physicians who provide concomitant care. Pathways also provide opportunities to standardize care choices in disease states with rapidly evolving treatment options. These developments have elevated the quality of care in hematologic malignancies in the Charlotte area, and made appropriate and complex care available close to home for these patients.
References
1. Gratwohl A, Pasquini MC, Aljurf M, et al. One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol. 2015;2(3):e91-e100.
2. Go RS, Bottner WA, Gertz MA. Making the case to study the volume-outcome relationship in hematologic cancers. Mayo Clin Proc. 2015;90(10):1393-1399.
3. Loberiza FR Jr, Zhang MJ, Lee SJ, et al. Association of transplant center and physician factors on mortality after hematopoietic stem cell transplantation in the United States. Blood. 2005;105(7):2979-2987.
4. Luznik L, O’Donnell PV, Fuchs EJ. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Semin Oncol. 2012;39(6):683-693.
5. Copelan EA, Hamilton BK, Avalos B, et al. Better leukemia-free and overall survival in AML in first remission following cyclophosphamide in combination with busulfan compared with TBI. Blood. 2013;122(24):3863-3870.
6. Ghosh N, Karmali R, Rocha V, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: a center for international blood and marrow transplant research analysis. J Clin Oncol. 2016;34(26):3141-3149.
7. Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(14):1319-1331.
8. Druhan LJ, McMahon DP, Steuerwald N, et al. Chronic neutrophilic leukemia in a child with a CSF3R T618I germline mutation [published online August 31, 2016]. Blood. pii:blood-2016-07-730606.
