Payment and Care for Hematopoietic Cell Transplantation Patients: Toward a Specialized Medical Home for Complex Care Patients.

Patient-centered medical home models are fundamental to the advanced alternative payment models defined in the Medicare Access and Children's Health Insurance Plan Reauthorization Act (MACRA). The patient-centered medical home is a model of healthcare delivery supported by alternative payment mechanisms and designed to promote coordinated medical care that is simultaneously patient-centric and population-oriented. This transformative care model requires shifting reimbursement to include a per-patient payment intended to cover services not previously reimbursed such as disease management over time. Payment is linked to quality measures, including proportion of care delivered according to predefined pathways and demonstrated impact on outcomes. Some medical homes also include opportunities for shared savings by reducing overall costs of care. Recent proposals have suggested expanding the medical home model to specialized populations with complex needs because primary care teams may not have the facilities or the requisite expertise for their unique needs. An example of a successful care model that may provide valuable lessons for those creating specialty medical home models already exists in many hematopoietic cell transplantation (HCT) centers that deliver multidisciplinary, coordinated, and highly specialized care. The integration of care delivery in HCT centers has been driven by the specialty care their patients require and by the payment methodology preferred by the commercial payers, which has included bundling of both inpatient and outpatient care in the peritransplant interval. Commercial payers identify qualified HCT centers based on accreditation status and comparative performance, enabled in part by center-level comparative performance data available within a national outcomes database mandated by the Stem Cell Therapeutic and Research Act of 2005. Standardization across centers has been facilitated via voluntary accreditation implemented by Foundation for the Accreditation of Cell Therapy. Payers have built on these community-established programs and use public outcomes and program accreditation as standards necessary for inclusion in specialty care networks and contracts. Although HCT centers have not been described as medical homes, most HCT providers have already developed the structures that address critical requirements of MACRA for medical homes.

Estimating demand and unmet need for allogeneic hematopoietic cell transplantation in the United States using geographic information systems.

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) is an increasingly used therapy for many patients with hematologic malignancies and other marrow failure or immune system disorders. The purpose of this study was to quantify and visualize both the demand and unmet need for HCT. METHODS: HCT use for 2012 was described using the Center for International Blood and Marrow Transplant Research registry. Potential demand for HCT was calculated using 2012 SEER data and published literature for HCT-treatable conditions. Point locations of transplant centers were geocoded using geographic information system (GIS) software; Thiessen polygons were created to establish adult (age 20 to 74 years) and pediatric (age 0 to 19 years) market areas. Market-area population estimates were calculated using 2012 population estimates by age aggregated by census block. RESULTS: US market areas for HCTs were identified separately for transplant centers treating adult (n = 62) and pediatric patients (n = 52). Overall HCT demand among adults was 16,096, with an unmet need for HCTs of 10,276 patients. For pediatric patients, the total demand was 4,561, with an unmet need of 3,213 potential recipients. Evaluation of adult and pediatric market areas indicated that the largest unmet needs tended to be in areas with large populations. CONCLUSION: Market-area maps and statistics developed using GIS will help communicate the unmet need for HCT, inform policy, and assist transplant centers in planning for the anticipated growth in HCT use.

Therapeutic benefits in thalassemic mice transplanted with long-term-cultured bone marrow cells.

OBJECTIVE: Autologous bone marrow (BM) cells with a faulty gene corrected by gene targeting could provide a powerful therapeutic option for patients with genetic blood diseases. Achieving this goal is hindered by the low abundance of therapeutically useful BM cells and the difficulty maintaining them in tissue culture long enough to complete gene targeting without differentiating. Our objective was to devise a simple long-term culture system, using unfractioned BM cells, that maintains and expands therapeutically useful cells for ≥4 weeks. MATERIALS AND METHODS: From 2 to 60 million BM cells from wild-type (WT) mice or from mice carrying a truncated erythropoietin receptor transgene were plated with or without irradiated fetal-liver-derived AFT024 stromal cells in 25-cm(2) culture flasks. Four-week-cultured cells were analyzed and transplanted into sublethally irradiated thalassemic mice (1 million cells/mouse). RESULTS: After 4 weeks, cultures with AFT024 cells had extensive "cobblestone" areas. Optimum expansion of Sca-1-positive cells was 5.5-fold with 20 × 10(6) WT cells/flask and 27-fold with 2 × 10(6) truncated erythropoietin receptor transgene cells. More than 85% of thalassemic mice transplanted with either type of cells had almost complete reversal of their thalassemic phenotype for at least 6 months, including blood smear dysmorphology, reticulocytosis, high ferritin plasma levels, and hepatic/renal hemosiderosis. CONCLUSIONS: When plated at high cell densities on irradiated fetal-liver-derived stromal cells, BM cells from WT mice maintain their therapeutic potential for 4 weeks in culture, which is sufficient time for correction of a faulty gene by targeting.

Impending challenges in the hematopoietic stem cell transplantation physician workforce.

With increasing use of high dose chemotherapy with autologous and allogeneic transplants the need for the transplant physician workforce requires reassessment. The types of transplants and patients are also shifting toward transplants being done in patients with more comorbidities and more commonly these types of patients require more work effort per patient from the transplant physician. Additionally, HSCT survivors often require ongoing care at the transplant center due to the inability of the primary care workforce or the hematology/oncology workforce to absorb caring for post complex post transplant patients. The adult transplant workforce has had very few physicians join under age 40. Nearly 50% of adult transplant physicians are over age 50 whereas only 28% of pediatric transplant physicians are over age 50. By 2020, it is projected that we will need 1,264 new adult transplant physicians and 94 pediatric transplant physicians. Training time for a physician is approximately 15 years. The capping of both medical school slots and residency slots since the early '80s is now having a very big impact on supply, but other factors are also affecting supplies such as generational differences, lifestyle expectations, and the change of the medical workforce from being mostly men. Workforce shortages are being reported for many specialities. Workforce problems are also present for nurses, pharmacists and medical technologists. So increasing use of general internists and mid-level providers may not exist as a solution. Transplant physicians must be actively engaged in the medical education process to show young medical students and residents who are not committed to another sub specialty career the excitement and challenges of a career in bone marrow transplantation, so that our field will have providers for the future.

Utility of single versus tandem autotransplants for advanced testes/germ cell cancer: a center for international blood and marrow transplant research (CIBMTR) analysis.

Tandem autotransplants are used to treat advanced testis cancer patients but their value compared to a single autotransplant is unknown. To evaluate the results of autotransplant in relapsed testicular/germ cell cancer, data from 300 patients undergoing autotransplants 1989-2002 were reported to the Center for International Blood and Marrow Transplant Research. We compared results for those patients intended to undergo tandem autotransplant procedures (N = 102) versus patients in whom a second autotransplant was not planned (N = 198). Five-year survival probability was 35% (95% confidence interval = 25%-46%) in the planned tandem transplant cohort compared to 42% (35%-49%) in the group not planned to have a second transplant (P = .29). Probability of progression-free survival at 5 years for these cohorts was 34% (25%-44%) and 38% (31%-45%), respectively (P = .50). The planned tandem autotransplant cohort had significantly more advanced disease at diagnosis and greater likelihood of cisplatin resistance. Patients intended to receive tandem transplants had a lower treatment-related mortality at 1 year (3% versus 10%, P = .02). Using propensity score analysis the planned tandem autotransplant cohort had significantly lower treatment-related mortality (P = .044) but no different risk of relapse (P = .541) compared to the planned single transplant cohort. Tandem autotransplants for testicular cancer are associated with less treatment-related mortality than a planned single transplant, with no differences in disease-related outcomes or overall survival at 3 years. Patient selection bias for either transplant approach, however, may affect the results of this observational study; a randomized trial is needed to determine which approach, if either, is better.

Pathogenesis of thrombocytopenia in cyanotic congenital heart disease.

Although a significant minority of patients with cyanotic congenital heart disease (CCHD) are thrombocytopenic, the pathogenesis and prevalence have not been established. This study was designed to address these 2 issues. We included 105 patients with CCHD (60 men and 45 women; aged 21 to 54 years). Systemic arterial oxygen saturations were 69% to 78%. Hematocrits were 62% to 74% with normal iron indexes. In 26 of 105 patients (25%), platelet counts were <100x10(9)/L. The diagnosis was Eisenmenger syndrome in all 26 patients with thrombocytopenia. Platelet production was determined by flow cytometric reticulated platelet counts. Megakaryocyte mass was determined indirectly by thrombopoietin levels. Disseminated intravascular coagulation was based on prothrombin time, activated partial thromboplastin time, and D-dimers. Platelet activation was determined by levels of platelet factor 4 and beta thromboglobulin. Reference ranges were derived from 20 normal acyanotic controls. A reduction in absolute reticulated platelet counts implied decreased platelet production (p<0.001). Normal thrombopoietin levels implied normal megakaryocyte mass. Normal prothrombin time, activated partial thromboplastin time, and D-dimers excluded disseminated intravascular coagulation. Normal platelet factor 4 and beta thromboglobulin indicated absent or minimal platelet activation. Twenty-five percent of the patients with CCHD were thrombocytopenic because platelet production was decreased despite normal megakaryocyte mass. We hypothesized that right-to-left shunts deliver whole megakaryocytes into the system arterial circulation, bypassing the lungs where megakaryocytic cytoplasm is fragmented into platelets, thus reducing platelet production. In conclusion, platelet counts in CCHD appear to represent a continuum beginning with low normal counts and ending with thrombocytopenia.

Mesenchymal stem cell injection induces cardiac nerve sprouting and increased tenascin expression in a Swine model of myocardial infarction.

UNLABELLED: Stem Cell Induces Cardiac Nerve Sprouting. INTRODUCTION: Mesenchymal stem cell (MSC) transplantation is a promising technique to improve cardiac function. Whether MSC can increase cardiac nerve density and contribute to the improved cardiac function is unclear. METHODS AND RESULTS: Anterior wall myocardial infarction was created in 16 swine. One month later, 6 swine were given MSC and fresh bone marrow (BM) into infarcted myocardium (MSC group). Four swine were given fresh BM only (BM group), and 6 swine were given culture media (MI-only group). The swine were sacrificed 95.8 +/- 3.5 days after MI. Six normal swine were used as control. Immunocytochemical staining was performed using antibodies against growth-associated protein 43 (GAP43), tyrosine hydroxylase (TH), and three subtypes of tenascin (R, C, and X). Five fields per slide were counted for nerve density. The results show the following. (1). There were more GAP43-positive nerves in the MSC group than in the BM, MI-only, or Control group (P < 0.0001). TH staining showed higher nerve densities in the MSC group than in the MI-only (P < 0.01) or Control group (P < 0.0001) in the atria. (2). There were more sympathetic (TH-positive) nerves in myocardium distant from infarct than in the peri-infarct area (P < 0.05). (3). Optical intensity and color analyses showed significantly higher tenascin R and tenascin C expression in the MSC and BM groups than in the MI-only or Control group (P < 0.01). CONCLUSION: MSC injected with BM into swine infarct results in overexpression of cardiac tenascin, increased the magnitude of cardiac nerve sprouting in both atria and ventricles, and increased the magnitude of atrial sympathetic hyperinnervation 2 months after injection.