Porcine-human glioma xenograft model. Immunosuppression and model reproducibility.

BACKGROUND: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies. Therefore, development of a consistent and simple large animal glioma xenograft model would have significant translational benefits. METHODS: Immunosuppression was induced in twelve standard Yucatan minipigs. 3 pigs received cyclosporine only, while 9 pigs received a combined regimen including cyclosporine (55 mg/kg q12 h), prednisone (25 mg, q24 h) and mycophenolate (500 mg q24 h). U87 cells (2 × 106) were stereotactically implanted into the left frontal cortex. The implanted brains were imaged by MRI for monitoring. In a separate study, tumors were grown in 5 additional pigs using the combined regimen, and pigs underwent tumor resection with intra-operative image updating to determine if the xenograft model could accurately capture the spatial tumor resection challenges seen in humans. RESULTS: Tumors were successfully implanted and grown in 11 pigs. One animal in cyclosporine only group failed to show clinical tumor growth. Clinical tumor growth, assessed by MRI, progressed slowly over the first 10 days, then rapidly over the next 10 days. The average tumor growth latency period was 20 days. Animals were monitored twice daily and detailed records were kept throughout the experimental period. Pigs were sacrificed humanely when the tumor reached 1 - 2 cm. Some pigs experienced decreased appetite and activity, however none required premature euthanasia. In the image updating study, all five pigs demonstrated brain shift after craniotomy, consistent with what is observed in humans. Intraoperative image updating was able to accurately capture and correct for this shift in all five pigs. CONCLUSION: This report demonstrates the development and use of a human intracranial glioma model in an immunosuppressed, but nongenetically modified pig. While the immunosuppression of the model may limit its utility in certain studies, the model does overcome several limitations of small animal or genetically modified models. For instance, we demonstrate use of this model for guiding surgical resection with intraoperative image-updating technologies. We further report use of a surrogate extracranial tumor that indicates growth of the intracranial tumor, allowing for relative growth assessment without radiological imaging.

Harnessing the Collective Expertise of Patients, Care Partners, Clinical Teams, and Researchers Through a Coproduction Learning Health System: A Case Study of the Dartmouth Health Promise Partnership.

The coproduction learning health system (CLHS) model extends the definition of a learning health system to explicitly bring together patients and care partners, health care teams, administrators, and scientists to share the work of optimizing health outcomes, improving care value, and generating new knowledge. The CLHS model highlights a partnership for coproduction that is supported by data that can be used to support individual patient care, quality improvement, and research. We provide a case study that describes the application of this model to transform care within an oncology program at an academic medical center.

African Americans with translocation t(11;14) have superior survival after autologous hematopoietic cell transplantation for multiple myeloma in comparison with Whites in the United States.

BACKGROUND: Multiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard-risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent. METHODS: This study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187). RESULTS: African Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). Fewer African Americans with t(11;14) (21%) had a coexistent high-risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression-free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT-CI, and receipt of maintenance. CONCLUSIONS: Race may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.

Caregivers' Out-of-Pocket Expenses and Time Commitment Following Hematopoietic Stem Cell Transplantation at a Rural Cancer Center.

The emotional and physical toll on caregivers of cancer patients is well documented, but research evaluating the financial burdens and time commitments of caregivers is limited. We suspected that the rural location of our cancer center would intensify these burdens for caregivers. We conducted a prospective trial to assess the out-of-pocket expenses and time commitment of caregivers of hematopoietic stem cell transplantation recipients within the first 4 weeks after discharge from the hospital from a National Cancer Institute (NCI)-designated comprehensive cancer center. These results show that caregivers of autologous recipients paid out-of-pocket expenses of $196 over 4 weeks. If lost wages were included, the expenses increased to $736 during this period. Caregivers of allogeneic recipients had out-of-pocket expenses of $110 in 4 weeks, or a total of $610 when lost wages were included. In the month after discharge from the hospital, caregivers traveled a median distance of 450 miles or 560 miles, depending on whether the patient received an autologous transplant or an allogeneic transplant, respectively. These results demonstrate a compelling need to address caregiver support, given the significant financial out-of-pocket expenses and time commitment.

Extracorporeal photopheresis for graft versus host disease: Identifying a clinical pathway and associated resource utilization.

Extracorporeal photopheresis (ECP) is an established therapy for the treatment of graft-versus-host-disease (GVHD) following an allogeneic stem cell transplant. We performed a prospective analysis of patients receiving ECP treatment for GVHD to identify a clinical pathway and resource utilization of this process. The cohort included consecutive allogeneic stem cell recipients with GVHD. ECP was performed using the CELLEX Photopheresis System or the UVAR XTS Photopheresis System (Therakos, Inc, Exton, PA). A clinical pathway was developed and a time and motion study was conducted to define the resource utilization and costs associated with ECP. Patients were treated with either CELLEX (n = 18 procedures) or UVAR (n = 4 procedures). Total time commitment for each procedure for the 2 machines differed. The time for ECP was 117 min (median, range: 91-164 min) using CELLEX and 161 min (median; range: 140-210) using the UVAR-XTS machine. Total costs of each ECP procedure were $3420.50. There is a considerable time commitment of the patient and the clinical staff when employing ECP to treat GVHD. ECP costs are significant considering this is a prolonged therapy continued for several months. With this finalized pathway and costs, we have a standardized clinical pathway for the treatment of GVHD. We are addressing minimizing resource utilization while emphasizing quality care for these patients.

Peridischarge prophylactic platelet transfusions after stem cell transplant: is a tranfusion trigger needed?

BACKGROUND: We examined the appropriateness of prophylactic peridischarge platelet (PLT) transfusions and the feasibility of lowering the prophylactic PLT transfusion threshold in transplant recipients within 24 hours of discharge at a National Cancer Institute-designated comprehensive cancer center. STUDY DESIGN AND METHODS: From April 2011 to June 2014, each prophylactic PLT transfusion that was administered to transplant recipients within 24 hours of discharge was identified. Each transfusion was reviewed to identify the indication and to determine if the transfusion adhered to institutional guidelines. RESULTS: Of the 187 transplant patients identified, 44 patients received a prophylactic PLT transfusion within 24 hours of discharge. Of these 44 patients, transfusions were administered to fulfill a PLT count of 20 × 10(9) /L required for discharge (n = 25 patients), for the removal of a tunneled central venous catheter (n = 16 patients), for active bleeding (n = 1 patient), or due to active anticoagulation (n = 2 patients). CONCLUSIONS: The majority of PLT transfusions (95%) were appropriate, and only 5% were avoidable. If the prophylactic PLT transfusion threshold was decreased to 15 × 10(9) /L from 20 × 10(9) /L for central line removal and to fulfill discharge PLT count criteria, 41% of the currently appropriate PLT transfusions could have been avoided. These results suggest that a risk-adapted method to select autologous transplant recipients for prophylactic PLT transfusions may be beneficial. A future study is needed to address this issue.

Successful implementation of a rural extracorporeal photopheresis program for the treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease in a rural hospital.

OBJECTIVE: Extracorporeal photopheresis (ECP) is currently standard therapy for cutaneous T-cell lymphoma (CTCL) and Graft-versus-host disease (GVHD). Of the many challenges associated with outpatient ECP treatments, commuter travel to capable facilities can fragment and compromise the patient care. In 2008, our hospital implemented an ECP program providing patients to a treatment center over 120 minutes away. This study was undertaken to describe our experience with the establishment of a regional ECP program. METHODS: A retrospective review using a standardized template was performed of patients treated from May 2008 to 2012. The response to treatment was analyzed after a minimum of eight procedures. A partial response to treatment in individuals with CTCL, was more than 50% skin improvement, and GVHD, a reduction in steroid dose by 50%, liver function test improvement or documented improvement in skin findings. RESULTS: Of the 34 patients treated, 11 were for CTCL and 23 for GVHD. 95.8% of the 1,071 planned procedures were successfully. The average procedure time was 186 min for the UVAR-XTSTM and 93 min for the CELLEXTM. Patients travelled a median of 65.7 miles (range 4-133 miles). The median duration of therapy was 6 months (range 2-23) for CTCL and 5 months (range 1-27) for GVHD. A clinical benefit was observed in 7 of 11 (63.6%) patients with CTCL and in 15 of 23 (65.2%) with GVHD. CONCLUSION: Our regional ECP program was a viable option in improving access to care for patients requiring treatment for CTCL and chronic GVHD.

Hospital readmission following transplantation: identifying risk factors and designing preventive measures.

BACKGROUND: About 1 in 7 of all hospitalized patients is readmitted within 30 days of discharge. The cost of readmissions is significant, with Medicare readmissions alone costing the health care system an estimated $28 billion a year. OBJECTIVE: To identify the rates of and causes for readmission within 100 days of patients receiving a hematopoietic stem cell transplant. METHODS: We performed a retrospective review of 235 consecutive transplant recipients (autologous, n = 144; allogeneic, n = 91) to determine rates and causes for readmission within 100 days of patients receiving a transplant. Medical records and hospital readmissions were reviewed for each patient. RESULTS: 36 allogeneic patients accounted for 56 readmissions. 23 autologous patients accounted for 26 readmissions. Autologous transplant recipients were most commonly readmitted for the development of a fever (n = 15 patients) or cardiopulmonary issues (n = 4). The most prevalent reasons for readmission in the allogeneic recipients included a fever (n = 21) or the development or exacerbation of graft-versus-host disease (n = 5). The readmission length of stay was 6 days (median range, 1-91 days) for allogeneic patients and 4 days (median range, 1-22 days) for autologous patients. There was no difference in survival between the readmitted and the non-readmitted cohorts (𝑃 = .55 for allogeneic patients; 𝑃 = .24 for autologous patients). Although allogeneic graft recipients demonstrated a higher readmission rate (39.6%) compared with autologous recipients (16%), none of the variables examined, including age, gender, performance status, diagnosis, remission status at the time of transplant, comorbidities, type of preparative chemotherapy regimen or donor type, identified patients at increased risk for readmission. LIMITATIONS: Variations in clinical care, physician practices, and patient characteristics need to be considered when examining readmission rates. Most of the allogeneic patient population included unrelated donor recipients (65%) who received nonmyeloablative conditioning regimens (81% of allogeneic recipients). These features may not be characteristic of other centers. CONCLUSIONS: In these high-risk patients, readmissions following a transplant are common. Enhanced predischarge education by nurses and pharmacists, along with ongoing outpatient education and rigorous outpatient follow-up through phone calls or social media may decrease readmission rates.