From Theory to Practice: Implementation of Strategies to Reduce Acute Care Visits in Patients With Cancer.

Patients with cancer frequently seek acute care as a result of complications of their disease and adverse effects of treatment. This acute care comes at high cost to the health care system and often results in suboptimal outcomes for patients and their caregivers. The Department of Health and Human Services has identified this as a gap in our care of patients with cancer and has called for quality-improvement efforts to reduce this acute care. We highlight the efforts of three centers-a community practice, an academic practice, and a cancer center-to reduce acute care for their patients. We describe the foundational principles, the practice innovation and implementation strategy, the initial results, and the lessons learned from these interventions. Each of the described interventions sought to integrate evidence-based best practices for reducing unplanned acute care. The first, a telephone triage system, led to 82% of calls being managed at home and only 2% being directed to an emergency department (ED) or hospital. The second, a 24-hour continuity clinic, led to a 26% reduction in ED utilization for patients with cancer. The third, a digital symptom monitoring and management program for high-risk patients on active treatment, led to a 17% reduction in ED presentations. There is a need for innovative care delivery models to improve the management of symptoms for patients with cancer. Future research is needed to determine the elements of these models with the greatest impact and how successful models can be scaled to other institutions.

High-dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease: Case series and review of the literature.

Leptomeningeal metastasis (LM) in breast cancer is associated with significant morbidity and mortality. While there is currently no standard therapy, treatment options include craniospinal radiotherapy, intrathecal chemotherapy and systemic chemotherapy. Craniospinal radiotherapy has not demonstrated improved survival and intrathecal chemotherapy is often poorly tolerated due to associated neurotoxicity. The use of systemic chemotherapy can be limited by inadequate central nervous system penetration. High-dose systemic methotrexate administered intravenously (HD-MTX), has been reported to improve quality of life and provide durable remissions for LM in breast cancer. We present three cases of metastatic breast cancer and LM with prolonged survival after administration of HD-MTX. Based on our observations and review of the literature, HD-MTX seems to be a viable treatment option for patients with LM in breast cancer, and in select cases, the use of HD-MTX, as part of a multimodality treatment plan, may be associated with prolonged survival.

Immune Checkpoint Inhibitor-Associated Type 1 Diabetes Mellitus: Case Series, Review of the Literature, and Optimal Management.

With the introduction of immune checkpoint inhibitors into clinical practice, various autoimmune toxicities have been described. Antibodies targeting the receptor:ligand pairing of programmed death receptor-1 (PD-1) and its cognate ligand programmed death-ligand 1 (PD-L1) in rare reports have been associated with autoimmune diabetes mellitus. We report 2 cases of rapid-onset, insulin-dependent, type 1 diabetes mellitus in the setting of administration of nivolumab, a fully human monoclonal antibody to PD-1, and atezolizumab, a humanized monoclonal antibody to PD-L1. This appears to be the first report of autoimmune diabetes mellitus associated with atezolizumab. In addition, we provide a brief review of similar cases reported in the literature and a discussion of potential mechanisms for this phenomenon and propose a diagnostic and treatment algorithm.

Effect of Routine Surveillance Imaging on the Outcomes of Patients With Classical Hodgkin Lymphoma After Autologous Hematopoietic Cell Transplantation.

BACKGROUND: Patients with relapsed and refractory classical Hodgkin lymphoma (cHL) are often treated with autologous hematopoietic cell transplantation (auto-HCT). After auto-HCT, most transplant centers implement routine surveillance imaging to monitor for disease relapse; however, there is limited evidence to support this practice. PATIENTS AND METHODS: In this multicenter, retrospective study, we identified cHL patients (n = 128) who received auto-HCT, achieved complete remission (CR) after transplantation, and then were followed with routine surveillance imaging. Of these, 29 (23%) relapsed after day 100 after auto-HCT. Relapse was detected clinically in 14 patients and with routine surveillance imaging in 15 patients. RESULTS: When clinically detected relapse was compared with to radiographically detected relapse respectively, the median overall survival (2084 days [range, 225-4161] vs. 2737 days [range, 172-2750]; P = .51), the median time to relapse (247 days [range, 141-3974] vs. 814 days [range, 96-1682]; P = .30) and the median postrelapse survival (674 days [range, 13-1883] vs. 1146 days [range, 4-2548]; P = .52) were not statistically different. In patients who never relapsed after auto-HCT, a median of 4 (range, 1-25) surveillance imaging studies were performed over a median follow-up period of 3.5 years. CONCLUSION: A minority of patients with cHL who achieve CR after auto-HCT will ultimately relapse. Surveillance imaging detected approximately half of relapses; however, outcomes were similar for those whose relapse was detected using routine surveillance imaging versus detected clinically in between surveillance imaging studies. There appears to be limited utility for routine surveillance imaging in cHL patients who achieve CR after auto-HCT.

Liver biopsy findings in patients with hematopoietic cell transplantation.

Liver dysfunction is a frequent complication after hematopoietic cell transplantation. Liver biopsy has an important role for confirming the diagnosis of graft-versus-host disease (GVHD) or other liver diseases. The histological features of GVHD are not specific, and GVHD and other coexisting diseases may be present in the same biopsy, which makes the histologic interpretation of the liver biopsy more complex and challenging. The aim of the study is to improve the present diagnostic criteria. Fifty-two liver biopsies were studied. Most biopsies (47, 92%) showed some features of GVHD. Five (9.6%) had no GVHD, 20 (38.5%) had possible GVHD, and 27 (51.9%) had likely GVHD. Histologic features were analyzed semi-quantitatively and scored. Bile duct damage and intraepithelial lymphocytes were significantly more frequent in likely GVHD groups. Bile duct injury score calculated as the sum of bile duct damage and intraepithelial lymphocytes score was 2.3 in no GVHD and possible GVHD groups, and 4.2 in likely GVHD group (P<.001). A bile duct injury score ≥4 correlated well with a diagnosis of GVHD, with sensitivity 74% and specificity 88%. Many cases (36; 70.6%) had a concurrent disease process. Drug-induced liver injury (8, 16%) and sinusoidal obstruction syndrome (6, 12%) are particularly important causes of liver dysfunction. Moderate degree of bile duct injury and intraepithelial lymphocytes were the most helpful histologic findings to confirm the diagnosis of GVHD. In addition, it is important for the pathologist to be aware of the etiologies of liver dysfunction other than GVHD.

Impact of Routine Surveillance Imaging on Outcomes of Patients With Diffuse Large B-Cell Lymphoma After Autologous Hematopoietic Cell Transplantation.

BACKGROUND: For patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), autologous hematopoietic cell transplantation (auto-HCT) is commonly used. After auto-HCT, DLBCL patients are often monitored with surveillance imaging. However, there is little evidence to support this practice. PATIENTS AND METHODS: We performed a multicenter retrospective study of DLBCL patients who underwent auto-HCT (n = 160), who experienced complete remission after transplantation, and who then underwent surveillance imaging. Of these, only 45 patients experienced relapse after day +100 after auto-HCT, with relapse detected by routine imaging in 32 (71%) and relapse detected clinically in 13 (29%). RESULTS: Baseline patient characteristics were similar between the 2 groups. Comparing the radiographic and clinically detected relapse groups, the median time from diagnosis to auto-HCT (389 days vs. 621 days, P = .06) and the median follow-up after auto-HCT (2464 days vs. 1593 days P = .60) were similar. The median time to relapse after auto-HCT was 191 days in radiographically detected relapses compared to 492 days in clinically detected relapses (P = .35), and median postrelapse survival was 359 days in such patients compared to 123 days in patients with clinically detected relapse (P = .36). However, the median posttransplantation overall survival was not significantly different for patients with relapse detected by routine imaging versus relapse detected clinically (643 vs. 586 days, P = .68). CONCLUSION: A majority (71%) of DLBCL relapses after auto-HCT are detected by routine surveillance imaging. Overall, there appears to be limited utility for routine imaging after auto-HCT except in select cases where earlier detection and salvage therapy with allogeneic HCT is a potential option.

Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma: Impact of Disease Risk and Post Allograft Minimal Residual Disease on Survival.

BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative option for multiple myeloma (MM). We analyzed our experience of allo-HCT in MM and examined outcomes in 77 consecutive patients with MM receiving allo-HCT from matched sibling (n = 69) or unrelated donors (n = 8). The primary objectives were to assess overall survival (OS), progression-free survival (PFS), and non-relapse mortality in these patients. PATIENTS AND METHODS: Sixty-six patients received non-myeloablative/reduced-intensity conditioning regimens, while 11 received myeloablative regimens. The median follow-up of survivors was 50 months (range, 2.3-129.3 months). RESULTS: Twenty-seven (35.1%) patients had high-risk cytogenetics at diagnosis (t (4:14), 17p deletion, chromosome 1 abnormality, or t (14:16)). All of patients except 1 had prior auto transplant. On multivariate analysis, older age (hazard ratio [HR], 1.055; 95% confidence interval [CI], 1.001 = 1.11; P = .04), less than complete remission (CR) at allo-HCT (HR, 4.3; 95% CI, 1.3-14.1; P = .006), and cytomegalovirus reactivation (HR, 3.2; 95% CI, 1.38-7.6; P = .002) were associated with higher mortality risk. Less than CR at allo-HCT was also associated with higher risk for non-relapse mortality (HR, 5.8; 95% CI, 1.3-26.3; P = .02). There was no difference in OS or PFS between high-risk and standard-risk cytogenetics. No difference in OS and PFS was seen in those who had morphological complete response regardless of the minimal residual disease status. CONCLUSION: Allotransplant benefited younger patients and those in CR at the time of transplant. The adverse effect of high-risk cytogenetics may be overcome by the allo-HCT.