Assessing the Efficacy of Imiquimod Use in Patients With Persistent Locally Advanced Melanoma In Situ

BACKGROUND: The standard of care when treating melanoma in situ (MMIS) is an excision with at least 5 mm surgical margins.1 Some studies have suggested up to 9 mm margins to maximize local recurrence-free survival.2 This retrospective review aims to assess the efficacy of imiquimod as a topical treatment for persistently positive MMIS at the margins of prior excisions or where surgery is not an option. METHODS: Retrospective study conducted at Moffitt Cancer Center between 2019 and 2021 with patients aged > 18 years with MMIS at the margins of excision of an invasive melanoma or MMIS. Included patients were not ideal candidates for primary or additional surgical resection due to non-feasibility of surgery because of comorbidity or cosmetically sensitive location and/or the need for repeated skin grafting, or due to patient's refusal. Patients received imiquimod on protocol for 16 weeks and were monitored for treatment response and side effects. Following completion of the treatment, scouting biopsies were performed to assess histological response, and dermoscopy was used to determine the clinical disease status. RESULTS: Ten patients completed 16 weeks of imiquimod. Seven (75%) had a median of 2 surgical resections, and 3 refused surgery despite discussion that surgery was standard of care. Seven were deemed free of disease on post-imiquimod treatment scouting biopsies, while 2 were found to be clinically free of disease following confocal microscopy, indicating a tumor clearance rate of 90% with imiquimod treatment. One patient was found to have persistent residual disease following 2 rounds of imiquimod and was taken for an additional surgical excision after which they were deemed free of disease. Median follow-up duration from the onset of imiquimod therapy to the last clinic visit was 18 months, without any recurrences to date. CONCLUSION: Imiquimod appears to demonstrate an encouraging tumor clearance among patients with persistent MMIS after surgery where further surgical resection may not be feasible. Although long-term durability has not been demonstrated in this study, a 90% tumor clearance rate is promising. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.6987.

Survival Outcomes for Patients with Relapsed/ Refractory Aggressive B Cell Lymphomas Following Receipt of High-Dose Chemotherapy/Autologous Stem Transplantation and/or Chimeric Antigen Receptor-Modified T Cells.

Patients diagnosed with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL) may achieve prolonged survival following receipt of high-dose chemotherapy/autologous stem cell transplantation (HDC/ASCT) or CD19-directed chimeric antigen receptor modified T cell therapy (CART19). Although early results from randomized clinical trials suggest that assignment to CART19 versus salvage immunochemotherapy as second-line therapy results in improved survival, analysis of a large series of patients who actually received HDC/ASCT or CART19 has yet to be performed. Such an analysis may inform future research efforts to optimize the risk stratification of R/R DLBCL/HGBL patients who are candidates for either therapy. The aim of this study was to evaluate clinicopathologic factors predictive of freedom from treatment failure (FFTF) for R/R DLBCL/HGBL patients following receipt of HDC/ASCT or CART19, and to compare patterns of treatment failure (TF) in R/R DLBCL/HGBL patients receiving HDC/ASCT and those receiving CART19. THE STUDY GROUP COMPRISED: patients age ≤75 years with R/R DLBCL/HGBL who received HDC/ASCT demonstrating partial or complete metabolic response to salvage immunochemotherapy and/or CART19 in the standard of care setting at the University of Pennsylvania between 2013 and 2021. Survival analyses were performed from the time of infusion of either HDC/ASCT or CART19, as well as at landmark time points postinfusion for patients who achieved FFTF. For 100 HDC/ASCT patients with a median follow-up of 62.7 months, the estimated 36-month FFTF and overall survival (OS) rates were 59% and 81%, respectively. For 109 CART19 patients with a median follow-up of 37.6 months, the estimated 36-month FFTF and OS rates were 24% and 48%, respectively. HDC/ASCT patients had significantly higher rates of estimated 36-month FFTF when they achieved actual FFTF at 3, 6, 12 and 24 months. Additionally, the rates of baseline characteristics predictive of TF at 36 months for either HDC/ASCT or CART19 patients were either similar to or significantly lower for CART19 patients compared to HDC/ASCT patients who achieved actual FFTF at 3, 6, 12, and 24 months. Patients with R/R DLBCL/HGBL achieving response to salvage immunochemotherapy who received HDC/ASCT had a high rate of estimated FFTF regardless of whether they harbored features predictive of resistance to salvage immunochemotherapy, which may be more durable than that of R/R DLBCL/HGBL patients receiving CART19. These findings support further investigation of disease characteristics, such as molecular features, that may predict response to salvage immunochemotherapy in patients fit for HDC/ASCT.

Evaluation of rejection, infection, and malignancy outcomes in elderly liver transplant recipients receiving a similar level of immunosuppression compared to a younger group.

Elderly liver transplant (LTx) recipients at a lower risk of acute rejection compared to younger recipients due to immunosenescence. As such, they may benefit from reduced immunosuppression (IS) to minimize infectious and malignant complications. We aimed to evaluate outcomes in LTx recipients ≥60 years compared to a younger group of LTx recipients aged 18-59 years maintained on a similar level of IS. This was a single-center retrospective evaluation of adult LTx recipients from 2013 to 2018 who received methylprednisolone induction and were maintained on tacrolimus, mycophenolate mofetil (MMF), and a prednisone taper. A total of 143 LTx recipients were evaluated. Mean age in the older group was 65 ± 3.8 compared to 49 ± 10.4 years in the younger group (p < 0.0001). Mean tacrolimus levels and the duration of MMF and steroids were comparable. Both groups had a similar incidence of first rejection within 1 year (19.2% in the elderly group vs. 23.1% in the younger group, p = 0.57). There were no statistical difference in terms of infection, malignancy, or patient survival. In conclusion, our data suggests that elderly LTx recipients, when treated with a similar level of IS, had similar 1 year incidence of rejection, infection, malignancy, and patient survival as younger LTx recipients.

Tisagenlecleucel Therapy: Nursing Considerations for the Outpatient Setting.

OBJECTIVE: Tisagenlecleucel is a CD19-directed, genetically modified, autologous T-cell immunotherapy indicated for pediatric and young adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia and for adult patients with relapsed/refractory diffuse large B-cell lymphoma. Treatment with any chimeric antigen receptor (CAR)-T cell therapy is a multistep process in which nurses and nurse practitioners are key to managing patient safety. Managing patients receiving CAR-T cell therapy in the outpatient setting (as Penn does with tisagenlecleucel and lisocabtagene maraleucel) requires an even more complex process. The objective of this manuscript is to provide guidance on the role of nurses in the outpatient administration of tisagenlecleucel therapy and postinfusion care in adult patients with diffuse large B-cell lymphoma. Oncology and apheresis nurses discuss institutional processes and perspectives related to the patient experience with tisagenlecleucel therapy at the Hospital of the University of Pennsylvania. DATA SOURCES: Author experience. CONCLUSION: Nurses are vital for the success of the patient management processes involved with tisagenlecleucel therapy. Nurses must be thoroughly educated in tisagenlecleucel therapy and adverse event management and be able to effectively communicate all aspects of therapy among the multidisciplinary team of the hospital, the product manufacturer, and patients and families. Establishment of the nurse cellular therapy coordinator at the Hospital of the University of Pennsylvania was advantageous in facilitating effective communication in all these situations. IMPLICATIONS FOR NURSING: This encompassing approach to patient management is particularly necessary during administration of tisagenlecleucel therapy and other CAR-T cell therapies that are managed in the outpatient setting.

Neuroglian regulates Drosophila intestinal stem cell proliferation through enhanced signaling via the epidermal growth factor receptor.

The Drosophila intestine is an excellent system for elucidating mechanisms regulating stem cell behavior. Here we show that the septate junction (SJ) protein Neuroglian (Nrg) is expressed in intestinal stem cells (ISCs) and enteroblasts (EBs) within the fly intestine. SJs are not present between ISCs and EBs, suggesting Nrg plays a different role in this tissue. We reveal that Nrg is required for ISC proliferation in young flies, and depletion of Nrg from ISCs and EBs suppresses increased ISC proliferation in aged flies. Conversely, overexpression of Nrg in ISC and EBs promotes ISC proliferation, leading to an increase in cells expressing ISC/EB markers; in addition, we observe an increase in epidermal growth factor receptor (Egfr) activation. Genetic epistasis experiments reveal that Nrg acts upstream of Egfr to regulate ISC proliferation. As Nrg function is highly conserved in mammalian systems, our work characterizing the role of Nrg in the intestine has implications for the treatment of intestinal disorders that arise due to altered ISC behavior.

Effect of malnutrition-driven nutritional support protocol on clinical outcomes in autologous stem cell transplantation patients.

PURPOSE: Poor nutrition status in patients receiving high-dose chemotherapy and autologous stem cell transplant (ASCT) has been associated with inferior clinical outcomes. We aim to determine whether a malnutrition-driven nutritional support protocol can improve these outcomes. METHODS: In this prospective cohort study, we assessed adults for malnutrition who were consecutively admitted for ASCT between October 2017 and March 2019 (n = 251), and provided enteral or parenteral nutrition (EN/PN) to patients who were malnourished early in the transplantation admission. We compared their clinical outcomes with those of a historical cohort admitted between May 2016 and October 2017 (n = 257) for whom nutrition assessment and initiation of EN/PN were not protocol-driven. RESULTS: Patients receiving ASCT during the intervention period experienced decreased odds of prolonged hospital stay (p = 0.023), central line-associated bloodstream infection (p = 0.015), mucosal barrier injury (p = 0.037), and high weight loss (p = 0.002), in a multivariate analysis as compared with those receiving ASCT during the control period. Outcomes for ICU transfer, deconditioning on discharge, time to platelet engraftment, and unplanned 30-day hospital readmission did not differ significantly between groups. CONCLUSION: A malnutrition-driven nutritional support protocol may improve outcomes for ASCT patients.

Plerixafor mobilization leads to a lower ratio of CD34+ cells to total nucleated cells which results in greater storage costs.

BACKGROUND: Plerixafor (Mozobil, AMD3100) with granulocyte-colony stimulating factor (G-CSF) mobilizes more CD34+ cells/kg compared to G-CSF alone. Given that plerixafor enhances mobilization of multiple white blood cell lineages, we determined if more storage space is required for products collected from patients mobilized with plerixafor. METHODS: A review of the medical records of 15 patients mobilized with chemotherapy and G-CSF (control) and 14 patients mobilized with plerixafor plus G-CSF (plerixafor) was performed. Data on demographics, baseline characteristics, CD34+ cells/kg, total nucleated cells, total mononuclear cells, total apheresis sessions, and total bags for storage were collected. Mean values were determined and compared using Student's t-test. RESULTS: We found that the proportion of CD34+ cells among total nucleated cells was less in the plerixafor group compared to the control group (P = 0.0427). More nucleated cells (10.7 x 10(10) vs. 7.1 x 10(10), P =0.0452) and mononuclear cells (9.7 x 10(10) vs. 5.9 x 10(10), P = 0.0059) were mobilized with plerixafor plus G-CSF. However, there was no significant difference in CD34+ cells/kg, total CD34+ cells or the proportion of mononuclear cells among total nucleated cells between the two groups. More storage bags were required for the plerixafor group compared to the control group (15 vs. 9, P = 0.0299). CONCLUSION: Mobilization with plerixafor plus G-CSF resulted in a smaller proportion of CD34+ cells collected and a greater number of storage bags. An increase in the number of bags required for stem cell storage may be logistically problematic and will also lead to increased costs for storage of stem cells.

Do simultaneous bilateral tunneled infusion catheters in patients undergoing bone marrow transplantation increase catheter-related complications?

PURPOSE: Secure venous access with multiple lumens is necessary for the care of allogeneic hematopoietic stem cell transplant (HSCT) recipients. The outcomes associated with simultaneous bilateral tunneled internal jugular infusion catheter placement in the HSCT recipient population were investigated in an attempt to determine whether simultaneous introduction of these catheters compounds or magnifies the risks (infection, venous thrombosis) associated with tunneled catheters. MATERIALS AND METHODS: Patients undergoing HSCT and receiving bilateral tunneled infusion catheters in a single procedure were identified using a quality assurance data base. Medical records for the duration of catheterization were reviewed; 43 patients were included in the study (mean age, 42 years; range, 22-56). Diagnoses included acute lymphocytic leukemia (n = 4), acute myelogenous leukemia (n = 8), aplastic anemia (n = 2), chronic myelogenous leukemia (n = 17), chronic lymphocytic leukemia (n = 1), Hodgkin lymphoma (n = 1), myelodysplasia (n = 4), myelofibrosis (n = 2), and non-Hodgkin lymphoma (n = 4). Cox proportional hazards regression analysis was performed to determine differences in infection rates between dual- and triple-lumen catheters. RESULTS: Forty-three pairs of catheters were placed. All met venous access needs for HSCT recipient care. Complete follow-up was achieved for 77 of 87 (89%) catheters. The overall infection rate was 0.25 per 100 catheter-days. The rate was 0.19 and 0.33 for dual- and triple-lumen catheters, respectively (P =.15). Mechanical failure did not differ between catheter types (dual: 0.14 episodes per 100 days, triple: 0.05 per 100 days, P =.2). CONCLUSIONS: Bilateral multilumen tunneled infusion catheter placement in a single procedure using imaging guidance is safe with acceptable outcomes and meets venous access needs for HSCT. There is a trend toward higher infection rates, with more lumens and more mechanical failure with dual-lumen catheters.