Decision impact studies, evidence of clinical utility for genomic assays in cancer: A scoping review.

BACKGROUND: Decision impact studies have become increasingly prevalent in cancer prognostic research in recent years. These studies aim to evaluate the impact of a genomic test on decision-making and appear to be a new form of evidence of clinical utility. The objectives of this review were to identify and characterize decision impact studies in genomic medicine in cancer care and categorize the types of clinical utility outcomes reported. METHODS: We conducted a search of four databases, Medline, Embase, Scopus and Web of Science, from inception to June 2022. Empirical studies that reported a "decision impact" assessment of a genomic assay on treatment decisions or recommendations for cancer patients were included. We followed scoping review methodology and adapted the Fryback and Thornbury Model to collect and analyze data on clinical utility. The database searches identified 1803 unique articles for title/abstract screening; 269 articles moved to full-text review. RESULTS: 87 studies met inclusion criteria. All studies were published in the last 12 years with the majority for breast cancer (72%); followed by other cancers (28%) (lung, prostate, colon). Studies reported on the impact of 19 different proprietary (18) and generic (1) assays. Across all four levels of clinical utility, outcomes were reported for 22 discrete measures, including the impact on provider/team decision-making (100%), provider confidence (31%); change in treatment received (46%); patient psychological impacts (17%); and costing or savings impacts (21%). Based on the data synthesis, we created a comprehensive table of outcomes reported for clinical utility. CONCLUSIONS: This scoping review is a first step in understanding the evolution and uses of decision impact studies and their influence on the integration of emerging genomic technologies in cancer care. The results imply that DIS are positioned to provide evidence of clinical utility and impact clinical practice and reimbursement decision-making in cancer care. Systematic review registration: Open Science Framework osf.io/hm3jr.

Promising remissions in relapsed refractory classical Hodgkin lymphoma patients requiring multiple salvage regimens before transplantation in the brentuximab vedotin era.

Relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients refractory to first line salvage have poor outcomes. Herein we report the outcome of R/R cHL patients requiring ≥two vs. one line in the era of chemo-immunotherapy. Among 55 R/R cHL patients, 33 (60%) required one, 22 (40%) required ≥two lines. At 2 years, the estimated PFS and OS for patients requiring one vs. ≥two lines was 71.2% (50.1-84.7) vs. 51.9% (27.6-71.6), p= 0.16 and 84.6% (63-94) vs. 84% (58-95), p= 0.88, respectively. Patients requiring ≥two salvage lines prior to HCT can achieve comparable outcomes to those requiring one, possibly due to brentuximab vedotin leading to higher CMR rates.

Optimal pre-emptive cytomegalovirus therapy threshold in a patient population with high prevalence of seropositive status.

INTRODUCTION: Preemptive therapy (PET) for cytomegalovirus (CMV) reactivation post allogeneic hematopoietic stem cell transplantation (SCT) was shown to decrease the incidence of CMV disease. However, the optimal PET threshold is elusive. PURPOSE OF THE STUDY: To examine the efficacy of PET initiation at a viral threshold of 1000 copies/mL (1560 IU/mL) in a patient population with high prevalence of CMV seropositive status. PATIENTS AND METHODS: A single center retrospective review of patients that underwent allogeneic SCT was done. RESULTS: A total of 195 allogeneic SCT recipients were included with median follow up of 18.1 (0.7-95.6) months. A total of 178 (91 %) of patients had a positive CMV PCR with median days to initial reactivation post SCT of 17 (1-1187); 129 patients had peak CMV titer < 1000 copies/mL (low titer) whereas the remaining 49 patients had a peak titer ≥ 1000 copies/mL (high titer). 120 (93 %) of patients with low titers cleared spontaneously with median time to clearance of 40 days (4-188). One patient in the high titer group developed CMV disease. At multivariable analysis; age at SCT HR 1.02 (1.004-1.04; 0.017), malignant vs. benign condition HR 9.4 (2.47-61; 0.0005) and cGVHD HR 0.37 (0.2-0.65; 0.0005) were significant for OS. CONCLUSIONS: CMV reactivation post SCT was very common in patients with high prevalence of seropositive status. A PET threshold of 1000 copies/mL (1560 IU/mL) appears desirable as it was associated with spontaneous clearance in over 90 % of patients while minimizing treatment related toxicity. Validation of these observations is warranted.

Graft vs host disease impacts overall survival post allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia/lymphoma.

AIM: To examine the outcome and prognostic factors for high risk patients with acute lymphoblastic leukemia/lymphoma (ALL/LBL) who underwent allogeneic hematopoietic stem cell transplantation (HCT) at our center during the period of 2010-2017. METHODS: After due institutional review board approval, patients with high risk ALL/LBL post HCT were identified and included. All records were retrospectively collected. Time to event analysis was calculated from the date of HCT until event of interest or last follow up with Kaplan-Meir means. Cox regression model was used for multivariable analysis calculation. RESULTS: A total of 69 patients were enrolled and examined with a median age of 21 (14-61). After a median follow up of 15 mo (2-87.3), the 2-year cumulative incidence of relapse, cumulative incidence of non-relapse mortality, progression free survival and overall survival (OS) were 34.1%, 10.9%, 54.9% and 62.8%, respectively. In a multivariable analysis for OS; acute graft vs host disease (GVHD) and chronic GVHD were significant with corresponding hazard ratio 4.9 (1.99-12; P = 0.0007) and 0.29 (0.1-0.67; P = 0.0044), respectively. CONCLUSION: Allogeneic-HCT for high risk ALL/LBL resulted in promising remissions particularly for patients with cGVHD.

Lymphocyte recovery is an independent predictor of relapse in allogeneic hematopoietic cell transplantation recipients for acute leukemia.

AIM: To examine the optimal absolute lymphocyte count (ALC) cut-off utilizing receiver operator characteristics (ROC) in addition to graft characteristics associated with early ALC recovery. METHODS: Patients who received T-cell replete peripheral hematopoietic cell transplantation (HCT) for acute leukemia were identified. ALC cut-off was established using ROC analysis and subsequently the cohort was stratified. Time to endpoint analysis and cox regression modelling was computed to analyze outcomes. RESULTS: A total of 72 patients met the inclusion criteria and were analyzed. Optimal ALC cut-off was established to be on day 14 (D14) with ALC > 0.3 × 109/L. At 2 years, cumulative incidence of relapse was 16.9% vs 46.9% (P = 0.025) for early and delayed lymphocyte recovery cohorts, respectively. Chronic graft vs host disease was more prevalent in the early lymphocyte recovery (ELR) group at 70% vs 27%, respectively (P = 0.0006). On multivariable analysis for relapse, ELR retained its prognostic significance with HR = 0.27 (0.05-0.94, P = 0.038). CONCLUSION: ELR is an independent predictor for relapse in patients receiving allogeneic HCT for acute leukemia. ELR was influenced by graft characteristics particularly CD34 count.

Reducing Central Venous Catheter Use in Peripheral Blood Stem Cell Donation: Quality Improvement Report.

Peripheral blood stem cell (PBSC) collection from donors through apheresis has become the main source of stem cells for hematopoietic stem cell transplantation. This procedure requires a high blood flow venous access. A peripheral venous catheter (PVC), compared to a central venous catheter (CVC), is considered to provide safer venous access. However, initially at our institution, King Abdul-Aziz Medical City - Riyadh, a CVC was frequently used (72%). A quality improvement multidisciplinary team has been formed to conduct a systematic quality performance analysis to evaluate the current process of collecting donor PBSCs with the aim to reduce CVC use to less than the international benchmark (20%). A quality improvement methodology, rapid cycles of plan-do-study-act (PDSA), was used to test a set of initiatives. An Intravenous (IV) team assessed the donor's venous access and inserted an appropriate PVC when feasible. This project ran over 16 months with 42 adult donors undergoing PBSC collection. During the first PDSA cycle, 1 CVC was inserted for every 4 donors. In the second PDSA cycle, 1 CVC was inserted for every 8 apheresis donations. In the third PDSA cycle, no CVC was used for 30 apheresis donations. The targeted stem cell dose was collected successfully in one apheresis session in all donors assigned for PVC access with no complications. A significant reduction of CVC use from 72% to 0% was achieved. This quality improvement project demonstrated that a successful apheresis procedure can be achieved easily and safely in the majority of PBSC donors preventing the potential adverse events associated with CVCs. The interdisciplinary collaboration between the IV team, apheresis and clinical hematology teams was paramount to optimize the safe care of donors.