The impact of cytotoxic therapy on the risk of progression and death in clonal cytopenia(s) of undetermined significance.

ABSTRACT: Clonal cytopenia of undetermined significance (CCUS) is defined by a myeloid driver mutation in the context of otherwise unexplained cytopenia. CCUS has an inherent risk of progressing to myeloid neoplasm. However, it is unknown how exposure to previous cytotoxic therapy may impact the risk of progression and survival. We stratified patients with CCUS by prior exposure to DNA-damaging therapy. Of 151 patients, 46 (30%) had received cytotoxic therapy and were classified as therapy-related CCUS (t-CCUS), whereas 105 (70%) had de novo CCUS. A lower proportion of t-CCUS had hypercellular marrows (17.8% vs 44.8%, P = .002) but had higher median bone marrow blast percentages. After a median follow-up of 2.2 years, t-CCUS had significantly shorter progression-free survival (PFS, 1.8 vs 6.3 years; hazard ratio [HR], 2.1; P = .007) and median overall survival (OS; 3.6 years vs not reached; HR, 2.3; P = .007) compared with CCUS. Univariable and multivariable time-to-event analyses showed that exposure to cytotoxic therapy independently accounted for inferior PFS and OS. Despite the similarities in clinical presentation between CCUS and t-CCUS, we show that exposure to prior cytotoxic therapies was an independent risk factor for inferior outcomes. This suggests that t-CCUS represents a unique clinical entity that needs more stringent monitoring or earlier intervention strategies.

Is pathogen reduction an acceptable alternative to irradiation for risk mitigation of transfusion-associated graft versus host disease?

Transfusion-associated graft versus host disease (TA-GVHD) is a highly morbid and often fatal adverse event associated with transfusion of cellular blood products [platelets, red blood cells (RBCs) and whole blood] and more rarely with never-frozen plasma products. It is caused by residual viable donor T-lymphocytes that proliferate and actively target recipient tissues. Selective or universal irradiation of blood components using gamma-irradiation and more recently, X-ray irradiation, are the most commonly applied interventions and have been validated by the demonstration of in vitro T-lymphocyte inactivation, in murine models of TA-GVHD and by years of clinical experience. Irradiation, however, has multiple limitations including a sharp dose-response curve that renders quality control of dosage critically important, the use of radioactive radiation sources that are a terrorism risk, and selective implementation in many countries that leads to inadvertent omission and patient risk exposure. Certain pathogen reduction technologies (PRT) for platelets have been approved by regulatory authorities and endorsed by professional societies as an alternative to irradiation for reducing the risk of TA-GVHD, and PRT for RBCs and whole blood are in development. While the mechanism of action of T-lymphocyte inactivation differs from gamma/X-ray irradiation, the impact on T-lymphocyte inactivation for PRT is equivalent or superior to that of irradiation as demonstrated by sensitive in vitro lymphocyte proliferation assays and in vivo mouse models that approximate human TA-GVHD. Clinical trials and cumulative routine-use experience attest to the efficacy of PRT when used as an alternative to irradiation. While T-lymphocyte inactivation efficacy varies between PRT platforms, the implementation of PRT for platelets increases blood safety for patients beyond the mitigation of TA-GVHD, by decreasing the risk of transfusion transmitted infections with known viruses, bacteria and parasites as well as emerging pathogens.

The Las Vegas mass shooting: An analysis of blood component administration and blood bank donations.

BACKGROUND: The deadliest mass shooting in modern United States history occurred on October 1, 2017, in Las Vegas, killing 58 and overwhelming hospitals with more than 600 injured. The scope of the tragedy offers insight into medical demands, which may help guide preparedness for future mass shooting incidents. METHODS: Retrospective, deidentified, health care institution-provided data from all hospitals and blood banks providing care to Las Vegas shooting victims were gathered. Study authors independently reviewed all data and cross-referenced it for verification. Main outcomes and measures include the number of victims requiring hospital and intensive care admission, the amount and types of blood components transfused during the first 24 hours, and the amount of blood donated to local blood banks following the Las Vegas mass shooting. RESULTS: Two hundred twenty patients required hospital admission, 68 of them to critical care. Nearly 500 blood components were transfused during the first 24 hours in a red blood cell-to-plasma-to-platelet ratio of 1:0.54:0.81. Public citizens donated almost 800 units of blood immediately after the shooting; greater than 17% of this donated blood went unused. CONCLUSIONS: The amount of blood components transfused per patient admitted was similar in magnitude to other mass casualty events, and available blood supply met patient demand. The public call for blood donors was not necessary to meet immediate demand and led to resource waste. Preparation for future mass shooting incidents should include training the community in hemorrhage control, encouraging routine blood donation, and avoiding public calls for blood donation unless approved by local blood suppliers. LEVEL OF EVIDENCE: Therapeutic study, level V.

Ki-67 proliferative index predicts progression-free survival of patients with well-differentiated ileal neuroendocrine tumors.

Ki-67 proliferative index (Ki-67 index) is suggested to be an important prognostic variable and is included as one of the grading parameters for neuroendocrine tumors. The present study was undertaken to determine the usefulness of the Ki-67 index and the corresponding tumor grade in predicting progression-free survival (PFS) of patients with ileal well-differentiated neuroendocrine tumors (wNETs). Tumors from 57 patients with ileal wNETs were studied. Immunohistochemical staining for Ki-67 was performed on the primary as well as selected metastatic tumors and quantitated by computer-assisted image analysis using the Ariol system. The tumors were graded based on mitotic activity and Ki-67 index. Clinical and pathological variables affecting the PFS were analyzed. There were 29 women and 28 men, with a mean age of 59 years. At the time of initial presentation, 8 patients (14%) had localized disease (stages I and II), 29 patients (51%) had regional (nodal/mesenteric) spread (stage III), and 20 patients (35%) had distant metastasis (stage IV). Twelve patients experienced disease progression during subsequent follow-up. Patients with initial stage IV disease were more likely to experience disease progression (P = .005). Additionally, higher histological grade (as determined by Ki-67 index >2%) was associated with a decreased PFS (P = .001). Ki-67 index greater than 2% at either the primary site or the metastatic site was found to be the only significant predictor of PFS after consideration of all other variables in an adjusted analysis. In conclusion, the Ki-67 index predicts PFS of patients with ileal wNETs.