The effects of monoclonal anti-CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia.

BACKGROUND: CD47 is a novel therapeutic target in the treatment of solid-organ and hematologic malignancies. CD47 is also expressed on RBCs. Here, we report our experience of the RBC effects and the impact on blood bank testing and transfusion management in a Phase 1 trial of the humanized anti-CD47 monoclonal antibody Hu5F9-G4 in relapsed or primary refractory acute myeloid leukemia (AML) (NCT02678338). STUDY DESIGN AND METHODS: Nineteen patients with relapsed or primary refractory AML treated across five UK centers were included for analysis. Patients received escalating doses of Hu5F9-G4. Serial laboratory data were collected to evaluate impact on hemoglobin (Hb), markers of hemolysis (bilirubin, lactate dehydrogenase, reticulocyte count), transfusion requirements, and blood compatibility testing. RESULTS: A decline in Hb was observed with drug administration (median Hb change, -1.0 g/dL; range, 0.4-1.6) with associated increase in transfusion requirements. Patients responded to transfusion with a median Hb increment per unit of 1.0 g/dL. RBC agglutination was seen in all cases without associated change in Hb, lactate dehydrogenase, bilirubin, or reticulocyte count. Nine of 19 (47%) patients developed a newly positive antibody screen with a pan-agglutinin identified in plasma. Invalid ABO blood grouping occurred in 4 of 12 (33%) non-group O patients due to anomalous reactivity in the reverse ABO-type results. CONCLUSIONS: Treatment with Hu5F9-G4 in patients with AML resulted in an Hb decline and increased transfusion requirements. Problems with ABO blood typing and compatibility testing were widely observed and should be expected by centers treating recipients of Hu5F9-G4.

Targeting the endoplasmic reticulum mediates radiation sensitivity in colorectal cancer.

BACKGROUND: Radiotherapy is an established treatment modality for early and locally advanced rectal cancer as part of short course radiotherapy and long course chemoradiotherapy. The unfolded protein response (UPR) is a cellular stress response pathway often activated in human solid tumours which has been implicated in resistance to both chemotherapy and radiotherapy. This research has investigated whether the UPR pathway is upregulated in ex-vivo samples of human colorectal cancer and characterised the interaction between radiotherapy and UPR activation in two human colorectal cancer cell lines in vitro. METHODS: In vitro UPR expression was determined in response to clinical doses of radiotherapy in both the human colorectal adenocarcinoma (HT-29) cell line and a radio-resistant clone (HT-29R) using western blotting and quantitative polymerase chain reaction. The UPR was induced using a glucose deprivation culture technique before irradiation and radiosensitivity assessed using a clonogenic assay. Ex-vivo human colorectal cancer tissue was immuno-histochemically analysed for expression of the UPR marker glucose regulated protein 78 (GRP-78). RESULTS: The UPR was strongly up regulated in ex-vivo human colorectal tumours with 36 of 50 (72.0%) specimens demonstrating moderate to strong staining for the classic UPR marker GRP-78. In vitro, therapeutic doses of radiotherapy did not induce UPR activation in either radiosensitive or radioresistant cell lines. UPR induction caused significant radiosensitisation of the radioresistant cell line (HT-29R SF2Gy=0.90 S.E.M. +/-0.08; HT-29RLG SF2Gy=0.69 S.E.M. +/-0.050). CONCLUSION: This suggests that UPR induction agents may be potentially useful response modifying agents in patients undergoing therapy for colorectal cancer.

The impact of electronic decision support and electronic remote blood issue on transfusion practice.

OBJECTIVES: To assess the impact on transfusion practice of a two-stage electronic intervention: the introduction of a decision support system (DSS) followed by the addition of electronic remote blood issue (ERBI). BACKGROUND: With increasing evidence to show the benefit of restrictive transfusion policies, it is important to ascertain which interventions can increase clinician compliance with their implementation. A DSS provides patient-specific recommendations to clinicians. ERBI reduces delays in acquiring blood and may alter the transfusion behaviour of clinicians. METHODS: All electronically requested blood transfusions administered outside of surgical theatres or recovery were identified in an orthopaedic hospital. These were divided into three time periods corresponding to pre-intervention, the successive introduction of DSS alone and DSS with ERBI. Pre- and post-transfusion haemoglobin (Hb) concentration levels, and the number of units ordered and transfused were recorded. RESULTS: A total of 204 transfusions for 92 patients were assessed; 38 of 85 (45%) transfusions in the first time period were compliant. This did not significantly change after introduction of the DSS, but with DSS and ERBI together significantly increased to 39 of 60 (65%) (P < 0·05). Mean pre-transfusion Hb reduced from 8·24 g dl(-1) in the first time period to 7·67 g dl(-1) in the third (P < 0·0001). There was no significant change in overall blood usage, although ERBI significantly reduced the amount of unused blood orders from 70 to 25%. CONCLUSION: Electronic DSS was not sufficient to change practice in the form implemented in this study. ERBI can contribute to significant improvements in blood usage as well as the efficiency of blood provision.

UK Transfusion Laboratory Collaborative: minimum standards for staff qualifications, training, competency and the use of information technology in hospital transfusion laboratories 2014.

The SHOT Adverse Incident Reporting Scheme has consistently reported an unacceptably high level of errors originating in the laboratory setting. In 2006 an initiative was launched in conjunction with the IBMS, SHOT, RCPath, BBTS, UK NEQAS, the NHSE NBTC and the equivalents in Scotland, Wales and Northern Ireland that led to the formation of the UK TLC. The UK TLC in considering the nature and spread of the errors documented by SHOT concluded that a significant proportion of these errors were most likely to be related to either the use of information technology or staff education, staffing levels, skill mix, training and competency issues. In the absence of any formal guidance on these matters, the UK TLC developed a series of recommendations using the results of two laboratory surveys conducted in 2007 and 2008.

The risks of red cell transfusion for hip fracture surgery in the elderly.

BACKGROUND AND OBJECTIVES: The benefits and indications for blood transfusion among surgical patients are controversial. There is evidence which suggests that blood transfusion is associated with poor clinical outcomes and risks of infection, but there are few data in the elderly population. MATERIALS AND METHODS: Data were collected on haemoglobin concentrations and transfusions in 919 patients undergoing hip fracture repair at a university hospital over a 2-year period. 28-day and 180-day mortality were specified as primary outcomes. A composite infection outcome (chest infections, urinary tract infections and wound infections) was the main secondary outcome. Preoperative, operative and/or postoperative transfusions were the main exposure variable. Regression analyses were used to explore the associations between transfusion and outcomes, adjusting for pre-defined preoperative variables. RESULTS: 300 patients (32·6%) were transfused at least once during their admission. There was no evidence of a significant difference in either 28-day survival or 180-day survival between transfused and non-transfused hip fracture patients. The transfused group had higher adjusted composite infection rate (HR, 1·91; 95% CI, 1·41-2·59, P < 0·001) and prolonged length of stay in hospital than the non-transfused group (HR, 1·15; 95% CI, 1·07, 1·23, P < 0·001). Anaemia at the time of admission, extra capsular fracture and using walking aids in an indoor setting were preoperative variables, which predicted the need for transfusion. CONCLUSION: Among an elderly population with hip fracture, blood transfusion was not associated with changes in mortality, but was associated with an increased rate of postoperative infection. These data add to the wider literature about adverse clinical outcomes in patients receiving blood transfusions and emphasises the need for prospective trials to evaluate the role of transfusion in the elderly.

New quantitative parameters on a recently introduced automated blood cell counter--the XE 2100.

The XE 2100 (Sysmex Corporation) is a cell counter that furthers the technology of fluorescent flow cytometry developed from the earlier range of Sysmex analysers. The new diagnostic features are a nucleated red cell count (NRBC), the ability to measure platelets by impedance as well as an 'optical' platelet count using a fluorescence dye and an immature granulocyte (IG) count. The NRBC count was highly correlated (r = 0.97) with the manual reference count. For counts below 100 x 109/l the 'optical' method and the immunocount gave good a correlation (r = 0.97) optical and impedance counts were also well correlated (r = 0.89). The use of the 'optical' platelet count significantly improves the reliability of low platelet counts. The IG count correlated with visual counts (r = 0.81) and allows the detection of immature cells at an earlier stage in the laboratory process. The introduction of fluorescent flow cytometric analysis allows extended quantification of additional cell populations and so potentially improves screening and monitoring of various pathological conditions.