The Prospective Evaluation of the Net Effect of Red Blood Cell Transfusions in Routine Provision of Palliative Care.

"Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/jpm.2017.0072” This author accepted manuscript is made available following 12 month embargo from date of publication (June 2017) in accordance with the publisher’s archiving policyBackground Red Blood Cell (RBC) transfusions are commonly used in palliative care. RBCs are a finite resource, transfusions carry risks, and the net effect (benefits and harms) is poorly defined for people with life-limiting illnesses. Aim The aim of this study was to examine the indications and the effects of RBC transfusion in palliative care patients. Design This international, multisite, prospective consecutive cohort study assessed target symptoms (fatigue, breathlessness, generalised weakness, or dizziness) prior to transfusion and at day 7 by treating clinicians, using National Cancer Institute Common Terminology Criteria for Adverse Events. Assessment of harms was made at day 2. Setting/participants One-hundred and one transfusions with day 7 followup were collected. Median age was 72·0 (IQR 61·5-83·0) years, 58% male, and mean Australian-modified Karnofsky Performance Status of 48 (SD 17). Results A mean 2·1 (SD 0·6) units was transfused. The target symptom was fatigue (61%), breathlessness (16%), generalized weakness (12%), dizziness (6%) or other (5%). Forty-nine percent of transfusions improved the primary target symptom, and 78% of transfusions improved at least one of the target symptoms. Harms were infrequent and mild. An AKPS of 40-50% was associated with higher chances of symptomatic benefit in the target symptom, however no other predictors of response were identified. Conclusions In the largest prospective consecutive case series to date, clinicians generally reported benefit, with minimal harms. Ongoing work is required to define the optimal patient- and clinician-reported haematological and functional outcome measures to optimise the use of donor blood and minimise transfusion-associated risk

A study of the circulating myeloid progenitor cell in man / Luen Bik To

Thesis (M.D.) -- University of Adelaide, Dept. of Haematology, 198

A cohort study assessing the impact of small volume blood tubes on diagnostic test quality and iatrogenic blood loss in a cohort of adult haematology patients

to estimate the reduction in blood volume loss and diagnostic test quality associated with introduction of small volume blood tubes in a cohort of haematology inpatients compared to a historical comparator group.prospective cohort study.haematology unit of a tertiary referral hospital in Adelaide.haematology inpatients.small volume blood tubes were used in an intervention cohort admitted between 2012-2013 and compared to a control cohort admitted between 2009-2010 where standard volume tubes had been used.the diagnostic test quality, specimen integrity and total reduction in blood loss associated with small volume tubes were estimated.small volume tubes demonstrated acceptable collinearity on commonly assay haematological and biochemical parameters. Small volume tubes were associated with a 42% reduction in blood volume loss equating to 8.5ml per patient per day or 180ml of blood over a three-week admission. Small volume tubes were associated with a slight but significantly increased rate of fibrin contamination of EDTA samples (0.2 to 0.5% of specimens).small volume tubes are associated with a substantial reduction in total blood volume collected per day in haematology inpatients. They have similar diagnostic validity and sample integrity to that of standard volume containers

Hypoxia-inducible factor-2 is a novel regulator of aberrant CXCL12 expression in multiple myeloma plasma cells

Background: Multiple myeloma is an incurable malignancy of bone marrow plasma cells. Progression of multiple myeloma is accompanied by an increase in bone marrow angiogenesis. Studies from our laboratory suggest a role for the CXCL12 chemokine in this process, with circulating levels of CXCL12 correlating with bone marrow angiogenesis in patients with multiple myeloma. While the mechanisms responsible for aberrant plasma cell expression of CXCL12 remain to be determined, studies in other systems suggest a role for hypoxia and hypoxia-inducible transcription factors. Design and Methods: The expression of hypoxia-inducible factor protein was examined in patients’ bone marrow biopsy specimens using immunohistochemistry. The hypoxic regulation of CXCL12 was examined in multiple myeloma plasma cell lines using polymerase chain reaction and western blotting. The role of hypoxia-inducible factors-1 and -2 in the regulation of CXCL12 expression was examined using over-expression and short hairpin RNA knockdown constructs, electrophoretic mobility shift assays and chromatin immunoprecipitation. The contribution of CXCL12 to hypoxia-induced angiogenesis was examined in vivo using a subcutaneous murine model of neovascularization. Results: Strong hypoxia-inducible factor-2 protein expression was detected in CD138+ multiple myeloma plasma cells in patients’ biopsy specimens. Prolonged exposure to hypoxia strongly up-regulated CXCL12 expression in multiple myeloma plasma cells and hypoxia-inducible factor-2 was found to play a key role in this response. Promoter analyses revealed increased hypoxia-inducible factor-2 binding to the CXCL12 promoter under hypoxic conditions. Over-expression of hypoxia-inducible factor in multiple myeloma plasma cells strongly induced in vivo angiogenesis, and administration of a CXCL12 antagonist decreased hypoxia-inducible factor-induced angiogenesis. Conclusions: Hypoxia-inducible factor-2 is a newly identified regulator of CXCL12 expression in multiple myeloma plasma cells and a major contributor to multiple myeloma plasma cell-induced angiogenesis. Targeting the hypoxic niche, and more specifically hypoxia-inducible factor-2, may represent a viable strategy to inhibit angiogenesis in multiple myeloma and progression of this disease.Sally K. Martin, Peter Diamond, Sharon A. Williams, Luen Bik To, Daniel J. Peet, Nobutaka Fujii, Stan Gronthos, Adrian L. Harris, Andrew C.W. Zannettin

Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome

Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode,sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P<0.0001). In individual patients, red cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; P<0.0001). A significantly higher proportion of alloimmunized patients than non-alloimmunized patients had detectable autoantibodies (65% versus 18%; P<0.0001) and the majority of autoantibodies were detected within a short period of alloimmunization. In conclusion, this study characterizes alloimmunization in a large cohort of patients with myelodysplastic syndrome and demonstrates a signficant increase in red cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical hemolysis. Strategies to mitigate alloimmunization risk are critical for optimizing red cell transfusion support