Impact of red blood cell transfusion dose density on progression-free survival in lower-risk myelodysplastic syndromes patients

Progression-free survival of lower-risk myelodysplastic syndromes patients treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals of newly diagnosed lower-risk myelodysplastic syndromes patients from 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end of each interval divided by the time since the beginning of the interval in which the first transfusion was received - were analyzed using proportional hazards regression with time-varying co-variates, with death and progression to higher-risk myelodysplastic syndromes /acute myeloid leukemia as events. Of the 1267 patients included in the analyses, 317 patients died without progression, in 162 patients the disease had progressed. Progression-free survival was significantly associated with age, EQ-5D index, baseline WHO classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with progression-free survival (p<1x10-4): dose density had an increasing effect on hazard until a dose density of 3 units/16 weeks. The transfusion dose density effect continued to increase beyond 8 units/16 weeks after correction for the impact of treatment with erythropoietin agents, lenalidomide and/or iron chelators. Conclusion: the negative effect of transfusion treatment on progression-free survival already occurs at transfusion densities below 3 units/16 weeks. This indicates that transfusion dependency, even at relatively low dose densities, may be considered as an indicator of inferior progression-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00600860

Red blood cell transfusions in hemato-oncological patients: Don't iron out the consequences

Red blood cell transfusions are still the cornerstone of supportive care in many hemato-oncological patients. A chronic and underestimated side-effect of red blood cell transfusions is iron overload, which is associated with increased morbidity and mortality. This thesis focuses on red blood cell transfusion strategies and the management of iron overload due to frequently administered red blood cell transfusions. A nationwide survey showed a large variation in red blood cell transfusion practice throughout the Netherlands. This is probably due to the lack of high grade evidence-based guidelines. In a meta-analysis was demonstrated that a restrictive red blood cell transfusion strategy was safe and could lead to fewer side-effects and reduced costs in hemato-oncological patients. In order to diagnose iron overload, tissue biopsy is still the golden standard. Due to its risk of complications, tissue biopsies are not likely to be performed in this patient group. In this thesis, we assessed the value of bone marrow iron scores in frequently transfused acute myeloid leukemia patients. We concluded that bone marrow iron scores on routinely performed bone marrow aspirate specimens could guide iron-lowering therapy and/or transfusion strategies in an early stage. Finally, in a large European registry we showed that toxic iron species as non-transferrin bound iron and labile plasma iron are associated with inferior overall survival in lower-risk myelodysplastic syndrome patients. Likewise, treatment with iron chelation therapy led to an improvement in overall and progression-free survival in lower-risk myelodysplastic syndrome patients. Sanquin Blood SupplyLUMC / Geneeskund

Red blood cell transfusion support and management of secondary iron overload in patients with haematological malignancies in the Netherlands: a survey

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Improving a Rare Metabolic Disorder Through Kidney Transplantation: A Case Report of a Patient With Lysinuric Protein Intolerance.

Lysinuric protein intolerance (LPI) is a rare metabolic disorder with reduced renal and intestinal reabsorption of ornithine, lysine, and arginine. It is due to variants in SLC7A7, the gene encoding y+L amino acid transporter 1 (y+LAT1), which lead to urea cycle defects with protein intolerance. Chronic kidney disease in lysinuric protein intolerance is common and can progress to kidney failure and initiation of kidney replacement therapy. Kidney transplantation could in theory improve urine levels and, consequently, plasma levels of these amino acids and therefore improve clinical symptoms, as well as protein intolerance, in patients with lysinuric protein intolerance. However, data on kidney transplantation in patients with lysinuric protein intolerance are limited, and up until now no data on clinical and biochemical improvement after kidney transplantation have been reported. In this case report we describe a rare case of kidney transplantation in a lysinuric protein intolerance patient with substantial improvement in protein tolerance; in plasma and urine levels of ornithine, lysine, and arginine; and in lysinuric protein intolerance symptoms