A No-Prophylaxis Platelet-Transfusion Strategy for Hematologic Cancers

Stanworth, Simon; Estcourt, Lise J; Powter, Gillian; Kahan, Brennan C; Dyer, Claire; Choo, Louise; Bakrania, Lekha; Llewelyn, Charlotte; Littlewood, Timothy; Soutar, Richard; Norfolk, D. R.; Copplestone, Adrian; Smith, Neil R.; Kerr, Paul M.; Jones, Gail; Raj, Kavita; Westerman, David; Szer, Jeffrey; Jackson, Nicholas; Bardy, Peter; Plews, Dianne; Lyons, Simon; Bielby, Linley; Wood, Erica M.; Murphy, Michael; Investigators, Topps Study

doi:10.1056/nejmoa1212772

Cited by 395 publications

(515 citation statements)

References 18 publications

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“…These results are consistent with improved survival in the rHuIL-12-treated groups, and with the previous reports showing that the depth and duration of severe cytopenias are correlated with adverse clinical outcomes [8,9]. We have also observed that for severe cytopenias resulting from lethal radiation exposure, a less deep (attenuated) nadir generally predicts an increased potential for survival as this effect reflects early bone marrow regeneration (Gluzman-Poltorak et al, manuscript in preparation).…”

Section: Discussionsupporting

confidence: 91%

Recombinant interleukin‐12, but not granulocyte‐colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care: Evidence for the development of a frontline radiation medical countermeasure

2014

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Hematopoietic syndrome of acute radiation syndrome (HSARS) is a life‐threatening condition with no approved treatment. We compared recombinant human interleukin‐12 (rHuIL‐12; 175 ng/kg × 1) with vehicle, granulocyte‐colony‐stimulating factor (G‐CSF; 10 µg/kg/day × 18), or rHuIL‐12+G‐CSF after lethal irradiation in rhesus monkeys in a Good Laboratory Practice, randomized, blinded, placebo‐controlled study. Fluids, antibiotics, and blood products were not used. Survival at day 60 was significantly increased for rHuIL‐12 versus G‐CSF or vehicle. rHuIL‐12/G‐CSF combination provided no additional survival benefit over rHuIL‐12. Both rHuIL‐12 and rHuIL‐12+G‐CSF increased blood cell nadirs, induced earlier recovery of all hematopoietic lineages, and significantly decreased frequencies of severe cytopenias versus vehicle or G‐CSF. In bone marrow, rHuIL‐12 alone increased erythroid, myeloid, and megakaryocyte counts relative to vehicle or G‐CSF. Thus, a single injection of rHuIL‐12, without supportive medical intervention, significantly improved survival and promoted multilineage hematopoietic recovery in a nonhuman primate model of HSARS. Am. J. Hematol. 89:868–873, 2014. © 2014 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 91%

Recombinant interleukin‐12, but not granulocyte‐colony stimulating factor, improves survival in lethally irradiated nonhuman primates in the absence of supportive care: Evidence for the development of a frontline radiation medical countermeasure

2014

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“…Rationale No RCTs of prophylactic platelet transfusion in septic or critically ill patients exist. Current recommendations and guidelines for platelet transfusion are based on clinical trials of prophylactic platelet transfusion in patients with therapy-induced thrombocytopenia (usually leukemia and stem cell transplant) [320][321][322][323][324][325][326][327]. Thrombocytopenia in sepsis is likely due to a different pathophysiology of impaired platelet production and increased platelet consumption.…”

mentioning

confidence: 99%

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

et al. 2017

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Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods:The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.

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“…[5] The TOPPS was a randomized, open-label, non inferiority trial performed at 14 centers in the United Kingdom and Australia. Patients were randomly assigned to receive, or not to receive, prophylactic platelet transfusions when platelet counts were less than 10 9 10 9 /L [3,4].…”

Section: Discussionmentioning

confidence: 99%