Hemophagocytosis in Critically Ill Adult Patients (HCIAP)

Hemophagocytosis in Critically Ill Adult Patients With Cytopenias

The purpose of the study is to find out whether non-responsiveness to therapeutic recombinant human granulocyte colony-stimulation factor (rhG-CSF) is associated with hemophagocytosis in critically ill adult patients with cytopenias.

Study Overview

• Status: Recruiting
• Conditions: Hemophagocytosis

Detailed Description

In children with bi- or pancytopenia, hemophagocytosis is known as life-threatening hemophagocytic lymphohistiocytosis (HLH). The purpose of the study is to find out whether adult patients with bicytopenia or pancytopenia fulfilling the clinical HLH criteria used in children reflect life-threatening hemophagocytosis and whether hemophagocytosis is associated with responsiveness to recombinant human granulocyte colony-stimulation factor (rhG-CSF) or not.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Manfred E Weiss, MD; Phone Number: 49-731-50060226; Email: manfred.weiss@uniklinik-ulm.de
• Study Contact Backup: Name: Elisabeth M Schneider, PhD; Phone Number: 49-731-50060080; Email: marion.schneider@uni-ulm.de

Study Locations

• Germany
  • Ulm, Germany, 89075
    • Recruiting
    • Department of Anaesthesiology, University Hospital Ulm
    • Contact: Elisabeth M Schneider, PhD; Phone Number: 49 (0)731-500-60319; Email: marion.schneider@uni-ulm.de
    • Contact: Manfred E Weiss, MD; Phone Number: 49 (0)731-500-60226; Email: manfred.weiss@uniklinik-ulm.de
  • Ulm, Germany, 89075
    • Recruiting
    • Department of Internal Medicine III, Comprehensive Infectious Disease Center, University Hospital Ulm, Germany
    • Contact: Martin Bommer, MD; Phone Number: +49 (731) 500-45530; Email: Martin.Bommer@uniklinik-ulm.de
    • Contact: Elisabeth M Schneider, PhD; Phone Number: +49 (731) 500-60080; Email: marion.schneider@uni-ulm.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with leukopenia who are routinely treated with rhG-CSF

Description

Inclusion Criteria:

• age > 18 years
• critically ill adult patients
• leukopenia and thrombocytopenia
• rhG-CSF therapy

Exclusion Criteria:

• life expectancy < 24 hours
• inclusion in other studies
• trauma patients with reanimation on scene or immediately dying on hospital admission
• pregnancy
• hematologic disorder, malignancy
• high dose corticosteroid treatment or chemotherapy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

patients with cytopenias; Patients with sepsis and concomitant cytopenias (leukopenia with thrombocytopenia and anemia) who are routinely treated with rhG-CSF will be followed for reconstitution of peripheral blood cell counts. In cooperation with the Department of Hematology, patients are examined for bone marrow cellularity and hemophagocytosis if G-CSF treatment does not result in leukocyte increase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
responsiveness to recombinant human granulocyte colony-stimulating factor (rhG-CSF)	increase in leukocytes	within 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
8 clinical HLH criteria	degree of fulfillment x out of 8 clinical HLH criteria	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
differential blood count, enzymes,biomarkers,immunophenotype	Differential blood count, lactate dehydrogenase, C reactive protein, fibrinogen, triglycerides, ferritin,liver enzymes, aspartate aminotransferase, soluble cluster of differentiation 25, cytokines, procalcitonin biomarkers,immunophenotype (flow cytometry)	7 days

Collaborators and Investigators

• Sponsor: University of Ulm
• Investigators: Principal Investigator: Manfred E Weiss, MD, Department of Anesthesiology

Publications and helpful links

General Publications

• Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039.
• Schneider EM, Lorenz I, Muller-Rosenberger M, Steinbach G, Kron M, Janka-Schaub GE. Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell-induced apoptosis. Blood. 2002 Oct 15;100(8):2891-8. doi: 10.1182/blood-2001-12-0260.
• Weiss M, Nass M, Schneider EM. Hemophagocytic and/or macrophage activation syndromes may explain thrombocytopenia, leukopenia and anemia in critically ill postoperative/posttraumatic patients. Infection, vol. 39 Suppl. II September, no., pp. S118, 2011.
• Lorenz MR, Walther P, Weiss M, Huber-Lang M, Schneider EM. Autophagy as a unique biosignature in hemophagocytic cells of patients after major trauma. Infection, vol. 37 (Suppl. III), no. P111, pp. S28 - 29, 2009.
• Schneider EM, Flacke S, Liu F, Lorenz MR, Schilling P, Nass ME, Foehr KJ, Huber-Lang M, Weiss ME. Autophagy and ATP-induced anti-apoptosis in antigen presenting cells (APC) follows the cytokine storm in patients after major trauma. J Cell Commun Signal. 2011 Jun;5(2):145-56. doi: 10.1007/s12079-010-0113-z. Epub 2011 Jan 13.
• Weiss M, Bommer M, Hohmann H, Walther P, Schneider EM. The clinical definition of hemophagocytic lymphohistiocytosis (HLH) as used in children does not explain cytopenia in the majority of critically ill postoperative/posttraumatic patients. Infection 41 Suppl 1: S43 - S44, 2013. DOI 10.1007/s15010-013-0513-0

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: July 29, 2013
• First Submitted That Met QC Criteria: July 30, 2013
• First Posted (Estimated): August 1, 2013

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Hemophagocytosis, adults, rhG-CSF
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: Hemophagocytosis_Ulm