Patterns of monocyte subpopulations and their surface expression of HLA-DR during adverse events after hematopoietic stem cell transplantation

2014 ◽  
Vol 94 (5) ◽  
pp. 825-836 ◽  
Author(s):  
Michaela Döring ◽  
Karin Melanie Cabanillas Stanchi ◽  
Susanne Haufe ◽  
Annika Erbacher ◽  
Peter Bader ◽  
...  
Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2161-2161
Author(s):  
Michaela Döring ◽  
Susanne Haufe ◽  
Annika Erbacher ◽  
Ingo Müller ◽  
Rupert Handgretinger ◽  
...  

Abstract Abstract 2161 Background: Human leukocyte antigen DR (HLA-DR) surface expression in CD14++ monocytes reflects the activation state of these cells. Decreased HLA-DR expression levels have been described as an indicator of immunosuppression. According to CD14 and CD16 expression levels, monocyte subpopulations have been classified into “classical” CD14++/CD16- (M1), “non-classical” CD14+/CD16++ (M3), “intermediate” CD14++/CD16+ (M2) and CD14-/CD16++ (M4) monocytes (Figure 1). This study analyzes HLA-DR expression in these monocyte subpopulations after hematopoietic stem cell transplantation (HSCT) and in particular during transplant-related adverse events. Patient and Methods: 30 pediatric patients (< 15 years) (n = 23) and young adults (> 15 years) (n = 7) (7 autologous, 12 allogeneic and 11 allogeneic haploidentical transplanted) with hemato-oncological malignancies and immunodeficiency disorders were consecutively included after informed written consent. Median age was 9.5 years (range 0.5–38 years). Flowcytometric assessment of HLA-DR expression was started the day before conditioning therapy and continued up to 379 days after HSCT. Normal values of HLA-DR expression in monocyte subpopulations were established from a control group of healthy children and young adults (n = 20). Surface marker expression of CD14, CD16, CD56, and HLA-DR was determined by four-color flowcytometry. Results: Median data acquisiton period was 228 days (range of 43–379 days). By analysis of covariance (ANCOVA), HLA-DR expression in healthy controls varied in dependency of age. In young adults (> 15 years), HLA-DR expression was significantly (P < 0.05) lower in M2, M3 and M4 but not in M1 monocyte subpopulations (P = 0.084) compared to children and adolescents (< 15 years). After HSCT, a significant decrease of HLA-DR expression in M1 and M4 monocytes was observed during sepsis or bacteremia (P < 0.01). The onset of graft-versus-host-disease (GvHD)°III-°IV was associated with a significant increase of HLA-DR expression in M1 monocytes (P < 0.05). HLA-DR expression in monocyte subpopulations was not altered before or during veno-occlusive disease (VOD), a relapse of underlying disease or before death. Conclusion: The distinct HLA-DR expression pattern in monocyte subpopulations during sepsis and GvHD may facilitate identification of patients at risk after HSCT. Moreover, HLA-DR expression in monocyte subpopulations may be used to monitor treatment response in these entities. CD14++/CD16- (M1), CD14++/CD16+ (M2), CD14+/CD16++ (M3) and CD14-/CD16++(M4) Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1499-1499
Author(s):  
Michaela Döring ◽  
Ingo Müller ◽  
Annika Erbacher ◽  
Rupert Handgretinger ◽  
Michael Hofbeck ◽  
...  

Abstract Abstract 1499 The human leukocyte antigen DR (HLA-DR) surface expression on CD14+ monocytes reflects the degree of activation of these cells. In line with the central role of monocytes and macrophages in the immune system, a decreased HLA DR expression on CD14+ monocytes has been shown to be a hallmark of an altered immune status during the systemic inflammatory response syndrome (SIRS). We therefore hypothesized that HLA-DR expression might likewise be altered after hematopoietic stem cell transplantation (HSCT). HLA-DR surface expression of CD14+ monocytes was assessed by flow cytometry in 30 pediatric patients (below 15 years, n=23) and young adults (15 years and above, n=7) up to one year after HSCT (7 autologous and 23 allogeneic stem cell transplants). Normal values were derived from a control group of healthy children (n=18) and young adults (n=22). During the conditioning period, a significant increased HLA-DR expression in pediatric patients and young adults was observed. This increase could not be attributed to the administration of anti-thymocyte globulin (ATG). After HSCT, HLA-DR expression was not altered in general. However, HLA-DR expression decreased significantly up to 5 days before (p<0.05) and during (p<0.01) bacterial infections or sepsis. In contrast, HLA-DR expression levels were increased 7–10 days before and at the time of diagnosis of viral infections. HLA-DR expression was also elevated during acute graft-versus-host disease (GVHD). At the time of hepatic veno-occlusive disease (VOD), HLA-DR expression on CD14+ monocytes was reduced. Neither the administration of granulocyte colony-stimulating factor (G-CSF) nor the occurrence of a relapse was associated with a change of HLA-DR expression. In conclusion, adverse events after HSCT were associated with altered HLA-DR expression levels. Therefore, HLA-DR expression on CD14+ monocytes appears as a promising parameter which might allow identifying patients at risk after HSCT. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5211-5211
Author(s):  
De Pei Wu ◽  
Junjie Cao ◽  
Caixia Li ◽  
Xiaojin Wu

Abstract Objective: To compare the dendritic cells reconstitution after different allogeneic hematopoietic stem cell transplantation in early time Methods: From June 2004 to March 2005, Twenty-eight patients undergoing allo-HSCT were enrolled in this study. There were 16 patients who undergone normal HSCT, 8 patients who undergone Haploidentical HSCT and 4 patients who undergone Nonmyeloablative HSCT. Three-colour flow cytometry was applied to study the alteration of the percentage and number in circulating peripheral blood dendritic cells subsets on day 14,day 30,day 60 after transplantation among three distinct type HSCT. Results: The dendritic cells subsets number of myeloablative HSCT patients were very low. No difference was observed in the kinetics of DC1 (Lin−HLA-DR+CD11c+)and DC2 (Lin−HLA-DR+CD123+) reconstitution between the normal HSCT group and Haploidentical HSCT group patients(p&lt;0.05). There was significant difference between myeloablative HSCT group and normal healthy individuals(p&lt;0.01). There was significantly different between the non-myeloablative HSCT group and the myeloablative HSCT group in the kinetics of DC1 and DC2 reconstitution(p&lt;0.05). Conclusion: The early reconstitution of dendritic cells in Nonmyeloablative HSCT patients is earlier than the patients who undergone myeloablative HSCT. The early reconstitution of dendritic cells in normal HSCT and Haploidentical HSCT patients were later than others.


2021 ◽  
Vol 1 (8) ◽  
Author(s):  
Khai Tran ◽  
Hannah Loshak

Evidence from 2 randomized controlled trials and 4 retrospective studies with limited methodological quality suggests that treatment with autologous hematopoietic stem cell transplantation was associated with significant improvement in clinical outcomes (e.g., disease progression, clinical relapse), MRI outcomes, the composite outcome “No Evidence of Disease Activity,” and quality of life compared to disease-modifying therapies. Treatment with autologous hematopoietic stem cell transplantation was associated with no treatment-related mortality or life-threatening complications including progressive multifocal leukoencephalopathy. However, autologous hematopoietic stem cell transplantation was associated with expected short-term adverse events including febrile neutropenia, organ infections, sepsis, and viral reactivations; and long-term adverse events including the development of new autoimmune diseases, mainly thyroid disease. Both identified guidelines recommend the use of autologous hematopoietic stem cell transplantation as standard of care for the treatment of highly active relapsing-remitting multiple sclerosis patients refractory to disease-modifying therapies and suggest that the treatment may be appropriate for progressive forms of multiple sclerosis with an active inflammatory component. No cost-effectiveness studies were identified.


2021 ◽  
Vol 12 ◽  
Author(s):  
Patrick-Pascal Strunz ◽  
Matthias Froehlich ◽  
Michael Gernert ◽  
Eva Christina Schwaneck ◽  
Anna Fleischer ◽  
...  

Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective treatment for systemic sclerosis (SSc), but it also can cause immunological adverse events (iAEs). Therefore, we aimed to determine the frequency of iAEs [engraftment syndrome (ES) and secondary autoimmune disorder (sAD)] and to identify potential risk factors for their development in a retrospective analysis on 22 patients similarly transplanted due to SSc. While nine patients (41%) suffered from ESs, seven sADs occurred in six patients (27%). Patients who developed ES were older in our cohort (52.45 vs. 42.58 years, p = .0433, Cohen’s d = 0.86), and cardiac involvement by SSc was associated with development of ES (OR = 40.11, p = .0017). Patients with manifestation of sAD had a higher modified Rodnan skin score (mRSS) reduction after aHSCT (90.50% vs. 60.00%, p = .0064, r = .65). Thus, IAEs are common after aHSCT for SSc and can occur in different stages during and after aHSCT with characteristic clinical manifestations. Good cutaneous response after aHSCT might be considered as a risk factor for sAD, and higher age at aHSCT and cardiac involvement might be considered as risk factors for the development of ES.


JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 41-45
Author(s):  
Ana Carolina Amaral Perrone ◽  
Clarissa Ferreira Cunha ◽  
Ana Paula da Silva Pinheiro ◽  
Abrahão Elias Hallack Neto

Goal: The aim of this study was to describe the incidence of oral mucositis (OM) in patients undergoing autologous hematopoietic stem cell transplantation (auto-HSCT), relating it to the main clinical factors. Methodology: Descriptive analysis based on a randomized clinical study was conducted with patients undergoing HSCT at the University Hospital of Federal University of Juiz de Fora between January 2018 and June 2019. The World Health Organi­zation oral toxicity scale was used to assess the degree of oral mucositis and adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) 4.0 version. Results: Thirty-eight patients were evaluated. The incidence of OM and severe oral mucositis (SOM) was 57.9% and 21.0%, respectively. The mean duration of OM was 7.2 ± 2.6 days and the lomustine, etoposide, cytarabine and cyclophosphamide protocol (LEAC) pre­sented the longest mean time 8.1 ± 3.1 days (p-value 0.02). The number of viable CD34+ cells and the onset day of neutropenia were predictors of SOM. Conclusion: The incidence of OM in patients undergoing HSCT was lower than reported in the literature, being more severe in patients who received less CD34+ cells and in patients with early onset of neutropenia.


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