Surface HLA-DR Expression in Monocyte Subpopulations During Adverse Events After Hematopoietic Stem Cell Transplantation

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.


2018 ◽  
Vol 90 (7) ◽  
pp. 57-64 ◽  
Author(s):  
D A SHASHELEVA ◽  
A A MASCHAN ◽  
L N SHELIKHOVA ◽  
U N PETROVA ◽  
E E KURNIKOVA ◽  
...  

The main goal is to optimize hematopoietic stem cell transplantation (HSCT) approach among adolescents and young adults with paroxysmal nocturnal hemoglobinuria (PNH) by means of Graft-versus-host disease (GVHD) and post-transplant complications risk lowering. Materials and methods. We report our experience of HSCT from HLA-matched unrelated donors using TCR alfa/beta and CD19 depletion in 5 pts (1M/4F) with PNH, developed after successful immunosuppressive therapy (IST) of acquired aplastic anemia (AA). Median age of pts at the moment of transplantation was 17,8 years (range 14,5-22,7), median interval from IST to PNH was 4 years (5mo - 6,5 y). In all patients non-severe pancytopenia was present: granulocytes 0,8х109/l (0,8-1,8 х109/l) platelets 106 х109/l (27-143 х109/l) and Hb -78 g/l, median PNH clone size in granulocytes was 94 (range 75-99)%. One pts previously developed sinus thrombosis. Conditioning consisted of thoraco-abdominal irradiation 4-6 Gy, cyclophosphamide 100 mg/kg, fludarabine 150 mg/m2 and anti-thymocyte globulin (ATG) or alemtuzumab. Eculizumab was given from day (-7) till day (+14) (every 7 days, only 4 times). GVHD prophylaxis was tacrolimus ± methotrexate. Results. Infusedgraft characteristics were: CD34+ - 8,1х106/kg, CD3TCRab·150х103/kg, CD3gd+ - 7,3х106/kg, СD19+ - 221х103/kg, NK -6,4х108/kg. Engraftment was achieved in all 5 pts with a median of 15(12-18) и 13(10-18) days for granulocytes and platelets, respectively. Skin acute GVHD grade I developed in only 1 pt, and subsided with short course of glucocorticoids. CMV reactivation occurred in 1 pt; there were no episodes of Epstein-Barr Virus (EBV) o rAdenovirus (AdV) reactivation. Full donor myeloid chimerism was established in all pts by day +30. Immune reconstitution was delayed until 6 months after transplant but no severe infections occurred. All pts are alive 1,7-5,5 years (med 4 years) after HSCT with normal hematopoiesis and immune function, full donor chimerism and no late sequelae. Conclusions. Transplantation of TCRalfa/beta and CD19 depleted hematopoietic cells from matched unrelated donor after immunoablative conditioning and supported with short course of eculizumab is perfectly safe and efficient technology leading to cure in young patients with PNH.


2014 ◽  
Vol 132 (3-4) ◽  
pp. 313-325 ◽  
Author(s):  
Priti Tewari ◽  
Anna R. Franklin ◽  
Nidale Tarek ◽  
Martha A. Askins ◽  
Scott Mofield ◽  
...  

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