scholarly journals Role of Killer Immunoglobulin-Like Receptor and Ligand Matching in Donor Selection

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Meral Beksaç ◽  
Klara Dalva

Despite all efforts to improve HLA typing and immunosuppression, it is still impossible to prevent severe graft versus host disease (GVHD) which can be fatal. GVHD is not always associated with graft versus malignancy and can prevent stem cell transplantation from reaching its goals. Overall T-cell alloreactivity is not the sole mechanism modulating the immune defense. Innate immune system has its own antigens, ligands, and mediators. The bridge between HLA and natural killer (NK) cell-mediated reactions is becoming better understood in the context of stem cell transplantation. Killer immunoglobulin-like receptors (KIRs) constitute a wide range of alleles/antigens segregated independently from the HLA alleles and classified into two major haplotypes which imprints the person's ability to suppress or to amplify T-cell alloreactivity. This paper will summarize the impact of both activating and inhibitory KIRs and their ligands on stem cell transplantation outcome. The ultimate goal is to develop algorithms based on KIR profiles to select donors with maximum antileukemic and minimum antihost effects.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5431-5431 ◽  
Author(s):  
Peter Reimer ◽  
Thomas Ruediger ◽  
Florian Weissinger ◽  
Hans Konrad Mueller-Hermelink ◽  
Andreas Engert ◽  
...  

Abstract Introduction: Peripheral T-cell lymphomas (PTCL) are rare diseases and optimal treatment strategies still remain to be defined. With the exception of the ALK-positive anaplastic large cell lymphoma (ALCL) that shows a favourable outcome following conventional chemotherapy, PTCL are known for their poorer prognosis compared to aggressive B-cell lymphomas. However, the impact of the different PTCL-subtypes on treatment outcome has not been clearly demonstrated in prospective studies. PTCL unspecified (PTCL-U) and angioimmunoblastic T-cell lymphoma (AIL) represent the most common subtypes of PTCL in Western countries, accounting for approximately 70% of PTCL. We therefore analysed the data of our study on myeloablative radiochemotherapy followed by autologous stem cell transplantation (ASCT) in primary diagnosed PTCL with regard to the main histologic subtypes. Material and Methods: From 06/00 to 06/06 92 patients with confirmed diagnosis of PTCL entered the study. Primary cutaneous PTCL and ALK+ ALCL were excluded from the trial. Main subtypes were PTCL-U (n= 37) and AIL (n= 28) accounting for 65 of the 92 patients (71%). 0f these patients 53 (PTCL, n= 31; AIL, n= 22) were evaluable for the analysis (82%). Results: Median age was 50 years in the PTCL-U and 47.5 years in the AIL group, respectively. The International Prognostic Index (IPI) did not differ in both groups. In the PTCL-U and the AIL group a low/intermediate-low risk was found in 35% and 36%, respectively and a high/intermediate-high risk in 65% and 64%, respectively. There were slightly more patients in stage IV in the AIL group compared to the PTCL-U group (64% versus 53%). In addition, more patients in the AIL group complained of B-symptoms and had bone marrow involvement compared to the PTCL-U group (86% versus 66% and 48% versus 39%, respectively). However, in an intent-to treat analysis only 58% in the PTCL-U group compared to 82% in the AIL group underwent ASCT mainly due to a higher rate of patients with progressive disease in the PTCL-U group. The median overall survival (OS) was 11 months in the PTCL-NOS and 20 months in the AIL group. Regarding only patients undergoing ASCT, the median OS was 13.5 months in the PTCL-U and 25.5 months in the AIL group. Conclusion: Our analysis suggests that patients with AIL, although showing a slightly more unfavourable risk profile at diagnosis, benefit more from upfront autotransplantation than patients with PTCL-U in our study.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3038-3038
Author(s):  
Steven Le Gouill ◽  
Noel-Jean Milpied ◽  
Agnes Buzyn ◽  
Regis Peffault de la Tour ◽  
Jean-Paul Vernant ◽  
...  

Abstract Mature peripheral T/Natural killer (NK)-cell neoplasms represent 10–15% of non-Hodgkin’s lymphoma (NHL) in adults. T/NK-NHL have a worst prognosis compared with B-cell lymphomas. Allogeneic stem cell transplantation (allo-SCT) is an attractive option for these patients. On behalf of the SFGM-TC group, we conducted a retrospective analysis and included seventy-seven T/NK-cell lymphoma patients. Diagnosis were: ALCL (n=27), Peripheral T-cell Lymphoma Not-Otherwise Specified (PTCL-NOS) (n=27), Angioimmunoblastic T-cell Lymphoma (AITL) (n= 11), Hepatosplenic g/d lymphoma (HSL) (n=3), T-cell granular lymphocytic leukemia (T-GLL) (n=1), nasal NK/T-cell lymphoma (nasal-NK/L) (n=3) case or non-nasal NK/T-cell lymphoma (non nasal-NK/L) (n=2), enteropathy-Type T-cell (n=1) and HTLV-1 lymphoma (n=2). Fifty-seven patients received myeloablative conditioning regimen prior allo-SCT. Donors were HLA-matched in 70 cases and related in 60 cases. Patients status at the time of allo-SCT was CR in 31 cases, PR in 26 cases and SD/PD in other cases. Five-year toxicity-related mortality (TRM) rate was 34%. Major cause of death was infection. Five-year OS and EFS rates were 57% and 53.3%, respectively. In a multivariate analysis, chemoresistance disease (SD, refractory or progressing disease at the time of allo-SCT and aGVHD grade III/IV were the only adverse prognostic factors for OS (p= 0.027 and p=0.033, respectively). Disease status at transplantation influenced EFS (p= 0.0032) and a HLA-mismatched donor increased TRM (p= 0.0386). A plateau was reached after one and a half year after allo-SCT. Only 5 out of 59 patients in CR after allo-SCT experienced a relapse. The 5-year OS rate for chemo-resistant patients was also encouraging. These patients were not curable with conventional approaches and near of one third have taken advantage of allo-SCT. Furthermore, two patients received DLI at relapse and they both reached a second durable CR. Taken together, this suggests that there is a graft versus T-/NK-lymphoma effect which may play a role in the curative potential of allo-SCT. we conclude that randomized clinical trials comparing allo-SCT versus conventional chemotherapy upfront for PTCL, aggressive AITL or histopathological subtypes (HSL, HTLV-1 lymphomas) have to be encouraged.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jing-Rui Zhou ◽  
Da-Yu Shi ◽  
Rong Wei ◽  
Yu Wang ◽  
Chen-Hua Yan ◽  
...  

Reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV) is common after hematopoietic stem cell transplantation (HSCT). Previous researches have demonstrated that either CMV or EBV reactivation is associated with poor outcomes of HSCT. However, few studies investigate the impact of CMV and EBV co-reactivation after HSCT. In this study, we described the clinical characteristics of HSCT recipients with CMV and EBV co-reactivation (defined as CMV and EBV viremia occur at the same period of time). We conducted a longitudinal study of 247 patients who underwent HSCT in our center. A total of 24 (9.7%) patients had CMV and EBV co-reactivation. These patients showed higher incidence of viral pneumonitis (P=0.005). Patients with CMV and EBV co-reactivation had significant lower 1-year overall survival (OS) (P=0.004) and lower 1-year leukemia free survival (LFS) (P=0.016). Our further analysis suggested that duration of CMV (P=0.014), EBV (P<0.001), and CD4+CD25+ T cell counts at day 30 post-transplantation (P=0.05) are independent risk factors of virus co-reactivation. In conclusion, patients who developed co-reactivation of CMV and EBV had poor prognosis in terms of lower 1-year OS and LFS, and the CMV and EBV co-reactivation was associated with prolonged CMV or EBV duration and poor CD4+CD25+ T cell reconstitution at day 30 post-transplantation.


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