scholarly journals Early (Day −7) versus Conventional (Day −1) Inception of Cyclosporine-A for Graft-versus-Host Disease Prophylaxis after Unrelated Donor Hematopoietic Stem Cell Transplantation in Children. Long-Term Results of an AIEOP Prospective, Randomized Study

2009 ◽  
Vol 15 (6) ◽  
pp. 741-748 ◽  
Author(s):  
Edoardo Lanino ◽  
Roberto Rondelli ◽  
Franco Locatelli ◽  
Chiara Messina ◽  
Andrea Pession ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cyclosporine A ◽  
Randomized Study ◽  
Long Term Results ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Graft Versus Host

scholarly journals Impact of graft-versus-host disease prophylaxis on immune reconstitution in patients after allogeneic hematopoietic stem cell transplantation

2021 ◽  
Vol 23 (5) ◽  
pp. 1125-1136
Author(s):  
E. D. Mikhaltsova ◽  
N. N. Popova ◽  
M. Yu. Drokov ◽  
N. M. Kapranov ◽  
Yu. O. Davydova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Mycophenolate Mofetil ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cyclosporine A ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis

The graft-versus-host disease (GVHD) is among the most common complications after hematopoietic stem cell transplantation (allo-HSCT). The main tools for GVHD prevention remain calcineurin inhibitors (cyclosporin A, tacrolimus), methotrexate, mycophenolate mofetil. Upon implementation of reduced-intensity conditioning regimens, antithymocyte globulin was widely introduced. However, negative effects upon reconstitution of T-cell immunity have been noted, thus increasing risk of severe infectious complications and disease relapse. With extended practice of HSCT from alternative (partially matched or haploidentical) donors, cyclophosphamide was increasingly used. Our aim was to study reconstitution of immune cell subpopulations in the patients undergoing bone marrow transplantation (BMT), when using different GVHD prophylaxis regimens, including the schedules with post-transplant CP usage. The study concerned 44 cases classified into 2 groups. The first one included patients with standard immunosuppressive therapy, antithymocyte therapy, cyclosporine A, methotrexate, mycophenolate mofetil. The second group included the patients who received CP as immunosuppressive drug combined with other treatments (cyclosporine A, methotrexate, mycophenolate mofetil). At specified control terms, (D+14, +30, +60, +90) the blood leukocyte subpopulations were assayed by means of multicolor flow cytometry. Absolute counts of CD4+ cells in HSCT recipients treated with CP post-BMT proved to be sufficiently lower at D+14 and +30, than in those treated with classical immunosuppressive therapy. However, at later terms, (D+60, +90), these differences were not observed. Moreover, in CP-treated bone marrow recipients, absolute numbers of CD8+ cells was significantly higher, compared to the patients who received conventional GVHD prophylaxis. Reconstitution of the studied lymphocyte populations in hematopoietic cell recipients did not depend on the GVHD prophylaxis regimen. Usage of CP combined with bone marrow as a source of stem cells, brings about sufficient decrease of some cell populations (CD4+; CD8+; NK cells) at early terms post-transplant. Administration of CP combined with hematopoietic stem cells as the source of hematopoietic graft seems to be more reasonable.

CTLA-4 Polymorphisms: Influence on Transplant-Related Mortality and Survival in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 67-67
Author(s):  
Bernd Gruhn ◽  
Susan Wittig ◽  
Thomas Ernst ◽  
Judith Hammrich
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Cyclosporine A ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Graft Versus Host ◽  
Related Mortality

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative approach for a variety of hematologic diseases but is still associated with substantial morbidity and mortality. Transplant-related mortality (TRM) after HSCT depends mainly on the toxicity of the conditioning regimen, infections, and graft-versus-host disease (GVHD). Polymorphisms at major histocompatibility complex MHC) have been proven to be critical for successful allogeneic HSCT. Polymorphisms at non-MHC loci have been associated with HSCT outcome as well. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that down-regulates T-cell activation. The purpose of this study was to identify an association between CTLA-4 single nucleotide polymorphisms (SNPs) and TRM in children undergoing allogeneic HSCT. Methods: 153 donors and 153 children (median age, 11 years) with acute lymphoblastic leukemia (n=90), acute myeloid leukemia (n=58) or juvenile myelomonocytic leukemia (n=5) who underwent allogeneic HSCT in a single center were genotyped of CTLA-4 gene for rs3087243 (CT60 A/G), rs231775 (+49 A/G) and rs4553808 using TaqMan real-time polymerase chain reaction. 49 children were transplanted in first, 40 children in second and 15 in third complete remissions. 49 patients did not reach complete remission at the time of transplantation. The donor was HLA-matched unrelated in 59% of transplants and HLA-identical related in 41% of transplants. Conditioning regimen was myeloablative in all cases and based on total body irradiation in 52% of transplants or busulfan in 44% of transplants. Two forms of post-transplant immunosuppression predominated, cyclosporine A and methotrexate in 64% of transplants and cyclosporine A alone in 25% of transplants. Results: We observed a significant association between the donor´s CTLA-4 genotype of rs3087243 and TRM in children undergoing allogeneic HSCT. Genotype AG of CTLA-4 rs3087243 SNP was found in 78 donors (51%), GG in 44 donors (29%), and 31 donors were homozygous for AA (20%). 30 patients died of transplant-related causes. 16 patients died of multi-organ failure, 7 of infection, 3 of acute GVHD, 2 of chronic GVHD, and 2 of hepatic sinusoidal obstruction syndrome. Interestingly, we observed a significantly reduced TRM in children who were transplanted from a donor with the CTLA-4 genotype GG in comparison to genotype AG or AA of rs3087243 (9% versus 19% versus 36%, p=0.013). In addition, we found significant differences of event-free survival (EFS) depending on the donor´s genotype. The EFS was 64%, 46% or 32% if the patient was transplanted from a donor with CTLA-4 genotype GG, AG or AA of rs3087243, respectively (p=0.043). In multivariate analysis, CTLA-4 genotype of rs3087243 was an independent risk factor for TRM (0.021). The CTLA-4 genotypes, in either donors or recipients, had no significant impact on relapse rate, acute and chronic graft-versus host disease. Conclusions: This study provides the first evidence that the CTLA-4 polymorphisms are significant risk factors for TRM and survival in children undergoing allogeneic HSCT and should be evaluated in further trials. Disclosures No relevant conflicts of interest to declare.

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