References of "Baron, Frédéric"
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See detailUse of Tyrosine Kinase Inhibitors to Prevent Relapse After Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Position Statement of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Giebel, S.; Czyz, A.; Ottmann, O. et al

in Cancer (2016), 122(19), 2941-2951

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a standard of care for patients with Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL). The introduction of tyrosine ... [more ▼]

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a standard of care for patients with Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL). The introduction of tyrosine kinase inhibitors (TKIs) to first-line therapy has improved overall outcomes; however, a significant proportion of patients still relapse after alloHSCT. Posttransplant TKI maintenance was demonstrated to reduce the risk of relapse in a large retrospective study and, therefore, should be considered a valuable option. This consensus paper, written on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, presents an overview of clinical studies on the use of TKIs after alloHSCT and proposes practical recommendations regarding the choice of TKI, treatment timing, and dosage. It is hoped that these recommendations will become the state of art in this field and, more importantly, lead to a reduction of Ph-positive ALL relapse after alloHSCT. [less ▲]

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See detailAzacytidine mitigates experimental sclerodermic chronic graft-versus-host disease
Fransolet, Gilles ULg; Ehx, Grégory ULg; SOMJA, Joan ULg et al

in Journal of Hematology & Oncology (2016), 9

Background <br />Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express ... [more ▼]

Background <br />Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express the gene of the transcription factor Foxp3 whose CNS2 region is heavily methylated in conventional CD4+ T cells (CD4+Tconvs) but demethylated in Tregs. <br />Methods <br />Here, we assessed the impact of azacytidine (AZA) on cGVHD in a well-established murine model of sclerodermic cGVHD (B10.D2 (H-2d) → BALB/cJ (H-2d)). <br />Results <br />The administration of AZA every 48 h from day +10 to day +30 at the dose of 0.5 mg/kg or 2 mg/kg mitigated chronic GVHD. Further, AZA-treated mice exhibited higher blood and thymic Treg frequencies on day +35, as well as higher demethylation levels of the Foxp3 enhancer and the IL-2 promoter in splenocytes at day +52. Interestingly, Tregs from AZA-treated mice expressed more frequently the activation marker CD103 on day +52. AZA-treated mice had also lower counts of CD4+Tconvs and CD8+ T cells from day +21 to day +35 after transplantation, as well as a lower proportion of CD4+Tconvs expressing the Ki67 antigen on day +21 demonstrating an anti-proliferating effect of the drug on T cells. <br />Conclusions <br />Our results indicate that AZA prevented sclerodermic cGVHD in a well-established murine model of cGVHD. These data might serve as the basis for a pilot study of AZA administration for cGVHD prevention in patients at high risk for cGVHD. [less ▲]

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See detailNovel approaches for preventing acute graftversus- host disease after allogeneic hematopoietic stem cell transplantation
SERVAIS, Sophie ULg; BEGUIN, Yves ULg; Delens, Loïc ULg et al

in Expert Opinion on Investigational Drugs (2016), 9

Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers potential curative treatment for a wide range of malignant and nonmalignant hematological disorders. However, its success ... [more ▼]

Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers potential curative treatment for a wide range of malignant and nonmalignant hematological disorders. However, its success may be limited by post-transplant acute graft-versus-host disease (aGVHD), a systemic syndrome in which donor’s immune cells attack healthy tissues in the immunocompromised host. aGVHD is one of the main causes of morbidity and mortality after alloHSCT. Despite standard GVHD prophylaxis regimens, aGVHD still develops in approximately 40–60% of alloHSCT recipients. Areas covered In this review, after a brief summary of current knowledge on the pathogenesis of aGVHD, the authors review the current combination of a calcineurin inhibitor with an antimetabolite with or without added anti-thymocyte globulin (ATG) and emerging strategies for GVHD prevention. Expert opinion A new understanding of the involvement of cytokines, intracellular signaling pathways, epigenetics and immunoregulatory cells in GVHD pathogenesis will lead to new standards for aGVHD prophylaxis allowing better prevention of severe aGVHD without affecting graft-versus-tumor effects. [less ▲]

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See detailAzacytidine Enhances Regulatory T-Cells In Vivo and Prevents Experimental Xenogeneic Graft-Versus-Host Disease
Ehx, Grégory ULg; Fransolet, Gilles ULg; de Leval, Laurence ULg et al

in Biology of Blood and Marrow Transplantation (2016, March), 22(3), 393

Background. The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 ... [more ▼]

Background. The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Tregs). Objective. We investigated the impact of AZA on xenogeneic graft-versus-host disease (xGVHD) in a humanized murine model of transplantation, and described the impact of the drug on human T cells in vivo. Methods. In order to induce xGVHD, human peripheral blood mononuclear cells (huPBMC) were administered intravenously in NOD-scid IL-2Rγnull (NSG) mice. Results. AZA successfully improved both survival (p<0.0001) and xGVHD scores (p<0.0001). Further, AZA significantly decreased human T-cell proliferation as well as INF-γ and TNF-α serum levels, and reduced the expression of GRANZYME B and PERFORIN 1 by cytotoxic T cells. In addition, AZA administration significantly increased the function, proliferation and frequency of Tregs through demethylation of FOXP3i1 and higher secretion of IL-2 by conventional T cells due to IL2 gene promoter site 1 demethylation. Interestingly, among AZA-treated mice surviving the acute phase of xGVHD, there was an inverse correlation between the presence of Tregs and signs of chronic GVHD. Finally, Tregs harvested from the spleen of AZA-treated mice were suppressive and stable over time since they persisted at high frequency in secondary transplant experiments. Conclusion. These findings emphasize a potential role for AZA as prevention or treatment of GVHD and other autoimmune diseases. [less ▲]

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See detailImmunomodulatory effects of rapamycin in Graft versus Host Disease
Ehx, Grégory ULg; Hannon, Muriel ULg; Humblet-Baron, Stéphanie et al

Poster (2016, January 29)

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Several studies have shown that rapamycin (RAPA), an mTOR ... [more ▼]

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Several studies have shown that rapamycin (RAPA), an mTOR inhibitor with immunosuppressive properties, may reduce GVHD severity and mortality, notably by favoring regulatory T cells (Tregs) proliferation in vivo and in vitro. However, few data have been reported about the global impact of this drug on the immune system in the context of GVHD. The present work investigates the mechanisms by which RAPA impacts GVHD both in a xenogeneic GVHD mouse model (NSG mice transplanted with human PBMC) and in patients receiving postgrafting immunosuppression with tacro + RAPA versus patients receiving tacro + MMF. In mice, our results show that RAPA injections significantly reduces xenogeneic GVHD lethality and severity. Flow cytometric analyses highlighted a strong reduction of human cells chimerism in mice together with higher CD4+/CD8+ T cells balance due to a lower proliferation of CD8+ T cells. In addition, the frequencies of naive -CD4+ and -CD8+ T cells were higher and the CD4+ T cells showed a reduced effector phenotype (CD45RO+CD27-). Tregs were positively affected as RAPA up-regulated their expression of Bcl-2 and Ki67 as well as their STAT5 phosphorylation level, leading to higher Treg frequency in treated mice. In patients, preliminary results show that RAPA significantly reduce CD8+ T cells count in agreement with mouse experiments. Altogether these data suggest that RAPA ameliorates GVHD by lowering cytotoxic and effector CD4+ T cells frequency as well as promoting Tregs. [less ▲]

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See detailAzacytidine and Decitabine prevent experimental sclerodermic chronic graft-versus-host disease
Fransolet, Gilles ULg; Ehx, Grégory ULg; SOMJA, Joan ULg et al

Poster (2016, January 29)

Introduction: Graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Following allo-transplantation, 60% of the patients experience ... [more ▼]

Introduction: Graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Following allo-transplantation, 60% of the patients experience chronic GVHD while approximately 15% of them develop a sclerodermic form of chronic GVHD characterized by multiple organ fibrosis and loss of skin elasticity. Regulatory T cells (Tregs) play a pivotal protective role in the pathogenesis of chronic GVHD by inhibiting alloreactive conventional T cells (Tconvs). Several studies have shown that hypomethylating agents such as Azacytidine (AZA) or Decitabine (DAC) can demethylate the master transcription factor of Treg (FoxP3), thus promoting Treg differentiation from Tconvs. This work investigates the impact of AZA and DAC in a murine model of sclerodermic chronic GVHD. Methods: Lethally irradiated (7 Gy) BALB/cJ recipient mice were injected with 107 bone marrow cells + 7.107splenocytes from B10.D2 donor mice to induce scl-cGVHD. Recipients were injected with 0.5 or 2 mg/kg of AZA or 0.75 mg/kg of DAC every 48h from day 10 to 30 following transplantation. GVHD was scored using a five criteria scale (weight loss, activity, fibrosis, hair loss and mice posture; 0-1-2 points/criteria). Mice were sacrificed at a score of 8/10. Results: Mice treated with AZA 0.5 mg/kg (n=14) or 2 mg/kg (n=17) or DAC 0.75 mg/kg (n=5) had lower clinical scores of GVHD compared to control (n=15). FACS analyses showed a higher proportion of Treg in the blood of AZA 0.5 or 2 mg/kg or DAC 0.75 mg/kg mice than in control at day 35. Results also showed a decreased number of Tconv and CD8 in AZA and DAC treated mice while proliferation of these cells expressing Ki67 was lower during AZA/DAC treatment but higher after discontinuation. Histological analyses showed less skin fibrosis in mice treated with 2 mg/kg of AZA. Finally, analyses of the blood components demonstrated that AZA mice were leuco- and lymphopenic as compared to control at day 21 and 35. Conclusion : AZA and DAC prevented sclerodermic GVHD in this murine model. [less ▲]

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See detailSalt but not glucocorticoïds enhances Th17 differentiation from naïve T cells in vitro
Delens, Loïc ULg; SERVAIS, Sophie ULg; Vrancken, Louise et al

Poster (2016, January 29)

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See detailMultipotent mesenchymal stromal cell therapy for steroid-refractory acute graft-versus-host disease after allogeneic stem cell transplantation
SERVAIS, Sophie ULg; GREGOIRE, Céline ULg; BARON, Frédéric ULg et al

in Belgian Journal of Hematology (2016), 7

Steroid-refractory acute graft-versus-host disease is a severe complication after allogeneic stem cell transplantation. So far, its treatment remains very challenging since the current therapies do not ... [more ▼]

Steroid-refractory acute graft-versus-host disease is a severe complication after allogeneic stem cell transplantation. So far, its treatment remains very challenging since the current therapies do not offer significant benefits. Among the most recent approaches, multipotent mesenchymal stromal cell-based therapy has attracted great interest over the past decade. Here, we briefly reviewed the current knowledges about the immunomodulatory properties of multipotent mesenchymal stromal cells as well as results of preclinical and clinical studies having assessed their efficacy to modulate steroid-refractory acute graft-versus-host disease. [less ▲]

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See detailThe Prosurvival IKK-Related Kinase IKK« Integrates LPS and IL17A Signaling Cascades to Promote Wnt-Dependent Tumor Development in the Intestine
Göktuna, SI.; Shostak, Kateryna ULg; Chau, TL. et al

in Cancer Research (2016), 76

Constitutive Wnt signaling promotes intestinal cell proliferation, but signals from the tumor microenvironment are also required to support cancer development. The role that signaling proteins play to ... [more ▼]

Constitutive Wnt signaling promotes intestinal cell proliferation, but signals from the tumor microenvironment are also required to support cancer development. The role that signaling proteins play to establish a tumor microenvironment has not been extensively studied. Therefore, we assessed the role of the proinflammatory Ikk-related kinase Ikke in Wnt-driven tumor development. We found that Ikke was activated in intestinal tumors forming upon loss of the tumor suppressor Apc. Genetic ablation of Ikke in b-catenin-driven models of intestinal cancer reduced tumor incidence and consequently extended survival. Mechanistically, we attributed the tumor-promoting effects of Ikke to limited TNF-dependent apoptosis in transformed intestinal epithelial cells. In addition, Ikke was also required for lipopolysaccharide (LPS) and IL17A-induced activation of Akt, Mek1/2, Erk1/2, and Msk1. Accordingly, genes encoding proinflammatory cytokines, chemokines, and anti-microbial peptides were downregulated in Ikke-deficient tissues, subsequently affecting the recruitment of tumor-associated macrophages and IL17A synthesis. Further studies revealed that IL17A synergized with commensal bacteria to trigger Ikke phosphorylation in transformed intestinal epithelial cells, establishing a positive feedback loop to support tumor development. Therefore, TNF, LPS, and IL17A-dependent signaling pathways converge on Ikke to promote cell survival and to establish an inflammatory tumor microenvironment in the intestine upon constitutive Wnt activation. [less ▲]

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See detailRelapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT.
Tsirigotis, P.; Byrne, M.; Schmid, C. et al

in Bone Marrow Transplantation (2016)

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a ... [more ▼]

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.Bone Marrow Transplantation advance online publication, 13 June 2016; doi:10.1038/bmt.2016.167. [less ▲]

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See detailComparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio.
Versluis, J.; In 't Hout, F. E. M.; Devillier, R. et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2016)

Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom ... [more ▼]

Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1 and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148). Favorable overall survival (OS) was found for patients with mutated NPM1 without FLT3-ITD (71+/-4%). Outcome in patients with a high FLT3-ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23+/-8% and 12+/-6%, respectively. Patients with wild-type NPM1 without FLT3-ITD or with a low allelic burden of FLT3-ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P=0.022 and HR 0.50, P=0.004, respectively) or autoHSCT (HR 0.60, P=0.046 and HR 0.60, P=0.043, respectively). The lowest cumulative incidence of relapse (23+/-4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.Leukemia advance online publication, 15 July 2016; doi:10.1038/leu.2016.183. [less ▲]

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See detailIL-2 consumption by highly activated CD8 T cells induces regulatory T-cell dysfunction in patients with hemophagocytic lymphohistiocytosis.
Humblet-Baron, Stephanie; Franckaert, Dean; Dooley, James et al

in Journal of Allergy and Clinical Immunology (The) (2016), 138(1), 200-2098

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory condition driven by excessive CD8(+) T-cell activation. HLH occurs as both acquired and familial hemophagocytic ... [more ▼]

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory condition driven by excessive CD8(+) T-cell activation. HLH occurs as both acquired and familial hemophagocytic lymphohistiocytosis (FHL) forms. In both conditions, a sterile or infectious trigger is required for disease initiation, which then becomes self-sustaining and life-threatening. Recent studies have attributed the key distal event to excessive IFN-gamma production; however, the proximal events driving immune dysregulation have remained undefined. OBJECTIVE: We sought to investigate the role of regulatory T (Treg) cells in the pathophysiology of experimental FHL. METHODS: Because mutation in perforin is a common cause of FHL, we used an experimental FHL mouse model in which disease in perforin-deficient mice is triggered by lymphocytic choriomeningitis virus (LCMV). We assessed Treg and CD8(+) T-cell homeostasis and activation during the changing systemic conditions in the mice. In addition, human blood samples were collected and analyzed during the HLH episode. RESULTS: We found no primary Treg cell defects in perforin-deficient mice. However, Treg cell numbers collapsed after LCMV inoculation. The collapse of Treg cell numbers in LCMV-triggered perforin-deficient, but not wild-type, mice was accompanied by the combination of lower IL-2 secretion by conventional CD4(+) T cells, increased IL-2 consumption by activated CD8(+) T cells, and secretion of competitive soluble CD25. Moreover low Treg cell numbers were observed in untreated patients experiencing HLH flares. CONCLUSION: These results demonstrate that excessive CD8(+) T-cell activation rewires the IL-2 homeostatic network away from Treg cell maintenance and toward feed-forward inflammation. These results also provide a potential mechanistic pathway for the progression of infectious inflammation to persistent inflammation in patients with HLH. [less ▲]

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See detailRevised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation
Mohty, M.; Malard, F.; Abecassis, M. et al

in Bone Marrow Transplantation (2016)

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD ... [more ▼]

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (480%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation. [less ▲]

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See detailDecitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group
Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne et al

in Annals of Hematology (2016), 95

In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal ... [more ▼]

In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MKnegative (MK−), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK−patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p=0.03) and MK2+ (HR 0.50; 99%CI, 0.23; 1.06, p=0.016) but not in the MK−, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC. [less ▲]

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See detailMethods of ex vivo expansion of human cord blood cells: challenges, successes and clinical implications
Baron, Frédéric ULg; Ruggeri, A.; Nagler, A.

in Expert Review of Hematology (2016), 21

More than 40,000 unrelated cord blood transplantations (UCBT) have been performed worldwide as treatment for patients with malignant or non-malignant life threatening hematologic disorders. However, low ... [more ▼]

More than 40,000 unrelated cord blood transplantations (UCBT) have been performed worldwide as treatment for patients with malignant or non-malignant life threatening hematologic disorders. However, low absolute numbers of hematopoietic stem and progenitor cells (HSPCs) within a single cord blood unit has remained a limiting factor for this transplantation modality, particularly in adult recipients. Further, because UCB contains low numbers of mostly naïve T cells, immune recovery after UCBT is slow predisposing patients to severe infections. Other causes of UCBT failure has included graft-versus-host disease (GVHD), and relapse of the underlying disease. In this article, we first review the current landscape of cord blood engineering aimed at improving engraftment. This includes approaches of UCB-HSPCs expansion and methods aimed at improving UCB-HSCPs homing. We then discuss recent approaches of cord blood engineering developed to prevent infection (generation of multivirus-specific cytotoxic T cells (VSTs) from UCB), relapse (transduction of UCB-T cells with tumor-specific chimeric receptor antigens (CARs)) and GVHD (expansion of regulatory T cells from UCB). Although many of these techniques of UCB engineering remain currently technically challenging and expensive, they are likely to revolutionize the field of UCBT in the next decades. [less ▲]

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