References of "Haematologica"
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See detailCircadian and circannual variations in cord blood hematopoietic cell composition
Servais, Sophie ULg; BAUDOUX, Etienne ULg; Brichard, B. et al

in Haematologica (in press)

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See detailAllogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas
de Masson, Adele; Beylot-Barry, Marie; Bouaziz, Jean-David et al

in Haematologica (in press)

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See detailPre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors
SERVAIS, Sophie ULg; Porcher, Raphael; Xhaard, Aliénor et al

in Haematologica (2014), 99(3), 519-526

Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. Few studies have compared outcome of HLA-matched related and HLA-matched unrelated ... [more ▼]

Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. Few studies have compared outcome of HLA-matched related and HLA-matched unrelated donor peripheral blood stem cell transplants. We conducted a retrospectivesingle-center analysis of 442 patients with hematologic malignancies who underwent peripheral blood stem cell transplantationfrom matched related or matched unrelated donorand we analyzed prognostic factors for long-term survival.To account for disease/status heterogeneity, patients were risk-stratified according to theDisease Risk Index.Five-year overall survival was similar aftertransplants with matched related and unrelated donor. Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated donor (aged < 60 years by definition), matched related donor aged <60 yearsand matched related donoraged ≥60 years. In multivariate analysis, donor type/age groupand graft CD34+ and CD3+ cell doses significantly impactedlong-term survival. Transplants with matched unrelated donor and matched related donor<60years resulted in similar long-term survival while transplant with matched related donor≥60years was associated with higher risks for late mortality and treatment failure. Lower mortality risks were observed after transplant with CD34+ cell dose > 4.5 x 106/kgand CD3+ cell dose > 3 x 108/kg. The Disease Risk Index failed to predictsurvival. We builtan “Adapted Disease Risk Index” by modifying risks for myeloproliferative neoplasms and multiple myeloma, thatimproved stratification ability for progression-free survivalbut not for overall survival. [less ▲]

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See detailCD30-positive peripheral T-cell lymphomas share molecular and phenotypic features
Bisig, B.; de Reyniès, A.; Bonnet, Christophe ULg et al

in Haematologica (2013), 98/n°8

Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of ... [more ▼]

Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30+ peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30+ and CD30–; anaplastic large cell lymphomas, ALK+ and ALK–), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30– tumors, CD30+ peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK– anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30+ peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30– samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30– peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30+ subgroups. In conclusion, we show molecular and phenotypic features common to CD30+ peripheral T-cell lymphomas, and significant differences between CD30– and CD30+ peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups. [less ▲]

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See detailComparison of Immune Reconstitution after Hematopoietic Stem Cell Transplantation with Flu-TBI versus TLI-ATG Conditioning
Hannon, Muriel ULg; Humblet-Baron, S.; Graux, C. et al

in Haematologica (2012), 97(Supplement 1), 180

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See detailValue of infliximab (Remicade) in patients with low-risk myelodysplastic syndrome. Final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group
Baron, Frédéric ULg; Suciu, Stefan; Amadori, Sergio et al

in Haematologica (2012), 97(4), 529533

Tumor-necrosis factor alpha activity has been correlated to ineffective erythropoiesis in lower risk myelodysplastic syndromes. Infliximab (Remicade) is an anti-tumor-necrosis factor alpha chimeric ... [more ▼]

Tumor-necrosis factor alpha activity has been correlated to ineffective erythropoiesis in lower risk myelodysplastic syndromes. Infliximab (Remicade) is an anti-tumor-necrosis factor alpha chimeric antibody that is used in the treatment of patients with heumatoid arthritis or Crohn's disease. Forty-six patients with myelodysplastic syndromes and a relatively low risk of developing acute leukemia were included in a randomized phase II study assessing the therapeutic activity of two dosages of infliximab administration (3 mg/kg versus 5 mg/kg). The primary endpoint was the response rate. Responses were observed in 3 of 22 patients (13.1%) randomized to the 3 mg/kg arm, versus 0 of 21 patients randomized in the 5 mg/kg arm. According to the statistical design of the current study, neither of the two infliximab dose schedules tested showed sufficient activity as a single agent in this cohort of unselected patients with early myelodysplastic syndrome. [less ▲]

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See detailWhat is the Contribution of Host-Derived CMV Immunity after Allogeneic Transplantation following Non-Myeloablative Conditioning?
MENTEN, Catherine ULg; Castermans, E.; Hannon, Muriel ULg et al

in Haematologica (2012), 97(Supplement 1), 720

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See detailFamily-directed umbilical cord blood banking.
GLUCKMAN, E; ROCHA, V; BAUDOUX, Etienne ULg et al

in Haematologica (2011), 96(11), 1700-17007

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See detailLeukemic cell xenograft in zebrafish embryo for investigating drug efficacy.
Pruvot, Benoist ULg; Jacquel, Arnaud; Droin, Nathalie et al

in Haematologica (2011), 96(4), 612-6

Zebrafish were proposed as an alternative to mammalian models to assess the efficacy and toxicity of antileukemic drugs. Due to the limited number of transgenic zebrafish leukemia models, we explored ... [more ▼]

Zebrafish were proposed as an alternative to mammalian models to assess the efficacy and toxicity of antileukemic drugs. Due to the limited number of transgenic zebrafish leukemia models, we explored human leukemic cell xenograft in zebrafish embryos. Human leukemic cell lines and blast cells sorted from patients with acute myelogenous leukemia were injected 48 hours post-fertilization and remained in the circulation of zebrafish embryos for several days without affecting their development. Imatinib and oxaphorines did not demonstrate any toxicity on normal zebrafish embryos and decreased the leukemic burden in animals xenografted with sensitive leukemic cell lines. Two other molecules, all-trans retinoic acid and the translation inhibitor 4EGI-1, demonstrated teratogenic effects at concentrations shown to be efficient in vitro, which precluded investigation of their antileukemic activity in such models. Altogether, xenografted leukemic cells in zebrafish embryos are a pharmacologically relevant model for screening non-teratogenic drugs. [less ▲]

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See detailThymosin Beta 4 has tumor suppressive effects and its decreased expression results in poor prognosis and decreased survival in multiple myeloma
Caers, Jo ULg; Hose, Dirk; Kuijpers, Ine et al

in Haematologica (2010), 95(1), 163-167

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See detailProlonged ex vivo culture of human bone marrow mesenchymal stem cells influences their supportive activity toward NOD/SCID -repopulating cells and committed progenitor cells of B lymphoid and myeloid lineages
Briquet, Alexandra ULg; Dubois, Sophie ULg; Bekaert, Sandrine ULg et al

in Haematologica (2010), 95(1), 47-56

Background Bone marrow (BM) mesenchymal stem cells (MSC) support proliferation and differentiation of hematopoietic progenitor cells (HPC) in vitro. Since they represent a rare subset of BM cells, MSC ... [more ▼]

Background Bone marrow (BM) mesenchymal stem cells (MSC) support proliferation and differentiation of hematopoietic progenitor cells (HPC) in vitro. Since they represent a rare subset of BM cells, MSC preparations for clinical purposes involves a preparative step of ex vivo multiplication. The aim of our study was to analyze the influence of culture duration on MSC supportive activity. DESIGN AND METHODS: MSC were expanded for up to 10 passages. MSC and CD34(+) cells were seeded in cytokine-free co-cultures after which the phenotype, clonogenic capacity and in vivo repopulating activity of harvested hematopoietic cells were assessed. RESULTS: Early passage MSC supported HPC expansion and differentiation toward both B lymphoid and myeloid lineages. Late passage MSC did not support HPC and myeloid cell outgrowth but maintained B cell supportive ability. In vitro maintenance of NOD/SCID mouse repopulating cells cultured for one week in contact with MSC was effective until the fourth MSC passage and declined afterwards. CD34(+) cells achieved higher levels of engraftment in NOD/SCID mice when co-injected with early passage MSC; however MSC expanded beyond 9 passages were ineffective in promoting CD34(+) cell engraftment. Non-contact cultures indicated that MSC supportive activity involved diffusible factors. Among these, interleukin (IL)-6 and IL-8 contributed to the supportive activity of early passage MSC but not of late passage MSC. MSC phenotype as well as fat, bone and cartilage differentiation capacity did not change during MSC culture. Conclusions Extended MSC culture alters their supportive ability toward HPC without concomitant changes in phenotype and differentiation capacity. [less ▲]

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See detailEx vivo expansion of hematopoietic progenitor cells is associated with downregulation of alpha4 integrin- and CXCR4-mediated engraftment in NOD/SCID beta2-microglobulin-null mice
Foguenne, Jacques ULg; Di Stefano; Giet, Olivier ULg et al

in Haematologica (2009), 94

Several studies indicate that ex vivo cytokine-supported expansion induces defective hematopoietic stem cell engraftment. We investigated the role of alpha4 integrin, alpha5 integrin and CXCR4 in ... [more ▼]

Several studies indicate that ex vivo cytokine-supported expansion induces defective hematopoietic stem cell engraftment. We investigated the role of alpha4 integrin, alpha5 integrin and CXCR4 in engraftment of unmanipulated and cytokine-treated human cord blood CD34+ cells. [less ▲]

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See detailThe prevention of spontaneous apoptosis of follicular lymphoma B cells by a follicular dendritic cell line: involvement of caspase-3, caspase-8 and c-FLIP.
Goval, Jean-Jacques; Thielen, Caroline ULg; Bourguignon, Caroline et al

in Haematologica (2008), 93(8), 1169-77

BACKGROUND: Follicular lymphoma, the neoplastic counterpart of germinal center B cells, typically recapitulates a follicular architecture. Several observations point to the crucial role of the cellular ... [more ▼]

BACKGROUND: Follicular lymphoma, the neoplastic counterpart of germinal center B cells, typically recapitulates a follicular architecture. Several observations point to the crucial role of the cellular microenvironment in the development and/or progression of follicular lymphoma cells in vivo. The aim of our study was to characterize the spontaneous apoptosis of follicular lymphoma cells in vitro, and the modulation of this apoptosis by follicular dendritic cells. DESIGN AND METHODS: We used a cell line derived from follicular dendritic cells to model the functional interactions of these cells and lymphoma cells in co-culture. Follicular lymphoma cells were isolated from tissue biopsies. Apoptosis was quantified by flow cytometry and apoptotic pathways were investigated by western blotting. RESULTS: The spontaneous apoptosis of follicular lymphoma cells in vitro involves the activation of caspases-3 and -8 but not of caspase-9, occurs despite persistent high levels of BCL-2 and MCL-1, and is associated with down-regulation of c-FLIP(L). Spontaneous apoptosis of follicular lymphoma cells is partially prevented by co-culture with the follicular dendritic cells, which prevents activation of caspase-8, caspase-3 and induces an upregulation of c-FLIP(L). Using neutralizing antibodies, we demonstrated that interactions involving CD54 (ICAM-1), CD106 (VCAM-1) and CD40 are implicated in this biological process. CONCLUSIONS: Follicular dendritic cells constitute a useful tool to study the functional interactions between follicular lymphoma cells and follicular dendritic cells in vitro. Understanding the molecular mechanisms involved in these protective interactions may lead to the identification of therapeutic agents that might suppress the survival and growth of follicular lymphoma cells. [less ▲]

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See detailEvidence for neo-generation of T cells by the thymus after non-myeloablative conditioning.
Castermans, Emilie ULg; Baron, Frédéric ULg; Willems, Evelyne ULg et al

in Haematologica (2008), 93(2), 240-7

BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning ... [more ▼]

BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning. DESIGN AND METHODS: Fifty patients were randomized to receive either CD8-depleted (n=22) or non-manipulated (n=28) peripheral blood stem cells. The median patients age was 57 (range 36-69) years. The conditioning regimen consisted of 2 Gy total body irradiation with or without added fludarabine. Twenty patients received grafts from related donors, 14 from 10/10 HLA-allele matched unrelated donors, and 16 from HLA-mismatched unrelated donors. Graft-versus-host disease pro-phylaxis consisted of mycophenolate mofetil and cyclosporine. Immune recovery during the first year after hematopoietic cell transplantation was assessed by flow cytometry phenotyping, analyses of the diversity of the TCRBV repertoire, and quantification of signal-joint T-cell receptor excision circles (sjTREC). RESULTS: CD8-depletion of the graft reduced the recovery of CD8(+) T-cell counts in the first 6 months following transplantation (p<0.0001) but had no significant impact on the restoration of other T-cell subsets. Both sjTREC concentration and CD3(+) T-cell counts increased significantly between day 100 and 365 (p=0.010 and p=0.0488, respectively) demonstrating neo-production of T cells by the thymus. Factors associated with high sjTREC concentration 1 year after transplantation included an HLA-matched unrelated donor (p=0.029), a high content of T cells in the graft (p=0.002), and the absence of chronic graft-versus-host disease (p<0.0001). CONCLUSIONS: Our data suggest that while immune recovery is mainly driven by peripheral expansion of the graft-contained mature T cells during the first months after non-myeloablative transplantation, T-cell neo-generation by the thymus plays an important role in long term immune reconstitution in transplanted patients. [less ▲]

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See detailDuplication of the MYB oncogene in T-cell acute lymphoblastic leukemia
Lahortiga, Idoya; De Keersmaecker, Kim; Van Vlierberghe, Pieter et al

in Haematologica (2007, June), 92(Suppl. 1), 164

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