References of "Haematologica"
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See detailPeripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia–A report from the ALWP of the EBMT
Savani, Bipin N.; Labopin, Myriam; Blaise, Didier et al

in Haematologica (2016)

Increasing numbers of patients are receiving reduced-intensity-conditioning regimen allogeneic hematopoietic stem-cell transplantation. We hypothesized that the use of bone-marrow graft might decrease the ... [more ▼]

Increasing numbers of patients are receiving reduced-intensity-conditioning regimen allogeneic hematopoietic stem-cell transplantation. We hypothesized that the use of bone-marrow graft might decrease the risk of graft-versus-host-disease compared to peripheral-blood after reduced-intensity-conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced-intensity-conditioning regimen allogeneic hematopoietic stem-cell transplantation from 2000-2012 for acute leukemia and reported to the acute-leukemia-working-party of the EBMT were included in the study. Eight hundred thirty-seven patients receiving bone-marrow grafts were compared with 9011 peripheral-blood transplant recipients after reduced-intensity conditioning regimen. Median follow-up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil≥0.5x109/L at day 60) was lower in bonemarrow recipients, 88 vs. 95% (p<0.0001). Grade II to IV acute graft-versus-hostdisease was lower in bone-marrow recipients, 19% vs. 24% for peripheral-blood (p=0.005). In multivariate analysis, after adjusting for differences between both groups, overall survival (HR 0.90; p=0.05) and leukemia-free-survival (HR 0.88; p=0.01) were higher in patients transplanted with peripheral-blood compared to bone-marrow grafts. Furthermore, peripheral-blood graft was also associated with decreased risk of relapse (HR 0.78; p=0.0001). Non-relapse-mortality was not significantly different between recipients of bone-marrow and peripheral-blood grafts, and chronic graft-versus-host-disease was significantly higher after peripheral blood grafts (HR 1.38; p<0.0001). Despite the limitation of a retrospective registry based study, we found that peripheral-blood grafts after reduced-intensity-conditioning regimens had better overall and leukemia-free survival than bone-marrow grafts. However, there is an increase in chronic graft-versus-host-disease after peripheral-blood grafts. Long-term follow-up is needed to clarify if chronic graft-versus-host-disease related deaths might increase the risk of late morbidity and mortality. [less ▲]

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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 (2015), 100(1), 32-34

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See detailDeficiency in mouse hyaluronidase 2: a new mechanism of chronic thrombotic microangiopathy.
Onclinx, Cecile; Dogne, Sophie; Jadin, Laurence et al

in Haematologica (2015)

Hyaluronan is a major component of the extracellular matrix and glycocalyx. Its main somatic degrading enzymes are the hyaluronidases 1 and 2, none of which is active in the bloodstream. We generated ... [more ▼]

Hyaluronan is a major component of the extracellular matrix and glycocalyx. Its main somatic degrading enzymes are the hyaluronidases 1 and 2, none of which is active in the bloodstream. We generated hyaluronidase 2 deficient mice. They suffer from mild chronic anemia and thrombocytopenia, in parallel with a 10-fold increase in plasma hyaluronan concentration. The current study explores the mechanism of these hematological anomalies. The decreased erythrocyte and platelet counts were assigned to peripheral consumption. The erythrocyte half-life was reduced from 25 to 8 days without signs of premature aging. Hyaluronidase 2 deficient platelets were functional. Major intrinsic defects in erythrocyte membrane or stability, as well as detrimental effects of high hyaluronan levels on erythrocytes, were ruled out in vitro. Normal erythrocytes transfused into hyaluronidase 2 deficient mice were quickly destroyed but neither splenectomy nor anti-C5 administration prevented from chronic hemolysis. Schistocytes were present in hyaluronidase 2 deficient smears at a level of 1 to 6%, while virtually absent in control mice. Hyaluronidase 2 deficient mice had increased markers of endothelial damage and microvascular fibrin deposition, without renal failure, accumulation of ultra-large multimers of von Willebrand factor, deficiency of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motifs, member 13 (ADAMTS13), or hypertension. There was no sign of structural damage in hepatic or splenic sinusoids, or in any other microvessels. We conclude that hyaluronidase 2 deficiency induces chronic thrombotic microangiopathy with hemolytic anemia in mice. The link between this uncommon condition and hyaluronidase 2 remains to be explored in man. [less ▲]

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See detailEngraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen
RUGGERI, ANNALISA; LABOPIN, MYRIAM; SORMANI, MARIA PIA et al

in Haematologica (2014), 99

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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 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 (2014), 99(3), 527-534

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See detailThe role of positron emission tomography-computed tomography and magnetic resonance imaging in diagnosis and follow up of multiple myeloma.
CAERS, Jo ULg; WITHOFS, Nadia ULg; Hillengass et al

in Haematologica (2014), 99(4), 629-37

Multiple myeloma is the second most common hematologic malignancy and occurs most commonly in elderly patients. Almost all multiple myeloma patients develop bone lesions in the course of their disease or ... [more ▼]

Multiple myeloma is the second most common hematologic malignancy and occurs most commonly in elderly patients. Almost all multiple myeloma patients develop bone lesions in the course of their disease or have evidence of bone loss at initial diagnosis. Whole-body conventional radiography remains the gold standard in the diagnostic evaluation, but computed tomography, magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography are increasingly used as complementary techniques in the detection of bone lesions. Moreover, the number of lesions detected and the presence of extramedullary disease give strong prognostic information. These new techniques may help to assess treatment response in solitary plasmacytoma or in multiple myeloma. In this article, we review recent data on the different imaging techniques used at diagnosis and in the assessment of treatment response, and discuss some current issues. [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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