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See detailSputum cytokines levels in patients undergoing hematopoietic SCT (HSCT) and comparison with healthy subjects and COPD: a pilot study
MOERMANS, Catherine ULg; BONNET, Christophe ULg; WILLEMS, Evelyne ULg et al

in Bone Marrow Transplantation (in press)

Patients undergoing hematopoietic stem cell transplantation (HSCT) display an airway neutrophilic inflammation before the transplantation that persists over the years. In this study, we have investigated ... [more ▼]

Patients undergoing hematopoietic stem cell transplantation (HSCT) display an airway neutrophilic inflammation before the transplantation that persists over the years. In this study, we have investigated the cytokine profile over a period of one year in sputum supernatant of patients who underwent HSCT. We have measured sputum supernatant levels of TNF-α, TGF-β1, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, and IFN-γ in 49 HSCT patients and compared the results with those found in 40 COPD and 54 healthy subjects matched for age. Compared to healthy subjects, before the transplantation, HSCT patients exhibited raised levels of IL-6 (p<0.001) and IL-8 (p<0.05) while the other cytokines were generally poorly detectable. This picture was rather similar to what is seen in COPD even if cytokine levels were much greater in the latter with IL-8 being significantly greater in COPD than in HSCT patients (p<0.0001). In the 1 year following the transplantation, sputum IL-6 and IL-8 did not differ any longer compared to healthy subjects. Overall in HSCT patients, sputum IL-8 and IL-6 correlated with sputum neutrophil counts (r=0.4, p<0.0001; r=0.42, p<0.0001, respectively). In conclusion, sputum IL-6 and IL-8 may play a role in neutrophilic airway inflammation seen in patients undergoing HSCT. [less ▲]

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See detailPractical management of Chronic Myeloid Leukemia in Belgium
Benghiat, FS.; Beguin, Yves ULg; Dessars, B. et al

in Belgian Journal of Hematology (in press)

Imatinib has drastically changed the outcome of patients with chronic myeloid leukemia (CML), with the majority of them showing a normal life span. Recently, the development of second and third generation ... [more ▼]

Imatinib has drastically changed the outcome of patients with chronic myeloid leukemia (CML), with the majority of them showing a normal life span. Recently, the development of second and third generation tyrosine kinase inhibitors (TKIs) and the possibility of treatment discontinuation made the management of these patients more challenging. In this review, practical management guidelines of CML are presented, adapted to the Belgian situation in 2014. In first line chronic phase patients, imatinib, nilotinib and dasatinib can be prescribed. While second generation TKIs give faster and deeper responses, their impact on long-term survival remain to be determined. The choice of the TKI depends on CML risk score, priority for a deep response to allow a treatment-free remission protocol, age, presence of comorbid conditions, side effect profile, drug interactions, compliance concerns and price. Monitoring the response has to be made according the 2013 ELN criteria, and is based on the bone-marrow cytogenetic response during the first months and on the blood molecular response. Molecular follow-up is sufficient in patients with a complete cytogenetic response. For patients who fail frontline therapy, nilotinib, dasatinib, bosutinib and ponatinib are an option depending of the type of intolerance or resistance. T315I patients are only sensitive to ponatinib, which has to be carefully handled due to cardiovascular toxicity. Advanced phase diseases are more difficult to handle, with treatments including allogeneic stem cell transplantation, which is also an option for patients failing at least two TKIs. The possibility of treatment-free remission and pregnancy are also discussed. [less ▲]

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See detailBHS guidelines for the treatment of Burkitt lymphoma
BONNET, Christophe ULg; Janssens, A.; Wu, KL. et al

in Belgian Journal of Hematology (in press)

Burkitt lymphoma (BL) is a rare but very aggressive non-Hodgkin’s lymphoma characterized by an isolated translocation t(8;14)(q24;q32). The sporadic form is the subentity most frequently encountered in ... [more ▼]

Burkitt lymphoma (BL) is a rare but very aggressive non-Hodgkin’s lymphoma characterized by an isolated translocation t(8;14)(q24;q32). The sporadic form is the subentity most frequently encountered in our country. Diagnosis and initial work-up must be completed rapidly to start treatment as soon as possible. Positron emission tomography (PET) scan is useful for initial staging and to evaluate the chemosensitivity of the tumor during and after treatment. After debulking, it is recommended to add rituximab to chemotherapy. Currently intensive short-cycle chemotherapies (ISCC) and low intensity chemotherapies (LIC) are two valuable options. Radiotherapy is not indicated except in case of central nervous system involvement. Patients achieving complete remission must be followed carefully during the first year to detect recurrence of the disease. More than 80% of patients sustain their remission one year following initial treatment and are considered cured. For patients in partial remission or with chemosensitive relapse, autologous stem cell transplantation is recommended following re-induction with non-cross-resistant polychemotherapy. Monitoring complete blood counts and cognitive functions is important to detect late toxicity of the applied therapies. [less ▲]

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See detailAllogeneic hematopoietic stem cell transplantation in solid organ transplant recipients: a retrospective, multicenter study of the EBMT
Basak, GW.; Wiktor-Jedrzejczak, W.; Labopin, M. et al

in American Journal of Transplantation (in press)

We conducted a questionnaire survey of the 565 European Society for Blood and Marrow Transplantation centers to analyze the outcome of allogeneic hematopoietic stem cell transplantation (alloSCT) in ... [more ▼]

We conducted a questionnaire survey of the 565 European Society for Blood and Marrow Transplantation centers to analyze the outcome of allogeneic hematopoietic stem cell transplantation (alloSCT) in recipients of solid organ transplantation (SOT). We investigated 28 patients with malignant (N=22) or nonmalignant diseases (N=6), who underwent 31 alloSCT procedures: 12 after kidney, 13 after liver, and three after heart transplantation. The incidence of solid organ graft failure at 60 months after first alloSCT was 33% (95% confidence interval [CI], 16–51%) for all patients, 15% (95% CI, 2–40%) for liver recipients, and 50% (95% CI, 19–75%) for kidney recipients (p = 0.06). The relapse rate after alloSCT (22%) was low following transplantation for malignant disorders, despite advanced stages of malignancy. Overall survival at 60 months after first alloSCT was 40% (95% CI, 19–60%) for all patients, 51% (95% CI, 16–86%) for liver recipients, and 42% (95% CI, 14–70%) for kidney recipients (p = 0.39). In summary, we show that selected SOT recipients suffering from hematologic disorders may benefit from alloSCT and experience enhanced long-term survival without loss of organ function. [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 (in press)

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See detailEstablishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation
Binsfeld, Marilène ULg; Beguin, Yves ULg; Belle, Ludovic et al

in PLoS ONE (in press)

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic ... [more ▼]

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT) has remained controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice (previously injected with the MOPC315.BM myeloma cell line), based on a chronic graft-versus-host disease (GvHD) murine model. Methods and results: Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received 30 days later an allogeneic (B10.D2 donor) or autologous (Balb/cJ donor) transplantation by intravenous administration of bone marrow cells and splenocytes. We observed a graft-versus-myeloma effect in 94% of the allogeneic transplanted mice, as luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma evolution. Lower serum paraprotein levels and myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect, while allogeneic mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggest the involvement of effector memory CD4 and CD8 T cells in the GvM effect. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR V spectratyping analysis identified V families within CD4 and CD8 T cells which were associated with both GvM effects and GVHD, whereas other V families within CD4 T cells were associated exclusively with either GvM or GvHD responses. Conclusions: We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first immunocompetent murine model which is based on a MM model closely resembling human MM disease (bone marrow tropism, ...) and using allo-SCT after the disease establishment, as a curative treatment [less ▲]

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See detailGammapathie monoclonale de signification indéterminée : information destinée aux médecins référents
CAERS, Jo ULg; Binsfeld, Marilène ULg; Muller, Joséphine ULg et al

in Revue Médicale de Liège (in press)

Les gammapathies monoclonales de signification indéterminée (GMSI) sont fréquentes dans la population générale. Leur potentiel évolutif malin impose une surveillance clinique régulière et prolongée ... [more ▼]

Les gammapathies monoclonales de signification indéterminée (GMSI) sont fréquentes dans la population générale. Leur potentiel évolutif malin impose une surveillance clinique régulière et prolongée. Cependant, les GMSI forment un groupe très hétérogène et tous les patients n’ont pas le même risque de transformation maligne. Plusieurs critères biologiques simples, disponibles en routine ont été identifiés comme facteurs prédictifs de la transformation. Les scores prédictifs de transformation maligne combinant plusieurs de ces facteurs permettront probablement la classification des patients en fonction de leur risque évolutif. La prise en charge pourra ainsi être adaptée au risque individuel de chaque patient [less ▲]

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See detailRituximab therapy for hairy cell leukemia : a retrospective study of 41 cases
Leclerc, Mathieu; Suarez, Felipe; Noël, Marie-Pierre et al

in Annals of Hematology (in press)

The purine analogs (PAs) cladribine and pentostatin have transformed the prognosis of hairy cell leukemia (HCL). However, some patients still relapse after PAs, or fail to reach an optimal response, and ... [more ▼]

The purine analogs (PAs) cladribine and pentostatin have transformed the prognosis of hairy cell leukemia (HCL). However, some patients still relapse after PAs, or fail to reach an optimal response, and new agents are needed to further improve treatment outcome. We retrospectively studied 41 HCL patients from 10 centers in France and Belgium, who received 49 treatment courses with the anti-CD20 monoclonal antibody rituximab. Most of the patients were treated at relapse (84 % of cases) and rituximab was combined to a PA in 41 % of cases. Overall, response rate is 90 % including 71 % complete hematologic responses (CHRs). Frontline treatment, combination therapy, and absolute neutrophil count were associated with response in multivariate analysis. Three-year relapse-free and overall survivals are 68 and 90 %, respectively. When combined to a PA, rituximab yields a 100 % response rate, even beyond frontline therapy. In contrast, response rate is only 82 % (59 % CHR) when rituximab is used alone. In this latter setting, relapse rate is 56 % and median time to relapse is 17.5 months. All eight patients who were treated two times with the antibody responded again to retreatment. We confirm the high efficacy of the combination rituximab + PA. However, when rituximab is used as monotherapy, response rate is lower and the high relapse rate is a concern. Prospective clinical trials are needed to confirm the superiority of the combination rituximab + PA over PA alone, both as frontline therapy and at relapse. [less ▲]

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See detailRationale for the potential use of mesenchymal stromal cells in liver transplantation
Vandermeulen, M.; DE ROOVER, Arnaud ULg; BRIQUET, Alexandra ULg et al

in World Journal of Gastroenterology (in press)

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See detailLeucémie myéloblastique aiguë : sécrétion paranéoplasique de GH et de PRL ?
VALDES SOCIN, Hernan Gonzalo ULg; Potorac, Iulia ULg; DE PASQUAL, Aurelie ULg et al

in Abstract book - Annales d'Endocrinologie : 31ème Congrès de la Société Françaose d'Endocrinologie, Lyon 5-8 novembre 2014 (2014, October)

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See detailIntérêt des cellules stromales mésenchymateuses en transplantation d’organes solides
Delens, Loic ULg; Jouret, François ULg; DETRY, Olivier ULg et al

in Revue Médicale Suisse (2014), 10

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological ... [more ▼]

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties. [less ▲]

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See detailIntérêt des cellules stromales mésenchymateuses en transplantation d’organes solides
Delens, Loic ULg; Jouret, François ULg; DETRY, Olivier ULg et al

in Revue Médicale Suisse (2014), 10

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological ... [more ▼]

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties. [less ▲]

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See detailIntérêt des cellules stromales mésenchymateuses en transplantation d’organes solides
Delens, Loic ULg; Jouret, François ULg; DETRY, Olivier ULg et al

in Revue Médicale Suisse (2014), 10

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological ... [more ▼]

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties. [less ▲]

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See detailIntérêt des cellules stromales mésenchymateuses en transplantation d’organes solides
Delens, Loic ULg; Jouret, François ULg; DETRY, Olivier ULg et al

in Revue Médicale Suisse (2014), 10

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological ... [more ▼]

Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties. [less ▲]

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See detailInfusion of clinical-grade enriched regulatory T cells delays experimental xenogeneic graft-versus-host disease
Hannon, Muriel ULg; LECHANTEUR, Chantal ULg; Lucas, Sophie et al

in Transfusion (2014), 54(February), 353-363

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See detailImmunomodulatory effects of Rapamycin in xenogeneic GVHD
Ehx, Grégory ULg; HANNON, Muriel ULg; DUBOIS, Sophie ULg et al

Poster (2014, January 27)

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See detailImpact of co-transplantation of mesenchymal stem cells on lung function after unrelated allogeneic hematopoietic stem cell transplantation following non-myeloablative conditioning
MOERMANS, Catherine ULg; LECHANTEUR, Chantal ULg; BAUDOUX, Etienne ULg et al

in Transplantation (2014), 98(3), 348-353

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal ... [more ▼]

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal models, MSC were shown to cause pulmonary alterations after systemic administration. The impact of MSC infusion on lung function has not been studied in humans. The objective of the study was to investigate the impact of MSC co-infusion on lung function and airway inflammation as well as on the incidence of pulmonary infections and cytomegalovirus (CMV) reactivation after HSCT. Methods: We have prospectively followed 30 patients who underwent unrelated HSCT with MSC co-infusion after non-myeloablative conditioning (NMA). Each patient underwent detailed lung function testing (FEV1, FVC, FEV1/FVC, RV, TLC, DLCO and KCO) and measurement of exhaled nitric oxide before HSCT and 3, 6 and 12 months posttransplant. The incidence of pulmonary infections and CMV reactivation were also monitored. This group was compared with another group of 28 patients who underwent the same type of transplantation but without MSC co-infusion. Results: Lung function tests did not show important modifications over time and did not differ between the MSC and control groups. There was a higher 1-year incidence of infection, particularly of fungal infections, in patients having received a MSC co-infusion. There was no difference between groups regarding the 1-year incidence of CMV reactivation. Conclusions: MSC co-infusion does not induce pulmonary deterioration 1 year after HSCT with NMA conditioning. MSC appear to be safe for the lung but close monitoring of pulmonary infections remains essential. [less ▲]

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