References of "BARON, Frédéric"
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See detailThe Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia
Holter-Chakrabarty, Jennifer; Pierson, Namali; Zhang, Mei-Jie et al

in Biology of Blood & Marrow Transplantation (in press)

Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n ¼ 948; TBICy, n ... [more ▼]

Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n ¼ 948; TBICy, n ¼ 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosomeepositive acute lymphoblastic leukemia, HLAmatched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P ¼.67; relative risk, 1.01; P ¼.91), leukemia relapse (27% versus 29% at 3 years, P ¼ .34; relative risk, .89, P ¼.18), leukemia-free survival (49% versus 48% at 3 years, P ¼.27; relative risk, .93; P ¼ .29), chronic GVHD (45% versus 47% at 1 year, P ¼.39; relative risk, .9; P ¼ .11), or overall survival (53% versus 52% at 3 years, P ¼.62; relative risk, .96; P ¼.57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P ¼ .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning. [less ▲]

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See detailImmune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation following Flu-TBI versus TLI-ATG Conditioning
HANNON, Muriel ULg; BEGUIN, Yves ULg; Ehx, Grégory ULg et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (in press)

Purpose: A conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) combining total lymphoid irradiation (TLI) plus anti-thymocyte globulin (ATG) has been develop to induce graft ... [more ▼]

Purpose: A conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) combining total lymphoid irradiation (TLI) plus anti-thymocyte globulin (ATG) has been develop to induce graft-versus-tumor effects without graft-versus-host disease (GVHD). Experimental Design: We compared immune recovery in 53 patients included in a phase II randomized study comparing nonmyeloablative HCT following either fludarabine plus 2 Gy total body irradiation (TBI arm, n=28) or 8 Gy TLI plus anti-thymocyte globulin (TLI arm, n=25). Results: In comparison to TBI patients, TLI patients had a similarly low 6-month incidence of grade II-IV acute GVHD, a lower incidence of moderate/severe chronic GVHD (P=0.02), a higher incidence of CMV reactivation (P<0.001), and a higher incidence of relapse (P=0.01). While recovery of total CD8+ T cells was similar in the two groups, with median CD8+ T cell counts reaching the normal values 40-60 days after allo-HCT, TLI patients had lower percentages of naïve CD8 T cells. Median CD4+ T cell counts did not reach the lower limit of normal values the first year after allo-HCT in the two groups. Further, CD4+ T cell counts were significantly lower in TLI than in TBI patients the first 6 months after transplantation. Interestingly, while median absolute regulatory T cell (Treg) counts were comparable in TBI and TLI patients, Treg/naïve CD4+ T cell ratios were significantly higher in TLI than in TBI patients the 2 first years after transplantation. Conclusions: Immune recovery differs substantially between these two conditioning regimens possibly explaining the different clinical outcomes observed (NCT00603954). [less ▲]

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

Poster (2015, January 30)

Introduction: Graft-versus-host disease (GVHD) remains one major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Following unmanipulated peripheral-blood stem cell ... [more ▼]

Introduction: Graft-versus-host disease (GVHD) remains one major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Following unmanipulated peripheral-blood stem cell 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 role in the pathology of chronic GVHD by inhibiting alloreactive conventional T cells. Several studies have shown the hypomethylating agent Azacytidine (Aza) can demethylate the master transcription factor of Treg (Forkhead box protein 3 factor, FoxP3), thus promoting Treg differentiation of conventional T cells. This work investigates the impact of Aza in a classical murine model of sclerodermic chronic GVHD (B10.D2  BALB/cJ). Methods: Lethally irradiated BALB/cJ recipient mice were injected with 107 bone marrow cells + 7.107splenocytes from B10.D2 donor mice. Recipients were treated with subcutaneous injections of Aza at the dose of 0,5 or 2 mg/kg every two days from day 10 to 30 following transplantation. Mice GVHD was evaluated with five criteria (weight loss, activity, fibrosis, hair loss and mice posture; 0-1-2 points/criteria). Mice were sacrificed at a score of 8/10 (or > 20% weight loss). Results: Mice treated with Aza 0.5 mg/kg (n = 14) or 2 mg/kg (n = 17) had significant lower clinical scores compared to control ones (n = 15) after treatment. FACS analysis showed a higher proportion of Treg among CD4+ T cells in the blood of Aza 2 mg/kg mice than in control mice (P = 0.047), as well as a higher percentage of Tregs expressing the KI67 proliferative marker on the same day (P = 0.0005). Finally, analyses of the cellular blood components with Cell-dyn demonstrated that Aza 2 mg/kg treated mice were significantly lymphopenic as compared to control mice (P = 0.05). Conclusion : Aza prevented sclerodermic GVHD in this classical murine model of chronic GVHD. [less ▲]

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See detailHigh numbers of mobilized CD34+ cells collected in AML in first remission are associated with high relapse risk irrespective of treatment with autologous peripheral blood SCT or autologous BMT
Hengeveld, M.; Suciu, S.; Chelgoum, Y. et al

in Bone Marrow Transplantation (2015), 50

The faster hematopoietic recovery after autologous peripheral blood SCT (APBSCT) in patients with AML may be offset by an increased relapse risk as compared with autologous BMT (ABMT). The EORTC and ... [more ▼]

The faster hematopoietic recovery after autologous peripheral blood SCT (APBSCT) in patients with AML may be offset by an increased relapse risk as compared with autologous BMT (ABMT). The EORTC and GIMEMA Leukemia Groups conducted a trial (AML-10) in which they compared, as second randomization, APBSCT and ABMT in first CR patients without an HLA compatible donor. A total of 292 patients were randomized. The 5-year DFS rate was 41% in the APBSCT arm and 46% in the ABMT arm with a hazard ratio (HR) of 1.17; 95% confidence interval = 0.85–1.59; P = 0.34. The 5-year cumulative relapse incidence was 56% vs 49% (P = 0.26), and the 5-year OS 50% and 55% (P = 0.6) in the APBSCT and ABMT groups, respectively. APBSCT was associated with significantly faster recovery of neutrophils and platelets, shorter duration of hospitalization, reduced need of transfusion packed RBC and less days of intravenous antibiotics. In both treatment groups, higher numbers of mobilized CD34+ cells were associated with a significantly higher relapse risk irrespective of the treatment given after the mobilization. Randomization between APBSCT and ABMT did not result in significantly different outcomes in terms of DFS, OS and relapse incidence. [less ▲]

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See detailNon-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2 Gy TBI or ATG plus 8 Gy TLI: a phase II randomized study from the Belgian Hematological Society
Baron, Frédéric ULg; Zachée, Pierre; Maertens, Johan et al

in Journal of Hematology & Oncology (2015), 8(4), 10118613045-014-0098-9

Background: Few studies thus far have compared head-to-head different non-myelooablative conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT). Methods: Here, we report the ... [more ▼]

Background: Few studies thus far have compared head-to-head different non-myelooablative conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT). Methods: Here, we report the results of a phase II multicenter randomized study comparing non-myeloablative allo-HCT from HLA-identical siblings (n = 54) or from 10/10 HLA-matched unrelated donors (n = 40) with either fludarabine plus 2 Gy total body irradiation (Flu-TBI arm; n = 49) or 8 Gy TLI + anti-thymocyte globulin (TLI-ATG arm; n = 45) conditioning. Results: The 180-day cumulative incidences of grade II-IV acute GVHD (primary endpoint) were 12.2% versus 8.9% in Flu-TBI and TLI-ATG patients, respectively (P = 0.5). Two-year cumulative incidences of moderate/severe chronic GVHD were 40.8% versus 17.8% in Flu-TBI and TLI-ATG patients, respectively (P = 0.017). Five Flu-TBI patients and 10 TLI-ATG patients received pre-emptive DLI for low donor chimerism levels, while 1 Flu-TBI patient and 5 TLI-ATG patients (including 2 patients given prior pre-emptive DLIs) received a second HCT for poor graft function, graft rejection, or disease progression. Four-year cumulative incidences of relapse/progression were 22% and 50% in Flu-TBI and TLI-ATG patients, respectively (P = 0.017). Four-year cumulative incidences of nonrelapse mortality were 24% and 13% in Flu-TBI and TLI-ATG patients, respectively (P = 0.5). Finally, 4-year overall (OS) and progression-free survivals (PFS) were 53% and 54%, respectively, in the Flu-TBI arm, versus 54% (P = 0.9) and 37% (P = 0.12), respectively, in the TLI-ATG arm. Conclusions: In comparison to patients included in the Flu-TBI arm, patients included in the TLI-ATG arm had lower incidence of chronic GVHD, higher incidence of relapse and similar OS. [less ▲]

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See detailBoosting regulatory T-cell function with the humanized CD4-specific humanized monoclonal antibody Tregalizumab (BT-061)
Humblet-Baron, Stéphanie; Baron, Frédéric ULg

in Immunology & Cell Biology (2015), 1-2

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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 (2014), 49(11), 1382-1388

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 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 detailComprehensive plasma profiling for the characterization of graft-versus-host disease biomarkers
De Bock, Muriel; BEGUIN, Yves ULg; Leprince, Pierre ULg et al

in Talanta (2014), 125

Acute graft-versus-host disease (aGVHD) remains a life-threatening complication of hematopoietic stem cell transplantation (HSCT), limiting its application. To optimize management of aGVHD and reduce ... [more ▼]

Acute graft-versus-host disease (aGVHD) remains a life-threatening complication of hematopoietic stem cell transplantation (HSCT), limiting its application. To optimize management of aGVHD and reduce therapy-related toxicity, early specific markers are needed. The main objective of this study was thus to uncover diagnostic biomarkers comparing plasma protein profiles of patients at the time of acute GVHD diagnosis and of patients undergoing HSCT without aGVHD. Additional analysis of samples taken 15 days before aGVHD diagnosis was also performed to evaluate the potential of the newly discovered biomarkers for early diagnosis. To extract a maximum of information from plasma samples, we used three complementary proteomic approaches, namely 2D-DIGE, SELDI-TOF-MS and 2D-LC-MSE. We identified and confirmed by means of a independent techniques, the differential expression of several proteins indicating significantly increased inflammation response and disturbance in the coagulation cascade. The variation of these proteins was already observed 15 days before GVHD diagnosis, suggesting the potential early detection of the disease before symptoms appearance. Finally, logistic regression analysis determines a composite biomarker panel comprising fibrinogen, fragment of fibrinogen beta chain, SAA, prothrombin fragments, apolipoprotein A1 and hepcidin that optimally discriminated patients with and without GVHD. The area under the receiver operating characteristic curve distinguishing these 2 groups was 0.95. [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 detailEffect of postremission therapy before reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission
Warlick, Erica; Paulson, Kristjan; Brazauskas, Ruta et al

in Biology of Blood & Marrow Transplantation (2014), 20(2), 202-208

The impact of pre transplant (HCT) cytarabine consolidation therapy on post HCT outcomes has yet to be evaluated after reduced intensity or non-myeloablative conditioning. We analyzed 604 adults with ... [more ▼]

The impact of pre transplant (HCT) cytarabine consolidation therapy on post HCT outcomes has yet to be evaluated after reduced intensity or non-myeloablative conditioning. We analyzed 604 adults with acute myeloid leukemia (AML) in first complete remission (CR1) reported to the CIBMTR who received a RIC or NMA HCT from an HLA-identical sibling, HLA-matched unrelated donor (URD), or umbilical cord blood (UCB) donor in 2000-2010. We compared transplant outcomes based on exposure to cytarabine post remission consolidation. Three year survival rates were 36% (29-43%, 95% CI) in the no consolidation arm and 42% (37-47%, 95% CI) in the cytarabine consolidation arm (p=0.16). Disease free survival was 34% (27-41%, 95% CI) and 41% (35-46%, 95% CI) (p=0.15), respectively. Three year cumulative incidences of relapse were 37% (30-44%, 95% CI) and 38% (33-43%, 95% CI), respectively (p=0.80). Multivariate regression confirmed no effect of consolidation on relapse, DFS and survival. Prior to RIC/NMA HCT, these data suggest pre-HCT consolidation cytarabine does not significantly alter outcomes and support prompt transition to transplant as soon as morphologic CR1 is attained. If HCT is delayed while identifying a donor, our data suggest that consolidation does not increase transplant TRM and is reasonable if required. [less ▲]

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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 detailImatinib improves survival of chronic Graft-versus-host disease by inhibiting TGF-β and PDGF-R in mice
Fransolet, Gilles ULg; Belle, Ludovic ULg; SOMJA, Joan ULg et al

Poster (2014, January)

Introduction: Graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Approximately 15% of the patients develop the sclerodermatous ... [more ▼]

Introduction: Graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Approximately 15% of the patients develop the sclerodermatous cGvHD (scl-cGvHD) form of the disease characterized by multiple organ fibrosis and loss of skin elasticity. A few studies have suggested potential benefits of imatinib, a tyrosine kinase inhibitor, as a treatment of fibrosis in scl-cGVHD due to its ability to inhibit simultaneously the PDGF receptor and TGF-β pathways (via ABL inhibition), which are both involved in fibrosis . Aim: This work investigates the impact of imatinib on fibrosis in the B10.D2 to BALB/cJ scl-cGvHD murine model. Lethally irradiated BALB/cJ recipient mice were injected with 107 bone marrow cells + 7.107 splenocytes from B10.D2 donor mice. Recipients were treated with imatinib 150 mg/kg/day (50 mg/kg in the morning followed by 100 mg/kg in the evening) by oral gavage or the same volume of sterile water. Mice health status was evaluated with a scoring system encompassing five criteria (weight loss, activity, fibrosis, hair loss and mice posture; 0-1-2 points/criteria). Mice were sacrificed at a score of 8/10 according to our local ethical committee. Results: Mice given daily 150 mg/kg imatinib had a better survival than control mice (42 versus 33 days, p = 0,0357). cGvhD scores were suggestively lower in imatinib-treated than in control mice (p ≤ 0,15). Further, histological analyses evidenced reduction in the levels of both PDGF receptor (p = 0,033) and c-Abl (p = 0,185) phosphorylation in imatinib as compared to control mice. Finally, no significant differences were observed in the number or frequency of lymphocyte subsets in the 2 groups of mice. Conclusion: Imatinib slightly decreased fibrosis and significantly improved survival in a severe scl-cGvHD murine model. [less ▲]

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See detailImpact of cotransplantation 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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See detailReduced-Intensity Conditioning With Fludarabine and Busulfan Versus Fludarabine and Melphalan for Patients With Acute Myeloid Leukemia: A Report From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation
Baron, Frédéric ULg; Labopin, Myriam; Peniket, Andy et al

in Cancer (2014)

BACKGROUND: Fludarabine plus busulfan (FB) and fludarabine plus melphalan (FM) are 2 widely used reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (allo ... [more ▼]

BACKGROUND: Fludarabine plus busulfan (FB) and fludarabine plus melphalan (FM) are 2 widely used reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (allo-SCT). METHODS: The current survey compared transplantation outcomes for a cohort of 394 acute myeloid leukemia (AML) patients given bone marrow or peripheral blood stem cells from human leukocyte antigen–identical siblings after FB (n5218) or FM (n5176). Patients given manipulated grafts and those given Tcell–depleting agents (anti-thymocyte globulins or alemtuzumab) were not included. RESULTS: At the time of transplantation, 266 patients (68%) were experiencing their first complete remission (CR), 69 (18%) were experiencing a later CR, and 59 (15%) had advanced disease. The incidences of acute and chronic graft-versus-host disease were similar in the 2 groups of patients. The 2-year relapse incidence (RI), nonrelapse mortality (NRM) rate, leukemia-free survival (LFS) rate, and overall survival (OS) rate were 31%63%, 18%63%, 51%64%, and 54%64%, respectively, for FB patients and 20%63% (P5.007), 20%63% (P5.4), 60%64% (P5.08), and 62%64% (P5.2), respectively, for FM patients. Among FB patients given intravenous busulfan (n581), the 2-year RI, NRM, LFS, and OS rates were 26%65% (P5.43 vs FM patients), 25%66% (P5.18), 49%67% (P5.07), and 54%67% (P5.13), respectively. In multivariate analyses, FM was associated with a lower RI (hazard ratio [HR], 0.5; P5.01) and a trend toward higher NRM (HR, 1.6; P5.1) with similar LFS (HR, 0.8; P5.2) and OS (HR, 0.9; P5.6). CONCLUSIONS: These results suggest that although FM provides better AML control than FB as an RIC regimen for allo-SCT, the 2 regimens provide similar survival. Multicenter randomized studies are needed to confirm these findings. [less ▲]

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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 (2014), (doi:10.1371), 113764

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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