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See detailImmunosuppresseurs dans la prévention de la réaction du greffon contre l'hôte : rapport de la SFGM-TC
Belaiche, S.; Yafour, N.; Balcaen, S. et al

in Pathologie Biologie (2014), 62

In the attempt to harmonize dinical practîces between different French transplantation centers, the Frenell Society of Bane Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual ... [more ▼]

In the attempt to harmonize dinical practîces between different French transplantation centers, the Frenell Society of Bane Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and taak place in September 2013 in Lille. Here we report our recommendatÎons regarding the use of immunosuppressive treatment in the prevention of graft versus hast disease: repOlt by the SFGM-TC. [less ▲]

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See detailUpfront allogeneic stem cell transplantation after reduced-intensity/nonmyeloablative conditioning for patients with myelodysplastic syndrome : a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire
Damaj, Gandhi; Mohty, Mohammad; Robin, Marie et al

in Biology of Blood & Marrow Transplantation (2014), 20

Cytoreduction before allogeneic stem cell transplantation (allo-SCT) for patients with myelodysplastic syndromes remains a debatable issue. After excluding patients who had received preconditioning ... [more ▼]

Cytoreduction before allogeneic stem cell transplantation (allo-SCT) for patients with myelodysplastic syndromes remains a debatable issue. After excluding patients who had received preconditioning induction chemotherapy, we analyzed 128 consecutive patients with myelodysplastic syndrome who received reducedintensity or nonmyeloablative conditioning (RIC/NMA) allo-SCT. Among them, 40 received azacitidine (AZA) before transplant (AZA group) and 88 were transplanted up front (best supportive care [BSC] group). At diagnosis, 55 patients had intermediate 2 or high-risk scores per the International Prognostic Scoring System and 33 had a high cytogenetic risk score. Progression to a more advanced disease before allo-SCT was recorded in 22 patients. Source of stem cells were blood (n ¼ 112) or marrow (n ¼ 16) from sibling (n ¼ 78) or HLA-matched unrelated (n ¼ 50) donors. With a median follow-up of 60 months, 3-year overall survival, relapse-free survival, cumulative incidence of relapse, and nonrelapse mortality were, respectively, 53% versus 53% (P ¼ .69), 37% versus 42% (P ¼ .78), 35% versus 36% (P ¼ .99), and 20% versus 23% (P ¼ .74), for the AZA group and BSC group, respectively. Multivariate analysis confirmed the absence of statistical differences in outcome between the AZA and BSC groups, after adjusting for potential confounders using the propensity score approach. The absence of cytoreduction before RIC/NMA allo-SCT did not seem to alter the outcome. However, our results emphasize the need to perform prospective protocols to delineate the role of debulking strategy and to identify subsets of patients who may benefit from this approach. [less ▲]

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See detailA propos de l'encéphalopathie du nouveau-né
Battisti, Oreste ULg; Beguin, Yves ULg

in Percentile (2014), 19

Editorial sur l'hypoxie périnatale et les cellules souches.

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See detailVaccination guidelines in hematopoietic transplant patients : recommendations from the BHS Transplant Committee
Moors, I.; Schoemans, H.; Callens, S. et al

in Belgian Journal of Hematology (2014), 6

Over the past years, hematopoietic stem cell transplantation (HSCT) is increasingly used as a consolidation therapy in several haematological diseases and solid tumours. In the post-transplantation period ... [more ▼]

Over the past years, hematopoietic stem cell transplantation (HSCT) is increasingly used as a consolidation therapy in several haematological diseases and solid tumours. In the post-transplantation period, the immunity of HSCT recipients is impaired due to toxicity of the pre-HSCT treatment (chemo- and/or radiotherapy) and the conditioning regimen with reset of the immune system and – in case of allogeneic stem cell transplantation – possible graft-versus-host-disease (GVHD) and use of immunosuppressive drugs. This leads to a considerably increased risk of infections, with higher morbidity and mortality in these patients. Therefore, prevention of infections, through antibiotic prophylaxis, life style adjustments, germfree nutrition and revaccination, is of major importance to improve outcomes. In this article we present the Belgian guidelines for vaccination after hematopoietic stem cell transplantation, based on available data in the literature and international guidelines, taking into account the availability of vaccines and - if applicable - their reimbursement in Belgium. We present a general vaccination schedule for post-HSCT patients, a proposition for pre-transplant vaccination and donor vaccination, and an overview of special indications such as travel vaccinations and vaccinations of close contacts and health care workers, with guidelines for titer follow up. [less ▲]

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See detailA European patient record study on diagnosis and treatment of chemotherapy-induced anaemia
Ludwig, H.; Aapro, M.; Bokemeyer, C. et al

in Supportive Care in Cancer (2014), 22

Purpose – Patients with cancer frequently experience chemotherapy‐induced anaemia (CIA) and iron deficiency (ID). Erythropoiesis‐stimulating agents (ESA), iron supplementation and blood transfusions are ... [more ▼]

Purpose – Patients with cancer frequently experience chemotherapy‐induced anaemia (CIA) and iron deficiency (ID). Erythropoiesis‐stimulating agents (ESA), iron supplementation and blood transfusions are available therapies. This study evaluated routine practice in CIA management. Methods – Medical oncologists and/or haematologists from nine European countries (n=375) were surveyed on their last five cancer patients treated for CIA (n=1730). Information was collected on tests performed at diagnosis of anaemia, levels of haemoglobin (Hb), serum ferritin and transferrin saturation (TSAT), and applied anaemia therapies. Results – Diagnostic tests and therapies for CIA varied across Europe. Anaemia and iron status were mainly assessed by Hb (94%) and ferritin (48%) measurements. TSAT was only tested in 14%. At anaemia diagnosis, 74% of patients had Hb ≤10g/dL, including 15% with severe (Hb <8g/dL) anaemia. Low iron levels (ferritin ≤100ng/mL) were detected in 42% of evaluated patients. ESA was the most commonly used treatment (63%) and 30% of ESA‐treated patients also received iron supplementation. Most iron‐treated patients (74%) received an oral iron; intravenous iron was administered to 26%. 52% of patients received transfusions and in 76% of these, transfusions formed part of a regular anaemia treatment regimen. Management practices were similar in 2009 and 2011. Conclusion – Management of anaemia and iron status in patients treated for CIA varies substantially across Europe. Iron status is only assessed in half of the patients. In contrast to clinical evidence, iron treatment is underutilised and mainly based on oral iron supplementation. Implementation of guidelines needs to be increased, particularly the minimisation of blood transfusions. [less ▲]

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See detailThinking out of the box - New approaches to controlling GVHD
Baron, Frédéric ULg; Humblet-Baron, Stéphanie; Ehx, Grégory ULg et al

in Current Hematologic Malignancy Reports (2014), 9

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD ... [more ▼]

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD prophylaxis regimens continue to bebased on the combination of a calcineurin inhibitor with an antimetabolite, while first line treatmentsstill relies on high-dose corticosteroids. Further, no second line treatment has emerged thus far in acute or chronic GVHD patients who failed on corticosteroids. After briefly reviewing current standards of GVHD prevention and treatment, this article will discuss recent approaches that might change GVHD prophylaxis / treatment in the next decades, with a special focus on recently developed immunoregulatory strategies based on infusion of mesenchymal stromal or regulatory T-cells, or on injection of lowdose interleukin-2. [less ▲]

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See detailGalectin expression in the multiple myeloma microenvironment
Muller, Joséphine ULg; CAERS, Jo ULg; Binsfeld, Marilène ULg et al

in Belgian Journal of Hematology (2014)

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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 Belgian Journal of Hematology (2014)

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See detailMultiple myeloma cells instruct myeloid-derived suppressor cells to release pro-angiogenic cytokines
Binsfeld, Marilène ULg; Heusschen, Roy ULg; Lamour, Virginie et al

in Belgian Journal of Hematology (2014)

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See detailHemolytic crisis induced by rasburicase administration revealing G-6-PD deficiency.
SID, Sélim ULg; Dugauquier, D.; DE PRIJCK, Bernard ULg et al

in Belgian Journal of Hematology (2014)

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See detailAntithymocyte globulin before allogeneic stem cell transplantation for progressive myelodysplastic syndrome : a study from the French Society of Bone Marrow Transplantation and Cellular Therapy
Duléry, Rémy; Mohty, Mohamad; Duhamel, Alain et al

in Biology of Blood & Marrow Transplantation (2014), 20

We investigated the impact of rabbit antithymocyte globulins (ATG) on patient outcomes after allogeneic stem cell transplantation (allo-SCT) for progressive myelodysplastic syndrome (MDS). Of the 242 ... [more ▼]

We investigated the impact of rabbit antithymocyte globulins (ATG) on patient outcomes after allogeneic stem cell transplantation (allo-SCT) for progressive myelodysplastic syndrome (MDS). Of the 242 consecutive patients who underwent allo-SCT for progressive MDS between October 1999 and December 2009, 93 received ATG (ATG group) at the median dose of 5 mg/kg, whereas 149 patients did not (no-ATG group). Donors were sibling (n ¼ 153) or HLA-matched unrelated (n ¼ 89). Patients received blood (n ¼ 90) or marrow (n ¼ 152) grafts after either myeloablative (n ¼ 109) or reduced-intensity (n ¼ 133) conditioning. Three-year overall and event-free survival, nonrelapse mortality, relapse, and chronic graft-versus-host disease (GVHD) development were not significantly different between the 2 groups. In contrast, acute grade II to IV GVHD occurred more often in the no-ATG group (55% of the patients) than in the ATG group (27%, P < .0001). Similar results were observed with acute grade III to IV GVHD (28% and 14% in the no-ATG group and ATG group, respectively; P ¼ .009). In multivariate analysis, after adjustment with propensity score, the absence of ATG was the strongest parameter associated with an increased risk of acute grade II to IV GVHD (hazard ratio, 2.13; 95% confidence interval, 1.35 to 3.37; P ¼.001]. ATG had no impact on overall and event-free survival or cumulative incidence of the relapse. In conclusion, the addition of ATG to allo-SCT conditioning did not increase the incidence of relapse of patients with progressive MDS. The incidence of acute GVHD was decreased without compromising outcomes. [less ▲]

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See detailAdequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients wih lower risk myelodysplastic syndromes
Delforge, Michel; Selleslag, Dominik; BEGUIN, Yves ULg et al

in Leukemia Research (2014), 38

Background: Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of ironoverload and associated organ damage, and death. Emerging evidence indicates that iron chelation ther ... [more ▼]

Background: Most patients with myelodysplastic syndromes (MDS) require transfusions at the risk of ironoverload and associated organ damage, and death. Emerging evidence indicates that iron chelation ther-apy (ICT) could reduce mortality and improve survival in transfusion-dependent MDS patients, especiallythose classified as International Prognostic Scoring System (IPSS) Low or Intermediate-1 (Low/Int-1).Methods: Follow-up of a retrospective study. Sample included 127 Low/Int-1 MDS patients from 28 centersin Belgium. Statistical analysis stratified by duration (≥6 versus <6 months) and quality of chelation (adequate versus weak). Results: Crude chelation rate was 63% but 88% among patients with serum ferritin ≥1000 g/L. Of the 80chelated patients, 70% were chelated adequately mainly with deferasirox (26%) or deferasirox followingdeferoxamine (39%). Mortality was 70% among non-chelated, 40% among chelated, 32% among patientschelated ≥6 m, and 30% among patients chelated adequately; with a trend toward reduced cardiacmortality in chelated patients. Overall, median overall survival (OS) was 10.2 years for chelated and 3.1years for non-chelated patients (p < 0.001). For patients chelated ≥6 m or patients classified as adequatelychelated, median OS was 10.5 years. Mortality increased as a function of average monthly transfusionintensity (HR = 1.08, p = 0.04) but was lower in patients receiving adequate chelation or chelation ≥6 m(HR = 0.24, p < 0.001). Conclusion: Six or more months of adequate ICT is associated with markedly better overall survival. Thissuggests a possible survival benefit of ICT in transfusion-dependent patients with lower-risk MDS. [less ▲]

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See detailLe myélome multiple asymptomatique : le paysage thérapeutique change
CAERS, Jo ULg; BEGUIN, Yves ULg

in Oncol. Hematol. (2014), 8

Le myélome multiple est le deuxième cancer hématologique en termes de fréquence avec plus de 700 nouveaux cas chaque année en Belgique. Le myélome asymptomatique, ou smoldering mye/omo, est un stade ... [more ▼]

Le myélome multiple est le deuxième cancer hématologique en termes de fréquence avec plus de 700 nouveaux cas chaque année en Belgique. Le myélome asymptomatique, ou smoldering mye/omo, est un stade précurseur du myélome multiple. En moyenne, les patients présentant un myélome asymptomatique ont un risque annuel de progression en myélome déclaré de 10%. Différents facteul"s ont été combinés dans des modélisations pronostiques: le rapport des chaînes légères, les anomalies radiologiques, la présence d'une gammapathie évolutive et l'infiltration médullaire > 60% ont récemment été identifiés comme facteurs prédictifs d'une progression précoce pour lesquels certains auteurs évoquent la mise en roùte d'un traitement anti-myélome. Cette stratégie thérapeutique précoce a démontré son efficacité dans une étude randomisée qui comparait un traitement par lénalidornide et dexaméthasone avec une approche attentiste chez des patients à risque. [less ▲]

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See detailOutcomes of adults with active or progressive hematological malignancies at time of allogeneic stem cell transplantation : a survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Chevallier, P.; Labopin, M.; Milpied, N. et al

in Bone Marrow Transplantation (2014), 49

Previous data suggested that allo-SCT might be an effective therapy in the setting of chemo-refractory/relapsed diseases because of the potent long-term immune-mediated tumor control. This retrospective ... [more ▼]

Previous data suggested that allo-SCT might be an effective therapy in the setting of chemo-refractory/relapsed diseases because of the potent long-term immune-mediated tumor control. This retrospective study aimed to analyze the outcome of adult patients who received allo-SCT in a chemo-refractory/relapsed status. The series included 840 patients with active or progressive disease at the time of transplant. Median age was 50 years. With a median follow-up of 40 months, 3-year OS, disease-free survival (DFS), and non-relapse mortality rates were 29±2, 23±2, and 30±2%, respectively. At the last follow-up, 252 patients (30%) were still alive (of whom 201 were in CR (24%). In a Cox multivariate analysis, the use of a reduced-intensity conditioning (RIC) before allo-SCT and use of an HLA-identical sibling donor remained independently associated with a better OS (hazard ratio (HR)¼0.82; 95% confidence interval (CI), 0.69–0.98, P¼0.03; and HR¼0.79; 95% CI, 0.66–0.93, P¼0.006, respectively). Also, a diagnosis of myelodysplastic syndrome/myeloproliferative disorder, Hodgkin lymphoma and non-Hodgkin lymphoma compared with acute leukemia had a favorable impact on OS (HR¼0.55; 95% CI, 0.45–0.68, Po0.0001; HR¼0.49; 95% CI, 0.31–0.75, P¼0.001; and HR¼0.47; 95% CI, 0.35–0.63, Po0.0001, respectively). In conclusion, this study suggests that allo-SCT may be of benefit in some subgroups of patients with active or progressive hematological malignancies at the time of allo-SCT. [less ▲]

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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

Acutegraft-versus-hostdisease(aGVHD)remainsalife-threateningcomplicationofhematopoieticstem cell transplantation(HSCT)thereforelimitingitsapplication.TooptimizethemanagementofaGVHDand reduce therapy ... [more ▼]

Acutegraft-versus-hostdisease(aGVHD)remainsalife-threateningcomplicationofhematopoieticstem cell transplantation(HSCT)thereforelimitingitsapplication.TooptimizethemanagementofaGVHDand reduce therapy-relatedtoxicity,earlyspecific markersareneeded.Themainobjectiveofthisstudywas to uncoverdiagnosticbiomarkersbycomparingplasmaproteinprofiles ofpatientsatthetimeofacute GVHDdiagnosiswiththoseofpatientsundergoingHSCTwithoutaGVHD.Additionalanalysisofsamples taken 15daysbeforeaGVHDdiagnosiswasalsoperformedtoevaluatethepotentialofournewly discoveredbiomarkersforearlydiagnosis.Togetcomplementaryinformationfromplasmasamples, we usedthreedifferentproteomicapproaches,namely2D-DIGE,SELDI-TOF-MSand2D-LC-MSE. Weidentified andconfirmed bythemeansofindependenttechniques,thedifferentialexpression of severalproteinsindicatingsignificantly increasedinflammation responseanddisturbanceinthe coagulation cascade.Thevariationoftheseproteinswasalreadyobserved15daysbeforeGVHD diagnosis, suggestingthepotentialearlydetectionofthediseasebeforesymptomsappearance. Finally,logisticregressionanalysisdeterminedacompositebiomarkerpanelcomprising fibrinogen, fragment of fibrinogenbetachain,SAA,prothrombinfragments,apolipoproteinA1andhepcidinthat optimallydiscriminatedpatientswithandwithoutGVHD.Theareaunderthereceiveroperating characteristiccurvedistinguishingthese2groupswas0.95. [less ▲]

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See detailEpidemiological and nonclinical studies investigating effects of iron in carcinogenesis-A critical review
Beguin, Yves ULg; Aapro, M.; Ludwig, H. et al

in Critical Reviews in Oncology/Hematology (2014), 89

The efficacy and tolerability of intravenous (i.v.) iron in managing cancer-related anemia and iron deficiency has been clinically evaluated and reviewed recently. However, long-term data in cancer ... [more ▼]

The efficacy and tolerability of intravenous (i.v.) iron in managing cancer-related anemia and iron deficiency has been clinically evaluated and reviewed recently. However, long-term data in cancer patients are not available; yet, long-term i.v. iron treatment in hemodialysis patients is not associated with increased cancer risk. This review summarizes epidemiological and nonclinical data on the role of iron in carcinogenesis. In humans, epidemiological data suggest correlations between certain cancers and increased iron exposure or iron overload. Nonclinical models that investigated whether iron can enhance carcinogenesis provide only limited evidence relevant for cancer patients since they were typically based on high iron doses as well as injection routes and iron formulations which are not used in the clinical setting. Nevertheless, in the absence of long-term outcome data from prospectively defined trials in i.v. iron-treated cancer patients, iron supplementation should be limited to periods of concomitant anti-tumor treatment. [less ▲]

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See detailINFUSION OF THIRD-PARTY MESENCHYMAL STEM CELLS (MSC) AFTER KIDNEY AND LIVER TRANSPLANTATION: A PHASE I-II, OPEN-LABEL, CLINICAL STUDY (EudraCT 2011-001822-81 & NCT01429038)
DETRY, Olivier ULg; DELBOUILLE, Marie-Hélène ULg; LECHANTEUR, Chantal ULg et al

Poster (2013, May 30)

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC ... [more ▼]

MSC cells have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aims to be the first evaluation of the safety and tolerability of third party MSC infusion after cadaveric kidney and liver transplantation in a prospective phase I-II study, taking advantage of our centre expertise and experience in MSC use in graft-versus-host disease (GVHD) after bone marrow transplantation and using an already functioning GMP-compliant laboratory producing clinical-grade MSC. Secondary end-points will help to evaluate the immunosuppressive potential of MSC after organ transplantation, and the opportunity to develop larger randomised, controlled, phase III trials. After successful transplantation, 10 liver and 10 kidney transplant recipients under standard immunosuppression (tacrolimus, MMF, steroids) will receive an intravenous infusion of 1.5-3x106/kg of third-party MSC on post-operative day 3±2. These patients will be prospectively compared to 10 liver and 10 kidney recipients who meet the inclusion criteria but deny MSC infusion. Safety will be assessed by recording side effects, including opportunistic infections and cancers. Immunosuppressive potential will be evaluated by rejection episode rates, by graft/patient survivals, by immunohistology of 3-months kidney and 6-month liver graft biopsies and by in vitro evaluation of the immunity profile of the recipients. In a second step, reduction (kidney) and progressive weaning (liver) of immunosuppression will be attempted in recipients who received MSC. This ongoing study is supported by research grants from the CHU of Liège, University of Liège, and by the Senior Clinical Research Grant from ESOT. The first patients were included and treated in early 2012, and final results expected in late 2013. [less ▲]

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See detailImpact of bone marrow-derived mesenchymal stromal cells on experimental xenogeneic graft-versus-host disease
Bruck, France; Belle, Ludovic ULg; LECHANTEUR, Chantal ULg et al

in Cytotherapy (2013), 15(3), 267-279

Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous ... [more ▼]

Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous studies have suggested that mesenchymal stromal cells (MSCs) could exert potent immunosuppressive effects. Methods. The ability of human bone marrow derived MSCs to prevent xenogeneic GVHD in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice and in NOD/SCID/interleukin-2Rg(null) (NSG) mice transplanted with human peripheral blood mononuclear cells (PBMCs) was assessed. Results. Injection of 200 106 human PBMCs intraperitoneally (IP) into sub-lethally (3.0 Gy) irradiated NOD/SCID mice also given anti-asialo GM1 antibodies IP 1 day prior and 8 days after transplantation induced lethal xenogeneic GVHD in all tested mice. Co-injection of 2 106 MSCs IP on day 0 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Similarly, injection of 30 106 human PBMCs IP into sub-lethally (2.5 Gy) irradiated NSG mice induced a lethal xenogeneic GVHD in all tested mice. Injection of 3 106 MSCs IP on days 0, 7, 14 and 21 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Conclusions. Injection of MSCs did not prevent xenogeneic GVHD in these two humanized mice models. [less ▲]

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