Lymphome du manteau : prise en charge 2011
Bonnet, Christophe ; CAERS, Jo ; DE PRIJCK, Bernard et al
in Revue Médicale Suisse (2011), 7
Le lymphome du manteau (LM) représente 6% des lymphomes non hodgkiniens (LNH). Le diagnostic repose sur l'immunophénotypage et la démonstration de la présence de la location entre les chromosomes 11 et 14 ... [more ▼]
Le lymphome du manteau (LM) représente 6% des lymphomes non hodgkiniens (LNH). Le diagnostic repose sur l'immunophénotypage et la démonstration de la présence de la location entre les chromosomes 11 et 14, avec surexpression de la cycline D1. Le traitement de première ligne du sujet jeune associe trois cures de R-CHOP21 alternées avec trois cures de R-DHAP21, suivies d'une autogreffe conditionnée par irradiation corporelle totale, cyclophosphamide et aracytine. Le sujet de plus de 65 ans peut bénéficier de huit cures de R-CHOP21. L'intérêt du traitement de maintenance est en cours d'évaluation. L'allogreffe de cellules souches hématopoïétiques offre une chance de guérison aux patients en rechute en bon état général. Les traitements ciblés permettront une amélioration du pronostic de cette maladie. [less ▲]Detailed reference viewed: 42 (4 ULg)
Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning.
Baron, Frédéric ; Lechanteur, Chantal ; Willems, Evelyne et al
in Biology of Blood & Marrow Transplantation (2010), 16(6), 838-47
Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD ... [more ▼]
Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. The primary endpoint was safety, defined as a 100-day incidence of nonrelapse mortality (NRM) <35%. One patient had primary graft rejection, whereas the remaining 19 patients had sustained engraftment. The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 35%, whereas 65% of the patients experienced moderate/severe chronic GVHD (cGVHD). One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe. [less ▲]Detailed reference viewed: 49 (25 ULg)
Co-transplantation of mesenchymal stem cells might mitigate acute GvHD without abrogating graftversus- tumour alloreactivity after allogeneic transplantation with non-myeloablative conditioning
Baron, Frédéric ; WILLEMS, Evelyne ; LECHANTEUR, Chantal et al
Background: Results of nonmyeloablative HCT in pts with HLA-mismatched donors have been disappointing due to high incidence of graft rejection and severe acute GVHD. Recent studies have suggested that ... [more ▼]
Background: Results of nonmyeloablative HCT in pts with HLA-mismatched donors have been disappointing due to high incidence of graft rejection and severe acute GVHD. Recent studies have suggested that infusion of mesenchymal stem cells (MSC) the day of HCT might promote engraftment and prevent acute GVHD after myeloablative allogeneic HCT. However, some studies suggested that MSC co-infusion might abrogate graft-versus-host alloreactivity and graft-versus-tumor effects. This prompted us to investigate whether MSC infusion a few hours before HCT could allow nonmyeloablative HCT from HLA-mismatched donors to be performed safely (i.e. with a 100-day incidence of nonrelapse mortality < 35%). Methods: 20 patients with hematological malignancies were given MSC (1-2 x 10E6 cells/kg) from third party donors a few hours before PBSC from HLA-mismatched unrelated donors, after conditioning with 2 Gy TBI and fl udarabine 90 mg/m. Postgrafting immunosuppression included tacrolimus (day -3 to +180; tapered by day +365) and mycophenolate mofetil (tid days 0 to +42). HLA-compatibility was assessed at the HLA-A, -B, -C, -DRBI and DQBI loci: 13 pairs were mismatched for at least one HLA class I antigen (including 4 pairs who were also mismatched for 1 HLA-class II antigens (n=3) or 1 HLA-class I allele (n=1)), 1 pair was mismatched for 2 HLA class II alleles, while 6 pairs were mismatched for a single HLA class I (n=3) or HLA class II (n=3) alleles. Results: Median follow-up for surviving patients was 288 (range, 76-571) days. One patient with secondary AML had primary graft rejection, while the remaining 19 patients had sustained engraftment. Median donor T-cell chimerism levels on days 28, 100, 180 and 365 after HCT were 90%, 98%, 96%, and 98%, respectively. Grade II, III and IV acute GVHD were seen in 5, 2 and 1 patients, respectively, while 7 experienced NIH moderate/severe chronic GVHD. Three of 7 patients with measurable disease at transplantation achieved complete remission on days 41, 104 and 353 after HCT. Two patients died of nonrelapse causes on days 74 and 114 after HCT, while 3 died of disease progression. Projected 1-yr overall and progressionfree survivals were 77% and 61%, respectively. Conclusions: HLA-mismatched nonmyeloablative HCT with MSC co-infusion appeared to be safe, with MSC co-infusion possibly mitigating graft-versus-host alloreactivity without abrogating graft-versus-tumor effects. Survival is encouraging. [less ▲]Detailed reference viewed: 12 (3 ULg)
Non-myeloablative transplantation with CD8-depleted or unmanipulated peripheral blood stem cells: a phase II randomized trial.
Willems, Evelyne ; Baron, Frédéric ; Baudoux, Etienne et al
in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2009), 23(3), 608-10Detailed reference viewed: 70 (34 ULg)
Selective defect of anti-pneumococcal IgG in a patient with persistent polyclonal B cell lymphocytosis.
Hafraoui, Kaoutar ; Moutschen, Michel ; et al
in European Journal of Internal Medicine (2009), 20(3), 62-5
BACKGROUND: Persistent polyclonal B cell lymphocytosis (PPBL) is a rare condition characterized by increased IgM and large excess of B cells with an IgD(+) CD27(+) phenotype. In normal individuals, these ... [more ▼]
BACKGROUND: Persistent polyclonal B cell lymphocytosis (PPBL) is a rare condition characterized by increased IgM and large excess of B cells with an IgD(+) CD27(+) phenotype. In normal individuals, these cells play a central role in the defense against pneumococcal infection. So far, few studies have characterized humoral immune responses in PPBL patients. We therefore measured IgG directed against S. pneumoniae antigens in a 51 yr-old woman with PPBL before and after vaccination with a pneumococcal 23-valent polysaccharide vaccine. METHODS: Antibodies against pneumococcal antigens were measured first with an overall immunoassay using microplates coated with the 23-valent pneumococcal vaccine. A serotype-specific test was also performed according to the WHO consensus protocol. RESULTS: Despite a large number of IgD(+) CD27(+) cells, our patient had low baseline titers of IgG directed against pneumococcal antigens and did not significantly respond to a 23-valent polysaccharide vaccine against S. pneumoniae. On the contrary, she had good titers of IgG directed against tetanus toxoid. CONCLUSION: IgM(+) IgD(+) CD27(+) cells which accumulate in this patient with typical PPBL patient failed to perform IgG isotype switch after a polysaccharide vaccine. The potential mechanisms and relationships with the main features of PPBL are discussed. Further studies on a larger number of similar patients are needed. [less ▲]Detailed reference viewed: 27 (6 ULg)
Cancers secondaires après allogreffe de cellules souches hématopoïétiques
Hafraoui, Kaoutar ; Beguin, Yves ; Baron, Frédéric
in Revue Médicale de Liège (2009), 64(10), 496-499
This article reviews the incidence, risk factors and prevention of secondary malignancies after allogeneic hematopoietic cell transplantation.Detailed reference viewed: 82 (9 ULg)
Recombinant human erythropoietin therapy after allogeneic hematopoietic cell transplantation with a nonmyeloablative conditioning regimen: low donor chimerism predicts for poor response.
; Baron, Frédéric ; Willems, Evelyne et al
in Experimental hematology (2006), 34(7), 841-50
PURPOSE: After allogeneic hematopoietic stem cell transplantation with nonmyeloablative conditioning (NMHCT), many patients experience prolonged anemia and require red blood cell (RBC) transfusions. We ... [more ▼]
PURPOSE: After allogeneic hematopoietic stem cell transplantation with nonmyeloablative conditioning (NMHCT), many patients experience prolonged anemia and require red blood cell (RBC) transfusions. We enrolled 60 consecutive patients undergoing NMHCT in a phase II trial to determine the optimal utilization of recombinant human erythropoietin (rHuEPO) therapy in this setting. PATIENTS AND METHODS: The first 14 NMHCT recipients did not receive rHuEPO (control group). Nineteen patients were scheduled to start rHuEPO on day 0 (EPO group 2) and 27 patients on day 28 after the transplant (EPO group 1). RHuEPO was administered subcutaneously once weekly at a dose of 500 U/kg/wk with the aim of achieving hemoglobin (Hb) levels of 13 g/dL. The 3 groups were well balanced for major characteristics. RESULTS: During the first month (p < 0.0001) as well as days 30 to 100 (p < 0.0001) and days 100 to 180 (p < 0.0001), Hb values were higher in patients receiving rHuEPO compared to those not receiving it. However, transfusion requirements were significantly decreased only in the first month in EPO group 2 (p = 0.0169). T-cell chimerism above 60% on day 42 was the best predictor of Hb response (p < 0.0001) or Hb correction (p = 0.0217), but myeloid chimerism above 90% also predicted for Hb response (p = 0.0069). Hb response was also decreased in patients receiving CD8-depleted grafts and increased in the few patients not receiving TBI, but only in univariate analysis. CONCLUSIONS: Anemia after NMHCT is sensitive to rHuEPO therapy, but less so than after conventional allogeneic HCT. RHuEPO decreases transfusion requirements only in the first 30 days posttransplant. T-cell chimerism below 60% on day 42 impaired Hb response, suggesting possible inhibition of donor erythropoiesis by residual recipient lymphocytes. A prospective randomized trial should be performed with rHuEPO starting on the day of transplantation to assess its clinical benefit in terms of transfusion requirements and quality of life. [less ▲]Detailed reference viewed: 46 (3 ULg)
Infections after allogeneic hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen.
Frere, Pascale ; Baron, Frédéric ; Bonnet, Christophe et al
in Bone Marrow Transplantation (2006), 37(4), 411-8
Hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning (NMSCT) may be associated with a reduced risk of infection compared to standard allogeneic HCT. We retrospectively analyzed ... [more ▼]
Hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning (NMSCT) may be associated with a reduced risk of infection compared to standard allogeneic HCT. We retrospectively analyzed incidence and risk factors of infection in 62 patients undergoing NMSCT with low-dose TBI +/- fludarabine and postgrafting CsA and MMF. The proportion of patients with any infection was 77%, but the majority of infectious events occurred beyond day 30. Donor other than sibling, older age, early disease and male gender were significant risk factors. The incidence of bacteremia was 55% at 1 year and the number of bacteremic episodes was 0.9 per patient (0.08 before day 30). The risk of bacteremia increased with older age and the use of a donor other than an HLA-identical sibling, but not with neutropenia. The incidence of infections other than bacteremia correlated with the use of corticosteroids. The risk of CMV infection increased with high-risk CMV serology, and risk of CMV disease with high-risk CMV serology, older age, first transplantation and a diagnosis of lymphoma. In conclusion, after NMSCT, infections are not frequent in the first 30 days post transplant but careful long-term monitoring is necessary thereafter. [less ▲]Detailed reference viewed: 38 (5 ULg)
Efficacy of recombinant human erythropoietin therapy started one month after autologous peripheral blood stem cell transplantation.
; Baron, Frédéric ; Frere, Pascale et al
in Haematologica (2005), 90(9), 1269-70
On day 30 after autologous peripheral blood stem cell transplantation (PBSCT), 20 patients were randomized to receive either erythropoietin at a dose of 500 U/kg/week s.c. (Epo group) or no treatment ... [more ▼]
On day 30 after autologous peripheral blood stem cell transplantation (PBSCT), 20 patients were randomized to receive either erythropoietin at a dose of 500 U/kg/week s.c. (Epo group) or no treatment (control group). After 3 weeks, hemoglobin (p<0.0001) and serum transferrin receptor (p<0.0001) concentrations were higher in the Epo group. Hb response (+2 g/dL) was achieved in 100% vs 28% (p<0.0001) and Hb correction (> or =13 g/dL) in 70% vs 10% (p=0.0238) of the patients, respectively. This is the first randomized study showing an efficacy of erythropoietin therapy on Hb levels after autologous PBSCT. [less ▲]Detailed reference viewed: 35 (3 ULg)
Comment je traite ... la leucemie myeloide chronique (LMC).
Hafraoui, Kaoutar ; Humblet-Baron, Stéphanie ; Baron, Frédéric et al
in Revue Médicale de Liège (2003), 58(1), 7-12
This review article describes the identification of the tyrosine kinase BCR/ABL as the hallmark of chronic myeloid leukemias (CML) as well as the development of a specific inhibitor of this tyrosine ... [more ▼]
This review article describes the identification of the tyrosine kinase BCR/ABL as the hallmark of chronic myeloid leukemias (CML) as well as the development of a specific inhibitor of this tyrosine kinase, the STI571 (Glivec, imatinib mesylate). The authors discuss the results of a phase I and three phase II trials reporting the efficacy of STI571 as treatment for CML patients and propose two simplified algorithms that may help to guide decision-making for the individual patient. [less ▲]Detailed reference viewed: 183 (6 ULg)