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)
Evidence for neo-generation of T cells by the thymus after non-myeloablative conditioning.
Castermans, Emilie ; Baron, Frédéric ; Willems, Evelyne et al
in Haematologica (2008), 93(2), 240-7
BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning ... [more ▼]
BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning. DESIGN AND METHODS: Fifty patients were randomized to receive either CD8-depleted (n=22) or non-manipulated (n=28) peripheral blood stem cells. The median patients age was 57 (range 36-69) years. The conditioning regimen consisted of 2 Gy total body irradiation with or without added fludarabine. Twenty patients received grafts from related donors, 14 from 10/10 HLA-allele matched unrelated donors, and 16 from HLA-mismatched unrelated donors. Graft-versus-host disease pro-phylaxis consisted of mycophenolate mofetil and cyclosporine. Immune recovery during the first year after hematopoietic cell transplantation was assessed by flow cytometry phenotyping, analyses of the diversity of the TCRBV repertoire, and quantification of signal-joint T-cell receptor excision circles (sjTREC). RESULTS: CD8-depletion of the graft reduced the recovery of CD8(+) T-cell counts in the first 6 months following transplantation (p<0.0001) but had no significant impact on the restoration of other T-cell subsets. Both sjTREC concentration and CD3(+) T-cell counts increased significantly between day 100 and 365 (p=0.010 and p=0.0488, respectively) demonstrating neo-production of T cells by the thymus. Factors associated with high sjTREC concentration 1 year after transplantation included an HLA-matched unrelated donor (p=0.029), a high content of T cells in the graft (p=0.002), and the absence of chronic graft-versus-host disease (p<0.0001). CONCLUSIONS: Our data suggest that while immune recovery is mainly driven by peripheral expansion of the graft-contained mature T cells during the first months after non-myeloablative transplantation, T-cell neo-generation by the thymus plays an important role in long term immune reconstitution in transplanted patients. [less ▲]Detailed reference viewed: 155 (85 ULg)
Downregulation of CD94/NKG2A inhibitory receptors on CD8+ T cells in HIV infection is more pronounced in subjects with detected viral load than in their aviraemic counterparts.
Zeddou, Mustapha ; Rahmouni, Souad ; Vandamme, Arnaud et al
in Retrovirology (2007), 4
The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small ... [more ▼]
The CD94/NKG2A heterodimer is a natural killer receptor (NKR), which inhibits cell-mediated cytotoxicity upon interaction with MHC class I gene products. It is expressed by NK cells and by a small fraction of activated CD8+ T lymphocytes. Abnormal upregulation of the CD94/NKG2A inhibitory NKR on cytotoxic T cells (CTLs) could be responsible for a failure of immunosurveillance in cancer or HIV infection. In this study, CD94/NKG2A receptor expression on CD8+ T lymphocytes and NK cells was assessed in 46 HIV-1-infected patients (24 viraemic, 22 aviraemic) and 10 healthy volunteers. The percentage of CD8+ T lymphocytes expressing the CD94/NKG2A inhibitory heterodimer was very significantly decreased in HIV-1-infected patients in comparison with non-infected controls. Within the HIV infected patients, the proportion of CD8+ T lymphocytes and NK cells expressing CD94/NKG2A was higher in subjects with undetectable viral loads in comparison with their viraemic counterparts. No significant difference was detected in the proportion of CD8+ T lymphocytes expressing the activatory CD94/NKG2C heterodimer between the HIV-1 infected patients and the healthy donors, nor between the vireamic and avireamic HIV-1 infected patients. In conclusion, chronic stimulation with HIV antigens in viraemic patients leads to a decreased rather than increased CD94/NKG2A expression on CD8+ T lymphocytes and NK cells. [less ▲]Detailed reference viewed: 154 (72 ULg)
Immune reconstitution after CD8-depleted or unmanipulated peripheral blood stem cells transplantation with nonmyeloablative conditioning
Castermans, Emilie ; Baron, Frédéric ; Willems, Evelyne et al
in Acta Clinica Belgica (2006), 61(2), 113Detailed reference viewed: 24 (9 ULg)
Low incidence of acute graft-versus-host disease after non-myeloablative stem cell transplantation with CD8-depleted peripheral blood stem cells: an update.
Baron, Frédéric ; Frere, Pascale ; Baudoux, Etienne et al
in Haematologica (2003), 88(7), 835-7Detailed reference viewed: 18 (3 ULg)
Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC.
Baron, Frédéric ; Baudoux, Etienne ; Frere, Pascale et al
in Bone Marrow Transplantation (2003), 32(8), 829-34
We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen ... [more ▼]
We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report. [less ▲]Detailed reference viewed: 46 (3 ULg)
Rhinitis/Bronchopneumonia syndrome in Irish Wolfhounds.
Clercx, Cécile ; ; Peeters, Dominique et al
in Journal of Veterinary Internal Medicine (2003), 17(6), 843-9
This study describes the clinical, immunologic, genetic, and pathologic features of Irish Wolfhounds with rhinitis/bronchopneumonia syndrome. The dogs examined were from Belgium, The Netherlands, UK ... [more ▼]
This study describes the clinical, immunologic, genetic, and pathologic features of Irish Wolfhounds with rhinitis/bronchopneumonia syndrome. The dogs examined were from Belgium, The Netherlands, UK, Canada, Germany, and Switzerland. Signs included transient to persistent mucoid or mucopurulent rhinorrhea, cough, and respiratory dyspnea. Radiographic, rhinoscopic, and bronchoscopic findings were variable. Analysis of ciliary ultrastructure was performed in 5 affected dogs, but no characteristic primary ciliary defects (primary ciliary dyskinesia) were detected. Serum and bronchoalveolar lavage fluid (BALF) concentrations of IgA, IgG, and IgM were determined in some affected dogs and clinically normal Irish Wolfhounds. Serum IgA concentration was below the reference range in 5 of 8 affected dogs tested, whereas BALF IgA concentration was above the normal range in 2 affected adult dogs. The CD4 to CD8 lymphocyte subset ratio (CD4:CD8) in peripheral blood was tested in 3 affected dogs and was within the normal range. BALF CD4:CD8 was tested in 1 affected dog and was higher than the normal range. Decreased neutrophil phagocytosis was observed in 1 of the 4 dogs tested. Analysis of pedigrees of the Belgian, Canadian, German, and Swiss dogs revealed common ancestry, suggesting a heritable syndrome. [less ▲]Detailed reference viewed: 45 (2 ULg)
T-cell reconstitution after unmanipulated, CD8-depleted or CD34-selected nonmyeloablative peripheral blood stem-cell transplantation.
Baron, Frédéric ; Schaaf-Lafontaine, Nicole ; Humblet-Baron, Stéphanie et al
in Transplantation (2003), 76(12), 1705-13
BACKGROUND: We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem ... [more ▼]
BACKGROUND: We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem-cell transplantation (NMSCT). In this study, we analyze the effect of CD8 depletion or CD34 selection of the graft on early T-cell reconstitution. METHODS: Nonmyeloablative conditioning regimen consisted in 2 Gy total-body irradiation (TBI) alone, 2 Gy TBI and fludarabine, or cyclophosphamide and fludarabine. Patients 1 to 18 received unmanipulated PBSC, patients 19 to 29 CD8-depleted PBSC, and patients 30 to 35 CD34-selected PBSC. RESULTS: T-cell counts, and particularly CD4+ and CD4CD45RA+ counts, remained low the first 6 months after nonmyeloablative stem-cell transplantation (NMSCT) in all patients. CD34 selection (P<0.0001) but not CD8 depletion of PBSC significantly decreased T-cell chimerism. Donor T-cell count was similar in unmanipulated compared with CD8-depleted PBSC recipients but was significantly lower in CD34-selected PBSC recipients (P=0.0012). T cells of recipient origin remained stable over time in unmanipulated and CD8-depleted PBSC patients but expanded in some CD34-selected PBSC recipients between day 28 and 100 after transplant. Moreover, whereas CD8 depletion only decreased CD8+ counts (P<0.047), CD34 selection reduced CD3+(P<0.001), CD8+(P<0.016), CD4+ (P<0.001), and CD4+CD45RA+ (P<0.001) cell counts. T-cell repertoire was restricted in all patients on day 100 after hematopoietic stem-cell transplantation but was even more limited after CD34 selection (P=0.002). CONCLUSIONS: Despite of the persistence of a significant number of T cells of recipient origin, T-cell counts were low the first 6 months after NMSCT. Moreover, contrary with CD8 depletion of the graft that only affects CD8+ lymphocyte counts, CD34 selection dramatically decreased both CD8 and CD4 counts. [less ▲]Detailed reference viewed: 61 (8 ULg)
Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation.
Baron, Frédéric ; ; Schaaf-Lafontaine, Nicole et al
in Haematologica (2002), 87(1), 78-88
BACKGROUND AND OBJECTIVES: To maximize graft-versus-leukemia (GVL) effects while minimizing the risk of graft-versus-host disease (GVHD), we undertook a study of allogeneic CD34-selected peripheral blood ... [more ▼]
BACKGROUND AND OBJECTIVES: To maximize graft-versus-leukemia (GVL) effects while minimizing the risk of graft-versus-host disease (GVHD), we undertook a study of allogeneic CD34-selected peripheral blood stem cell (PBSC) transplantation followed by CD8-depleted donor lymphocyte infusion (DLI). DESIGN AND METHODS: Twenty-four patients with advanced hematologic malignancies were included. PBSC were collected in matched (N=16) or one-mismatch (N=8) related donors and CD34-selected. On day 60, donors donated lymphocytes that were CD8-depleted and separated into 3 aliquots containing 2 x 10(6), 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 1-13) or into 2 aliquots containing 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 14-24). The 1st aliquot was infused on day 60 and the other 1 (2) cryopreserved and infused on days 100 (and 140). RESULTS: An average of 100%, 100% and 84% of the scheduled dose could be administered in DLI 1, 2 and 3, respectively. Although the study group was at very high risk of GVHD, the actuarial incidence of grade II-IV acute GVHD was 28% (13% for HLA-identical siblings) with only 1 patient developing grade III-IV GVHD (after DLI). The actuarial 2-year probability of extensive chronic GVHD was similarly low (13% for all patients and 0% for HLA-identical siblings). Individual cases as well as a 30% relapse rate (0% for standard-risk patients versus 55% for high-risk patients) indicated preservation of the GVL effect. INTERPRETATION AND CONCLUSIONS: We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to prove that it preserves the GVL effect fully. [less ▲]Detailed reference viewed: 20 (3 ULg)
Nonmyeloablative stem cell transplantation with CD8-depleted or CD34-selected peripheral blood stem cells.
Baron, Frédéric ; Baudoux, Etienne ; Frere, Pascale et al
in Journal of Hematotherapy & Stem Cell Research (2002), 11(2), 301-14
To decrease the incidence of graft-versus-host disease (GVHD) observed after nonmyeloablative stem cell transplantation (NMSCT), we studied the feasibility of CD8-depleted or CD34-selected NMSCT followed ... [more ▼]
To decrease the incidence of graft-versus-host disease (GVHD) observed after nonmyeloablative stem cell transplantation (NMSCT), we studied the feasibility of CD8-depleted or CD34-selected NMSCT followed by CD8-depleted preemptive donor lymphocyte infusion (DLI) given in incremental doses on days 40 and 80. Fourteen patients with high-risk malignancies and an HLA-identical sibling (n = 8) or alternative donor (n = 6) but ineligible for a conventional transplant were included. Nonmyeloablative conditioning regimen consisted in 2 Gy total body irradiation (TBI) alone, 2 Gy TBI and fludarabine (previously untreated patients) or cyclophosphamide and fludarabine (patients who had previously received > or =12 Gy TBI). Patients 1-4 (controls) received unmanipulated peripheral blood stem cells (PBSC) and DLI and patients 5-14 CD8-depleted or CD34-selected PBSC followed by CD8-depleted DLI. Post-transplant immunosuppression was carried out with cyclosporine A (CsA) and mycophenolate mofetil (MMF). Initial engraftment was seen in all patients, but 1 patient (7%) later rejected her graft. The actuarial 180-day incidence of grades II-IV acute GVHD was 75% for patients 1-4 versus 0% for patients 5-14 (p = 0.0019). Five of 14 patients were in complete remission (CR) 180 days after the transplant and 6/14 had partial responses. The 1-year survival rate was 69%, and nonrelapse and relapse mortality rates were 16 and 18%, respectively. We conclude that CD8-depleted or CD34-selected NMSCT followed by CD8-depleted DLI is feasible and considerably decreases the incidence of acute GVHD while preserving engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report. [less ▲]Detailed reference viewed: 28 (6 ULg)
Le cas clinique du mois. Hepatite cholestatique apres administration de piperacilline.
; Martin, Pierre ; Schaaf-Lafontaine, Nicole
in Revue Médicale de Liège (2002), 57(9), 571-4
We describe a patient suffering from infection of the upper respiratory tract, who was treated with a dose of 4 x 4 g of piperacillin over 10 days. Two days after the end of the treatment, she developed ... [more ▼]
We describe a patient suffering from infection of the upper respiratory tract, who was treated with a dose of 4 x 4 g of piperacillin over 10 days. Two days after the end of the treatment, she developed jaundice and had elevated alkaline phosphatase, gammaglutamyltransferase and transaminases. After exclusion of viral hepatitis, a vascular problem, and gall stone disease, the possibility of piperacillin-induced hepatitis was discussed. Lymphocyte transformation test for piperacillin was positive, suggesting an immunological mechanism for the observed hepatopathy. The patient was discharged a few days after in good clinical condition and with reduced liver values. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 2 months. We conclude that short-term therapy with piperacillin can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Positive lymphocyte transformation is compatible with an immunological mechanism. [less ▲]Detailed reference viewed: 97 (3 ULg)
Administration of erythopoietin and granulocyte colony-stimulating factor in donor/recipient pairs to collect peripheral blood progenitor cells (PBPC) and red blood cell units for use in the recipient after allogeneic PBPC transplantation.
Sautois, Brieuc ; Baudoux, Etienne ; Salmon, Jean et al
in Haematologica (2001), 86(11), 1209-18
BACKGROUND AND OBJECTIVES: It may be useful to reduce the exposure of transplant recipients to homologous blood. This may be achieved by procuring donor-derived red blood cell (RBC) units, collecting more ... [more ▼]
BACKGROUND AND OBJECTIVES: It may be useful to reduce the exposure of transplant recipients to homologous blood. This may be achieved by procuring donor-derived red blood cell (RBC) units, collecting more peripheral blood progenitor cells (PBPC) with a combination of granulocyte colony-stimulating factor (G-CSF) + recombinant human erythropoietin (rHuEpo) and by administering rHuEpo post-transplantation. DESIGN AND METHODS: Eight ABO-compatible donors were treated with rHuEpo and intravenous iron to collect 12 RBC units for use in their recipients. PBPC were collected after mobilization with rHuEpo and G-CSF in the same donors. The recipients received G-CSF and rHuEpo post-transplantation. A control group of 10 donor/recipient pairs received G-CSF alone for PBPC mobilization and after the transplantation. RESULTS: Eighty-six out of 91 planned RBC units were collected in the donors without significant decrease in hematocrit because of a 4-fold increase in RBC production despite functional iron deficiency. After 2 leukaphereses, the cumulative yields of NC and CFU-GM were lower in the study group while those of BFU-E, CFU-Mix and CD34+ cells were similar. However, erythroid recovery was significantly accelerated in the study group. INTERPRETATION AND CONCLUSIONS: Collection of 12 RBC units within 6 weeks is feasible with rHuEpo and intravenous iron; this strategy allows a dramatic reduction in recipient exposure to homologous blood; rHuEpo has no synergistic effect with G-CSF for mobilization of PBPC in normal donors and may even be deleterious; and rHuEpo in the recipient may enhance erythroid engraftment. [less ▲]Detailed reference viewed: 35 (1 ULg)
Successful mobilization of peripheral blood HPCs with G-CSF alone in patients failing to achieve sufficient numbers of CD34+ cells and/or CFU-GM with chemotherapy and G-CSF.
; Sautois, Brieuc ; Baudoux, Etienne et al
in Transfusion (2000), 40(3), 339-47
BACKGROUND: Mobilization with chemotherapy and G-CSF may result in poor peripheral blood HPC collection, yielding <2 x 10(6) CD34+ cells per kg or <10 x 10(4) CFU-GM per kg in leukapheresis procedures ... [more ▼]
BACKGROUND: Mobilization with chemotherapy and G-CSF may result in poor peripheral blood HPC collection, yielding <2 x 10(6) CD34+ cells per kg or <10 x 10(4) CFU-GM per kg in leukapheresis procedures. The best mobilization strategy for oncology patients remains unclear. STUDY DESIGN AND METHODS: In 27 patients who met either the CD34 (n = 3) or CFU-GM (n = 2) criteria or both (n = 22), the results obtained with two successive strategies-that is, chemotherapy and G-CSF at 10 microg per kg (Group 1, n = 7) and G-CSF at 10 microg per kg alone (Group 2, n = 20) used for a second mobilization course-were retrospectively analyzed. The patients had non-Hodgkin's lymphoma (5), Hodgkin's disease (3), multiple myeloma (5), chronic myeloid leukemia (1), acute myeloid leukemia (1), breast cancer (6), or other solid tumors (6). Previous therapy consisted of 10 (1-31) cycles of chemotherapy with additional chlorambucil (n = 3), interferon (n = 3), and radiotherapy (n = 7). RESULTS: The second collection was undertaken a median of 35 days after the first one. In Group 1, the results of the two mobilizations were identical. In Group 2, the number of CD34+ cells per kg per apheresis (0.17 [0.02-0.45] vs. 0.44 [0.11-0.45], p = 0. 00002), as well as the number of CFU-GM (0.88 [0.00-13.37] vs. 4.19 [0.96-21.61], p = 0.00003), BFU-E (0.83 [0.00-12.72] vs. 8.81 [1. 38-32.51], p = 0.00001), and CFU-MIX (0.10 [0.00-1.70] vs. 0.56 [0. 00-2.64], p = 0.001134) were significantly higher in the second peripheral blood HPC collection. However, yields per apheresis during the second collection did not significantly differ in the two groups. Six patients in Group 1 and 18 in Group 2 underwent transplantation, and all but one achieved engraftment, with a median of 15 versus 12 days to 1,000 neutrophils (NS), 22 versus 16 days to 1 percent reticulocytes (NS), and 26 versus 26 days to 20,000 platelets (NS), respectively. However, platelet engraftment was particularly delayed in many patients. CONCLUSION: G-CSF at 10 microg per kg alone may constitute a valid alternative to chemotherapy and G-CSF to obtain adequate numbers of peripheral blood HPCs in patients who previously failed to achieve mobilization with chemotherapy and G-CSF. This strategy should be tested in prospective randomized trials. [less ▲]Detailed reference viewed: 61 (7 ULg)
Translocation (2;3)(P21;Q26) as the Sole Anomaly in a Case of Primary Myelofibrosis
Herens, Christian ; ; Tassin, Françoise et al
in Cancer Genetics & Cytogenetics (1999), 110(1), 62-4
Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with ... [more ▼]
Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with the 11 other previously published myeloid-associated t(2p;3q) cases confirms that this nonrandom translocation involves a pluripotent stem cell and is associated with a poor prognosis. [less ▲]Detailed reference viewed: 22 (3 ULg)
Peripheral blood progenitor cell collections in cancer patients: analysis of factors affecting the yields.
Sautois, Brieuc ; ; Baudoux, Etienne et al
in Haematologica (1999), 84(4), 342-9
BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify ... [more ▼]
BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify parameters that could predict the yield of PBPC after mobilization with chemotherapy (CT) with or without granulocyte colony-stimulating factor (G-CSF) in cancer patients. DESIGN AND METHODS: One hundred and fifty patients underwent 627 PBPC collections during the recovery phase following CT with (n = 469) or without (n = 142) G-CSF. Hemogram, CFC-assays and CD34+ cell count were performed on peripheral blood and leukaphereses products. After log transformation of the data, differences between groups were assessed with the unpaired t-test or one-way analysis of variance. RESULTS: Seventeen and two patients required 2 and 3 mobilization cycles respectively to reach our target of 15x10(4) CFU-GM/kg. In patients with lymphoma but not in those with leukemia, the yields of both CFU-GM and CD34+ cells/kg were dramatically increased when G-CSF was added to CT for mobilization. In collections primed with CT and G-CSF, better yields were obtained in patients with breast cancer or small-cell lung carcinoma (SCLC) as opposed to other solid tumors and leukemia. Among potential predictive factors of CT- and G-CSF-primed harvests, we found that the CD34+ cell count in peripheral blood (PB) was strongly correlated with both the CFU-GM and CD34+ cell yields. Except in leukemia patients, more than 1x10(6) CD34+ cells/kg were harvested when the CD34+ cell count in blood was above 20x10(6)/L. Similarly, better results were obtained in collections performed when the percentage of myeloid progenitors in blood on the day of apheresis was above 5 % or when the leukocyte count in blood was above 5x10(9)/L. INTERPRETATION AND CONCLUSIONS: A diagnosis of breast cancer or SCLC, a leukocyte count in PB of more than 5x10(9)/L, more than 5% myeloid progenitors or more than 20x10(6) CD34+ cells/L in PB were associated with higher yields of PBPC in collections mobilized with CT+G-CSF. [less ▲]Detailed reference viewed: 51 (8 ULg)
Les syndromes myélodysplasiques: syndromes préleucémiques
Tassin, Françoise ; ; Schaaf-Lafontaine, Nicole et al
in Revue Médicale de Liège (1998), 53(6), 357-62
The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by peripheral blood cytopenias with a hypercellular bone marrow exhibiting dyspoiesis. The predominant in elderly ... [more ▼]
The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by peripheral blood cytopenias with a hypercellular bone marrow exhibiting dyspoiesis. The predominant in elderly patients are associated with a high risk of progression to acute myelogenous leukemia. The etiology of MDS is unknown in most cases. About 10% of MDSs are secondary. MDS are classified by the French American British (FAB) classification into five subgroups. The incidence of the disorders is difficult to estimate but it seems to be increasing. Clonal cytogenetic aberrations are found in 30 to 50% of de novo MDS. The only currative treatment for MDS is allogeneic bone marrow transplantation. [less ▲]Detailed reference viewed: 76 (6 ULg)
Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.
Louis, Edouard ; ; Piron, Anne et al
in Clinical & Experimental Immunology (1998), 113(3), 401-406
TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some ... [more ▼]
TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals. [less ▲]Detailed reference viewed: 48 (11 ULg)
Further Characterization of Cytotoxic T Cells Generated by Short-Term Culture of Human Peripheral Blood Lymphocytes with Interleukin-2 and Anti-Cd3 Mab
Jacobs, Nathalie ; Greimers, Roland ; et al
in Cancer Immunology, Immunotherapy (1996), 42(6), 369-75
In this study we have specifically investigated the participation of T cells in the cytotoxic activity of peripheral blood lymphocytes (PBL) activated by interleukin-2 (IL-2, 50 U/ml) alone or in ... [more ▼]
In this study we have specifically investigated the participation of T cells in the cytotoxic activity of peripheral blood lymphocytes (PBL) activated by interleukin-2 (IL-2, 50 U/ml) alone or in combination with an anti-CD3 mAb (BMA030, 10 ng/ml, IgG2a). Purified CD3+ T cells, incubated in the presence of the anti-CD3 mAb for 4 days, mediated a cytotoxic activity against HL60 and U937 tumor cell lines. Several findings suggested the involvement of a redirected-cytotoxicity phenomenon, since the lytic process was restricted to target cell lines bearing the high-affinity Fc gamma receptor (Fc gamma RI) and T lymphocytes stimulated by IL-2 alone did not lyse these cell lines. Furthermore, anti-CD3 mAb F(ab')2, anti-CD3 IgG1 (UCHT1), phytohemagglutinin or staphylococcal enterotoxin A did not induce a similar cytotoxic activity in T lymphocytes. The cytotoxic process occurred in the presence of a very low level of anti-CD3 antibodies (in the nanomolar range). The cytotoxic activity of T cells stimulated by IL-2 or by IL-2 + BMA030, against OVCAR-3 cells (MOv18+ ovarian tumor cell line), was also compared in the presence of a bispecific antibody OC/TR, anti-CD3 x MOv18). The stimulation by IL-2 + BMA030 induced approximately a twofold higher cytotoxic activity than IL-2-activated T cells. This could be related to the state of activation of effector cells stimulated by IL-2 + BMA030, since the phenotypic analysis showed an increased proportion of T cells expressing several activation/differentiation markers (CD25, HLA-DR, CD45R0, adhesion molecules). These findings could be applied to the design of therapeutic protocols using anti-CD3 x antitumoral bispecific antibodies. [less ▲]Detailed reference viewed: 26 (4 ULg)
Presence of gd TcR+ Tumor Infiltrating Lymphocytes (TILs) in One Case of Pediatric Osteogenic Sarcoma
Moutschen, Michel ; Jacobs, Nathalie ; Hoyoux, Claire et al
in International Journal of Pediatric Hematology/Oncology (1994)
To characterize ab and gd TcR expression in cultured TILs from a metastatic osteogenic sar- coma.Patient and methods: TILs were isolated from a lung metastasis of an osteogenic sarcoma in a 16- year-old ... [more ▼]
To characterize ab and gd TcR expression in cultured TILs from a metastatic osteogenic sar- coma.Patient and methods: TILs were isolated from a lung metastasis of an osteogenic sarcoma in a 16- year-old female patient. Culture conditions were IL- 2 and anti-CD3 MoAb+IL-2. TcR expression and surface phenotype were studied by flow cytometry. 4h-chromium release assays were used to assess cytotoxicity. Results:IL-2-expanded tumor infiltrating T-lym- phocytes contained 50% gd TcR+ cells whereas gd TcR+ cells represented 20% of T-cells in cultures expanded with anti-CD3 MoAb+IL-2. The phenotype of gd TcR+ cells was CD3+, CD16-, CD4-, CD8-, and CD29+. AnH-CD3 MoAb + IL-2-expanded TILs mediated a significant lysis of thé autologous tumor and of an allogeneic lymphoma and displayed a higher activity against thé NK-sensitive target K562. In cold target experiments, unlabeled autol- ogous tumor cells blocked thé lysis of K562, indicating that MHC-unrestricted effectors were involved in thé lysis of both targets. Conclusions: This report demonstrates thé ex- pansion of large numbers of gd TcR+ T-cells after short-term culture of TILs from a metastatic os- teosarcoma. Further studies are needed to déter- mine thé role of gd TcR+ cells in host immune responses directed against this tumor. [less ▲]Detailed reference viewed: 17 (3 ULg)
Efficient Immunoselection of Cytolytic Effectors with a Magnetic Cell Sorter
Jacobs, Nathalie ; ; Boniver, Jacques et al
in Research in Immunology (1993), 144(2), 141-50
This paper describes a rapid and efficient method for the sorting of in vitro activated cytolytic effectors cells. For cytotoxic assays, a large number of cells with conserved function must be rapidly ... [more ▼]
This paper describes a rapid and efficient method for the sorting of in vitro activated cytolytic effectors cells. For cytotoxic assays, a large number of cells with conserved function must be rapidly obtained. Immunomagnetic sorting was chosen because it is faster than flow cytometry sorting. The MACS system requires the use of paramagnetic beads of small diameter (100-150 nm), reputed to interfere minimally with cell function. In order to generate the cytolytic effectors, peripheral blood lymphocytes were cultivated in the presence of interleukin-2 (50 U/ml) and anti-CD3 monoclonal antibody (BMA030, 100 ng/ml) for 4 days. Cell separation was based on the membrane expression of the CD3 complex. The purity obtained for positive (CD3+) cell sorting with the MACS was higher than 95%. The purity of negative (CD3-) cell fraction was more variable, but further purification by flow cytometry rapidly yielded purity higher than 95%. Cytotoxic assays were performed against four target cell lines (K562, Daudi, HL60 and U937) and proliferation assays showed that both negatively and positively selected populations had conserved their function acquired during culture in the presence of anti-CD3 mAb and IL2. [less ▲]Detailed reference viewed: 28 (11 ULg)