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F Lefrère,
S Zohar,
D Ghez,
R Delarue,
F Audat,
F Suarez,
O Hermine,
G Damaj,
N Maillard,
J A Ribeil,
M Azagury,
R Misbahi,
K Jondeau,
M Cavazzana-Calvo, L Dal Cortivo,
B Varet
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ABSTRACT: A study was conducted to compare the efficiency and toxicity of two peripheral blood stem cell (PBSC) mobilization procedures for newly diagnosed patients with multiple myeloma. Patients from group 1 (n=51) were treated by high-dose cyclophosphamide (HD-CY) plus G-CSF (5 microg/kg/day), and the second group (n=31) by VAD regimen plus G-CSF administration (10 microg/kg/day). Successful mobilization, defined by a minimal count of 2.5 x 10(6) CD34(+) cells/kg collected, was achieved in 96 and 90% of patients in groups 1 and 2, respectively (P=0.15). The mean peripheral blood CD34(+) cells concentration and the mean CD34(+) cells/kg collected were higher in group 2 than in the group 1 (P=0.05). The mean number of leukaphereses necessary to collect a count of 2.5 x 10(6) CD34(+) cells/kg was reduced in group 2 compared to group 1. Adverse events, blood products consumption and time spent in the hospital were significantly greater after HD-CY. In conclusion, VAD plus a G-CSF dose of 10 microg/kg administration seems preferential to HD-CY plus a G-CSF dose of 5 microg/kg for PBSC collection because of equivalent or better efficiency in stem cell mobilization, strong favorable toxicity profile and reduced cost.
Bone Marrow Transplantation 05/2006; 37(8):725-9. · 3.75 Impact Factor
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ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematologic malignancies and inherited disorders of the hematopoietic system. Ex vivo T-cell depletion (TCD) of the graft and post-transplantation immunosuppression efficiently prevents the development of GvHD in no- MHC-identical settings. However, the consequence of these non-specific strategies is a long-lasting immunodeficiency associated with increased incidence of disease relapse, graft rejection and reactivation of viral infections. Donor lymphocyte infusion, which is used for treating leukemic relapse after allogeneic HSCT, can result in severe GvHD. Several strategies are being optimized specifically to inactivate anti-host T cells while preserving anti-leukemic or anti-microbial immunocompetence. Based on the ex vivo or in vivo elimination of anti-host T cells, or on the modulation of their anti-host activity, these approaches, which have been explored extensively in pre-clinical studies and tested in some preliminary clinical trials, are discussed in this paper.
Cytotherapy 02/2005; 7(2):102-8. · 3.63 Impact Factor
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ABSTRACT: Donor potential to exert NK cell alloreactivity has been shown to confer survival advantage in haploidentical hematopoietic cell transplantation for hematological malignancies. We investigated killer immunoglobulin receptor (KIR) ligand incompatibility in 40 children receiving haploidentical transplantation for primary immunodeficiencies. The conditioning regimen consisted of busulfan and cyclophosphamide. T-cell depletion of the graft used complement-dependent lysis or CD34+ selection. Two patients died in the first month. The remaining 38 patients were divided into those with (n=13) and those without (n=25) donor potential to exert NK cell alloreactivity. Engraftment was similar in the two groups (61.5 and 64%, respectively). The incidence of grade II-IV acute graft-versus-host disease (GVHD) tended to be lower in the group with donor potential to exert NK cell alloreactivity, but the difference was not significant. In conclusion, in this series of patients with primary immunodeficiencies, donor potential to exert NK cell alloreactivity was not associated with significant advantages in engraftment and prevention of acute GVHD.
Bone Marrow Transplantation 01/2005; 34(11):945-7. · 3.75 Impact Factor
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S Caillat-Zucman,
F Le Deist,
E Haddad,
M Gannagé, L Dal Cortivo,
N Jabado,
S Hacein-Bey-Abina,
S Blanche,
J-L Casanova,
A Fischer,
M Cavazzana-Calvo
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ABSTRACT: Hematological inherited diseases can be cured by hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical sibling donor (MSD), but the outcome of unrelated donors (URD) or haploidentical donors (HMD) has been a cause of concern. In all, 94 children affected with inherited diseases underwent HSCT at a single center using MSD (group A, n=31), URD (group B, n=23) or HMD (group C, n=40). There was no difference in the rate of engraftment or in the incidence of grades III-IV acute graft-versus-host disease (GVHD) between the groups. Survival rate was 80.6% in group A, 62.5% in group B and 47.5% in group C (P=0.023). In group B, survival rate was 73.7% in the subgroup with zero or one class I mismatch, and 25% in the subgroup with two or more class I mismatches (P=0.04). In group C, survival rate was 83.3% in the 9/10-identical subgroup, 64.3% in the seven or 8/10 subgroup, and 25% in the five or 6/10 subgroup (P=0.0007). Thus, engraftment, incidence of GVHD and survival are similar in recipients of grafts from MSD, URD with 0-1 class I-mismatch, or HMD with at least 7/10 HLA matches. The low success of HSCT using more disparate donors suggests reserving them for patients with very poor prognosis.
Bone Marrow Transplantation 07/2004; 33(11):1089-95. · 3.75 Impact Factor
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ABSTRACT: During the last years, high-dose chemotherapy and hematopoietic stem cell support have been thought to improve the treatment of poor-prognosis breast cancer. Nevertheless, the question remained as to whether the reinfusion of contaminating residual malignant cells could contribute to relapse. By using an immunocytochemical method, we have analyzed the tumor cell contamination of peripheral blood stem cells (PBSC) collected from advanced breast cancer patients. We studied 153 PBSC samples from 117 stage III and IV breast cancer patients and compared two screening methods-the usual microscopic observation and the automated cellular image analysis system (ACIS-assisted) screening. With manual observation, we found that 7 of 117 patients (5.9%) presented circulating epithelial tumor cells in 9 of 153 (5.8%) PBSC analyzed, whereas automated screening allowed positive detection in 15 of the same 117 patients (12.8%) and in 18 of the 153 PBSC (11.7%). No difference was found between presence or absence of circulating tumor cells and previous chemotherapy treatment (p = 0.5) or stage TNM (p = 0.13) in this group of poor-prognosis breast cancer. We did not find incidence of infusion of contaminated PBSC on overall survival or time to progression.
Journal of Hematotherapy & Stem Cell Research 01/2002; 10(6):855-62.
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R Morariu-Zamfir,
V Rocha,
A Devergie,
G Socié,
P Ribaud,
H Esperou,
N Parquet,
P Guardiola, L Dal Cortivo,
H Bittencourt,
F Garnier,
R Traineau,
J P Marolleau,
S Chevret,
E Gluckman
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ABSTRACT: In order to study the influence of bone marrow CD34(+) cell dose on the outcome of allogeneic bone marrow transplantation (BMT), we analysed the results of BMT from HLA-identical siblings donors in 50 patients with chronic myeloid leukaemia (CML). The median numbers of nucleated cells (NC) and CD34(+) cells infused were 2.18 x 10(8)/kg (0.05-4.14 x 10(8)/kg) and 3.12 x 10(6)/kg (0.35-8.52 x 10(6)/kg), respectively. All patients engrafted. In univariate analysis, there was no correlation between the number of CD34(+) cells infused and the time to neutrophil recovery (P = 0.17). The Kaplan-Meier estimate of grade II-IV acute graft-versus-host disease (GVHD) at day 100 was 53 +/- 14% and 2-year survival was 46 +/- 15%. A number of CD34(+) cells infused greater than the median was the main factor increasing survival (P = 0.0006) and decreasing 100 day transplant-related mortality (P = 0.009). Patient-, disease- and transplant-related characteristics were not statistically different among patients receiving more or less than the median number of CD34(+) cells. The rate of infectious deaths was significantly higher in patients receiving less than 3.12 x 10(6) CD34/kg (48% vs 16%, P = 0.01). In a multivariable analysis, two factors associated with increased risk of death were advanced disease status at transplant (HR: 2.5 (95% CI: 1.09-5.75), P = 0.03) and a lower number of marrow CD34(+) cells infused/kg (HR: 4.55 (95% CI: 1.87-10.90), P = 0.0008).
Bone Marrow Transplantation 04/2001; 27(6):575-80. · 3.75 Impact Factor
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ABSTRACT: Cryopreserved cord blood (CB) banking, space storage, and ABO major incompatibility transfusion as well as potential progenitor cell loss during processing, are the subjects of this study. We evaluate processing of fresh and thawed CB on "Procord" (Terumo Corp., Japan). On 16 freshed CBs, mean NC, CD34, CFU-GM yields were, respectively, 54% (SD +/- 20), 75% (SD +/- 25), and 171% (SD +/- 168) in a final volume of 20 ml. Final product was enriched in mononuclear cells (mean 69% granulocytes depletion) with reproducible erythrocyte and platelet depletions means of 97% (SD +/- 1.5) and 93% (SD +/- 8). On seven previous whole frozen CB units, Procord gave comparable red blood cell (98%) depletion with 53% (SD +/- 30) mean CD34 recovery. Procord is an efficient method for erythrocyte depletion of CB, and recoveries of NC and progenitor cells are comparable to those obtained with similar processing. Nevertheless, as all existing methods, it is associated with cell and progenitor cell loss.
Journal of Hematotherapy & Stem Cell Research 01/2001; 9(6):885-90.
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ABSTRACT: This study was undertaken to evaluate the risk of haematogenous dissemination of epithelial cells induced by endoscopic resection and/or cystoprostatectomy for transitional cell carcinoma of the bladder. Thirty-three patients were studied. Thirty-one had different stages and grades of bladder cancer and two patients had benign bladder conditions. Twenty-five cancer patients required transurethral resection of their bladder tumour. Of those, 20 had superficial disease (pTaG1-G2: n = 19; pT1G2: n = 1) and five had muscle invasive tumours (pT2G3: n = 2; pT3aG3: n = 1; pT4G3: n = 2). Five patients underwent radical cystoprostatectomy for muscle invasive cancers (pT2G3: n = 3; pT3bG3: n = 1; pT4G3: n = 1) and one man received chemotherapy for metastatic disease. Venous blood (10 ml) was obtained from the antecubital fossa in each patient, before and 1-2 h after completion of surgery, and prior to treatment in the metastatic patient. An indirect immunocytochemical technique was used to detect circulating epithelial cells after centrifugation on Ficoll gradient and fixation of mononuclear cells on slides, using a monoclonal antibody directed against three cytokeratins: CK8, CK18 and CK19. Circulating epithelial cells were detected only in the patient with metastatic disease. None of the other patients had evidence of epithelial circulating cells before or after surgery. The results suggest that irrespective of disease stage and grade, neither endoscopic nor open bladder surgery leads to detectable dissemination of urothelial cells in the peripheral circulation. These procedures are therefore unlikely to increase the risk of progression and metastasis in transitional cell carcinoma of the bladder.
British Journal of Cancer 12/1999; 81(5):832-4. · 5.04 Impact Factor
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ABSTRACT: Harvesting of peripheral blood stem cells (PBSCs) following chemotherapy and G-CSF administration is currently performed for hematological therapies. However, a procedure based on the use of a large quantity of G-CSF is relatively costly. Therefore, we retrospectively compared the effects of two PBSC mobilization procedures in a population with recently diagnosed multiple myeloma. The first procedure consisted of chemotherapy and systematic G-CSF administration (group 1: 24 patients). The second consisted of chemotherapy alone, G-CSF having been administered only in the case of failure of PBSC mobilization or delayed white blood cell (WBC) recovery (group 2: 28 patients). Leukapheresis was performed when WBC recovery reached 1 x 10(9)/l if the peripheral blood CD34+ cell count was over 10/microl. Leukapheresis was maintained until a total of 2.5 x 10(6) CD34+ cells/kg was harvested. A significant difference was observed between the two groups only in regard to the median period of WBC recovery (delayed for group 2) and the number of CD34+ cells/kg collected on the first leukapheresis (higher for group 1) but not to the proportion of patients with failure of PBSC collection. Ten group 2 patients, who had insufficient CD34+ cells after WBC recovery or delayed WBC recovery, received G-CSF which resulted in sufficient PBSC harvesting in nine. To obtain a sufficient CD34+ cell level, the patients without systematic G-CSF administration had more leukaphereses (2.1 vs 1.5) but the mean consumption of G-CSF per patient was eight times less than in the other group. Nonsystematic use of G-CSF before WBC recovery or preferentially its introduction just after, could be an interesting economical alternative in PBSC mobilization but should be assessed by a prospective controlled study of cost/efficacy.
Bone Marrow Transplantation 10/1999; 24(5):463-6. · 3.75 Impact Factor
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ABSTRACT: Positive selection of CD34+ cells is being increasingly performed to support hematological reconstitution following high-dose and dose-intensive chemotherapy and to reduce the non-target cell content of transplants. The present study was designed to evaluate the performance of an immunomagnetic cell selection system, including comparison of enzyme and peptide releasing agents and of semi-automated and fully automated selection systems. A total of 74 immunomagnetic CD34+ cell selection procedures were performed involving 55 subjects, the majority of whom had hematologic malignancies. Median CD34+ cell purity with a newly developed specific octapeptide releasing agent (98.5%; 81.0-99.0%) was significantly higher (P = 0.002) than that with chymopapain (85.8%; 28.1-99.7%). No significant differences were observed between semi-automated and fully automated systems in CD34+ cell purity or yield or time to WBC or platelet recovery. Immunomagnetic selection was found to provide highly purified populations of CD34+ cells in sufficient numbers for use in transplantation procedures. CD34+ cell transplants supported rapid and reliable hematologic reconstitution. Use of a fully automated system markedly reduced the time and labor required for immunomagnetic selection, potentially affording more standardized and reproducible positive selection of CD34+ cells.
Bone Marrow Transplantation 05/1999; 23(8):819-26. · 3.75 Impact Factor
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Bone Marrow Transplantation 08/1998; 22 Suppl 1:S11. · 3.75 Impact Factor
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ABSTRACT: Umbilical cord blood T cells are less functional. Different explanations have been proposed. In this study we analyze the Vbeta T cell cord blood repertoire. All the Vbeta families are expressed. We found only the overexpression of three Vbeta: Vbeta 5-1, Vbeta 5-2, Vbeta 21-2.
Bone Marrow Transplantation 08/1998; 22 Suppl 1:S39-40. · 3.75 Impact Factor
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ABSTRACT: Hematopoietic progenitor cells are present in umbilical cord blood; placental blood (PB) previously considered as waste product now constitutes an alternative source of hematopoietic stem cells for bone marrow reconstitution. This has promoted the establishment of cord blood banks for use in unrelated transplants. The banking of PB offers many advantages: the donors do not require anesthesia, stored PB can be a valuable source of stem cells for patients from ethnic minorities underrepresented in volunteer registers, and stored PB can be made available much faster than bone marrow from unrelated donors. Preliminary clinical experience suggests that, due to the immunological immaturity of PB cells, graft versus host disease might be lower than when using bone marrow from adult donors and HLA restrictions might be less stringent. If the number of nucleated cells in PB often appears low for patients weighing more than 40 kg, clinical data suggest that the number of stem cells may be sufficient for adult transplantation. The number of cord blood banks throughout the world is increasing rapidly. In the USA and Europe, more than 10,500 PB units are stored and available for transplantation. In the next 5 years, a total of 50,000 PB will be reached which may be sufficient to provide for the majority of candidates for unrelated BM transplantation. The practices of umbilical cord blood collection, mother selection, infectious disease screening, cell manipulation and storage must be standardized. Some accreditation process should be mandatory for assessing operating procedures and the quality assurance programs of the banks, and for allowing the international exchange of placental blood between transplant centers.
Transfusion Clinique et Biologique 03/1998; 5(1):56-63. · 0.80 Impact Factor
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ABSTRACT: A novel retroviral vector has been designed based on a Friend-murine leukemia virus (Fr-MuLV) FB29 strain. The latter has been selected according to characteristics of pathogenicity in mice where it induces a disease of the haemopoietic system affecting all lineages. Higher infectivity has also been demonstrated as compared to other strains. In accordance with these findings, the amphotropic producer clone used in this study carrying along the neomycine resistance gene (FOCH-Neo), harbors viral titers over 10(7) cfu/ml. To investigate the potential of genetically engineering hematopoietic precursors, CD34+ progenitors were selected from cord blood, bone marrow, and peripheral blood mobilized stem cells (patients + solid tumors) and transduced with FOCH-Neo. High transduction rates were achieved using virus supernatant and minimal doses of hematopoietic growth factors during pretransduction and transduction steps. A polymerase chain reaction (PCR) assay investigating the presence of both neomycin-encoding and viral vector sequences tested positive in 45-90% of granulocyte-macrophage colony-forming units (CFU-GM) generating cells (bone marrow and peripheral blood derived cells) following transduction. An average of 35% colonies showed resistance to G418. Such levels of transduction proved reproducible using only supernatants harboring over 10(7) cfu/ml. In those experiments where long-term in vitro cultures could be maintained over 5 weeks (all cord blood and 5 among 23 PBSC), efficient transduction of long-term culture initiating cell (LTC-IC) hematopoietic progenitors was demonstrated on the basis of both resistance to G418 and virus integration. In the latter case, the PCR assay tested positive in as much as 35-60% of late unselected CFU-colonies. This novel retroviral vector harbors interesting features toward genetic modification of hematopoietic progenitors.
Human Gene Therapy 02/1998; 9(2):207-16. · 4.22 Impact Factor
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ABSTRACT: To evaluate CD34+ selection of peripheral blood stem cells (PBSC) as a graft for autologous transplantation. Eight relapsing follicular lymphoma (FL) patients were submitted to CD34+ autologous stem cell transplantation (ASCT). All patients received at least two front line conventional therapies; mean time to treatment failure (TTF) was 4.5 months. Patients had disseminated stage III-IV disease after a median number of 2.1 relapses. Chemotherapy and G-CSF were used as mobilization for leukapheresis. CEPRATE SC concentrator (CellPro, Inc, Bothell, WA) was used to select CD34+ cells from leukapheresis products. With a mean of 1.8 leukaphereses per patient, 8.1 x 10(8) mononuclear cells (MNCs)/kg were collected. After the selection process, the median number of MNCs was 9.4 x 10(6)/kg; 4.3 x 10(6)/kg CD34+ cells and 17 x 10(4)/kg CFU-GM, with a purity of 83.7% and a viability of 89.2%. Mbr bcl2/IgH PCR analysis of 5 grafts showed that initial buffy-coat, and CD34- fractions were negative in 3 cases and positive in 2 cases (from whom selected CD34+ fraction remained positive in 1 case). After a conditioning regimen including total body irradiation, cyclophosphamide and etoposide, CD34+ selected cells were reinfused. All patients but one had successful engraftment, median time to WBC > 1 x 10(9)/l was 12 days and platelets > 50 x 10(9)/l 17 days. No severe infectious complications were seen. After transplant, with a minimum follow up of 2 years, 5 patients are still in complete remission (CR). Three patients have relapsed after 1 year of transplant with a mean TTF of 15.6 months. We conclude that PBSC CD34+ selection for ASCT was a safe technique, capable of reconstituting hemopoiesis without severe complications for high risk FL patients included in this study. The effects of tumor cell purging need to be evaluated in a larger series.
Hematology and Cell Therapy 03/1997; 39(1):33-40.
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Hematology and Cell Therapy 05/1996; 38(2):205-6.
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ABSTRACT: Granzyme B and perforin are cytoplasmic granule-associated proteins used by cytotoxic T lymphocytes and natural killer (NK) cells to kill their targets. However, granzyme B gene expression has also been detected in a non-cytotoxic hematopoietic murine multipotent stem cell line, FDCP-Mix. The objective of the present study was to investigate whether granzyme B and perforin could be expressed in human hematopoietic CD34+ cells and if present, discover what their physiologic relevance could be. The primitive CD34+ human cell line KG1a was investigated first and was found to express granzyme B and perforin. Highly purified hematopoietic stem/progenitor cells were then selected using the CD34 surface antigen as marker. Steady-state bone marrow (BM) CD34+ cells did not contain these proteins. Peripheral blood (PB) CD34+ cells, which had been induced to circulate, were also analyzed. After chemotherapy (CT) and granulocyte colony-stimulating factor (G-CSF) treatment, CD34+ cells strongly expressed mRNAs and proteins of granzyme B and perforin. In contrast, CD34+ cells mobilized by G-CSF alone were negative. Western blot analysis further showed that granzyme B and perforin proteins were identical in CD34+ cells and activated PBLs. Such proteins might be implicated in the highly efficient migration of CD34+ stem/progenitor cells from BM to PB after CT and G-CSF treatment. The cellular adhesion mechanisms involved in the BM homing of CD34+ cells are disrupted at least temporarily after CT. The Asp-ase proteolytic activity of granzyme B on extracellular matrix proteins could be used by progenitor cells for their rapid detachment from BM stromal cells and perforin might facilitate their migration across the endothelial cell barrier.
Blood 12/1995; 86(9):3500-6. · 9.90 Impact Factor
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ABSTRACT: Thirty-nine patients with acute myeloblastic or lymphoblastic leukaemia had peripheral blood mononuclear cells collected by 3 continuous-flow leukapheresis as they entered first remission after induction chemotherapy. CFU-GM were assayed as a measure of the number of haemopoietic stem cells in each collection. Numbers of CFU-GM harvested varied among the patients (for example 0.27 to 155.10(4)/kg for ANLL patients). Nineteen patients underwent peripheral blood stem cells autografts after a conditioning regimen with high dose cyclophosphamide and TBI. The patients were transfused with a median of 2.2.10(4)/kg CFU-GM cells (0.28 to 100.10(4) CFU-GM/kg). Only 1 patient had a graft failure. The rate of haemopoietic recovery was studied for our patients and those reported in the literature. A strong correlation exists between the numbers of CFU-GM transfused and the rate of granulocytes and platelets recovery. Very rapid recovery are regularly obtained when the number of CFU-GM transfused is superior to 5.10(4)/kg.
Nouvelle revue française d'hématologie 02/1988; 30(1-2):69-73.
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S Hacein-Bey-Abina,
A. Garrigue,
GP. Wang,
J Soulier,
A Lim,
E Morillon,
E Clappier,
L. Caccavelli,
E Delabesse,
K Beldjord, [......],
B H Belohradsky,
U Wintergerst,
M.C. Velez,
L.E. Leiva,
R. Sorensen,
N.M. Wulffraat,
S Blanche,
FD. Bushman,
A Fischer,
M Cavazzana-Calvo
