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J P Marolleau

Publications and source records attributed to J P Marolleau.

At least 19 recordsLinked to original sources
PubMed2006

Ex vivo expansion of umbilical cord blood CD34 cells in a closed system: a multicentric study.

BACKGROUND AND OBJECTIVES: The Dideco 'Pluricell System' is a CE-marked medical device allowing haematopoietic stem cell (HSC) expansion. It comprises a kit of cGMP cytokines and reagents, a closed-cell expansion chamber and a cell-washing set. We tested the system in a multicentric study by expanding CD34(+) cells from eight fresh umbilical cord blood (UCB) samples. MATERIALS AND METHODS: During culture, the mean nucleated cell (NC) count, the mean CD34(+) cell count, fold expansion, viability and apoptosis were measured. Clonogenic assays and immunophenotypical characterization were performed on days 0, 7 and 12. On the expanded cellular product, in three cases cell genotyping, endotoxin level and mycoplasma detection (by polymerase chain reaction) were performed. RESULTS: The mean CD34(+) cell expansion on days 7 and 12 was sevenfold and 12-fold respectively and the mean NC expansion was 69-fold and 180-fold. The mean NC viability on day 12 was 96.9% (94.4-99.1). After 12 days, granulocyte-macrophage colony-forming units (GM-CFU) showed a 20-fold increase: a slight increase in CD34(+) cell apoptosis was observed during culture. In all of three cases neither chromosomal alterations nor mycoplasma contamination was detected. No significant endotoxin levels were detected after expansion. CONCLUSIONS: The device allows the ex vivo expansion of NC and CD34(+) cells in a closed system. The expanded cellular product is a mixture of progenitors (CD34(+) cells) and differentiated (mainly myeloid and megakaryocytic) cells. To reduce cell apoptosis, more frequent cell feeding during culture should be tested.

Antigens, CD34↗
PubMed2004

High-dose therapy and autologous stem cell transplantation in relapsing cutaneous lymphoma.

Treatment of cutaneous T-cell and B-cell lymphomas is difficult and relapses are frequent. To evaluate the efficiency of high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) on relapsing cutaneous lymphomas, we conducted a retrospective study of 14 patients. We investigated the clinical and histological parameters of the lymphoma, previous treatments to ASCT, short-term complications of ASCT, and occurrence of a relapse. There were 11 males and three females, with a median age of 42 years. Most often, the skin disease was disseminated without extracutaneous involvement. Four patients had a B-cell lymphoma and 10 a T-cell lymphoma. CD30 was negative in 8/10 T-cell lymphomas. Before ASCT, 13 patients had chemosensitive disease; one had refractory disease. The conditioning regimen included TBI in nine cases. No toxic death occurred. Relapse of the lymphoma occurred in eight cases (T-cell lymphoma in seven cases), within 4 months after ASCT in six cases. Relapses were treated with local treatment, interferon or classical chemotherapy. At the end of the study, 11 patients were alive and three patients had died. HDT and ASCT do not benefit patients with T-cell lymphomas. For patients with disseminated relapsing cutaneous B-cell lymphomas, this procedure should be considered.

Adult↗
PubMed2002

Cell transplantation for post-ischemic heart failure.

Post-ischemic heart failure is becoming a major issue for public health in occidental countries and therapeutical options are limited. Therefore cell transplantation was developed as an alternative strategy to improve cardiac structure and function. This review describes the multiple cell types and clinical trials considered for use in this indication. The transplantation of fetal or neonatal cardiomyocytes has proven to be functionally successful, but ethical as well as technical reasons make their clinical use limited. Recent reports, however, suggested that adult autologous cardiomyocytes could be prepared from stem cells present in various mesenchymal tissues. Alternatively, endothelial progenitors originating from bone marrow or peripheral blood could promote the neoangiogenesis within the scar tissue. Finally, the transplantation of skeletal muscle cells (SMC) in the infarcted area improved myocardial function, in correlation with the development of skeletal muscle tissue in various animal models. The latter results paved the way for the development of a first phase I clinical trial of SMC transplantation in patients with severe ischemic heart failure. It required the scale-up of human cell production according to Good Manufacturing Procedures, it started in June 2000 in Paris and was terminated in November 2001, and it was followed by several others. The results were encouraging and prompted the onset of a blinded, multicentric phase II clinical trial for SMC transplantation. Meanwhile, clinical trials also evaluate the safety and efficacy of various cells types originating from the bone marrow.

Bone Marrow Transplantation↗
PubMed2001

High-dose sequential epirubicin and cyclophosphamide with peripheral blood stem cell support for advanced breast cancer: results of a phase II study.

The aim of this study was to evaluate the feasibility of a high-dose intensity and high-dose density multicycle epirubicin and cyclophosphamide regimen with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to September 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) received 205 courses of cyclophosphamide 3 g x m(-2) and epirubicin 100 mg x m(-2) every 14 days. G-CSF 5 microg x kg(-1) x day(-1) was administered from day 3 to neutrophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, with > or = 2 x 10(6) CD34+ PBSC x kg(-1) required for each reinfusion. 48 patients (86%) received all 4 planned courses. Early withdrawal was consecutive to infectious complications (n = 4), severe asthenia (n = 3), haemorrhagic cystitis (n = 1). A median number of 10.8 x 10(6) CD34+ PBSC x kg(-1) (range, 3-80) was harvested with 1 or 2 apheresis in 48 patients (94%). Median relative dose intensity was 91.3% (range, 72-102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (median duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Objective response rate was 69% in stage IV patients (31/45 evaluable pts), with a 16% complete response rate. Their median progression-free and overall survivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-related progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate its real benefit.

Adult↗
PubMed2001

Myoblast transplantation for heart failure.

Intramyocardial skeletal muscle transplantation has been shown experimentally to improve heart function after infarction. We report success with this procedure in a patient with severe ischaemic heart failure. We implanted autologous skeletal myoblasts into the postinfarction scar during coronary artery bypass grafting of remote myocardial areas. 5 months later, there was evidence of contraction and viability in the grafted scar on echocardiography and positron emission tomography. Although this result is encouraging, it requires validation by additional studies.

Aged↗
PubMed2001

Primary plasma cell leukaemia: a report of 18 cases.

Primary plasma cell leukaemia (P-PCL) is a variant of multiple myeloma (MM) first diagnosed in the leukemic phase, with >2000/mm(3) circulating plasma cells (PCs) and plasmacytosis >20% of the white cell count. We investigated the clinical characteristics, therapy, immunophenotype and prognosis factors of 18 patients. Common features at diagnosis were asthenia (seven patients), renal insufficiency (ten patients), bone pain (seven patients), splenomegaly or hepatomegaly (five patients). Hypercalcemia was present at diagnosis in seven patients and was the most potent poor prognosis factor (P<0.05). Most patients (16 out of 18) were treated with an anthracyclin containing regiment; complete remission was attained in one patient and partial remission in 11 patients while six patients had no response. The median survival time from diagnosis was 7 months (2--12, 95% confidence interval), but response to treatment had favorable predictive value (P<0.05). The PCs were usually positive for mature B-cell markers (PCA-1, CD38). They expressed integrins which may increase their binding to endothelial cells and thus participate in PCL physiopathology by favoring plasmocyte extramedullary spread.

Adult↗
PubMed2001

Influence of bone marrow graft lymphocyte subsets on outcome after HLA-identical sibling transplants.

OBJECTIVE: The aim of this study was to analyze bone marrow lymphocyte subsets and CD34 cell dose and their influence on the outcomes of bone marrow transplantation. MATERIALS AND METHODS: Forty-eight patients (median age 30 years, range 5-54) receiving HLA-identical sibling bone marrow transplantation for hematologic malignancies were analyzed. RESULTS: Median number (range) of nucleated cells and CD34+ cells infused were 2.4 (0.4-6.0) x 10(8)/kg and 3.5 (0.5-13.0) x 10(6)/kg, respectively. Probability of neutrophil recovery was 97%. In a multivariate analysis, time to neutrophil recovery was shortened when a higher number of CD3/CD8 cells was infused (> or =1.0 x 10(7)/kg) (hazard ratio [HR] = 2.13, p = 0.018); when the patient was female or had negative cytomegalovirus serology (HR = 2.03, p = 0.03; HR = 0.41, p = 0.009; respectively). The incidence of grade II to IV acute graft-vs-host disease (GVHD) was 47%. Infusion of >1 x 10(7) CD4 infused/kg increased the risk of acute GVHD (HR = 2.86, p = 0.03). Nineteen of 40 patients at risk experienced chronic GVHD, the risk of which was increased by diagnosis of chronic leukemia (p = 0.03), <2.0 x 10(8) nucleated cells infused/kg (p = 0.05), and a low number of all lymphocyte subsets, except CD19. Estimated 3-year survival rate was 54%. Risk of death was increased in patients receiving <3.5 x 10(6)CD34 infused/kg (HR = 0.37, p = 0.02). Only six patients relapsed. CONCLUSIONS: A high cell dose of CD3/CD8 is associated with faster neutrophil recovery, whereas a high cell dose of CD4+ cells increases the incidence of acute GVHD. A high number of nucleated cells and CD34+ cells infused was associated with decreased risk of chronic GVHD and improved survival, respectively.

Acute Disease↗
PubMed2001

[Role of dendritic cells in the modulation of innate effectors of immunity].

CD8+ cytotoxic T lymphocytes (CTL), specifically directed against tumor-associated antigens, can be used in immunotherapy as effector cells in order to induce antitumor immune response. However, natural killer (NK) cells, that belong to the innate immune system, might also play a role on the anti-tumoral immune response. Our data show that quiescent NK cells can be activated by direct cell contact with dendritic cells (CD). Such a NK cells activating ability places DC at the frontier between innate and cognate immunity and then may encourage their use in clinical trials designed to elicit both CTL and NK responses.

Animals↗
PubMed2001

Human cytomegalovirus infection of bone marrow myofibroblasts enhances myeloid progenitor adhesion and elicits viral transmission.

Human cytomegalovirus (CMV) infection of bone marrow transplant recipients can cause pancytopenia, as well as life-threatening interstitial pneumonia. CMV replicates actively in bone marrow stromal cells, whereas it remains latent in hematopoietic progenitors. Our aim was to study the influence of CMV infection on adherence of CD34(+) cells to the myofibroblastic component of human bone marrow and examine transmission of virus from myofibroblasts to CD34(+) cells. We show that smooth actin, but not fibronectin, organization is markedly modified by CMV infection of bone marrow stromal myofibroblasts. Nonetheless, CMV infection led to increased adherence of the CD34(+) progenitor cell line, KG1a, relative to adherence to uninfected myofibroblasts from the same donors. Adherence of CD34(+) cells to infected bone marrow myofibroblasts resulted in transfer of virions and viral proteins through close cell-to-cell contacts. This phenomenon may play a role in the pathophysiology of CMV bone marrow infection and in eventual virus dissemination.

Actins↗
PubMed2001

Tandem autotransplant as first-line consolidative treatment in poor-risk aggressive lymphoma: a pilot study of 36 patients.

PURPOSE: In the previous LNH87-2 study, consolidative high-dose therapy followed by stem cell transplantation (HDT) improved disease-free survival, as well as survival for patients (pts) presenting with two or three factors of the age-adjusted international prognostic index (Aa-IPI) in first complete remission (CR). In order to improve further the outcome of such patients, we conducted a pilot study of consolidative tandem autotranplant. PATIENTS AND METHODS: Thirty-six patients (pts) under 60 years of age with two or three factors of the Aa-IPI were enrolled. Their main characteristics were: diffuse large B-cell lymphoma (83%), Aa-IPI three factors (50%), and marrow involved (36)%. The procedure consisted of 1) induction with four cycles of ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) 2) in responding pts, peripheral blood stem cell (PBSC) collection after the fourth cycle of ACVBP (11 pts) or after an additional mobilization regimen (Cyclophosphamide-VP16) (17 pts) 3) a first HDT (mitoxantrone, cyclophosphamide, VP16 and carmustine) followed by PBSC infusion 4) a second HDT (busulfan, carboplatin and melphalan) followed by PBSC infusion. Among the 29 patients responding to induction, 28 received the first HDTand 24 the second. RESULTS: The rates of three-year-event free survival and survival are 47% (95% confidence interval (95% CI: 31%-63%) and 50% (95% CI: 37%-69%), respectively. Eighteen patients remained free of evolutive disease and 18 patients have died, 15 from disease progression and three from treatment-related toxicity after tandem transplant (two veno-occlusive disease and one cerebral toxoplasmosis). CONCLUSION: We conclude that tandem transplant did not improve the results of the LNH87-2 study in which patients received a single consolidative HDT.

Adolescent↗
PubMed2001

Influence of CD34(+) marrow cell dose on outcome of HLA-identical sibling allogeneic bone marrow transplants in patients with chronic myeloid leukaemia.

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).

Adolescent↗
PubMed2001

Cytokines and vascular cell adhesion molecule-1 in the blood of patients undergoing HPC mobilization.

BACKGROUND: The mechanism of HPC mobilization in humans is unclear. In this study, the relationship between PBPC mobilization and blood levels of G-CSF, endogenous cytokines (IL-8, SCF, thrombopoietin [TPO]), and the vascular cell adhesion molecule-1 (VCAM-1) was analyzed in patients with malignancy who were undergoing a PBPC mobilization regimen. STUDY DESIGN AND METHODS: Fifty-four patients with multiple myeloma (MM) and 29 with breast cancer (BC) underwent a mobilization regimen combining conventional chemotherapy and G-CSF up to the last day of PBPC collection. The CD34+ cell count was determined on each day when leukapheresis was scheduled. Venous blood samples (n = 117) were drawn before apheresis for CD34+ cell count (flow cytometry) and cytokine (G-CSF, IL-8, SCF, TPO) and VCAM-1 measurements (ELISA). RESULTS: In multiple regression analysis, SCF was a significant determinant of CD34+ cell levels in BC patients (R = 0.50, p = 0.03) and of VCAM-1 levels in MM patients (R = 0.32, p = 0.02). SCF was negatively correlated with CD34+ cell count in patients with BC. SCF and VCAM-1 blood levels were correlated in MM and BC patients. CONCLUSION: SCF and VCAM-1 could play a role in PBPC mobilization in patients and could be useful measures by which to study patients undergoing a mobilization regimen.

Adult↗
PubMed2001

Residual tumor cell contamination in peripheral blood stem cells collections of 117 breast cancer patients evaluated by immunocytochemical technique.

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.

Adult↗
PubMed2001

[Transplantation of autologous skeletal myoblasts in ischemic cardiac insufficiency].

Despite medical therapeutic advances, congestive heart failure (CHF), which is the common ultimate consequence of many primary cardiovascular diseases, remains a major and growing public health problem. Although orthotopic heart transplantation is the gold standard, there is now growing evidence that one therapeutic option could be cellular cardiomyoplasty. Autologous adult skeletal myoblast transplantation seems to be the most clinically relevant, compared with other cell types, in that it avoids immunosuppression therapy, availability and ethical issues. Previous experimental studies have documented the efficacy of myoblast transplantation in improving function of infarcted myocardium. Although the mechanisms involved in this improvement are not elucidated, it has been demonstrated convincingly enough to consider ripping to clinical trials.

Animals↗
PubMed2000

Myelodysplasias and leukemias after autologous stem cell transplantation for lymphoid malignancies.

The incidence of secondary myelodysplastic syndromes and acute leukemia (MDS/AL) was reported for 395 patients autografted for Hodgkin's disease (HD) (n = 96) and non-Hodgkin's lymphoma (NHL) (n = 299) between 1987 and 1998. Eleven patients developed secondary MDS/AL (crude rate at 2.8%) including two lymphoblastic AL cases. The mean time of occurrence was at 32 months after autologous stem cell transplantation (ASCT) and 71 months after diagnosis. The estimated actuarial incidence at 10 years was at 6.3% (+/-4%). Karyotyping revealed complex chromosomal aberrations in only one patient, and two translocations [t(8;21) and t(8;16)]. No features of topoisomerase II inhibitor-related leukemia were found. Only one patient had received ASCT in first remission. The remaining 10 patients had received multiple courses of chemotherapy before stem cell collection and four had relapsed after ASCT and before the occurrence of secondary MDS/AL. Five of 11 patients had received localized radiotherapy and five others received TBI in their conditioning regimen. Ten patients died despite chemotherapy and/or supportive care and only one patient is alive and well after genoidentical allogeneic transplantation. We suggest a cumulative leukemogenic role of pre-ASCT radiation and chemotherapy in the occurrence of these secondary MDS/AL more than the high-dose therapy itself.

Acute Disease↗
PubMed2000

Interleukin-6 stimulates HHV-8 replication in bone marrow cultures and infected cell lines.

INTRODUCTION: The significance of HHV-8 DNA detection in bone marrow stromal cells from patients with multiple myeloma is still controversial. Since IL-6 plays a key role in the pathogenesis of myeloma, we studied the effect of this lymphokine on HHV-8 DNA detection. MATERIALS AND METHODS: Amplification of HHV-8 DNA from long-term bone marrow cultures established from normal individuals in the presence or absence of 1 ng/ml IL-6 and from an HHV-8 infected ISI cell line. RESULTS AND CONCLUSIONS: IL-6 increased HHV-8 replication in seven of ten bone marrow cultures as well as in the ISI cell line. Quantitative PCR showed a 3-100-fold increase in HHV-8 DNA copy number/microg DNA. These data suggest that when IL-6 is present in the micro-environment, HHV-8 replicates and may be amplified in the absence of systemic infection in patients without cellular immune deficiency.

Bone Marrow Cells↗