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P Colombat

Publications and source records attributed to P Colombat.

At least 55 records · Page 3Linked to original sources
PubMed1997

Is the International Prognostic Index for aggressive lymphomas useful for low-grade lymphoma patients? Applicability to stage III-IV patients. The GOELAMS Group, France.

BACKGROUND: The International Prognostic Index (IPI) is widely used to predict outcome of patients with aggressive lymphomas. Our goal was to assess the prognostic value of this index for low-grade lymphoma. PATIENTS AND METHODS: One hundred eighty-two patients with disseminated (stage III or IV) low-grade lymphoma were enrolled in a prospective multicenter trial. According to the initial features, treatment either was started immediately or was deferred until indicated by disease progression. Patients received the same polychemotherapy regimen, given monthly for six cycles. They were assigned to one of four risk groups according to the number of presenting risk factors: low-risk (0 or 1), low-intermediate-risk (2), high-intermediate-risk (3), high-risk groups (4). RESULTS: Survival curves (Kaplan-Meier method) demonstrated a high significant difference for the four groups (log-rank: P < 0.0001). Median survival for the low-risk group has yet to be reached, while that for the three other groups are, respectively, 65, 34, and 12 months. CONCLUSIONS: In this study, the IPI has been found to be an important prognostic tool in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

Humans↗
PubMed1996

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study.

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Improved pharmacodynamics of L-asparaginase-loaded in human red blood cells.

To evaluate the modification of pharmacodynamic parameters induced by the administration of L-asparaginase loaded into red blood cells, 13 patients received a single dose of L-asparaginase internalised into the carrier. The enzyme was loaded using a reversible lysis-resealing process. The dose per patient ranged from 30 to 200 i.u. kg-1. Considerable heterogeneity occurred between patients. the level of L-asparaginase circulating after 24 h represented 47% of the total injected dose as compared to 74.8% for red blood cells (RBCs). However, the half-life of the enzyme remaining in the circulation was very similar to that of the RBC carrier, i.e. 29 days and 27 days, respectively, compared with 8-24 h for the free enzyme. Sustained elimination of plasma L-asparagine occurred, the duration of which was dependent on the injected dose. A single injection of 30.i.u.kg-1 was sufficient to eliminate plasma L-asparagine over 10 days. With 150-200 IU.kg-1 the elimination period was extended to 50 days. These data show that the use of RBCs as carriers of L-asparaginase greatly improves the pharmacodynamic parameters of the drug.

Adolescent↗
PubMed1996

Purging of bone marrow in autologous bone marrow transplantation for non-Hodgkin's lymphoma: a case-matched comparison with unpurged cases by the European Blood and Marrow Transplant Lymphoma Registry.

PURPOSE: The use of in vitro purging of bone marrow in autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) has been a controversial issue; its benefit is as yet unproven. Its effect on the clinical outcome of ABMT in these patients is still unclear. We look at this issue using data from the European Blood and Marrow Transplant (EBMT) Lymphoma Registry. PATIENTS AND METHODS: Seventeen hundred twenty-six patients with NHL have been reported to the EBMT registry, of whom 270 had bone marrow purged at transplant. Two hundred twenty-four of these patients were compared with a case-matched group of 224 unpurged patients who had undergone the same procedure. The case matching was made following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. Response, complications, and outcome in ABMT were analyzed. RESULTS: Time to hematologic engraftment, response to ABMT, and number of procedure-related deaths were similar in purged and unpurged patients. The overall survival (OS) rate was 54% at 5 years in purged patients and 48.3% in unpurged patients (P = .1813). The PFS rate was 44.3% and 44.6%, respectively (P = .1961). Patterns of relapse, including bone marrow relapse, were similar in both groups. Patients with low-grade lymphoma did not have a significantly improved PFS if the bone marrow was purged (P = .1757); however, they did have a significantly improved OS (P = .00184). This increased OS was found to be associated with non-totalbody irradiation (TBI) conditioning and also with the purged patients undergoing transplantation at large transplant centers (P = .0016). CONCLUSION: Purging of bone marrow in ABMT for NHL does not affect the rate of hematologic engraftment or risk of procedure-related death (PRD). There is no significant difference in PFS for patients whose bone marrow is purged as compared with unpurged.

Adolescent↗
PubMed1996

Development of listeriosis during vancomycin therapy in a neutropenic patient.

Vancomycin and aminoglycosides are widely used for fever in neutropenic patients. This combination of antibiotics has also been proposed for the treatment of Listeria monocytogenes bacteremia. We report a case of fatal listeriosis in a 33-year-old man during acute lymphoblastic leukemia induction therapy in a total protective environment despite him having been on vancomycin for 8 days for treatment of staphylococcus bacteremia. Vancomycin and aminoglycoside cannot be proposed for the treatment of L. monocytogenes bacteria in neutropenic patients. Neutropenia might be a risk factor for listeriosis in cancer patients.

Adult↗
PubMed1996

High-dose therapy and autologous bone marrow transplantation in first complete or partial remission for poor prognosis Hodgkin's disease.

We report the experience of three French centres which evaluated high-dose therapy (HDT) as consolidation therapy for poor prognosis Hodgkin's disease (HD). From March 1986 to April 1990, 23 consecutive patients with poor prognosis stage IV HD underwent HDT followed by autologous bone marrow transplantation (ABMT) after achieving either complete remission (CR1) or good partial response (GPR1) (reduction mass> 75%). The median age was 31 years (range 18 to 55 years), 14 were male. All patients except one initially had at least 2 poor prognosis factors such as: systemic symptoms (n = 19), bulky tumor (n = 16), more than one extranodal site (n = 9), bone marrow involvement (n = 5), lymphocyte count < or = 1.10(9)/1 (n = 8) and biological stage B (n = 21). All patients had previously been treated with alternating MOPP/ABVD. Ten patients were in GPR1 and 13 in CR1 before transplant. The conditioning regimens were: CBV (n = 17), BEAM (n = 5), BEAC (n = 1) followed by bone marrow rescue. Radiotherapy was introduced just before the conditioning regimen for 6 patients or after ABMT for 5 patients. Nine of 10 patients in GPR1 achieved CR after ABMT but one died early of treatment-related toxicity. Five of 22 patients who were in CR posttransplant, relapsed (3, 4, 4, 18, 36 months). Seventeen patients remain alive in continuous CR with a median follow-up of 60 months (range: 30-100 months). The overall survival (OS) and disease-free survival (DFS) projected at 5 years are 92% and 77% respectively. Consolidation by HDT and ABMT proved to be well tolerated. An international trial is currently underway to attempt to demonstrate a clear benefit on survival for this subset of poor prognosis HD patients.

Adolescent↗
PubMed1996

Platelet transfusions in advanced hematological malignancies: a position paper.

Treatment of patients with advanced-stage hematological malignancies (HM) includes frequent transfusions. Given present limited hospital budgets, administrative pressure is increasing on hematology services to limit the cost of these transfusions. An expert multidisciplinary panel involved in hematology formed a working party to draw up a series of proposals, including definitions of advanced stage disease and the indications for platelet transfusion. Their proposals included: (a) Platelet transfusions are indicated for the treatment of bleeding caused by low platelet counts; (b) Patients should receive full information, including the basic criteria for platelet transfusion; (c) Doctors should be trained to assess whether or not platelet transfusions are urgently required; and (d) The practice of home transfusions should be encouraged.

Bone Marrow Diseases↗
PubMed1996

Granulocyte-macrophage colony-stimulating factor accelerates hematopoietic recovery after autologous bone marrow or peripheral blood progenitor cell transplantation and high-dose chemotherapy for lymphoma.

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) as an adjunct to autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cell (PBPC) transplantation was evaluated in 59 lymphoma patients. Patients were divided into three groups. In group I (n = 21) patients received rhGM-CSF (5 micrograms/kg daily) at the time of PBPC collection and during the recovery phase post-infusion. In group II (n = 12) patients received rhGM-CSF as an adjunct to ABMT. In group III (n = 26) they were grafted with bone marrow without rhGM-CSF. Administration of rhGM-CSF (groups I and II) significantly reduced the time to myeloid engraftment, the number of febrile days and the median duration of antibiotics administration and of hospital stay when compared with the group in which patients did not receive rhGM-CSF. The only difference between ABMT and PBPC, given with rhGM-CSF support, was observed in the duration of hospitalization (group I > group II, P < 0.05). These data show that rhGM-CSF is highly effective in reducing the duration of aplasia following BMT and PBPC transfusion, and there appears to be little difference in efficacy between these techniques, provided that patients also receive rhGM-CSF.

Adolescent↗
PubMed1996

Value of autologous bone marrow transplantation (ABMT) in 42 patients with follicular lymphomas responsive to conventional chemotherapy: a "France Autogreffe" study.

The value of high-dose chemotherapy with hematologic stem cell rescue has not yet been established in the treatment of low-grade non-Hodgkin's lymphoma. We report the results of a retrospective "France Autogreffe" study of 42 patients grafted during first partial remission (N = 13) or chemosensitive relapse (N = 29) for follicular lymphoma before January 1990. The median age was 38 years (range: 26 to 61 years). Preparative therapy was chemotherapy alone in 22 patients and total body irradiation (TBI)-containing regimens in 20 patients. Thirty-seven patients received hematopoietic marrow stem cells. Bone marrow purging was performed in 15 patients. Five patients received peripheral blood stem cells. With a median follow-up of 43 months, relapse-free survival is 66%, event-free survival 58%, and overall survival 83%. To date, no prognostic factors have been shown. Nine of these patients were tested for evaluation of minimal residual disease by polymerase chain reaction analysis of bc12 rearrangement in the blood. Six were positive.

Adult↗
PubMed1995

[Peripheral blood stem cell transplantation: current status and perspectives].

Peripheral blood stem cell (PBSC) transplantation is now widely used as technics of stem cell transplantation. If it is efficacious in terms of short-term engraftment, many questions remain unanswered: which is the best technic of mobilization, what role for growth factors after graft, which benefit to add bone marrow stem cells? So, comparative trials are necessary to compare bone marrow transplantation and peripheral stem cell transplantation in terms of long-term engraftment and anti-tumoral effect. However, the present main point is to better define the adequate estimation of circulating hematopoietic progenitors according to the technics of collection: evaluation of CFU-GM and CD34+ levels are inadequate for estimation of immature progenitor cells which vary a lot according to the types of chemotherapy or of growth factors used for mobilization.

Antigens, CD↗
PubMed1995

Cytokine production in long-term marrow cultures after autologous bone marrow transplantation.

We compared the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF alpha) in the supernatant of long-term bone marrow cultures (LTBMC) derived from 10 control patients and from 14 patients before and 3 months after autologous bone marrow transplantation (BMT). The three cytokines were spontaneously present in the supernatant of cultures established from patients before and after autologous BMT, while GM-CSF remained undetectable in the supernatants of control patients. The maximal levels of cytokines were produced after the first week and were not statistically different between control, patients before and after grafts although the granulocyte-macrophage colony-forming unit (CFU-GM) production in long-term culture (LTC) was lower in patients after graft compared with control patients (median values at LTC initiation: 32 and 158, respectively, P < 0.001 and median values of the total production: 510 and 12406, respectively, P < 0.002). However, GM-CSF was more frequently detected in patients after graft than in control patients. This study demonstrated that the production of GM-CSF, G-CSF and TNF alpha is not impaired in patients after graft (medians 0, 870.5, 173.5 pg/ml and ranges 0-31.2, 0-10 000 and 0-1426, respectively) compared with control patients (medians 0, 69, 66 pg/ml and ranges 0, 0-13 280 and 0-1318, respectively), although patients after graft were shown to have lower marrow CFU-GM counts. These results suggest that the ability of the accessory cells to produce these cytokines was not reduced after autologous BMT.

Adolescent↗
PubMed1995

Long-term cultures to evaluate engraftment potential of CD34+ cells from peripheral blood after mobilization by chemotherapy with and without GM-CSF.

In this study we used a long-term culture system to evaluate engraftment potential of human peripheral blood (PB) cells mobilized by chemotherapy (CT) associated or not with granulocyte-macrophage colony-stimulating factor (GM-CSF). In six patients who underwent blood cell transplantation, PB CD34+ cells were cultured after mobilization and were compared to CD34+ cells in steady state from PB and bone marrow (BM). Qualitative differences were shown between PBC samples obtained after CT with and without GM-CSF. Despite similar CFU-GM counts at culture initiation, GM-CSF-mobilized CD34+ cells might contain a lower proportion of primitive stem cells, as suggested by the significant decrease in CFU-GM numbers produced beyond week 5 compared to CT-mobilized CD34+ cells (p = 0.033). Likewise, the percentage of CFU-GM produced beyond week 5 in relation to initial input was significantly lower than steady-state PB (p = 0.039) and than CT-mobilized CD34+ cells (p = 0.033). However, this CFU-GM production with GM-CSF-mobilized PB CD34+ cells was not different from cultures with BMC CD34+ cells. These results suggest that GM-CSF can mobilize CFU-GM in the blood mainly by differentiation at the expense of the primitive stem cell compartment. It appears valuable to define clearly for each mobilizing procedure a particular threshold of CFU-GM which reflects sufficient numbers of primitive stem cells to ensure long-term engraftment.

Adolescent↗
PubMed1994

Three courses of high dose therapy. Feasibility in the treatment of multiple myeloma--a "France autogreffe" study.

BACKGROUND: High dose melphalan is used widely in the treatment of multiple myeloma (MM) and in the conditioning regimen of autologous stem cell transplantation (ABST). Double courses of high dose melphalan and double autologous bone marrow transplantation (ABMT) programs also have been widely reported. However, there are no data about the feasibility and efficacy of three courses of high dose therapy, such as high dose melphalan or powerful therapies in the treatment of malignant disease. METHODS: In 1991, a retrospective study in France was initiated to evaluate how many patients with MM had received three courses of high dose therapy with or without hematopoietic stem cell rescue. RESULTS: This small study of six patients with multiple myeloma showed that three courses of high dose therapy with or without stem cell rescue can be performed with relative safety. Stem cell rescue appears to shorten the duration of aplasia. In terms of antitumor response, long term response could be obtained in patients with MM that responded to the first course of high dose melphalan. CONCLUSIONS: High dose therapy with or without ABMT can be an effective treatment for relapse in a subgroup of patients with MM who respond to high dose melphalan as initial treatment.

Adult↗
PubMed1994

Autologous bone marrow transplantation for low-grade non-Hodgkin's lymphoma: the European Bone Marrow Transplant Group experience. EBMT Working Party for Lymphoma.

BACKGROUND: Influenced by successful results treating intermediate- and high-grade non-Hodgkin's lymphoma (NHL), high-dose therapy followed by autologous bone marrow transplantation (ABMT) is increasingly applied in low-grade NHL. However, the published data are limited. PATIENTS AND METHODS: In the European Bone Marrow Transplant Group (EBMT) Registry 92 patients with low-grade NHL treated with ABMT could be identified. RESULTS: The overall progression-free survival was 52% at 5 years with a median follow-up of 19 months. Patients with a complete remission or responsive disease at ABMT had a better outcome. There was no benefit for patients transplanted with either total body irradiation in the conditioning regimen or a purged autograft. CONCLUSIONS: Although the median follow-up is short, the data are very promising and warrant a randomized trial analyzing the value of high-dose therapy and purging in low-grade NHL.

Adult↗
PubMed1994

Haemopoiesis of transplanted patients with autologous marrows assessed by long-term marrow culture.

We assessed the effect of antitumoural therapy at intensive doses on the haemopoietic system using long-term marrow cultures (LTMC) established from 33 patients (25 with haematological diseases and eight with solid tumours) after autologous bone marrow transplantation (ABMT). When compared to 42 pre-graft patients, a decreased CFU-GM production and a defect in stromal layer (SL) confluence were found after ABMT on day 90 but also on day 365. However, these abnormalities were observed only in patients with haematological diseases and no differences between pre-graft and post-graft results were found in patients with solid tumours. Among the patients with haematological diseases, on day 90 those with acute lymphoid leukaemias showed lower CFU-GM production whereas patients with non-Hodgkin's lymphomas developed more frequently subconfluent or confluent SL. Other factors studied such as sex, patient age, disease status, marrow purging and post-graft administration of growth factors did not appear to influence post-graft LTMC results. Multivariate analysis including all the patients has shown (a) that solid tumours were associated with higher CFU-GM production, and (b) that conditioning regimens with total body irradiation (TBI) or busulfan led more frequently to non-confluent SL. In conclusion, high-dose therapy followed by ABMT can induce a persistent impairment of the stem cell and stromal cell compartments, particularly in patients with haematological diseases conditioned with TBI, despite the absence of any alloimmune reaction and post-graft immunosuppressive therapy.

Adolescent↗