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Biomedical subjects

D Blaise

Publications and source records attributed to D Blaise.

At least 127 records · Page 7Linked to original sources
PubMed1995

Consolidation treatment of adult acute lymphoblastic leukemia: a prospective, randomized trial comparing allogeneic versus autologous bone marrow transplantation and testing the impact of recombinant interleukin-2 after autologous bone marrow transplantation. BGMT Group.

A prospective, randomized trial was initiated in adult acute lymphoblastic leukemia (ALL) to compare (1) disease-free survival (DFS) after allogeneic or autologous bone marrow transplantation (BMT) and (2) the relapse rate of patients treated with or without interleukin-2 (IL-2) after autologous BMT. A total of 135 previously untreated patients, aged under 55 years, received the Berlin-Frankfurt-Muster (BFM) induction regimen: 126 patients (93%), of which 120 were HLA-typed, achieved complete remission (CR). According to this genetic randomization, patients with (n = 43) or without an HLA-identical sibling (n = 77) were to receive allogeneic or autologous BMT, respectively. The 3-year post-CR probability of DFS was significantly higher in the HLA-identical sibling group than in the non-HLA-identical sibling group (68% v 26%; P < .001). Eligible patients were randomized to receive (n = 30) or not to receive (n = 30) IL-2 after autologous BMT: the 3-year post-BMT probability of continuous CR was similar in both groups (29% v 27%, respectively). We conclude that, in ALL, early allogeneic BMT after the BFM induction regimen is an effective consolidation treatment and that IL-2 does not decrease the high relapse rate observed after autologous BMT.

Adult↗
PubMed1995

Impairment of leukaemia-free survival by addition of interleukin-2-receptor antibody to standard graft-versus-host prophylaxis.

Graft-versus-host disease (GVHD) is the most important adverse effect of HLA-matched allogeneic bone-marrow transplantation. T-cell depletion of the graft eliminates GVHD but also causes an unacceptable increase in rejections and leukaemic relapses. We have attempted to block the activation of resting T cells with a monoclonal antibody against the interleukin-2 receptor (33B3.1). 101 patients with leukaemia (acute lymphocytic 22, acute myelogenous 34, chronic myeloid 45) in first complete remission or first chronic phase were randomly assigned to groups receiving standard post-transplantation immunosuppression (methotrexate plus cyclosporin; n = 50) or the standard treatment plus antibody 33B3.1 (n = 51). There were 2 graft failures in the 33B3.1 group. The antibody did not significantly affect the cumulative frequency of acute GVHD of grade 2 or worse (19 [38%] vs 23 [46%]) but merely delayed its onset (median 36 [IQR 21-70] vs 25 [11-44] days; p < 0.01). At median follow-up of 58 (range 41-71) months, the antibody-treated group had significantly lower leukaemia-free survival (p < 0.05) mainly because of a progressive increase in the rate of late relapses (p = 0.08). Our findings confirm the importance of T cells in transplantation for leukaemia. The fine balance between the early modulation of transplant immunity and leukaemic control suggests that further anti-leukaemic measures may be needed when attempts are made to improve tolerance between the graft and the leukaemic host.

Adolescent↗
PubMed1995

Allogeneic bone marrow transplantation for chronic myeloid leukemia in first chronic phase: a randomized trial of busulfan-cytoxan versus cytoxan-total body irradiation as preparative regimen: a report from the French Society of Bone Marrow Graft (SFGM).

From March 1988 to March 1991, 19 French bone marrow transplant (BMT) centers participated in a prospective randomized trial comparing two conditioning regimens for patients with chronic myeloid leukemia transplanted in first chronic phase with an HLA identical sibling donor. A total of 120 consecutive patients were randomized to receive either 120 mg/kg of cyclophosphamide followed by total body irradiation (CY-TBI; n = 55) or 16 mg/kg of busulfan followed by 120 mg/kg of CY (BU-CY; n = 65). Two different TBI regimens were used. Thirteen patients received a 10-Gy single-dose TBI (SDTBI), and 42 received a fractionated TBI (FTBI). Median time between diagnosis and BMT was 315 days. Overall 5-year actuarial survival was 62.9% (65.8% +/- 12.5% for CY-TBI and 60.6 +/- 11.7% for BU-CY; P = .5), and overall disease-free survival was 55% (51% +/- 14% for CY-TBI and 59.1% +/- 11.8% for BU-CY; P = .75). All patients conditioned with CY-TBI experienced sustained engraftment; in contrast, 4 of 65 patients conditioned with BU-CY rejected the graft (P = .18). There was no significant statistical difference between the two groups regarding transplant-related mortality (29% for CY-TBI and 38% for BU-CY; P = .44). So far, with a median follow up of 42 months, 11 patients have relapsed; 9 relapses occurred after CY-TBI, mostly after FTBI (8 of 9) and 2 after BU-CY (P = .02). The actuarial risk of relapse was 4.4% +/- 6.7% after BU-CY, 11.1% +/- 20.8% after SDTBI, and 31.3% +/- 18.1% after FTBI (P = .039). In addition, independently of the conditioning regimen, the increase of posttransplant immunosuppression in 16 patients with an anti-interleukin-2 receptor monoclonal antibody (MoAb) in addition to a short course of methotrexate and cyclosporine was shown to increase the actuarial risk of relapse (57% +/- 30% with MoAb v 9% +/- 7.3% without MoAb; P = .001). We conclude that BU is an acceptable alternative to TBI for patients with chronic myeloid leukemia in first chronic phase receiving BMT from HLA identical sibling donors. Both BU-CY and CY-TBI regimens gave similar transplant-related mortality, and the antileukemic efficiency of BU-CY regimen was either similar or even higher than that of CY-TBI.

Adolescent↗
PubMed1995

Fractionated or single-dose total body irradiation in 171 acute myeloblastic leukemias in first complete remission: is there a best choice? SFGM. Société Française de Greffe de Moelle.

PURPOSE: To evaluate the importance of fractionating total body irradiation (TBI) in patients receiving an allogenic bone marrow transplant (BMT) for an acute myeloblastic leukemia (AML) in first complete remission (CR1). METHODS AND MATERIALS: Between 1983 and 1990, 171 consecutive patients received either single dose TBI (STBI) (n = 65) or fractionated TBI (FTBI) (n = 106) after being conditioned with cyclophosphamide and before receiving a non-T-depleted Human Leucocyte Antigen (HLA)-identical marrow. Both groups were comparable except for date of BMT and diagnosis-to-BMT interval (D-BMT). RESULTS: After 63 months median follow-up, transplant-related mortality (TRM), probability of relapse, and 5-year disease-free survival (DFS) were 0.38 and 0.27 (p = 0.04), 0.29 and 0.26 (p = 0.22), 0.43 and 0.56 (p = 0.06), respectively, for STBI and FTBI. The supposed influence of the schedule of TBI disappeared in the multivariate analysis: TRM was enhanced by severe acute graft vs. host disease (p = 0.0002), early years of transplant (before January 1, 1987) (p = 0.0003), and longer D-BMT intervals (p = 0.038). Relapse was linked to early years of transplant (p < 0.00001), and the absence of chronic GVHD (p = 0.007). Longer DFSs were observed for later years of transplant (after January 1, 1987 and later) (p = 0.001), milder acute GVHD (p = 0.005), and shorter D-BMT intervals (p = 0.045). Important improvements of the results were made during the 7-year observation period: TRM, probability of relapse, and DFS were, respectively, 0.36, 0.28, and 0.46 for patients transplanted before January 1, 1987 vs. 0.21, 0.15, and 0.67 after that date. CONCLUSION: Our data strongly suggest that allogenic BMT is the best postremission treatment for AML in CR1, and the results are better when BMT shortly follows the achievement of remission. The schedule of TBI was of little importance compared with the improvements made in the management of patients undergoing BMT during the 1980s, and, therefore, reports concerning data prior to 1985 should be interpreted cautiously.

Adult↗
PubMed1995

Patient condition affects the collection of peripheral blood progenitors after priming with recombinant granulocyte colony-stimulating factor.

A total of 258 aphereses were performed in 79 patients with nonmyeloid malignancies after mobilization of peripheral blood stem cells (PBSC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF). Apheresis products were examined for viable mononuclear cell (VMC), CD34+ cell, and clonogenic cell contents. The number of progenitors in aphereses differs in subgroups of patients with different diagnoses. However, the number of CD34+ or clonogenic cells is dependent on age and amount of chemotherapy delivered to patients before collection rather than on the nature of the disease itself. In addition, the actual dose of rhG-CSF used to mobilize PBSC and the number of VMC in aphereses influenced the clonogenicity of CD34+ cells, although the daily dose of rhG-CSF seems to play little role on the number of clonogenic cells in each individual apheresis product. CD34+ cell and CFU-C (or CFU-GM) numbers are related parameters, and the relation can be described as linear. However, the linear relation varies in different patient groups, and most of the linearity is induced by the highest sets of values. We conclude that mobilization with low doses of rhG-CSF alone is feasible and that the probability of collecting a high number of peripheral blood progenitors is increased in young patients undergoing apheresis early in the course of the disease. Although the relationship between CD34+ cells and CFUs can be described as linear in well-defined situations, its relevance may be limited because it is not a universal finding.

Adolescent↗
PubMed1995

Direct evidence for dissociated megakaryocytic chimaerism in a Wiskott-Aldrich patient successfully allografted.

We report a Wiskott-Aldrich patient who underwent allogeneic bone marrow transplantation from his HLA-identical sister at the age of 25. Conditioning regimen consisted of cyclophosphamide (180 mg/kg) and thoraco-abdominal irradiation (6 Grays). Cytogenetic follow-up revealed rapid and complete lymphoid chimaerism, but prolonged mixed bone marrow chimaerism. Correlative interphase cytogenetics performed on bone marrow smears using dual-colour fluorescence in situ hybridization with X and Y specific probes showed that the proportion of donor cells was significantly higher within megakaryocytes than in other lineages. This patient therefore presented with dissociated lineage engraftment, which is not exceptional in congenital diseases and aplastic anaemia, but has not previously been described in Wiskott-Aldrich syndrome. Bone marrow transplantation was successful despite this delayed engraftment which ensured adequate production in the involved cell lines.

Adult↗
PubMed1995

[Comparison of anxiety and pain in two procedures of hematopoietic stem cell collection: cytapheresis and bone marrow collection].

The aim of this study was to compare anxiety, pain and discomfort of cancer patients submitted to two procedures of hematopoietic stem cells collection: peripheral blood stem cells collection (PBSCC) or bone marrow collection (BMC). Patients, randomized (July 1993-February 1994), in view of autograft, to receive the first procedure or the second one, completed self-administered questionnaires before, during and after the procedure. Anxiety was evaluated by State-Trait Anxiety Inventory. Pain was assessed using visual analogical scale (VAS) and McGill Pain questionnaire. Before the procedure, in comparison with PBSCC patients (n = 40), BMC patients (n = 25) experienced more State-anxiety due to the procedure approach (p < 0.01) and more trouble or inconvenience for having to come and stay at the hospital (p < 0.0001). During the procedure, pain related to BMC, as assessed by VAS, is significatively higher than pain induced by PBSCC, whichever the access used (p < 0.001). The McGill total score is twice as high for BMC patients than for patients submitted to PBSCC with femoral catheter (n = 19). The latter patients significatively reported more pain than patients without femoral catheter (n = 21). At the discharge from hospital, 32% of BMC patients judged the procedure quite difficult vs 5% of PBSCC patients (p < 0.05). These results explain a higher acceptability of the peripheral blood stem cells collection.

Adult↗
PubMed1995

Long-term side-effects in children receiving allogeneic bone marrow transplantation in first complete remission of acute leukaemia.

We evaluated the long-term side-effects of allogeneic BMT performed early in the course of childhood acute leukaemia (first complete remission and interval between diagnosis and BMT not exceeding 6 months). Thirteen patients fulfilled these criteria. Conditioning regimens included TBI in eight cases. Evaluation of growth and pubertal development, ophthalmological examination, assessment of thyroid, cardiac and pulmonary functions were performed. Neuropsychological evaluation included IQ score, memory tests and cranial MRI. Median follow-up after BMT was 5 years (range 2-10 years). Growth was normal in seven patients. Six patients experienced a decrease in SD score for height (range -0.1 to -1.9). Four children were evaluable for puberty: pubertal development was normal in three children and delayed in one case. Thyroid and left ventricular function were normal in all cases. Three patients had mild abnormalities of pulmonary function. In two patients cataracts were noted 7 and 10 years after fTBI. Mean full-scale IQ score was 102. Memory tests, performed in 12 cases, were in the normal range for 11 patients. In our study, frequency and severity of long-term side-effects following BMT for leukemia appeared lower than usually reported. A possible explanation is that children were transplanted very early in the course of their disease with neither cranial irradiation nor long exposure to chemotherapy prior to transplant.

Acute Disease↗
PubMed1995

Comparison of anxiety, pain and discomfort in two procedures of hematopoietic stem cell collection: leukacytapheresis and bone marrow harvest.

The aim of this study was to compare anxiety, pain and discomfort of cancer patients submitted to either peripheral blood progenitor cell collection (PBPCC) or bone marrow harvest (BMH). Patients, randomized (7/1993-2/1994), in view of autograft, to receive the first procedure or the second one, completed self-administered questionnaires. Anxiety was assessed by the State Trait Anxiety Inventory and pain using visual analogical scale (VAS) and McGill Pain questionnaire. Before the procedure, BMH patients (n = 25) experienced more anxiety (P < 0.01) and more trouble or inconvenience for having to come and stay at the hospital (P < 0.0001) than PBPCC patients (n = 40). Pain due to BMH is significantly higher than pain induced by PBPCC (P < 0.001 for VAS and total McGill score). However, patients submitted to PBPCC with a femoral catheter (n = 19) had significantly higher total McGill scores and sensory sub-scores than patients without it (n = 21). At discharge from the hospital, PBPCC patients expressed more positive judgements towards the collection procedure than BMH patients. These results suggest that a better patient acceptability of high-dose chemotherapy followed by autograft may be obtained by substituting PBPCC for BMH for stem cell collection.

Adult↗
PubMed1995

Isepamicin once daily plus ceftriaxone versus amikacin plus ceftriaxone in febrile neutropenic patients.

Isepamicin is a new aminoglycoside with in-vitro activity superior to amikacin. It is a poor substrate for the 6'-aminoacetyltransferase-I enzyme which inactivates amikacin and therefore organisms possessing this enzyme are not resistant to isepamicin. The aim of this study was to compare the efficacy and safety of co-administration of isepamicin once daily plus ceftriaxone to amikacin twice daily plus ceftriaxone to amikacin twice daily plus ceftriaxone in febrile neutropenic cancer patients. Febrile episodes in 235 patients (156 in isepamicin group and 79 in amikacin group) were treated in this study. They occurred in 218 different patients. Fifteen patients were enrolled twice and one three times. Response rates to the two treatment regimens for microbiologically documented episodes, clinically documented episodes and further unexplained fever were similar. Tolerance of the treatment regimens, as measured by serum creatinine levels, hypoaccousia and cutaneous allergy was also similar in both treatment groups. In conclusion, isepamicin given once daily when combined with ceftriaxone in the treatment of febrile episodes in neutropenic cancer patients was as effective and no more toxic than amikacin.

Adolescent↗
PubMed1995

Ex vivo expansion of human peripheral blood progenitors.

Culture of human hematopoietic progenitors on a large scale could lead to several clinical applications within the near future, including the production of differentiated and functional cells, the increase in the number of early progenitors, especially stem cells, with such use as gene transfer, or the improvement of grafts used to limit the hematological toxicity associated with high-dose chemotherapy. In this case, one can still distinguish different objectives: improvement of grafts that contain low numbers of progenitors because of prior chemotherapies or because of marrow involvement for example, and qualitative changes in the graft content that would allow to envision the disappearance, or the further reduction, in the duration of absolute neutropenia that follows delivery of high dose chemotherapy ("nadir rescue"), despite substitution of mobilized blood cells to marrow cells and the in vivo use of hematopoietic growth factors. Additional advantages may be related to tumor purging in autologous expanded cells, and to the change in the ratio between hematopoietic progenitors and immunocompetent cells in allogeneic expanded populations. Therefore it appears that in vitro expansion currently raises two types of questions: the first ones are related to the definition of clinical or biological endpoints to be achieved, the second ones are related to "bioengineering", and deal with the efficiency and safety of progenitor cell cultures to be used for clinical applications. We here present preliminary results preparing future pilot clinical studies with ex vivo cultured human hematopoietic cells.

Antigens, CD↗
PubMed1994

Discrete early pro-B and pre-B stages in normal human bone marrow as defined by surface pseudo-light chain expression.

Vpre-B and lambda-like genes are selectively expressed in B cell precursors and encode polypeptide chains associated in a mu-pseudo light chain (mu-psi L) complex which is thought to regulate some early steps of B cell differentiation. We have generated anti-Vpre-B monoclonal antibodies which allowed us to identify different steps of differentiation from the pro-B to the immature B cells by following surface expression of Vpre-B, mu and light chains in normal adult human bone marrow. Already present at the surface of a small fraction of B cell progenitors (CD34+/CD19+) the Vpre-B molecule was consistently found coexpressed with CD19 and was also found with the sequentially occurring CD10, CD20, CD21, CD22 and CD5 markers. Three discrete cell types were identified: (i) a subpopulation expressing Vpre-B without mu and which represented an early stage of differentiation, (ii) a minor subpopulation co-expressing Vpre-B and mu without the conventional light chains and (iii) a major subpopulation co-expressing Vpre-B, mu and kappa or lambda chains, considered an intermediate pre-B/B stage. The presence of the psi L chain in various cell subpopulations, in possible association with discrete molecules and/or different contexts, suggests its involvement at several steps of early B cell differentiation.

Adult↗
PubMed1994

In vivo stimulation of neutrophil function by lenograstim (glycosylated rHuG-CSF) in oncohematologic patients: results of a phase I trial.

The aim of this work was to study the evolution of neutrophil functions in non-neutropenic cancer patients. Thirty non-neutropenic patients, median age 35 years (range 19-52), with solid tumors (n = 21) or lymphomas (n = 9) entered a phase I study of five days of s.c. (n = 24) or i.v. bolus (n = 6) lenograstim, recombinant human glycosylated granulocyte colony-stimulating factor (rHuG-CSF Chugai-Rhône-Poulenc), with dose escalation from 1 to 40 micrograms/kg/day. Neutrophil functions were studied before lenograstim (D1) and 24 h after the last dose (D6). Granulocyte count rose in a significant way, and enzyme release, phagocytosis and bacterial killing were stimulated. All patients had improvement of at least one neutrophil function. Directed migration was depressed, although it was still in the normal range. These findings confirm that lenograstim is a potent activator of neutrophil functions in non-neutropenic cancer patients and may be useful as an adjunct to conventional antimicrobial therapy.

Adult↗
PubMed1994

High-dose therapy and autologous bone marrow transplantation in first complete remission for adult patients with high-grade non-Hodgkin's lymphoma: the EBMT experience. Lymphoma Working Party of the European Group for Bone Marrow Transplantation.

One hundred and eighteen patients presenting with high-grade non-Hodgkin's lymphoma, undergoing autologous bone marrow transplantation (ABMT) in first complete remission (CR), have been reported to the European Group for Bone Marrow Transplantation (EBMT). Of these, 102 were eligible for inclusion in this study following review of registration forms. Patients with lymphoblastic lymphoma were excluded. Remission induction and high-dose regimens varied between contributing centres. A maintained CR was observed in 90% of patients. Early relapse was observed in 6%, and 4% suffered toxic deaths. With a median follow-up of 45 months (3-112 months), the 5-year actuarial overall and progression-free survivals are both 70%. Nineteen (18%) patients relapsed at a median of 3.5 months (0.25-52 months) after ABMT, only 1 achieving a further durable CR. The only factor with prognostic significance was histological subtype, with diffuse small noncleaved-cell lymphoma having a significantly worse outcome. High-dose therapy and ABMT has produced effective consolidation of first remission in this group of patients, even in those with poor prognostic features at presentation.

Adolescent↗
PubMed1994

Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation--a report from the Société Française de Greffe de Moelle.

PURPOSE: To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS: The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS: The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION: Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Phase I study of in vivo lenograstim (rHuG-CSF) for stem cell collection demonstrates improved neutrophil recovery after autologous bone marrow transplantation.

Colony stimulating factors and especially rHuG-GSF, the first available neutrophil growth factor, have led to considerable interest in the field of stem cell transplantation because of their ability to induce stem cell peripheralization either alone or in association with high-dose chemotherapy. Few data exist, however, on the impact of rHuG-CSF on large scale bone marrow collection and autologous bone marrow transplantation (ABMT). This phase I, non-randomized, dose escalation study of rHu-G-CSF (lenograstim) administered to 30 patients at doses ranging from 1 to 40 micrograms/kg/day for 5 days before bone marrow harvesting showed that priming with rHu-G-CSF in vivo increased the number of bone marrow cells and D14 myeloid restricted progenitors (CFU-GM) and led to a better neutrophil recovery after ABMT compared with a contemporary unprimed control population. Otherwise, this study established that 5 days of rHuG-CSF therapy, as a sole stimulus, induced a tenfold increase in the circulating CFU-GM amongst which immature progenitors, estimated by the Delta assay (secondary CFU-GM grown after 7 days of liquid culture/primary CFU-GM), are detected. These conclusions were valid for doses as low as 2 micrograms/kg/day which induced only mild neutrophilia up to the highest dose (40 micrograms/kg/day) and suggest that a short course of rHuG-CSF is beneficial in increasing the stem cell collection.

Adolescent↗