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D Blaise

Publications and source records attributed to D Blaise.

At least 73 records · Page 4Linked to original sources
PubMed2000

Autologous blood cell vs marrow transplantation for acute myeloid leukemia in complete remission: an EBMT retrospective analysis.

In order to compare autologous bone marrow (BMT) and blood cell transplantation (BCT) in patients with acute myeloid leukemia (AML) in first remission (CR1), we retrospectively reviewed the data of 1393 patients registered to EBMT and undergoing either BCT (n = 100), purged (n = 252) or unpurged (n = 1041) BMT. Hematopoietic recovery was significantly quicker after BCT than after either purged or unpurged BMT. The 2-year leukemia-free survival (LFS), relapse incidence (RI) and overall survival for the entire population of patients were 52 +/- 1%, 43 +/- 1% and 58 +/- 1% and were significantly influenced by FAB subtype (M3 vs other) and the intervals between diagnosis and CR1 or CR1 and transplant. After BCT, LFS and RI were 44 +/- 6% and 50 +/- 6% and did not differ significantly from that found for unpurged BMT (49 +/- 2% and 45 +/- 2%; P = NS). However, LFS (57 +/- 3%) and RI (37 +/- 3%) of patients undergoing purged BMT were significantly different from that found for BCT patients (P = 0.01 and P = 0.006). As some characteristics of patients undergoing BCT or purged BMT differed significantly (age, intervals between diagnosis and CR1 or CR1 and transplant), the better outcome observed for purged BMT over BCT patients needs to be prospectively investigated.

Acute Disease↗
PubMed2000

The dismal outcome in patients with acute leukaemia who relapse after an autograft is improved if a second autograft or a matched allograft is performed. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

All patients receiving autografts for acute leukaemia in remission between 1 January 1981 and 31 December 1996 and reported to the European Group for Blood and Marrow Transplantation and had a relapse, were included. The patients underwent an allograft (n = 90, group A), were treated with chemotherapy (n = 2584, group B) or received a second autograft (n = 74, group C). The 2-year survival after relapse was 32 +/- 5%, 11 +/- 1% and 42 +/- 6% in groups A, B and C, respectively. In group A, those with an HLA-A, -B and -DR compatible related or unrelated donor had a 2-year survival of 37 +/- 7% compared to 13 +/- 8% for those receiving a graft from an HLA mismatched donor (n = 20). The following factors were associated with better survival in multivariate analyses: an interval from first autograft to relapse >5 months (P < 0.00001), a first autograft performed later than 1991 (P < 0.00001), patient age below 26 years (median, P < 0.002), group B vs HLA mismatches from group A (P = 0.002), group C vs group B (P < 0.005), patients who were not treated with total body irradiation at first autograft (P < 0.02) and patients in first remission at first autograft (P = 0.02). To conclude, the poor outcome in these patients was improved if a second autograft was feasible (P < 0.005), or if an HLA-matched allograft was performed (NS). Bone Marrow Transplantation (2000).

Acute Disease↗
PubMed2000

High rate of secondary viral and bacterial infections in patients undergoing allogeneic bone marrow mini-transplantation.

New approaches using nonmyeloablative-conditioning regimens have been developed to cause minimal procedure-related toxicity. Such novel therapeutic options are being explored with good preliminary results concerning feasibility and engraftment. However many aspects remain under-evaluated, and few data are available about viral and nonviral infections after these highly immunosuppressive regimens. We present our preliminary data on 21 patients receiving a highly immunosuppressive conditioning strategy, focusing on early infectious complications. Early viral infections before day 45, especially CMV, occurred at a high rate (65%). Furthermore, 33% of patients presented with late bacterial infections (predominately gram negative) although they were not neutropenic compared to conventional conditioning regimens. Although there is presently real interest in these new conditioning regimens which result in reduced immediate transplant-related mortality, it is important that investigators be aware of these pitfalls which may secondarily increase transplant toxicity. Further studies are needed to confirm these findings.

Adult↗
PubMed2000

Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Société Française de Greffe de Moelle (SFGM).

To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 +/- 4%, 20 +/- 4%, 45 +/- 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age <15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graft-versus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication.

Acute Disease↗
PubMed2000

Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Française de Greffe de moelle (SFGM).

Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) >/= grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 +/- 8% and 30 +/- 8%, respectively, with a risk of relapse of 44 +/- 12% and a transplant-related mortality of 45 +/- 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant.

Acute Disease↗
PubMed2000

No impact of high-dose cytarabine on the outcome of patients transplanted for acute myeloblastic leukaemia in first remission. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

High-dose cytarabine is currently used in combination with anthracycline in the treatment of acute myeloblastic leukaemia (AML). Moreover, high-dose cytarabine has been reported to produce long-term disease-free survival in a proportion of patients, especially in certain subtypes of AML. However, it remains unknown whether the outcome of patients undergoing allogeneic or autologous stem cell transplantation is influenced by previous treatment with high-dose cytarabine. To this end, 1672 patients with AML in first remission who were reported to the Acute Leukaemia Working Party registry of the European Group for Blood and Marrow Transplantation (EBMT) and who were transplanted between 1980 and 1995 were analysed according to the dose intensity of cytarabine given at induction and/or consolidation. Autologous stem cell transplantation (ABMT) was performed in 846 patients and allogeneic bone marrow transplantation (BMT) in 826 patients. This study shows that the dose of cytarabine (Ara-C) given at induction and/or consolidation did not influence the relapse incidence in patients subsequently allografted or autografted. In addition, it did not give any advantage in terms of overall outcome. Therefore, high-dose (HD) Ara-C may not be needed for patients who have a planned stem cell transplantation (SCT) as post-remission therapy. Nevertheless, HD Ara-C may be utilized in certain subtypes of AML that are believed to be curable by chemotherapy alone.

Adolescent↗
PubMed2000

Second early allogeneic stem cell transplantations for graft failure in acute leukaemia, chronic myeloid leukaemia and aplastic anaemia. French Society of Bone Marrow Transplantation.

In this retrospective multicentre study, we analysed the results of 82 consecutive second early allogeneic transplants for primary (n = 28) or secondary ([n = 54) graft failures performed between 1985 and 1997 in patients with acute leukaemia (n = 33), aplastic anaemia (n = 29) or chronic myeloid leukaemia (n = 20). HLA-matched siblings were used in 64 cases. The same donors were used for both transplants in 56 cases and the first transplant was T-cell depleted in 30 cases. The median age at transplant was 25 years and the median intertransplant time interval was 2 months. Estimates of the 3-year overall survival and day 100 transplant-related mortality were 30% and 53% respectively. A recipient age < 34 years at transplant, an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology were predictors of a better outcome. The use of cyclosporin A (CsA) after second transplant had a dramatic impact on outcome, the best results being observed with CsA alone. The day 40 probability of neutrophil recovery was 73%. The use of peripheral blood progenitor cells (PBPCs) was associated with a higher and faster neutrophil recovery. Other factors associated with neutrophil recovery were an intertransplant time interval > or = 80 d and a positive recipient cytomegalovirus serology. Therefore, second early allogeneic transplantation for graft failure is an effective treatment, especially if patients can receive CsA for graft-versus-host disease prevention and are retransplanted more than 80 d from first transplant.

Adolescent↗
PubMed2000

Is there a graft-versus-leukaemia effect in the absence of graft-versus-host disease in patients undergoing bone marrow transplantation for acute leukaemia?

During a 13-year period, 5200 autografts, 1039 HLA-identical sibling transplants without acute or chronic graft-vs.-host disease (GVHD) and 67 twins were reported to the European Group for Blood and Marrow Transplantation EBMT. Follow-up time was a median of 32 months. Diagnoses were acute myeloid leukaemia (AML, 4521) and acute lymphoblastic leukaemia (ALL, 1785) in first complete remission. The probability of relapse at 5 years was 51 +/- 1% in the autografts, 45 +/- 8% in the twins and 34 +/- 2% among the HLA-identical siblings (auto vs. sibs, P < 0.0001). In multivariate analyses, the following factors were significantly associated with an increased risk of relapse: ALL vs. AML M3 [relapse rate (RR) 2.29, P < 0.0001], AML non-M3 vs. AML M3 (RR 1.8, P < 0.0001), autograft vs. sibling transplant (RR 1.76, P < 0.0001), interval diagnosis to transplantation < 261 d (RR 1.45, P < 0.001) and other conditioning vs. total body irradiation (RR 1.16, P = 0.001). Transplant-related mortality was the same in the three groups at approximately 10% at 2 years. Five-year leukaemia-free survival was 42 +/- 1% in the autografts, 44 +/- 8% in the twins and 58 +/- 2% among the siblings (auto vs. sibs, P < 0.0001). The factors significant for relapse were also significant in multivariate analyses for leukaemia-free survival. In addition, children had a significantly better leukaemia-free survival than adults (RR 0.82, P < 0.0001). Recipients of bone marrow from HLA-identical siblings without GVHD had a lower risk of relapse and a better leukaemia-free survival than recipients of autografts. This may be as a result of a graft-vs.-leukaemia effect in the absence of GVHD.

Acute Disease↗
PubMed2000

Ex vivo expansion of human hematopoietic progenitors and cells to support high-dose chemoradiation therapy: five years of clinical experience.

The identification of cytokines-soluble or membrane-bound regulators of hematopoietic stem and progenitor cell survival, proliferation, and differentiation - and the definition of culture conditions that enable cell and progenitor expansion, has lead to the first clinical trials using cultured cells in addition to or in place of unmanipulated cells. The use of ex vivo expanded cells can improve several aspects of autologous and allogeneic hematopoietic cell and progenitor transplantation, such as reducing or abolishing the nadir that follows high-dose chemoradiation therapy regimens, or reducing the clinical risks associated with the use of small numbers of progenitors as in cord blood transplantation and in autologous transplantation for poor mobilizers. In addition, biological questions raised by ex vivo expansion are shared by scientists and clinicians interested in gene transfer into hematopoietic stem cells. We here review the biological problems associated with ex vivo expansion: defining efficient culture conditions, considering not only scientific and biological issues but also regulatory and commercial issues, defining appropriate surrogate endpoints that predict engraftment and superior clinical efficacy to that obtained with the use of unmanipulated grafts. We also review the results of the first clinical trials that have demonstrated the feasibilty of this approach, and have shown some of its limitations; demonstration of clinical efficacy will require more preclinical and clinical work.

Antineoplastic Agents↗
PubMed2000

CD34(+) immunoselected cells for poor graft function following allogeneic BMT.

BACKGROUND: Poor graft function without signs of graft rejection following allogeneic BMT (allo-BMT) occurs in around 9% of patients. A high incidence of hazardous complications may be encountered, leading to life-threatening situations. METHODS: We describe three patients who underwent allo-BMT for acute leukemia in first complete remission and untreated myelodysplastic syndrome. The three patients experienced prolonged and profound granulocytopenia, anemia and thrombocytopenia, despite growth factors and transfusions. This was not corrected by donor leukocytes infusion. They received a boost of CD34(+) positively-selected cells from their HLA-identical sibling donors. RESULTS: A rapid improvement of peripheral blood cell counts was observed in both patients who were in full donor chimerism status at time of boost infusion, whereas the patient with mixed chimerism did not show any signs of improvement. Neither patient suffered further exacerbation of GvHD. DISCUSSION: Allogeneic positively-immunoselected CD34(+) cells can represent an interesting alternative treatment for poor graft function following allo-BMT, in the absence of graft rejection signs.

Adult↗
PubMed2000

Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle.

PURPOSE: To compare hematologic recovery in patients receiving allogeneic blood cell transplantation (BCT) with those receiving allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: One hundred eleven patients with leukemia in the early stages and with HLA-matched sibling donors were randomized in this study. One hundred one underwent transplantation. Standard procedures for collection and transplantation were used. Patients did not receive prophylactic granulocyte colony-stimulating factor after undergoing transplantation. In addition to clinical end points being established, a prospective and comparative economic evaluation of the first 6 months after transplantation was performed. RESULTS: Groups were balanced for patient, donor, and transplant characteristics. Blood cell collection led to the collection of a higher number of CD34(+) and CD3(+) cells than did bone marrow collection (P < 10(-6)) without reported side effects for the donor. Patients in the BCT group reached platelet counts of 25 and 50 x 10(9) platelets/L 8 and 11 days earlier than did the BMT group (P < 10(-4) and P < 10(-5)), respectively. This resulted in fewer platelet transfusions during the first 180 days after transplantation (P =.002) for the former group. The time to reach neutrophil counts of 0.5 and 1 x 10(9) neutrophils/L was 6 and 7 days shorter, respectively, in the BCT group than in the BMT group (P < 10(-5)). This quicker hematologic recovery was associated with a shorter length of hospitalization and a decrease in total cost of procedure during the first 6 months. CONCLUSION: This study establishes that allogeneic BCT results in quicker hematologic recovery but is associated with a higher occurrence of chronic graft-versus-host disease.

Acute Disease↗
PubMed2000

Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission.

Immunological control of acute leukemia may be achieved after allogeneic transplant. Despite promising preliminary results, the impact of immunotherapy with interleukin-2 (r-IL-2) on patients with acute leukemia (AL), in first complete remission (CR1) remains unclear. We conducted a prospective multicenter randomized trial to compare outcome in patients with AL in CR1, treated with autologous bone marrow transplantation (BMT) with or without postgraft r-IL-2. One hundred and thirty patients with AL in CR1 (myeloblastic (AML): N = 78; lymphoblastic (ALL): N = 52) were randomized at time of BMT to receive (N = 65) or not (N = 65) r-IL-2. r-IL-2 (RU 49637 from Roussel Uclaf) was started after hematological recovery, as a five cycle regimen (12 M IU/m2/day continuous infusion on day 1-5, 15-17, 29-31,43-45 and 57-59). The two groups were balanced for patient and transplant characteristics. Analysis was based on an intent to treat. Thirty-eight (59%) of the 65 patients randomized into the study group started r-IL-2 at a median of sixty-eight days (23-140) after transplant and received 77% (16-100) of the scheduled dosage. They received a median of 120 x 10(6) IU/m2 (25-156) over 10 (3-13) days during a total median period of 56 (3-78) days. With a median follow-up of 7 years (5.4-8.1 years), 79 patients relapsed (study group: 43 (66%); control group: 36 (55%): p = NS). Survival and leukemia-free survival estimates were 33% (23-45) versus 43% (22-52) and 29% (19-41) versus 36% (24-51) respectively for study and control groups (all p = NS). These results show that leukemic control after autologous BMT is not increased by r-IL-2 therapy. Further studies should investigate more appropriate r-IL-2 schedules and the possibilities offered by better antigen recognition and activated effector cells.

Adult↗
PubMed1999

Positive selection of CD34+ peripheral blood progenitor cells in patients with low-grade lymphoid malignancies and bone marrow involvement.

PURPOSE: 16 patients with low-grade lymphoid malignancies and bone marrow involvement were transplanted with selected CD34 positive Peripheral Blood Progenitor Cell (PBSC) prepared from autologous aphereses. PATIENT AND METHODS: All but one patients were mobilized with a combination of chemotherapy (including high-dose cyclophosphamide and VP16 or adriamycin, aracytin with cysplatyl) and recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF). RESULTS: A median of 3 (range, 1 to 9) aphereses yielded 15.35 x 10(6) CD34+ cells/kg (range, 4.45 to 70.88). A median of 5.01 x 10(6) adsorbed CD34+ cells/kg (range 2.01 to 24.13) was obtained after selection (median purity: 86%; range, 59-99%). The CD34 PBSC were infused one day after either one of two conditioning regimens: 11 patients received the association of cyclophosphamide (120 mg/kg) and TBI (8Gy), and 5 patients received the BEAM regimen. No recombinant hematopoietic growth factor was used after cell reinfusion. Median days to 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets were 13 (range, 9 to 18) and 16 (range, 11 to 35), respectively. The median number of red blood cell (RBC) unit transfusions was 4 (range, 0 to 10). The median number of platelet transfusions was 3.5 (range, 0 to 8). No individual received backup PBSC, nor required platelet transfusion beyond 3 months post-transplant. CONCLUSION: This study confirms the feasability of using blood CD34 cells to support hematopoietic recovery after myelo-suppressive or myelo-ablative regimens, in patients with low-grade NHL.

Adult↗
PubMed1999

Optimization of peripheral blood stem cell collection by leukopheresis. Interaction between economic and clinical assessment of an innovation.

Using the example of substitution of peripheral blood stem cell (PBSC) collection to bone marrow harvest for autologous transplantation in cancer patients, our study attempts to illustrate how economic assessment, starting at an early stage of medical innovation, can influence the development and diffusion process of a new technological procedure whose optimal design has not yet been established. Two cost minimization studies comparing costs for obtaining a clinically reinfusable graft using bone marrow harvest or alternatively various protocols of PBSC collection contributed to a change in the French clinical standard for this procedure.

Bone Marrow Transplantation↗
PubMed1999

CD34+ cell enumeration in peripheral blood and apheresis samples, using two laboratory diagnostic kits or an institutional protocol.

In order to prepare the substitution of a commercially available diagnostic kit, ProCOUNT (Becton Dickinson) or Stem-Kit (Coulter Immunotech), for our institutional protocol, we compared the three techniques for the numeration of CD34+ progenitor cells in 50 peripheral blood and 51 apheresis samples, obtained from cancer patients or healthy donors. We show here that the three techniques yield results of the same order of magnitude. Although statistical analyses demonstrate significant differences between the three methods, these differences turned out to be clinically insignificant in most situations. Observed differences mostly affect samples with the highest content of CD34+ cells, while the three assays provide equivalent results for values that are close to clinically relevant thresholds (20 x 10(3) CD34+ cells/ml in peripheral blood to start apheresis, and accumulated number above 3 x 10(6) CD34+ cells/kg to stop apheresis). This study also supports the view that institutional protocols can provide a highly reliable determination of CD34+ cells counts and percentages. However, because institutional protocols often use research reagents and vary from institution to institution, the use of diagnostic kits may be prefered as one way to improve quality assurance in the practice of cell therapy.

Antigens, CD34↗
PubMed1999

Intensive sequential chemotherapy (ISC 95) with growth factors and blood stem cell support in high-intermediate and high-risk (IPI 2 and IPI 3) aggressive non-Hodgkin's lymphoma: an oligocentric report on 42 patients.

We previously reported feasibility and efficacy of a monocentric pilot study of intensive sequential chemotherapy (ISC) in poor-risk aggressive non-Hodgkin's lymphoma (NHL) in patients < 60 years. To validate these results on a large cohort of patients, we designed a new and oligocentric study. After a COP (cyclophosphamide (Cy), vincristine (Vcr), prednisone (Pred) debulking, patients received four courses of high-dose CHOP (Cy, doxorubicin (Doxo), Ver, Pred), with the addition of etoposide and cisplatin during the two last courses. G-CSF was delivered after each cycle, and peripheral blood stem cells (PBSC) were used to support the two last cycles. Total duration of chemotherapy was 13 weeks, with a planned dose-intensity (DI) of 1420 mg/m2/week and 23 mg/m2/week for Cy and Doxo, respectively. Radiotherapy (involved fields) was then delivered for patients with node size > or = 5 cm at diagnosis. Forty-two patients were enrolled in this study; 36 completed the treatment and received 75% or more of the planned DI for both Cy and Doxo. Median duration of grade 4 neutropenia was 14 days (range, 2 to 28) for the regimen as a whole, and median duration of rehospitalization for febrile neutropenia was 18 days (range, 4 to 41). Overall response rate was 83%, with 29 patients (69%) in complete response (CR). Six patients failed to respond and one died of toxicity. With a median follow-up of 22.5 months (range, 10 to 42), the 3-year event-free survival (EFS) is 55% (95% CI, 39-71), while disease-free survival (DFS) is 79% (95% CI, 63-95). Ambulatory ISC is accessible and feasible in an oligocentric study. PBSC allow repeated delivery of high-dose chemotherapy cycles, and result in encouraging CR, EFS, and DFS rates for poor-risk aggressive NHL's patients.

Adult↗
PubMed1999

Treatment of chronic myelogenous leukemia with interleukin-2: a phase II study in 21 patients.

We designed a phase II study to assess the activity of recombinant interleukin-2 (rIL-2) in patients with chronic myelogenous leukemia (CML). Study population included 11 patients in the chronic phase of CML (6 in hematologic remission and 5 with active disease), 6 patients in the accelerated phase, and 4 in blastic phase of CML. Patients received three 5-day cycles administrated every other week. rIL-2 was given as intravenous bolus infusions of 8 x 10(6) IU/m2 three times a day during cycle 1 and twice a day during cycles 2 and 3. Response to rIL-2 was assessed on day 45. No hematologic response was achieved in the patients with evaluable disease. One patient in hematologic remission with rIL-2 achieved a major response (from 72% to 9% Ph+ metaphases), and two patients had some degree of reduction of Ph+ metaphases. Responses were short-lived (< 6 months), but two of these three patients achieved a new cytogenetic response with interferon given post-rIL-2. A significant immune activation was achieved with rIL-2 including a marked increase in CD3+/CD25+ cells, CD56+ cells, and in natural killer/lymphokine activated killer cell cytotoxic activity. These results confirm preclinical studies, which showed that IL-2 has antileukemic activity in CML. However, the responses observed were short lived and restricted to a subgroup of patients with low disease burden. This invites further studies testing its impact in situations of minimal disease or in combination with other cytokines.

Adolescent↗