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Biomedical subjects

D Maraninchi

Publications and source records attributed to D Maraninchi.

At least 55 records · Page 3Linked to original sources
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

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 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↗
PubMed2000

[A study based on national DRG data to evaluate work load and practice relating to cancer patients in not-for-profit hospitals].

BACKGROUND: In France there is no reliable information describing the organisation of hospital care for patients with cancer. The present study attempts to clarify this issue taking advantage of an information source that has up to now been unused, namely the national PMSI (Information System Medical program) data base. METHODS: A quantitative study has been carried out regarding cancer management in France using information filed with the PMSI which compiles data related to hospital admissions in all institutions with more than 100 beds and subject to a defined global budget. The "cancer" component of hospital activity was extracted using a specific algorithm which utilized the diagnostic and intervention codes included in the admission summaries. By using the unit of activity as defined by the ISA (Activity Synthetic Index) and the scale of relative cost according to the GHM (Homogeneous Group of patients) it was possible to analyse the information in terms of a balance sheet. RESULTS: The study provided information regarding the costs and methods of management, including therapeutic strategies, for each type of hospital establishment. It is shown that with one death out of six, cancer covers a quarter of all hospital stays, and one sixth of annual hospital expenses. This accounts for 16.2% of ISA ie approximately 29 billion francs (4.6 billion dollars) for the public and semipublic sectors. Surgery, which accounted for 32% of expenditures, appeared to be the most expensive intervention, ahead of chemotherapy (16.3%) and radiotherapy (9.1%). Each type of hospital organisation (university, cancer centre, district hospital) had their own relative figures. CONCLUSION: Through this study the current situation regarding cancer care in hospital has been documented. It has also demonstrated the value of the PMSI data base as a source of information for large scale quantitative studies of health care economics. However, the PMSI does not yet provide details regarding infrastructure or succession of hospital stay. Ultimately, this analysis does not provide any information on the quality or efficacy of care but does define a typological system for health care organisations which could provide information on distribution of resources.

Costs and Cost Analysis↗
PubMed1999

Concomitant chemoradiotherapy for patients with nonmetastatic breast carcinoma: side effects, quality of life, and organization.

BACKGROUND: This study was designed to investigate the personal experience of patients with nonmetastatic breast carcinoma who were treated with the concurrent administration of radiotherapy and chemotherapy in terms of side effects and quality of life (QL). METHODS: One hundred nine patients with nonmetastatic breast carcinoma, recruited between May 1995 and February 1997, were included in a protocol combining chemotherapy with mitoxantrone and cyclophosphamide, administered intravenously in 4 cycles of 21 days, and concomitant radiotherapy. Side effects of treatment and its impact on patients' daily lives were measured using ad hoc questionnaires; QL was measured by the European Organization for Research and Treatment of Cancer QLQ-C30 QL questionnaire, and pain was measured by a visual analogue scale (VAS). RESULTS: All patients agreed to participate. The mean number of chemotherapy and radiotherapy symptoms per cycle were: 7.2+/-2.5 and 2.4+/-1.8, respectively. Chemotherapy symptoms generally were more frequent and distressing than those of radiotherapy. The average pain score reported on the VAS by patients during treatment was 3.0+/-2.0. Multidimensional QL assessment showed that treatment mainly affects physical functioning and global QL. Multivariate analysis showed that the main determinants of QL at the end of treatment were fatigue, pain, and loss of appetite experienced during treatment. Moreover, 62.8% of patients required specific help for transportation to the hospital and/or home upkeep. CONCLUSIONS: The concurrent administration of chemotherapy and radiotherapy deteriorates patients' QL but in a proportion similar to sequential administration while presenting the advantage of a shorter duration of treatment. However, increased fatigue, pain, and loss of appetite as well as difficulties in patients' daily lives have to be taken into account in therapeutic decision-making analysis.

Activities of Daily Living↗
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

The role of autologous hematopoietic progenitor and cell reinfusion for intensive chemotherapy in women with poor-prognosis breast cancer. Clinical studies with ex-vivo expanded cells produced with the Aastrom Replicell technology.

In recent years, we have initiated two clinical studies, to evaluate the usefulness of ex-vivo expanded cells in patients with breast cancer who receive sequential high-dose chemotherapy. Ex-vivo expanded cells were produced from autologous cryopreserved bone marrow nucleated cells, using a biomedical device. The Aastrom Replicell system cultures cells in animal serum-replete medium, with a combination of flt3-L, PIXY321 and Epo, for 12 days. The initial pilot trial was set up to establish the feasibility and safety of the technique: 6 patients completed the study. An ongoing randomized study searches to establish whether ex-vivo expanded cells provide a clinical benefit.

Antineoplastic Combined Chemotherapy Protocols↗
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

Association of angiogenesis and poor prognosis in node-positive patients receiving anthracycline-based adjuvant chemotherapy.

UNLABELLED: Tumoral angiogenesis has been described as associated with poor prognosis in breast cancer, particularly for node negative breast cancer. The purpose of this study was to evaluate the influence of angiogenesis in node-positive breast cancer and particularly its potential impact on adjuvant chemotherapy. PATIENTS AND METHODS: One hundred and thirty-five node-positive breast cancer patients who received anthracycline or derivative based adjuvant chemotherapy were selected from the data base of the Institut Paoli Calmettes. Angiogenesis was evaluated using CD31 antibody. Other prognosis variables studied were: hormonal status, tumor size, hormonal receptors, Elston and Ellis grade, and number of involved lymph nodes. RESULTS: In multivariate analysis, a high level of angiogenesis was independently associated with a diminution of survival (p = 0.007), and of metastasis-free survival (p = 0.003). Other variables associated with poor survival were progesterone receptor status (p = 0.003) and Elston's grade (p = 0.003), and with metastasis-free survival, progesterone receptor status (p = 0.018). CONCLUSION: Tumoral angiogenesis appears to be an independent prognostic factor for node-positive breast cancer, when treated with adjuvant chemotherapy. Adjuvant strategies for patients with a high level of angiogenesis should be discussed.

Adult↗
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

Phase III efficacy study of interleukin-3 after autologous bone marrow transplantation in patients with malignant lymphoma.

We evaluated the efficacy of recombinant human interleukin-3 (rhIL-3) in reducing the number of platelet transfusions and major infections after autologous bone marrow transplantation (ABMT) in patients with malignant lymphoma. 198 patients with non-Hodgkin's lymphoma (NHL, n = 111) and Hodgkin's disease (HD, n = 87) were randomized to receive rhIL-3 10 microgram/kg/d (n = 130) or placebo (n = 68) for a maximum of 28 d after ABMT. Several well-known conditioning regimens were used. From day 1 after ABMT patients were treated with placebo or rhIL-3 at a dose of 10 microgram/kg/d by continuous i.v. infusion for 7 d and then by s.c. administration for 21 d or until platelet (50 x 109/l) and neutrophil (0.5 x 109/l) recovery had occurred. Treatment was completed in 54% of the patients in the rhIL-3 group versus 75% in the placebo group (P < 0.004). Adverse events were the main reason for premature discontinuation in the IL-3 group (23% IL-3 v 5% placebo). The median number of platelet transfusions was not significantly different between the IL-3 group and the placebo group (8.0 IL-3 v 6.0 placebo, P = 0.09). Platelet engraftment (>/= 20 x 109/l) was not significantly faster in the IL-3 group (28 d in the IL-3 and 27 d in the placebo group, P = 0.06) and the incidence of haemorrhagic complications was similar in both groups. In patients receiving the full intended dose of rhIL-3, platelet engraftment to >/= 20 x 109/l was delayed (P = 0.007). The median time to neutrophil engraftment was 23 d in the IL-3 and 25 d for the placebo group (P = 0.39). There was no difference in the incidence of major infections. We conclude that treatment with IL-3 has no clinical benefit in patients receiving ABMT for malignant lymphoma.

Bone Marrow Transplantation↗
PubMed1999

Phase II study of a combination of low-dose cisplatin with 13-cis-retinoic acid and interferon-alpha in patients with advanced head and neck squamous cell carcinoma.

Preclinical and clinical data have suggested antitumor efficacy in squamous cell carcinoma (SCC) of interferon (IFN)-alpha and 13-cis-retinoic acid (13-c-RA) as single agent with greater activity in combination. Cisplatin was added to potentiate activity. Twenty-three patients with pretreated advanced or metastatic head and neck squamous cell carcinoma were given a combination of IFN-alpha (6 x 10(6) U/day, 84 days s.c.), 13-c-RA (1 mg/kg/day, 84 days) and cisplatin (40 mg/kg/day, day 1, 28 and 56). Seventeen patients had discontinuation of treatment and three patients received overall treatment without dose reduction. Hematological toxicity was more frequent; only three patients experiencing grade 3 or higher extra-hematological toxicity. Four out of 14 evaluable patients were in response, with one in complete pathological response. Median duration of response was 6 months with a 9 month median survival. Association of IFN-alpha, 13-c-RA and cisplatin induces modest but definite antitumor activity with moderate and manageable toxicity. Further studies of different combination modality therapy with chemotherapy and differentiating agents need to be performed in less pretreated patients.

Aged↗
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↗
PubMed1999

Production of ex vivo expanded hematopoietic cells and progenitors in a closed bioreactor, starting with a small volume marrow collection: A feasibility study in patients with poor-risk breast cancer and receiving high-doses of cyclophosphamide.

We report a clinical pilot study conducted in 6 women with poor-prognosis breast cancer. The goal was to evaluate the feasibility and safety of producing hematopoietic progenitors and cells from a small marrow sample, for clinical use after high-dose cyclophosphamide. A small volume marrow collection was obtained, using local anesthesia and conscious sedation, before the first of two chemotherapy cycles. Cells were cryopreserved, and later thawed to inoculate two Aastrom Biosciences Inc Replicell bioreactors, on time to reinfuse ex vivo expanded cells after the second chemotherapy cycle. Patients recovered neutrophils and platelets at similar times after the first and second chemotherapy cycles, and showed comparable clinical events. This pilot study prepares future randomized trials, designed to evaluate clinical benefits associated with the use of ex vivo expanded cells in the setting of multicycle high-dose chemotherapy.

Aged↗