Cost-effectiveness of repeated aphereses in poor mobilizers undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
G Novakovitch
Publications and source records attributed to G Novakovitch.
Immune reconstitution and outcome after unrelated cord blood transplantation: a single paediatric institution experience.
We report the outcome of 12 children who underwent unrelated cord blood transplant (U-CBT) in a single institution between February 1997 and July 1998. The 1 year event-free survival was 67% (95% CI of 26%). Four children died with infectious complication as cause of death in three cases. Immune reconstitution was studied during first year post transplant by assaying total lymphocyte counts, B cells, NK cells and T cell subsets in the eight disease-free surviving patients. We observed a prompt recovery of CD19+ cell number which was greater than 500/microl at 9 months for all patients except the one with severe cGVHD. B cells constituted the predominant lymphocyte subset at 6 and 9 months post transplant with normal or elevated B cell numbers according to normal paediatric range. We noted normal serum immunoglobulin levels at 6 months post transplant for IgA and IgM and at 9 months for IgG. The CD3+ cell count and particularly the CD3+CD8+ T cell subset remained depressed until 12 months post transplant. Six months after unrelated CBT, seven out of eight patients had less than 100 CD3+CD8+ cells/microl. CD3+CD4+ cell recovery was less impaired with all children achieving an absolute count of CD3+CD4+ cells greater than 200/microl during the first year in a median of 5 months. The percentage of NK cells was elevated during the first 6 months after CBT but their absolute count remained within the normal range. Bone Marrow Transplantation (2000) 25, 53-57.
Adolescent↗
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↗
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↗
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↗
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↗
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↗
High-dose chemotherapy followed by reinfusion of selected CD34+ peripheral blood cells in patients with poor-prognosis breast cancer: a randomized multicentre study.
Seventy-one patients with poor-prognosis breast cancer were enrolled after informed consent in a multicentre randomized study to evaluate the use of selected peripheral blood CD34+ cells to support haematopoietic recovery following high-dose chemotherapy. Patients who responded to conventional chemotherapy were mobilized with chemotherapy (mainly high-dose cyclophosphamide) and/or recombinant human granulocyte colony-stimulating factor (rhG-CSF). Patients who reached the threshold of 20 CD34+ cells per microl of peripheral blood underwent apheresis and were randomized at that time to receive either unmanipulated mobilized blood cells or selected CD34+ cells. For patients in the study arm, CD34+ cells were selected from aphereses using the Isolex300 device. Fifteen patients failed to mobilize peripheral blood progenitors and nine other patients were excluded for various reasons. Forty-seven eligible patients were randomized into two comparable groups. CD34+ cells were selected from aphereses in the study group. Haematopoietic recovery occurred at similar times in both groups. No side-effect related to the infusion of selected cells was observed. The frequency of epithelial tumour cells in aphereses was low (8 out of 42 evaluated patients), as determined by immunocytochemistry. We conclude that selected CD34+ cells safely support haematopoietic recovery following high-dose chemotherapy in patients with poor-prognosis breast cancer.
Adult↗
Benefits of granulocyte-colony-stimulating factor after stem cell transfusion in intensive sequential chemotherapy for breast cancer.
The aim of this study was to evaluate the clinical and economic benefit of filgrastim given with intensive sequential chemotherapy. Women with poor-prognosis breast cancer received four cycles of high-dose cyclophosphamide (3 g/m2) and doxorubicin (75 mg/m2), followed by filgrastim 5 microg/kg/dy, stem cell collection after the cycle 1, and stem cell infusion after cycle 3 and cycle 4. The first cohort received filgrastim after the fourth cycle but the second cohort did not.Thirty three patients were included in the first cohort and 13 in the second. The results indicate that the duration of grade IV neutropenia was shorter in the group given filgrastim as was the median time to recover an absolute neutrophil count (ANC) > 1.0 x 10(9)/L. The rate and duration of the rehospitalizations were higher in the group not receiving filgrastim. We found that costs such as drugs and hospitalizations were significantly higher (p = 0.032 and p = 0.049) in the non-filgrastim-treated group. Using ANC > 1.0 x 10(9)/L as an intermediary efficiency criterion it was more cost effective to give filgrastim. It can be concluded from this study that filgrastim can decrease the duration of grade IV neutropenia in patients receiving intensive sequential chemotherapy. This, in turn, reduces the cost of hospitalization. However, in our study, this reduction of neutropenia did not have any impact on further therapy.
Adult↗
Clinical and economic comparison of lenograstim-primed blood cells (BC) and bone marrow (BM) allogeneic transplantation.
The study presented is a clinical and economic comparison of bone marrow (BM) and blood cells (BC) allogeneic transplantation. We performed a case-control study to compare 17 patients receiving allogeneic BC transplant in a pilot study to an historical group of 17 patients allografted with BM. We evaluated the clinical outcomes and the direct medical costs of transplantation from conditioning regimen until day 100 by detailed observation of patients' medical records. Patients in the BC group received a median of 8 x 10(6)/kg CD34+ cells (1.58-29.1) and 266 x 10(6)/kg CD3+ cells (128-469). All patients had neutrophil engraftment with a median of 14 days in the BC group vs 19 days in the BM group (P < 0.05). The Kaplan-Meier estimation of the median number of days to a platelet count of > 25 x 10(9)/l, independent of platelet transfusion, was significantly shorter in the BC group (15 (9-74)) compared with the BM group (25 (15-45)). Acute graft-versus-host disease (AGVHD) of grade > or = 2 was not significantly different between the two groups. Patients treated with BC presented a US$16,134 decrease in the cost of the first 100 days (29%, P = 0.006). Our comparison suggested that platelet reconstitution and total costs were in favor of the BC group.
Adjuvants, Immunologic↗
[Cell grafts: current and perspectives. II. Cells and transformation procedure challenge and future].
All medical doctors are concerned by the medical scientific, ethical, economic and reglementary aspects of cells transplantation. However, hematopoietic stem cells are the most used cells in transplantation in case of leukemia, and solid tumor. Other human or animal cells are used to graft burned patients, patients with severe liver failure, knee traumatism and other exceptional disease. Autologous expanded keratinocytes, chondrocytes, hepatocytes are sometime transplanted. Most cellular products are processed before being transplanted. These processes, more or less complicated, use physical, immunological and functional characteristics of the cells. Most cellular products are processed by non profit organisms as said by the "94 bioethic law".
Cell Line, Transformed↗
CNS axonal regeneration with peripheral nerve grafts cryopreserved by vitrification: cytological and functional aspects.
To test cool-warm protocols for storing peripheral nerves, 4-cm-long-nerve segments were removed from the hindleg of adult rats and cryopreserved using a vitrification solution (or cryoprotective mixture) containing a mixture of polyalcohols (2,3-butanediol, 1,2-propanediol, polyethylene glycol, and Belzer U.W. medium). Schwann cell viability and morphology were studied with regard to the effect of (i) cryoprotective mixture concentration (100, 50, and 30% diluted in human serum albumin at 4%), (ii) duration of exposure (10, 15, or 30 min in a single step) of nerves to the cryoprotective mixture, (iii) cooling rate (F1/F2, F3, and F4: 3, 12, and 231 degrees C/min, respectively), and (iv) type of replacement of cryoprotectant (T1, one step; or T2, perfusion) after warming. Nerves exposed 10 min to cryoprotective mixture 50% (2,3-butanediol, 1.926 mol.liter-1; 1,2-propanediol, 3.063 mol.liter-1; polyethylene glycol, 0.084 mol.liter-1; and Belzer U.W., 22.4 mosm-1) and cooled-warmed with the F2/F3/F4-T2 protocols contained live and correctly cryopreserved Schwann cells. The capacity of these cryopreserved nerve segments (n = 6) to be subsequently repopulated by regenerating axons from central neurons was compared to that of fresh nerves when used as peripheral nerve autografts implanted within the spinal cord at the level of the descending respiratory pathways. All cryopreserved nerve grafts were successfully reinnervated by regenerated central axons. Unitary spontaneous action potentials propagated along these axons were assessed by recording the discharge of tested nervous filaments (T) from the grafts in artificially ventilated and paralyzed animals. Out of 535 T, 32 (6 +/- 1.2%) presented spontaneous unitary activity with respiratory (R, n = 2) and nonrespiratory (NR, n = 30) pattern of discharge. The T mean number, the occurrence rate referenced to the total number of T (R/T, NR/T, and R + NR/T) and the mean number of spontaneous units (R, NR, R + NR) were compared to those of fresh spinal peripheral nerve grafts. Except for T, cryopreserved peripheral nerve grafts contained statistically significantly (P < 0.05) less spontaneous R and NR unitary activity, which represented, respectively, 6.2 +/- 6.2 and 26.8 +/- 5.7% of that found in the control group. These data indicate that nerves cryopreserved with the protocols described above contain viable Schwann cells which constitute a suitable support to induce regeneration of central fibers. The effectiveness of nerve cryopreservation by vitrification is discussed with regard to Schwann cell viability following cool-warm protocols and to subsequent reinnervation of the cryopreserved peripheral nerve grafts.
Animals↗
Growth potential of aortic autografts and allografts: effects of cryopreservation and immunosuppression in an experimental model.
OBJECTIVE: An animal model has been used to evaluate the potential of growth of vascular autografts and allografts, and the effects of cryopreservation, rejection and immunosuppression on this growth. METHODS: In 35 animals (seven groups of five female NZW rabbits; age 5-6 weeks; weight 1.1 kg), a graft interposition was performed at the level of the infrarenal aorta. Different groups included fresh autografts, fresh and cryopreserved consanguineous allografts (donor: litter sister), fresh and cryopreserved immunosuppressed (IS) consanguineous allografts (receiving cyclosporin 10 mg/kg per day) and fresh and cryopreserved allografts. Animals were allowed to grow normally and were sacrificed at the mean weight of 2.89 kg. We studied the growth of the native aorta and of the graft and calculated the growth ratio (growth of the graft/growth of native vessel). Grafts and adjacent aorta were histologically studied. RESULTS: Growth of the graft was normal (mean ratio 1.08; S.D. = 0.21) for autografts, and for fresh and cryopreserved IS consanguineous grafts. Growth was absent (mean ratio 0.12; S.D. = 0.15) for fresh and cryopreserved allografts (P = 0.0001). In consanguineous grafts without IS, growth was absent or normal, presumably according to genetic compatibility, but never intermediate. Histological study showed normal optic microscopic aspects when growth was normal and, when growth was absent, aspects compatible with rejection including mainly intimal hyperplasia and medial thinning. CONCLUSIONS: (1) Normal growth of arterial autografts was confirmed; (2) cryopreservation did not prevent potential growth of an arterial graft; and (3) in an allogenic situation, without IS, an aortic graft, fresh or cryopreserved, never showed any growth potential.
Animals↗
Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin's lymphoma.
PURPOSE: To demonstrate the feasibility and efficacy of six ambulatory high-dose sequential chemotherapy courses that include three intensified cycles supported by stem-cell infusion in high-risk and high-intermediate-risk untreated non-Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS: A pilot nonrandomized study included 20 untreated patients aged less than 60 years with aggressive histologically identified NHL and two or three adverse-prognosis criteria (International Index). Patients received an ambulatory regimen with high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF) and repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 years (range, 20 to 59), with 13 men and seven women. Chemotherapy consisted of one cycle every 21 days for a total of six cycles. The first three cycles (A1, A2, and A3) consisted of cyclophosphamide (Cy) 3,000 mg/m2, doxorubicin (Doxo) 75 mg/m2, and vincristine 2 mg (plus corticosteroids). The last three cycles (B4, B5, and B6) consisted of the same drug combination plus etoposide 300 mg/m2 and cisplatin 100 mg/m2. For an expected duration of 18 weeks, the projected dose-intensity was 25 mg/m2/wk for Doxo and 1,000 mg/m2/wk for Cy. G-CSF 300 micrograms was administered from day 6 following each cycle until neutrophil reconstitution. Two aphereses were performed at approximately day 13 after each A cycle, and PBSCs were injected at day 4 of each B cycle. Radiotherapy on tumor masses > or = 5 cm was scheduled after completion of the last cycle. RESULTS: The median duration of grade 4 neutropenia was 1 day (range, 0 to 7) for each A cycle and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of grade 4 thrombopenia was 0 days (range, 0 to 8) for each A cycle and 6 days (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile neutropenia was required for 18% and 44% of patients during cycles A and B, respectively (P < .01). Only three patients did not complete the protocol: one due to emergency surgery after cycle B4, one who died after cycle B5 from interstitial pneumonia, and one with delayed hematologic reconstitution after cycle B4. Chemotherapy delivery was optimal (median actual relative dose-intensity, 97%; range, 66 to 100). The median total dose administered over 18 weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to 450), 900 mg etoposide (range, 300 to 900), and 300 mg cisplatin (range, 100 to 300). Evaluation of response after six courses showed 13 complete remissions ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), and one toxic death. With a median follow-up period of 25 months (range, 16 to 43), 15 patients are alive, with 12 in continuous first CR; five patients relapsed (four of four PRs and one of 13 CRs). Two-year survival and failure-free survival (FFS) rates are 73% and 56%, respectively. The disease-free survival (DFS) rate for the CRs is 86%. CONCLUSION: PBSC support contributes to the feasibility of first-line, very-high-dose, ambulatory chemotherapy delivery in poor-risk NHL and is associated with a high rate of remission and FFS.
Adult↗
Effects of cryopreservation on the viscoelastic properties of human arteries.
The purpose of this study was to use our newly developed mock circulation loop to determine the effects of cryopreservation on the common carotid artery (CCA) and the superficial femoral artery (SFA). Fourteen healthy arteries (7 CCA and 7 SFA) harvested from multiple organ donors between the ages of 18 and 35 years were tested before and after cryopreservation at -140 degrees C using dimethyl sulfoxide and the vapor phase of liquid nitrogen. Mean storage time was 4.2 months. The mock pulse rate was 60 beats/min and the following four systolic/diastolic pressures settings were used: 50/110, 80/140, 110/170, and 140/200 mm Hg. Simultaneous measurements of intra-arterial pressure and external arterial diameter were made using an intra-arterial pressure sensor and external piezoelectric sensors. Measured data were used to calculate pulsatility, volumetric compliance, stiffness, midwall radial arterial stress, Young's modulus, and the incremental modulus. After SFA cryopreservation, no significant changes were observed. Conversely, CCA cryopreservation led to a significant decrease in compliance and pulsatility and a significant increase in stiffness. Young's modulus, the incremental modulus, and midwall radial arterial stress did not change significantly. A clearcut decrease in hysteresis was observed after cryopreservation in the CCA. No evidence of structural changes was detected on light and scanning electron microscopy. Baseline findings in this study were consistent with classification of the CCA as an elastic artery and the SFA as a muscular artery. Cryopreservation had no effect on the viscoelastic properties of muscular arteries (SFA). Cryopreservation affected only values related to the cylindrical shape of the elastic arteries (CCA). It had no effect on values related to wall structure.
Adult↗
[The cell as viewed by French foundations of transplantation: regular aspects].
Explore the source record for details and available documents.
Hematopoietic Stem Cell Transplantation↗
Autologous transplantation of blood stem cells mobilized with filgrastim alone in 93 patients with malignancies: the number of CD34+ cells reinfused is the only factor predicting both granulocyte and platelet recovery.
High-dose chemotherapy (HDC) supported by autologous transplantation of blood stem cells (BSC) is used increasingly for patients with poor-risk malignancies. We report our experience with 93 consecutive patients who were mobilized with recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone. They received a fixed dose of G-CSF for 5 or 6 days, and BSC were collected by leukapheresis. Aphereses were evaluated for MNC, CD34+ cells, and CFU-GM counts and cryopreserved. All patients received a conditioning regimen without TBI. Engraftment was assessed as the first of 2 consecutive days on which patients achieved 0.5 and 1 x 10(9)/L neutrophils and an unsupported platelet count of 25 x 10(9)/L. Multivariate analysis was performed to study patients and graft characteristics that could influence reconstitution. The G-CSF priming regimen was well tolerated and allowed collection of BSC for all patients, 66% of them achieving >3 x 10(6)/kg CD34+ cells, and 86% achieving >10 x 10(4) CFU-GM/kg. The numbers of collected CD34 and CFU-GM cells were highly correlated. The number of courses of chemotherapy prior to collection, a diagnosis of breast cancer, the use of rhG-CSF posttransplant, and the numbers of CFU-GM and CD34+ cells reinfused were correlated with hematologic recovery. In a multivariate analysis, however, the number of CD34+ cells was the only factor independently influencing both granulocyte and platelet recovery. Patients who received at least 3 x 10(6)/kg CD34+ cells achieved granulocyte reconstitution on day 11 after reinfusion (range 8-15) and an unsupported platelet count of 25 x 10(9)/l on day 14 (range 12-180), significantly earlier than patients who received fewer cells (p < 0.001). In addition, G-CSF administration postreinfusion independently enhanced granulocyte reconstitution but not platelet recovery. In conclusion, CD34+ cell number appears to be the only factor predicting both granulocyte and platelet reconstitution. Based on this study, the collection of a minimal number of 3 x 10(6)/kg CD34+ cells appears desirable.
Adolescent↗
[Comparative study of the costs for two hematopoietic cell specimen collections: cytapheresis and bone marrow collection].
The aim of this study, carried out at the Institut Paoli-Calmettes (Marseille-France), was to compare, in terms of monetary and non monetary costs, alternate procedures for hematopoietic stem cells collection i.e. peripheral blood stem cells collection (PBSCC) and bone marrow collection (BMC) used in cancer therapies. Monetary costs have been evaluated by calculating the direct costs of the two types of procedures and non monetary costs by comparing anxiety, discomfort and pain of cancer patients submitted to PBSCC or BMC. Patients, randomized (7/1993-2/1994), in view of autologous transplantation, to receive the first procedure or the second one received three self-administered questionnaires to complete before, during and after the procedure. Pain was assessed using visual analogical scale and McGill Pain questionnaire. Anxiety was evaluated by means of State-Trait Anxiety Inventory. Results showed that, under some conditions, presently realized in the current practice, direct costs of PBSCC (10,140 to 13,780 FF) were lower than BMC ones (16,509 FF) and that anxiety and pain experienced by patients submitted to PBSCC, with or without femoral catheter, were significantly less severe than in other group patients (State anxiety, before procedure : p < 0.01 ; pain related to the procedure assessed on VAS : p < 0.001 and total McGill score : p < 0.00001). These findings justify the substitution of bone marrow transplantation by peripheral blood stem cells transplantation, provided there is a demonstration of similar medical efficacy for cancer therapy.
Adult↗