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2.
Anticancer Res ; 20(3B): 2033-40, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10928147

RESUMO

We evaluated the feasibility of administering, in an out-patient setting, a sequential high dose alkylating regimen with hematopoietic growth factor (HGF) and stem cell support to patients with advanced breast cancer. Peripheral blood stem cells (PBSC) were previously collected after chemotherapy and HGF. Two consecutive cycles of alkylating agents were planned: Thiotepa (T) then, 15 days later, BCNU (B). Three dose levels of each agent were administered in cohorts of consecutive patients: 400, 500 and 600 mg/m2 respectively. HGF and reinfusion of PBSC followed both cycles. Toxicity and response were evaluated according to the WHO recommendations. From April 1996 to August 1988, 30 women were enrolled: 8 in the first, 12 in the second and 10 in the third dose level. In all cases, B was administered after T with a median delay of 25 days because of grade 3/4 hematological toxicity. 4 patients did not receive B because of previous lung radiotherapy, persistent tricytopenia or insufficient PBSC collection. 19 patients with measurable lesions were considered for response. The objective response rate was 48% (11% CR, 37% PR). We recommended T and B at a dose of 600 mg/m2 to conduct a phase II study in metastatic breast cancer and even to administer B before T.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças da Medula Óssea/induzido quimicamente , Doenças da Medula Óssea/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Estudos de Coortes , Terapia Combinada , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Filgrastim , Gastroenteropatias/induzido quimicamente , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Humanos , Metástase Neoplásica , Proteínas Recombinantes , Tiotepa/administração & dosagem , Tiotepa/efeitos adversos , Resultado do Tratamento
3.
Bone Marrow Transplant ; 25(1): 53-7, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10654015

RESUMO

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.


Assuntos
Sangue Fetal , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Imunidade , Adolescente , Criança , Pré-Escolar , Transplante de Tecido Fetal , Teste de Histocompatibilidade , Humanos , Lactente , Transplante Homólogo
4.
Cytotherapy ; 2(5): 367-70, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-12044228

RESUMO

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.


Assuntos
Antígenos CD34/imunologia , Células Sanguíneas/transplante , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/imunologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Imunoterapia/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Antígenos CD34/análise , Antígenos CD34/uso terapêutico , Células Sanguíneas/química , Doadores de Sangue , Rejeição de Enxerto , Antígenos de Histocompatibilidade/imunologia , Humanos , Imunossupressores/farmacologia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Irmãos , Quimeras de Transplante , Transplante Homólogo
5.
Int J Technol Assess Health Care ; 15(1): 161-72, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10407603

RESUMO

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.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/economia , Leucaférese/economia , Transplante de Medula Óssea/economia , Transplante de Medula Óssea/métodos , Custos e Análise de Custo , França , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucaférese/métodos , Neoplasias/economia , Neoplasias/terapia , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Transplante Autólogo/economia , Transplante Autólogo/métodos
6.
Int J Oncol ; 15(3): 511-8, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10427133

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Reatores Biológicos , Neoplasias da Mama/terapia , Células-Tronco Hematopoéticas , Manejo de Espécimes/métodos , Idoso , Exame de Medula Óssea , Neoplasias da Mama/tratamento farmacológico , Criopreservação , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Fatores de Risco , Células Tumorais Cultivadas
7.
Hematol Cell Ther ; 41(2): 78-81, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10344557

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Técnicas de Cultura de Células/métodos , Terapia Combinada , Feminino , Humanos , Projetos Piloto , Transplante Autólogo , Resultado do Tratamento
8.
Psychooncology ; 8(1): 55-63, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10202783

RESUMO

Peripheral blood stem cell (PBSC) allogeneic transplantation is an innovative medical procedure which has many advantages in comparison with bone marrow (BM) transplantation, but it involves administering haematopoietic growth factors (HGFs) to donors, the long-term physiological effects of which have not yet been established. The main aim of the present study was to analyse how family PBSC donors cope when confronted with this particular risk context. In addition to data collected on the personal and social aspects of the donors' experience, questionnaires were used to measure their quality of life (pain and anxiety) before, during and after donation, and they were subsequently interviewed in depth by a psychologist. Twenty-two donors participated in this study. They did not all react to the experience of blood cell donation in the same way, in terms of their own personal feelings, attitudes towards the donation, their relationships with the other members of the family, and their awareness of the risk involved.


Assuntos
Adaptação Psicológica , Transplante de Células-Tronco Hematopoéticas/psicologia , Doadores de Tecidos/psicologia , Adulto , Fatores Estimuladores de Colônias/administração & dosagem , Saúde da Família , Relações Familiares , Feminino , Humanos , Masculino , Medição de Risco , Fatores de Risco , Irmãos , Estresse Psicológico , Obtenção de Tecidos e Órgãos
9.
Hematol Cell Ther ; 41(1): 5-11, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10193640

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B/terapia , Linfoma não Hodgkin/terapia , Adulto , Antígenos CD34 , Medula Óssea/patologia , Terapia Combinada , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Células-Tronco Hematopoéticas/patologia , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia , Transplante Autólogo
10.
Cytotherapy ; 1(6): 469-77, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-20443236

RESUMO

BACKGROUND: Enrichment in mononuclear cells (MNC) is a prerequisite for CD34(+) cell selection from BM allografts. However, centrifugation over a density gradient (Ficoll), does not comply with good manufacturing practice (GMP), because Ficoll is not a clinical grade reagent. We evaluated the COBE Spectra cell separator as an alternative and evaluated the recovery of MNC and CD34(+) cells. CD34(+) cell selection was then performed using either the Nexell Isolex 300i or the CEPRATE SC (CellPro) device. METHODS: 20 allogeneic BM grafts were processed, with an initial enrichment of MNC using the COBE Spectra processor, followed by immunoselection of CD34(+) cells (13 Isolex 300i and seven CEPRATE SC). We evaluated total nucleated cells (TNC), MNC and CD34(+) cells recoveries when using COBE Spectra and compared CD34(+) cells recovery and T-cell depletion when using Isolex 300i or CEPRATE SC. RESULTS: Median recoveries of the product using the COBE Spectra were 31.2% (18.1-68.9%) for TNC, 76.9% (29.5-148.1%) for MNC and 79.6% (60.9-191%) for CD34(+) cells. Median recoveries of CD34(+) cells were 39.4% (15.1-75.8%) and 36.7% (26.2-64.3%) with the Isolex 300i and CEPRATE SC devices, respectively. CD34(+) purity was 85% (64.4-94.5%) and 84.4% (66.8-86.8%). Colony-forming unit granulocyte/macrophage (CFU-GM) recoveries were 10.9% (0.2-152%) and 36% (0.0-67.3%). Median log depletion for T-cell numbers, B-cell numbers and natural killer (NK) cell numbers were 2.8 log (2.1-3.8), 2.0log (0.95-3.1) and 3.1log (2.40-4.8), respectively. DISCUSSION: Processing with COBE Spectra produces a cell population that is suitable for CD34(+) cell selection. The Isolex 300i and CEPRATE SC devices demonstrate similar performances. The two-step procedure allows allo-BMT in patients with high risk of GvHD.


Assuntos
Transplante de Medula Óssea/métodos , Leucócitos Mononucleares/citologia , Depleção Linfocítica/métodos , Linfócitos T/citologia , Antígenos CD34/biossíntese , Contagem de Células , Separação Celular/métodos , Citometria de Fluxo/métodos , Doença Enxerto-Hospedeiro/imunologia , Humanos , Separação Imunomagnética/métodos , Espectrofotometria/métodos , Linfócitos T/metabolismo , Transplante Homólogo/métodos
11.
Br J Cancer ; 78(7): 913-21, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9764583

RESUMO

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.


Assuntos
Antígenos CD34 , Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Remoção de Componentes Sanguíneos , Neoplasias da Mama/tratamento farmacológico , Separação Celular/métodos , Terapia Combinada , Feminino , Mobilização de Células-Tronco Hematopoéticas , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
12.
Bone Marrow Transplant ; 21 Suppl 3: S92-8, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9712506

RESUMO

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.


Assuntos
Transplante de Medula Óssea , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Adjuvantes Imunológicos/farmacologia , Adulto , Transplante de Medula Óssea/economia , Custos e Análise de Custo , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/economia , Humanos , Lenograstim , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia , Transplante Homólogo , Resultado do Tratamento
13.
Eur Cytokine Netw ; 9(1): 93-8, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9613683

RESUMO

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.


Assuntos
Neoplasias da Mama/terapia , Fator Estimulador de Colônias de Granulócitos/economia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Adulto , Transfusão de Sangue/economia , Neoplasias da Mama/economia , Terapia Combinada , Análise Custo-Benefício , Quimioterapia Combinada , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Custos de Cuidados de Saúde , Doenças Hematológicas/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/economia , Humanos , Pessoa de Meia-Idade , Readmissão do Paciente/economia , Proteínas Recombinantes , Resultado do Tratamento
14.
Eur J Cardiothorac Surg ; 11(5): 943-52, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9196313

RESUMO

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.


Assuntos
Aorta Abdominal/crescimento & desenvolvimento , Aorta Abdominal/transplante , Criopreservação , Terapia de Imunossupressão , Animais , Ciclosporina/uso terapêutico , Feminino , Rejeição de Enxerto/fisiopatologia , Rejeição de Enxerto/prevenção & controle , Histocompatibilidade , Imunossupressores/uso terapêutico , Coelhos , Transplante Autólogo , Transplante Homólogo
15.
J Clin Oncol ; 15(5): 1722-9, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9164178

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Assistência Ambulatorial , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Linfoma não Hodgkin/radioterapia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/terapia , Projetos Piloto , Transfusão de Plaquetas , Prednisona/administração & dosagem , Trombocitopenia/etiologia , Trombocitopenia/terapia , Resultado do Tratamento , Vincristina/administração & dosagem
16.
Cryobiology ; 34(3): 214-39, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9160994

RESUMO

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.


Assuntos
Axônios/fisiologia , Criopreservação/métodos , Regeneração Nervosa/fisiologia , Nervos Periféricos/transplante , Animais , Axônios/ultraestrutura , Sobrevivência Celular , Sistema Nervoso Central/fisiologia , Sistema Nervoso Central/ultraestrutura , Crioprotetores , Eletrofisiologia , Estudos de Avaliação como Assunto , Feminino , Humanos , Nervos Periféricos/fisiologia , Nervos Periféricos/ultraestrutura , Ratos , Ratos Sprague-Dawley , Células de Schwann/citologia , Transplante Autólogo
17.
Rev Prat ; 47(18 Spec No): S50-2, 1997 Nov 15.
Artigo em Francês | MEDLINE | ID: mdl-9501598

RESUMO

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".


Assuntos
Transplante de Células/tendências , Linhagem Celular Transformada , Previsões , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Fígado/citologia , Pele/citologia
18.
J Hematother ; 5(6): 663-70, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9117255

RESUMO

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.


Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Antígenos CD34 , Contagem de Células Sanguíneas , Plaquetas/patologia , Feminino , Filgrastim , Granulócitos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Transplante Autólogo
20.
Bull Cancer ; 83(8): 649-53, 1996 Aug.
Artigo em Francês | MEDLINE | ID: mdl-8869045

RESUMO

The purpose of the present study was the detection of tumor cells in aphereses after mobilization of peripheral blood stem cells (PBSCs) with G-CSF from 39 breast cancer patients. Circulating tumor cells were searched using sensitive immunocytochemical technique (APAAP) with three anticytokeratin monoclonal antibodies. Counting of mononuclear cells and CD34 progenitor cells was also performed. Circulating tumor cells were detected in 35% of the patients. Cytokeratin-positive cells were detected in 45% of the patients of the metastatic group compared with 20% of the non metastatic one. Aphereses contamination was not correlated with lymph node involvement. Numbers of mononuclear cells and CD34 cells were not significantly different in positive and negative PBSCs collections. In our study, presence of tumor cells was associated with advanced clinical stage and could not be related to a higher CD34 cells mobilization by G-CSF.


Assuntos
Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Citaferese , Células Neoplásicas Circulantes , Adulto , Antígenos CD34 , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/patologia , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
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