RESUMEN
The platelet refractoriness is a complication of transfusion treatments potentially dramatic in onco-haematology. Chemo-treatment of haematological malignancies or packs of allogeneic bone marrow transplants require iterative platelet transfusion requirements. The discovery of a platelet refractoriness along with its support should be the most reactive as possible but also adapted to the cause. In the case of allo-immunization, it may be expected. The purpose of this presentation is to recall the different etiologies and perform a feedback on the support transfusion platelet of onco-haematology adult patients at Institut Paoli-Calmettes (IPC) in partnership with the EFSAM.
Asunto(s)
Plaquetas/inmunología , Neoplasias Hematológicas/inmunología , Isoanticuerpos/inmunología , Transfusión de Plaquetas , Trombocitopenia/terapia , Academias e Institutos/organización & administración , Aloinjertos/inmunología , Antígenos de Plaqueta Humana/inmunología , Bancos de Sangre , Trasplante de Médula Ósea , Manejo de la Enfermedad , Francia , Neoplasias Hematológicas/terapia , Hematología , Departamentos de Hospitales , Humanos , Inmunización , Relaciones Interinstitucionales , Oncología Médica , Transfusión de Plaquetas/efectos adversos , Bazo/fisiopatología , Trombocitopenia/etiología , Trombocitopenia/inmunologíaRESUMEN
Cytomegalovirus (CMV) infection is a serious complication that may occur in the weeks or months following bone marrow transplantation. However, both Ganciclovir and the CMV infection itself can cause marrow toxicity, notably neutropenia, that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. The aim of this retrospective study was to identify factors associated with the occurrence of grade III-IV neutropenia among patients receiving pre-emptive Ganciclovir therapy after allogeneic stem cell transplantation at our Institution. We identified 547 consecutive patients transplanted from January 2005 to June 2011 at our Institution. In all, 190 patients (35%) presented with CMV reactivation of whom 30 patients (5%) were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally, 160 (29%) patients were analysed. According to multivariate analysis, at the time of treatment initiation, the risk factors significantly associated with a grade III-IV Ganciclovir-related neutropenia included a high viral load (hazard ratio (HR) = 2.68, 95% CI 1.25-5.737, p 0.01); an absolute neutrophil count >3000 was a protective factor (HR = 0.26, 95% CI 0.125-0.545, p <0001) whereas serum creatinine >2 mg/dL was associated with higher Ganciclovir-related neutropenia (HR = 2.4, 95% CI 1.11-5.17, p 0.002). This large analysis revealed three risk factors for Ganciclovir-related neutropenia among patients with CMV reactivation after allogeneic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, so reducing the morbidity and mortality associated with CMV reactivation.
Asunto(s)
Antivirales/efectos adversos , Infecciones por Citomegalovirus/tratamiento farmacológico , Ganciclovir/efectos adversos , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Adolescente , Adulto , Anciano , Antivirales/administración & dosificación , Femenino , Ganciclovir/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trasplante de Células Madre/efectos adversos , Trasplante Homólogo/efectos adversos , Adulto JovenRESUMEN
The use of recombinant human erythropoietin (rHuEPO) has been controversial after myeloablative allogeneic Stem cell transplantation (allo-SCT). Reduced intensity conditioning regimens (RIC) offer a novel approach that might translate into a different profile of erythropoietic recovery. We treated 20 consecutive patients with rHuEPO early after matched sibling RIC allo-SCT. Conditioning included fludarabine, busulfan and antithymocyte globulin. EPO treatment was analyzed in terms of toxicity, impact on the frequency of Red blood cell transfusions (RBCT) and kinetics of Hemoglobin recovery within the 60 days post-allo-SCT. Results were compared with 27 matched patients who did not receive rHuEPO. In the first 2 months after allo-SCT all patients receiving rHuEPO (100%) achieved an Hb level > 11 g/dl at a median of 30 (15-35) days post-allo-SCT, as compared to only 63% of the patients not receiving rHuEPO (P = 0.007) at a median of 35 (20-55) days (P = 0.03). A total of 70% (95% CI, 50-90) of rHuEPO patients maintained an Hb over 11 g/dl in the second month as compared to only 19% (95% CI, 4-34) in the other group (P = 0.0004). For patients receiving RBCT, the use of rHuEPO was associated with a trend towards reduced RBCT requirements. This pilot study suggests a potential benefit of early administration of rHuEPO after RIC allo-SCT on early erythropoietic recovery.
Asunto(s)
Eritropoyetina/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Hemoglobinas/efectos de los fármacos , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Eritropoyesis/efectos de los fármacos , Eritropoyetina/toxicidad , Femenino , Neoplasias Hematológicas/terapia , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Proyectos Piloto , Proteínas Recombinantes , Trasplante HomólogoRESUMEN
Using a genetic randomization through a 'donor' vs 'no donor' comparison, the aim of this analysis was to assess the real benefit of reduced intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) among 95 adult high-risk acute myeloid leukemia (AML) patients. In an 'intention-to-treat' analysis, leukemia-free survival (LFS) was significantly higher in the 'donor' group as compared to the 'no donor' group (P=0.01; 54 vs 30% at 4 years). The latter held true when restricting the analysis to the 25 patients who could actually receive the RIC-allo-SCT (P=0.001). Overall transplant-related mortality in the 'transplant' group was 12%, with overall survival (OS) being significantly higher in the 'transplant' group as compared to the 'no transplant' group (P=0.01). Also, in the 'intention-to-treat' analysis, OS was significantly higher in the 'donor' group as compared to the 'no donor' group (P=0.04). In the multivariate analysis, actual performance of RIC-allo-SCT (P=0.001; RR=4.0; 95% CI, 1.7-9.6) was the strongest factor significantly predictive of an improved LFS. We conclude that if a matched related donor is identified, RIC-allo-SCT should be proposed for AML patients not eligible for standard myeloablative allo-SCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide/terapia , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Enfermedad Aguda , Adulto , Anciano , Femenino , Humanos , Leucemia Mieloide/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
BACKGROUND: RBCT (RBCT) requirements of stem cell transplant (SCT) recipients are often substantial and may be related to transplant type. STUDY DESIGN AND METHODS: An analysis was done of RBCT requirements and Hb recovery kinetic in the first 60 days after HLA-identical sibling allogeneic SCT in a series of 110 consecutive patients treated for various malignant diagnoses. Patients were prepared with either an antithymocyte globulin (ATG) and reduced intensity chemotherapy-based conditioning (RIC) (n=64) or a myeloablative conditioning regimens (MAC; n=46). Patients received marrow (n=64) or PBPCs (n=46). RESULTS: Overall, intensity of conditioning regimen (RIC vs. MAC; p=0.0005) and graft source (PBPC vs. marrow; p<0.0001) independently predicted RBCT requirements. Hb recovery was accelerated after RIC when compared to MAC allo-SCT (p=0.02). In RIC patients, RBCTs were inversely correlated to Hb level before conditioning (p<0.0001) and the dose of ATG (p=0.009). Moreover, Hb level before allo-SCT significantly influenced Hb recovery kinetic after RIC but had no impact on RBCT requirements and Hb recovery after MAC. CONCLUSION: Thus, RIC conditioning creates a different pattern of erythropoiesis recovery as compared to a MAC regimen and suggest a need for studies aimed at further reducing RBCT and accelerating Hb recovery.
Asunto(s)
Antineoplásicos/farmacología , Transfusión de Eritrocitos/estadística & datos numéricos , Eritropoyesis/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Antineoplásicos/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemoglobinas/análisis , Humanos , Cinética , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Valor Predictivo de las Pruebas , Pronóstico , Trasplante HomólogoRESUMEN
The purpose of this study was to evaluate the presence of micrometastatic cells in the apheresis products from patients with breast cancer, and also to determine if repeated infusion of contaminated products had any clinical impact. A total of 94 patients with high-risk breast cancer were enrolled in a prospective single center study to evaluate the use of dose-intensified chemotherapy (doxorubicine 75 mg/m(2) and cyclophosphamide 3000 or 6000 mg/m(2) for four cycles) with repeated (x 2) stem cell reinfusion. All women were monitored for the presence of metastatic cells in aphereses, collected after first course of intensive chemotherapy, and following additional mobilization with rhG-CSF. Epithelial cells were screened with monoclonal antibodies directed to cytokeratin. Eight of the 94 patients had detectable tumor cells in one or several aphereses collected after intensive chemotherapy; this was unrelated to other tumor characteristics, including size, histology, Scarff Bloom and Richardson (SBR) grading (presence or absence of hormone receptors). Hemato-poietic reconstitution was similar in the cells from these eight patients, and in the total patient population. Three of these eight patients relapsed. This study has confirmed that contamination of apheresis products remains a rare event, which does not seem to affect clinical evolution, even when reinfused into the patient.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Eliminación de Componentes Sanguíneos/efectos adversos , Neoplasias de la Mama/terapia , Células Neoplásicas Circulantes/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Eliminación de Componentes Sanguíneos/normas , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Recuento de Células , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Femenino , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Estudios Prospectivos , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Eliminación de Componentes Sanguíneos/economía , Movilización de Célula Madre Hematopoyética/economía , Trasplante de Células Madre de Sangre Periférica/economía , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Células Sanguíneas , Estudios de Cohortes , Terapia Combinada , Análisis Costo-Beneficio , Femenino , Filgrastim , Supervivencia de Injerto , Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética/métodos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Proteínas Recombinantes , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
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.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Infecciones por Citomegalovirus/etiología , Infecciones por Bacterias Gramnegativas/etiología , Infecciones por Bacterias Grampositivas/etiología , Adulto , Trasplante de Médula Ósea/inmunología , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Terapia de Inmunosupresión/efectos adversos , Terapia de Inmunosupresión/métodos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Quimera por Trasplante , Acondicionamiento PretrasplanteRESUMEN
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.
Asunto(s)
Antígenos CD34/inmunología , Células Sanguíneas/trasplante , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/inmunología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Inmunoterapia/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Antígenos CD34/análisis , Antígenos CD34/uso terapéutico , Células Sanguíneas/química , Donantes de Sangre , Rechazo de Injerto , Antígenos de Histocompatibilidad/inmunología , Humanos , Inmunosupresores/farmacología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Hermanos , Quimera por Trasplante , Trasplante HomólogoRESUMEN
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.
Asunto(s)
Movilización de Célula Madre Hematopoyética/economía , Leucaféresis/economía , Trasplante de Médula Ósea/economía , Trasplante de Médula Ósea/métodos , Costos y Análisis de Costo , Francia , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/economía , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucaféresis/métodos , Neoplasias/economía , Neoplasias/terapia , Sensibilidad y Especificidad , Estadísticas no Paramétricas , Trasplante Autólogo/economía , Trasplante Autólogo/métodosRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sustancias de Crecimiento/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Femenino , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Sustancias de Crecimiento/efectos adversos , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Tasa de Supervivencia , Trombocitopenia/inducido químicamente , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Bioensayo/métodos , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas/patología , Antígenos CD34 , Recuento de Células Sanguíneas/métodos , Eliminación de Componentes Sanguíneos , Citometría de Flujo , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , HumanosRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Leucemia Linfocítica Crónica de Células B/terapia , Linfoma no Hodgkin/terapia , Adulto , Antígenos CD34 , Médula Ósea/patología , Terapia Combinada , Femenino , Factor Estimulante de Colonias de Granulocitos/farmacología , Células Madre Hematopoyéticas/patología , Humanos , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/patología , Linfoma no Hodgkin/sangre , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/farmacología , Trasplante AutólogoRESUMEN
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.
Asunto(s)
Trasplante de Médula Ósea/métodos , Leucocitos Mononucleares/citología , Depleción Linfocítica/métodos , Linfocitos T/citología , Antígenos CD34/biosíntesis , Recuento de Células , Separación Celular/métodos , Citometría de Flujo/métodos , Enfermedad Injerto contra Huésped/inmunología , Humanos , Separación Inmunomagnética/métodos , Espectrofotometría/métodos , Linfocitos T/metabolismo , Trasplante Homólogo/métodosRESUMEN
BACKGROUND: A group of 290 transfusion recipients enrolled in a prospective study of posttransfusion hepatitis was studied to determine the possibility of previously unrecognized hepatitis C virus (HCV) transmission. STUDY DESIGN AND METHODS: Before and after transfusion, blood specimens that were negative in first-generation enzyme immunoassay (EIA) were tested by current commercial EIAs, several single-antigen research EIAs, and supplemental tests. RESULTS: Current second- and third-generation EIAs identified five subjects (1.7% of total) who had chronic hepatitis C before transfusion. Twenty additional sera had some reactivity with research EIAs. However, those results were the same before and after transfusion (n = 7), had reverted to partially reactive or nonreactive (n = 8), or could not be confirmed by serologic tests or polymerase chain reaction in follow-up specimens (n = 5). CONCLUSIONS: Transient or restricted reactivity to HCV antigens measured by more sensitive research EIAs does not seem to correspond to recent HCV transmission by transfusion. Whether such reactivity could reflect remote HCV infection, with the potential for chronic or intermittent viremia, remains to be determined.
Asunto(s)
Transfusión de Componentes Sanguíneos/efectos adversos , Hepacivirus/inmunología , Antígenos de la Hepatitis C/análisis , Hepatitis C/transmisión , Hepatitis C/diagnóstico , Hepatitis C/inmunología , Antígenos de la Hepatitis C/inmunología , Humanos , Inmunoensayo , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
A 38-year-old man, blood group A+, was allotransplanted for multiple myeloma from his fully matched sister, blood group O+. Anti-A antibodies IgG and IgM titres of the donor were low. Allogeneic peripheral blood stem cells were harvested by leukapheresis after subcutaneous administration of G-CSF. Rapid engraftment occurred since 5.6 x 10(9)/l leukocytes were achieved on day +9 post-transplant. At this time a severe immune haemolytic syndrome occurred and direct antiglobulin test was positive (IgG and C3d). Elution showed an anti-A specificity. Evolution was rapidly unfavourable related to multiorgan failure. The patient died on day +20 post-transplant.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Incompatibilidad de Grupos Sanguíneos/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hemólisis , Adulto , Humanos , Masculino , Trasplante HomólogoRESUMEN
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.
Asunto(s)
Axones/fisiología , Criopreservación/métodos , Regeneración Nerviosa/fisiología , Nervios Periféricos/trasplante , Animales , Axones/ultraestructura , Supervivencia Celular , Sistema Nervioso Central/fisiología , Sistema Nervioso Central/ultraestructura , Crioprotectores , Electrofisiología , Estudios de Evaluación como Asunto , Femenino , Humanos , Nervios Periféricos/fisiología , Nervios Periféricos/ultraestructura , Ratas , Ratas Sprague-Dawley , Células de Schwann/citología , Trasplante AutólogoRESUMEN
OBJECTIVES: Most of the devices used to evaluate the cytotoxicity of resin-based composites in vitro use a dentin barrier test. However, it is difficult to obtain the number of freshly extracted teeth, all on the same day, that is necessary for powerful statistical analysis. Tooth cryopreservation provides a way to build up a supply of teeth. This in vitro study compared cryopreserved teeth and freshly extracted teeth in an evaluation of the cytotoxicity of resin-based composites. In addition, this study also evaluated the effects of pulsatile pressure and the importance of dentin permeability on the cytotoxic response to bonding resins. METHODS: Forty freshly extracted and forty cryopreserved third molars were used. A standardized Class I cavity was prepared within the dentin. The hydraulic conductance of each tooth was recorded. The cavities were filled either with Scotchbond Multi-Purpose Plus and Z 100 (3M Dental Products) or with Optibond and Herculite (Kerr). A plexiglas device was designed to permit 24 h long contact between culture medium and the roof of the pulp chamber while a pulsatile pulpal pressure was simulated. The viability of L 929 cells cultured with a control medium and evaluated by an MTT assay was compared to that of L 929 cells cultured with medium which remained for 24 h in contact with the pulp chamber of restored teeth. A three-way ANOVA was used to compare the cytotoxicity among the different groups. A simple least-squares linear regression was used to seek a relationship between the hydraulic conductance of dentin and the cytotoxicity of composite restorative materials. RESULTS: No significant differences in cytotoxicity were found between the freshly extracted teeth and the cryopreserved teeth (p = 0.53). The cytotoxicity of the resin adhesives was statistically higher when a pulsatile pulpal pressure was simulated (p = 0.04). A significant relationship was found between the hydraulic conductance of dentin and the cytotoxicity of resin-based composites (p = 0.02). SIGNIFICANCE: Cryopreserved teeth can be used for in vitro evaluation of the cytotoxicity of resin adhesives. Pulsatile pulpal pressure simulations increased the in vitro cytotoxicity of the tested materials.