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The aim of the study was to verify the utility of the clinical practice of administering thrombophilic screening and antithrombotic prophylaxis with low-molecular-weight heparin to healthy donors receiving granulocyte colony-stimulating factor to mobilize peripheral blood stem cells. Thrombophilia screening comprised of testing for factor V Leiden G1691A, prothrombin G20210A, the thermolabile variant (C677T) of the methylene tetrahydrofolate reductase gene, protein C, protein S, factor VIII and homocysteine plasmatic levels, antithrombin III activity, and acquired activated protein C resistance. We investigated prospectively 72 white Italian healthy donors, 39 men and 33 women, with a median age of 42 years (range, 18-65). Five donors (6.9%) were heterozygous carriers of Factor V Leiden G1691A; two healthy donors had the heterozygous prothrombin G20210A gene mutation; C677T mutation in the methylene tetrahydrofolate reductase gene was present in 34 (47.2%) donors in heterozygous and in 7 donors (9.7%) in homozygous. Acquired activated protein C resistance was revealed in 8 donors of the study (11.1%). The protein C plasmatic level was decreased in 3 donors (4.2%); the protein S level was decreased in 7 donors (9.7%). An elevated factor VIII dosage was shown in 10 donors (13.9%) and hyperhomocysteinemia in 9 donors (12.5%). Concentration of antithrombin III was in the normal range for all study group donors. The factor V Leiden mutation was combined with the heterozygous prothrombin G20210A in 2 cases and with protein S deficiency in one case; 2 healthy donors presented an associated deficiency of protein C and protein S. Although none of these healthy subjects had a previous history of thrombosis, low-molecular-weight heparin was administered to all donors during granulocyte colony-stimulating factor administration to prevent thrombotic events. No donor experienced short or long-term thrombotic diseases after a median follow-up of 29.2 months. Our data do not support this clinical practice because there is no evidence that the combination of granulocyte colony-stimulating factor to previous hypercoagulable conditions results in thrombotic events.
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Factor Estimulante de Colonias de Granulocitos/efectos adversos , Movilización de Célula Madre Hematopoyética/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Trombofilia/diagnóstico , Trombosis/prevención & control , Donantes de Tejidos , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Células Madre Hematopoyéticas , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Premedicación , Trombosis/inducido químicamenteRESUMEN
Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder and is caused by either a quantitative and/or qualitative defect of the multimeric glycoprotein vonWillebrand factor (VWF).[...].
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INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of neutrophil precursor cells. G-CSF-mobilized peripheral blood (PB) hematopoietic progenitor stem cells (HPSCs) collected by apheresis are being increasingly employed for allogeneic transplantation in patients with malignancies as an alternative to bone marrow (BM) transplant. Documenting the safety of G-CSF as a mobilizing agent for HPSC donation has long been a matter of importance for physicians, particularly when volunteer, unrelated adult donors are involved. AREAS COVERED: We review publications in the field with the goal of providing an overview of these approaches. EXPERT OPINION: Trials and international donor registries have not shown any long-term effects associated with G-CSF therapy and a threefold-or-greater increased risk of leukemia or other malignancies through PB HPSC donation can be excluded. Our conclusions are that the administration of G-CSF to healthy donors has a favorable long-term risk-benefit profile, although it is essential to encourage the enrolment of donors in carefully designed programs for follow-up monitoring.
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Donantes de Sangre , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Ensayos Clínicos como Asunto , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Neoplasias/etiologíaRESUMEN
INTRODUCTION: Extracorporeal photopheresis (ECP) has been extensively used for the treatment of immune-mediated diseases for over 20 years and has a consistent and predictable safety profile with long-term use. Documenting the efficacy of ECP as therapeutic treatment has long been a matter of importance for physicians. AREAS COVERED: The authors reviewed publications in this field with the goal of providing an overview of this therapeutic approach. EXPERT OPINION: ECP is efficacious in a high percentage of those cutaneous T-cell lymphoma patients who have circulating malignant T cells in the context of a still-near-normal immune competence. From the side of graft-versus-host disease (GVHD), the use of ECP showed a clinical benefit in patients with steroid-refractory acute GVHD (aGVHD) and it is believed that ECP deserves to be evaluated as part of a combination strategy in first-line therapy of aGVHD. In chronic GHVD, the published data show that ECP can be effective in extensive and long-standing disease even when treatment is initiated at an advanced stage after conventional immunosuppressive and corticosteroid therapy has failed. ECP should be considered most beneficial for patients with predominantly mucocutaneous chronic GVHD. The fields of application of the procedure could be vast, and could also include autoimmune and metabolic diseases. The most important methodological issues which affect ECP evaluation is that the large majority of data about ECP result from single-arm observational series and the significant efficacy is mainly based on small and retrospective studies. ECP has never been proved to offer any survival advantage in a context of a randomized trial and the above-mentioned limitation also affects the accuracy of many biological modifications observed during ECP. Starting from these considerations, the need of a prospective randomized study becomes increasingly urgent.
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Enfermedades Autoinmunes/terapia , Enfermedad Injerto contra Huésped/terapia , Linfoma Cutáneo de Células T/terapia , Fotoféresis , Enfermedades Autoinmunes/inmunología , Enfermedad Injerto contra Huésped/inmunología , Humanos , Linfoma Cutáneo de Células T/inmunología , Fotoféresis/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Different factors influence the clinical outcome of allogeneic transplants, the foremost being good immune recovery. MATERIALS AND METHODS: The purpose of this study was to evaluate the influence of different factors, such as stem cell source, type of donor, conditioning regimen and acute graft-versus-host disease, on early lymphocyte recovery after transplantation. We then analyzed the impact of early CD4+ cell count on overall survival, transplant-related mortality and disease-related mortality. RESULTS: Univariate analysis with Spearman's rho showed a significant correlation between early CD4+ cell recovery and overall survival, transplant-related mortality, stem cell source and type of donor. In multivariate analysis CD4+ cell count was significantly associated with (i) stem cell source, being higher in patients whose haematopoietic progenitor cells were obtained by apheresis than in those whose source of grafted cells was bone marrow, and (ii) type of donor, being higher in patients transplanted from sibling donors than in those whose graft was from an alternative donor. The ROC curve of CD4+ cell count indicated that a cut-off of 115 CD4+ cells/mL could differentiate groups with different outcomes. At 2 years follow-up, patients achieving this CD4+ cell count had significantly lower cumulative transplant-related mortality compared to patients who did not have this count (10%±4% versus 40%±8%, p=0.0026). At the 5-year follow-up, the overall survival rates were 77.5%±0.6% and 36%±7% (p=0.000) in patients with a CD4+ cell count ≥115/mL and in patients with CD4+ cell count ≤ 115/mL, respectively. CONCLUSION: Early CD4+ cell recovery after allogeneic transplantation has a relevant impact on overall survival and transplant-related mortality and is influenced by two factors: stem cell source and type of donor.
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Trasplante de Médula Ósea/inmunología , Linfocitos T CD4-Positivos/inmunología , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Anciano , Trasplante de Médula Ósea/métodos , Trasplante de Médula Ósea/mortalidad , Recuento de Linfocito CD4 , Niño , Femenino , Enfermedad Injerto contra Huésped/inmunología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Trasplante de Células Madre de Sangre Periférica/métodos , Trasplante de Células Madre de Sangre Periférica/mortalidad , Análisis de Supervivencia , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/inmunología , Trasplante Homólogo/métodos , Trasplante Homólogo/mortalidad , Adulto JovenRESUMEN
Although a double autologous peripheral blood stem cell transplant (APBSCT) is an effective therapy for patients (pts) with multiple myeloma and extends progression-free survival and overall survival, pts show a continued pattern of recurrent disease. The feasibility and tolerability of thalidomide (Thal) administered in the post-transplantation period as maintenance therapy was tested in 17 pts at a dose of 100 mg/d starting between 3 and 5 months after the second transplantation and continuing either until toxicity precluded further therapy or until pts had disease progression. After a median administration of 13 months (range: 3-26), 76.5% (13 pts) failed to tolerate Thal because of: transiet ischemic attack (three pts), severe fatigue (two), neutropenia (one), piastrinopenia (one), severe opportunistic infectious (two), erectile impotence (one), gastrointestinal toxicity (anorexia with weight loss one), peripheral neuropathy (two). After a median follow-up of 36 months (range: 10-59) from the second transplant, 13 patients attained a CR + near CR (with a conversion rate from 47.1% to 76.5%). In conclusion, Thal as maintenance therapy after double ASCT is associated with low feasibility and high toxicity and could prevent a lengthy use of this antineoplastic agent.
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Antineoplásicos/efectos adversos , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/terapia , Talidomida/efectos adversos , Adulto , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Trasplante Autólogo , Resultado del TratamientoRESUMEN
We undertook a comparative study of Pegfilgrastim vs. Filgrastim after high-dose melphalan and autologous peripheral blood stem cell transplantation (APBSCT) in multiple myeloma (MM) patients. Thirty-seven consecutive patients were randomly assigned to receive a single 6 mg dose of Pegfilgrastim on day 1 post-transplant (n = 18 patients) vs. daily subcutaneous injections of Filgrastim 5 microg/kg (n = 19 patients) starting on day 5 post-transplant. The median duration of grade 4 neutropenia in the Pegfilgrastim and Filgrastim groups was 5 and 6 d, respectively (P = ns). The results for the two groups were also not significantly different for time to neutrophil and platelet recovery, but incidence of febrile neutropenia (61.1% vs. 100%, P = 0.003) and duration of febrile neutropenia (1.5 d vs. 4 d, P = 0.005), were lower in the Pegfilgrastim arm. After initial haematopoietic reconstitution, we observed significantly higher value of leukocytes x 10(9) L on day 15 (6.0 vs. 2.7, P = 0.004), in the Pegfilgrastim group compared with the Filgrastim group. This study shows that a single injection Pegfilgrastim can be used with safety and efficacy similar to those provided by daily injections of Filgrastim and it is associated with a decrease incidence of infectious events after APBSCT in MM patients.
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Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Melfalán/administración & dosificación , Mieloma Múltiple/terapia , Agonistas Mieloablativos/administración & dosificación , Neutropenia/tratamiento farmacológico , Trasplante de Células Madre de Sangre Periférica , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Femenino , Filgrastim , Hematopoyesis/efectos de los fármacos , Humanos , Control de Infecciones/métodos , Infecciones/etiología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Neutropenia/etiología , Nimustina/administración & dosificación , Nimustina/efectos adversos , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Polietilenglicoles , Proteínas Recombinantes , Recuperación de la Función/efectos de los fármacos , Factores de Tiempo , Trasplante Autólogo , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
Angiogenesis is critical for the clinical progression of haematopoietic malignancies and depends on angiogenic factors. Angiogenin is a powerful factor produced by neoplastic cells and host microenvironment. High levels of soluble angiogenin (sAng) correlate with a poor prognosis in patients affected by acute myeloid leukaemia and myelodysplastic syndromes, but no data are available on sAng in chronic myeloproliferative disorders (CMD). Therefore, in this study we investigated the clinical significance of the angiogenin in sera of patients with chronic myeloid leukaemia (CML) (n = 14) or essential thrombocythaemia (ET) (n = 20), and correlated them with those of soluble transforming growth factor-beta(1) (sTGF beta(1)). Enzyme-linked immunosorbent assay detected (P < 0.05) higher levels of sAng in CMD compared with healthy subjects (1026.74 +/- 464.60 pg/mL and 196.00 +/- 39.90 pg/mL, respectively). The highest levels of sAng were detected in CML patients (1349.23 +/- 549.55 pg/mL). Interestingly, CML patients who achieved haematological remission after interferon therapy showed circulating levels of angiogenin significantly (P < 0.05) decreased when compared with those at diagnosis. In ET patients, levels of angiogenin (889.34 +/- 267.66 pg/mL) and sTGF beta(1) (76.69 +/-6.08 pg/mL) were higher (P < 0.05) compared with healthy controls (57.93 +/- 19.39 pg/mL). No correlation was found between levels of sAng and levels of sTGF beta(1) or platelet count among ET patients. Our results show for the first time that elevated blood levels of angiogenin feature chronic myeloid malignancies, suggesting a role of angiogenin in the pathogenesis of these diseases.