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1.
J Transl Med ; 17(1): 250, 2019 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-31383037

RESUMEN

BACKGROUND: Here, we isolated, expanded and functionally characterized regulatory T cells (Tregs) from patients with end stage kidney and liver disease, waiting for kidney/liver transplantation (KT/LT), with the aim to establish a suitable method to obtain large numbers of immunomodulatory cells for adoptive immunotherapy post-transplantation. METHODS: We first established a preclinical protocol for expansion/isolation of Tregs from peripheral blood of LT/KT patients. We then scaled up and optimized such protocol according to good manufacturing practice (GMP) to obtain high numbers of purified Tregs which were phenotypically and functionally characterized in vitro and in vivo in a xenogeneic acute graft-versus-host disease (aGVHD) mouse model. Specifically, immunodepressed mice (NOD-SCID-gamma KO mice) received human effector T cells with or without GMP-produced Tregs to prevent the onset of xenogeneic GVHD. RESULTS: Our small scale Treg isolation/expansion protocol generated functional Tregs. Interestingly, cryopreservation/thawing did not impair phenotype/function and DNA methylation pattern of FOXP3 gene of the expanded Tregs. Fully functional Tregs were also isolated/expanded from KT and LT patients according to GMP. In the mouse model, GMP Tregs from LT or KT patient proved to be safe and show a trend toward reduced lethality of acute GVHD. CONCLUSIONS: These data demonstrate that expanded/thawed GMP-Tregs from patients with end-stage organ disease are fully functional in vitro. Moreover, their infusion is safe and results in a trend toward reduced lethality of acute GVHD in vivo, further supporting Tregs-based adoptive immunotherapy in solid organ transplantation.


Asunto(s)
Criopreservación/métodos , Fallo Renal Crónico/inmunología , Hepatopatías/inmunología , Linfocitos T Reguladores/citología , Adulto , Anciano , Animales , Trasplante de Células , Metilación de ADN , Femenino , Factores de Transcripción Forkhead/genética , Enfermedad Injerto contra Huésped , Humanos , Inmunoterapia , Fallo Renal Crónico/cirugía , Hepatopatías/cirugía , Masculino , Ratones , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Persona de Mediana Edad , Fenotipo
2.
Biol Blood Marrow Transplant ; 24(12): 2450-2458, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30026107

RESUMEN

Chronic graft-versus-host disease (cGVHD) is a major complication after stem cell transplantation (HSCT). Several randomized studies already demonstrated that anti-T lymphoglobulin (ATLG) is effective in preventing GVHD after myeloablative unrelated and HLA-identical sibling transplants. However, the issue of doses and the potential increase of relapses still remain unsolved. Here we report data on 190 patients with acute leukemia and myelodysplastic syndrome who underwent an unrelated HSCT with low-dose ATLG (15 to 30 mg/kg) given at an earlier timing (days -6 to -2). HSCT was performed from HLA 10/10 (n = 62, 33%), 9/10 (n = 91, 48%), 8/10 (n = 30, 16%), and <8/10 (n = 7, 4%) identical unrelated donor. Peripheral blood was the stem cell source in 42% (n = 80). Median follow-up was 51 months. Grades II to IV and III to IV acute GVHD were 26% and 9%, respectively, and 2-year overall and moderate to severe cGVHD were 23% and 14%, respectively. The 3-year incidences of relapse and nonrelapse mortality were 26% and 18%, respectively. The rates of 3-year overall survival (OS), disease-free survival (DFS), and GVHD-free and relapse-free survival (GRFS) were 60%, 56% and 44%, respectively. Factors such as younger donor, good performance status, and early disease were associated with better outcome in terms of OS, DFS, and GRFS. Our data indicate that doses of ATLG lower that those used in randomized clinical trials can be used for GVHD prevention, even in the adult setting, without clear increases in relapse and infections; these findings need to be further validated by a prospective randomized study.


Asunto(s)
Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/tratamiento farmacológico , Adolescente , Adulto , Anciano , Suero Antilinfocítico/farmacología , Femenino , Humanos , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Estudios Retrospectivos , Donante no Emparentado , Adulto Joven
3.
Cytotherapy ; 19(12): 1447-1461, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28917627

RESUMEN

BACKGROUND AIMS: Growing evidence supports the therapeutic potential of bone marrow (BM)-derived stem/progenitor cells for end-stage liver disease (ESLD). We recently demonstrated that CD133+ stem/progenitor cell (SPC) reinfusion in patients with ESLD is feasible and safe and improve, albeit transiently, liver function. However, the mechanism(s) through which BM-derived SPCs may improve liver function are not fully elucidated. METHODS: Here, we characterized the circulating SPCs compartment of patients with ESLD undergoing CD133+ cell therapy. Next, we set up an in vitro model mimicking SPCs/liver microenvironment interaction by culturing granulocyte colony-stimulating factor (G-CSF)-mobilized CD133+and LX-2 hepatic stellate cells. RESULTS: We found that patients with ESLD show normal basal levels of circulating hematopoietic and endothelial progenitors with impaired clonogenic ability. After G-CSF treatment, patients with ESLD were capable to mobilize significant numbers of functional multipotent SPCs, and interestingly, this was associated with increased levels of selected cytokines potentially facilitating SPC function. Co-culture experiments showed, at the molecular and functional levels, the bi-directional cross-talk between CD133+ SPCs and human hepatic stellate cells LX-2. Human hepatic stellate cells LX-2 showed reduced activation and fibrotic potential. In turn, hepatic stellate cells enhanced the proliferation and survival of CD133+ SPCs as well as their endothelial and hematopoietic function while promoting an anti-inflammatory profile. DISCUSSION: We demonstrated that the interaction between CD133+ SPCs from patients with ESLD and hepatic stellate cells induces significant functional changes in both cellular types that may be instrumental for the improvement of liver function in cirrhotic patients undergoing cell therapy.


Asunto(s)
Antígeno AC133/metabolismo , Enfermedad Hepática en Estado Terminal/terapia , Células Estrelladas Hepáticas/citología , Hígado/citología , Trasplante de Células Madre/métodos , Células Madre/metabolismo , Proliferación Celular , Técnicas de Cocultivo , Enfermedad Hepática en Estado Terminal/patología , Factor Estimulante de Colonias de Granulocitos/metabolismo , Factor Estimulante de Colonias de Granulocitos/farmacología , Células Estrelladas Hepáticas/fisiología , Humanos , Hígado/metabolismo , Hígado/patología , Neovascularización Fisiológica , Células Madre/citología , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo
4.
Biol Blood Marrow Transplant ; 21(12): 2052-2060, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26271194

RESUMEN

The number of allogeneic hematopoietic stem cell (HSC) transplants performed globally each year continues to increase. Advances in HLA typing, better supportive care, and administration of reduced-intensity conditioning regimens allow treatment of older patients with older sibling donors. Pretransplant donor assessment and testing are very important processes affecting the quality and safety of donation. For unrelated HSC donors detailed recommendations for health assessment have been published, allowing donation only if they are unrestrictedly healthy. Eligibility criteria for related donors are less strict and vary significantly between centers. In situations where a family donor does not meet the suitability criteria for unrelated donors, involved physicians often struggle with the decision whether the matched relative is suitable for donation or not. On behalf of the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues, we intended to develop a consensus document with recommendations for donor workup and final clearance of family donors who would not be able to serve as unrelated donors because of their age or pre-existing diseases. This article covers different topics intending to support decision-making, with the goal of minimizing medical risk to the donor and protection of the recipient from transmissible diseases.


Asunto(s)
Trasplante de Médula Ósea/métodos , Toma de Decisiones Clínicas/ética , Estado de Salud , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Donante no Emparentado , Comités Consultivos , Factores de Edad , Consenso , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/patología , Prueba de Histocompatibilidad , Humanos , Consentimiento Informado , Cooperación Internacional , Riesgo , Hermanos , Acondicionamiento Pretrasplante , Trasplante Homólogo
5.
Blood ; 118(12): 3273-9, 2011 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-21791425

RESUMEN

Thirteen patients with acute myeloid leukemia, 5 with active disease, 2 in molecular relapse, and 6 in morphologic complete remission (CR; median age, 62 years; range, 53-73 years) received highly purified CD56(+)CD3(-) natural killer (NK) cells from haploidentical killer immunoglobulin-like receptor-ligand mismatched donors after fludarabine/cyclophosphamide immunosuppressive chemotherapy, followed by IL-2. The median number of infused NK cells was 2.74 × 10(6)/Kg. T cells were < 10(5)/Kg. No NK cell-related toxicity, including GVHD, was observed. One of the 5 patients with active disease achieved transient CR, whereas 4 of 5 patients had no clinical benefit. Both patients in molecular relapse achieved CR that lasted for 9 and 4 months, respectively. Three of 6 patients in CR are disease free after 34, 32, and 18 months. After infusion, donor NK cells were found in the peripheral blood of all evaluable patients (peak value on day 10). They were also detected in BM in some cases. Donor-versus-recipient alloreactive NK cells were shown in vivo by the detection of donor-derived NK clones that killed recipient's targets. Adoptively transferred NK cells were alloreactive against recipient's cells, including leukemia. In conclusion, infusion of purified NK cells is feasible in elderly patients with high-risk acute myeloid leukemia. This trial was registered at www.clinicaltrial.gov as NCT00799799.


Asunto(s)
Efecto Injerto vs Leucemia , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/administración & dosificación , Inmunoterapia Adoptiva/métodos , Células Asesinas Naturales , Leucemia Mieloide Aguda , Receptores KIR/análisis , Antígenos CD/análisis , Antígenos CD/biosíntesis , Separación Celular , Ciclofosfamida/administración & dosificación , Citometría de Flujo , Prueba de Histocompatibilidad , Humanos , Inmunofenotipificación , Interleucina-2/biosíntesis , Células Asesinas Naturales/citología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/trasplante , Leucaféresis , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión , Factores de Riesgo , Trasplante Homólogo , Vidarabina/administración & dosificación , Vidarabina/análogos & derivados
6.
Blood Transfus ; 21(6): 514-525, 2023 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-37146295

RESUMEN

Chimeric antigen receptor (CAR) T-cell therapy relies on T cells engineered to target specific tumor antigens such as CD-19 in B-cell malignancies. In this setting, the commercially available products have offered a potential long-term cure for both pediatric and adult patients. Yet manufacturing CAR T cells is a cumbersome, multistep process, the success of which strictly depends on the characteristics of the starting material, i.e., lymphocyte collection yield and composition. These, in turn, might be affected by patient factors such as age, performance status, comorbidities, and previous therapies. Ideally, CAR T-cell therapies are a one-off treatment; therefore, optimization and the possible standardization of the leukapheresis procedure is critical, also in view of the novel CAR T cells currently under investigation for hematological malignancies and solid tumors. The most recent Best Practice recommendations for the management of children and adults undergoing CAR T-cell therapy provide a comprehensive guide to their use. However, their application in local practice is not straightforward and some grey areas remain. An Italian Expert Panel of apheresis specialists and hematologists from the centers authorized to administer CAR T-cell therapy took part in a detailed discussion on the following: 1) pre-apheresis patient evaluation; 2) management of the leukapheresis procedure, also in special situations represented by low lymphocyte count, peripheral blastosis, pediatric population <25 kg, and the COVID-19 outbreak; and 3) release and cryopreservation of the apheresis unit. This article presents some of the important challenges that must be faced to optimize the leukapheresis procedure and offers suggestions as to how to improve it, some of which are specific to the Italian setting.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Niño , Adulto , Inmunoterapia Adoptiva/métodos , Leucaféresis/métodos , Receptores Quiméricos de Antígenos/uso terapéutico , Linfocitos , Tratamiento Basado en Trasplante de Células y Tejidos
7.
Front Immunol ; 12: 804988, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35173709

RESUMEN

Recently, many reports were published supporting the clinical use of adoptively transferred natural killer (NK) cells as a therapeutic tool against cancer, including acute myeloid leukemia (AML). Our group demonstrated promising clinical response using adoptive immunotherapy with donor-derived alloreactive KIR-ligand-mismatched NK cells in AML patients. Moreover, the antileukemic effect was correlated with the dose of infused alloreactive NK cells ("functional NK cell dose"). Herein, we update the results of our previous study on a cohort of adult AML patients (median age at enrollment 64) in first morphological complete remission (CR), not eligible for allogeneic stem cell transplantation. After an extended median follow-up of 55.5 months, 8/16 evaluable patients (50%) are still off-therapy and alive disease-free. Overall survival (OS) and disease-free survival (DFS) are related with the dose of infused alloreactive NK cells (≥2 × 105/kg).


Asunto(s)
Inmunoterapia Adoptiva/métodos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Anciano , Femenino , Antígenos de Histocompatibilidad/inmunología , Prueba de Histocompatibilidad , Humanos , Inmunoterapia Adoptiva/efectos adversos , Leucemia Mieloide Aguda/etiología , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento
8.
Bone Marrow Transplant ; 55(5): 946-954, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31768009

RESUMEN

Plerixafor inhibits CXCR4, thus inducing the mobilization of hematopoietic stem/progenitor cells in lymphoma and multiple myeloma (MM) patients eligible for autologous stem cell transplantation (ASCT). However, the kinetics of plerixafor-induced mobilization of lymphocyte subsets is poorly known. Here, we evaluated the graft content, the engraftment, and the immunological reconstitution of MM patients receiving plerixafor. Thirty-seven patients undergoing one or tandem ASCT were enrolled. After mobilization with cyclophosphamide plus G-CSF, plerixafor was added at hematological recovery regardless of CD34+ cell count. We evaluated the number of CD34+, CD34+/CD38-, CD3+, CD4+, CD8+, CD19+, CD56+/CD3-, CD4+/CD25+/FOXP3+, and CD138+/CD38+ cells on each apheresis. Hematological and immunological recovery were determined at 30 days, 3, 6, 9, and 12 months after ASCT. Overall, 34/37 patients mobilized a median of 10.1 × 106 CD34+ cells/Kg (IQ 7.7-13.4). Patients with <20/µL CD34+ cells at plerixafor administration (18/33) had a significantly higher CD34+ cell fold increase, but not a higher absolute number, than 16/33 patients with ≥20/µL CD34+ cells. A similar CD34+ and immune graft composition was reported. A higher number of CD3+ and CD8+ cells/µL was observed at 3 months after first ASCT (p < 0.05) in the group with ≥20 CD34+ cells/µL. Thus, in MM patients, the timing of plerixafor administration influences immunological recovery.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Mieloma Múltiple , Bencilaminas , Ciclamas , Factor Estimulante de Colonias de Granulocitos , Movilización de Célula Madre Hematopoyética , Humanos , Mieloma Múltiple/terapia , Trasplante Autólogo
9.
Bone Marrow Transplant ; 54(5): 717-725, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30232415

RESUMEN

Umbilical Cord Blood (UCB) represents a valid option for patients with hematopoietic malignancies lacking an HLA matched donor. To overcome the limitation of the low stem cell dose of UCB, the intrabone (IB) route has been proposed. We report the results of a prospective study on a poor-prognosis cohort of 23 patients receiving intrabone single UCB transplant (Clinicaltrials.gov NCT00886522). Cumulative incidence of hematological recovery at day 90 was 82 ± 9% (ANC > 0.5 × 109/L) and 70 ± 10% (platelet > 50 × 109/L) and correlated with CD34 + cells in the graft. NRM was 20 ± 9%. No severe aGVHD and only one extensive cGVHD occurred, with fast immune reconstitution. To test the hypothesis that the direct IB injection could affect the expression of stem cells regulatory pathways, CD34 + cells from BM aspirates at day + 10, + 20, + 30, processed in hypoxic conditions mimicking the BM-microenvironment (7%pO2), were studied for the expression of c-Mpl, Notch1 and CXCR4. We found that the expression of c-Mpl in CD34 + cells at day + 10 significantly correlated with hematological recovery. In conclusion, IB-UCB transplant success is associated with low incidence of GVHD and high-speed platelet recovery; intrabone route may preserve full hematopoietic stemness by direct delivery of UCB stem cells into the hypoxic HSC niche.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped/sangre , Neoplasias Hematológicas , Hematopoyesis , Recuperación de la Función , Células Madre , Adolescente , Adulto , Recuento de Células , Femenino , Neoplasias Hematológicas/sangre , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
10.
Clin Cancer Res ; 22(8): 1914-21, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-26787753

RESUMEN

PURPOSE: In acute myeloid leukemia (AML), alloreactive natural killer (NK) cells are crucial mediators of immune responses after haploidentical stem cell transplantation. Allogeneic NK cell infusions have been adoptively transferred with promising clinical results. We aimed at determining whether the composition of NK graft in terms of frequency of alloreactive NK cells influence the clinical response in a group of elderly AML patients undergoing NK immunotherapy. EXPERIMENTAL DESIGN: Seventeen AML patients, in first complete remission (CR; median age 64 years, range 53-73) received NK cells from haploidentical KIR-ligand-mismatched donors after fludarabine/cyclophosphamide chemotherapy, followed by IL2. To correlate donor NK cell activity with clinical response, donor NK cells were assessed before and after infusion. RESULTS: Toxicity was moderate, although 1 patient died due to bacterial pneumonia and was censored for clinical follow-up. With a median follow-up of 22.5 months (range, 6-68 months), 9 of 16 evaluable patients (0.56) are alive disease-free, whereas 7 of 16 (0.44) relapsed with a median time to relapse of 9 months (range, 3-51 months). All patients treated with molecular disease achieved molecular CR. A significantly higher number of donor alloreactive NK cell clones was observed in responders over nonresponders. The infusion of higher number of alloreactive NK cells was associated with prolonged disease-free survival (0.81 vs. 0.14, respectively;P= 0.03). CONCLUSIONS: Infusion of purified NK cells is feasible in elderly AML patients as post-CR consolidation strategy. The clinical efficacy of adoptively transferred haploidentical NK cells may be improved by infusing high numbers of alloreactive NK cells.


Asunto(s)
Inmunoterapia , Isoantígenos/inmunología , Células Asesinas Naturales/inmunología , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Donantes de Tejidos , Factores de Edad , Anciano , Terapia Combinada , Femenino , Genotipo , Haplotipos , Prueba de Histocompatibilidad , Humanos , Inmunofenotipificación , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Células Asesinas Naturales/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Prospectivos , Receptores KIR3DL1/genética , Receptores KIR3DL1/metabolismo , Recurrencia , Resultado del Tratamiento
11.
Haematologica ; 90(2): 225-31, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15710576

RESUMEN

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the efficacy of pegfilgrastim, in combination with salvage chemotherapy, in mobilizing CD34(+) stem cells into the peripheral blood of pretreated lymphoma patients. DESIGN AND METHODS: This was an open-label phase II study including 25 pretreated patients (Hodgkin's disease=4; aggressive non-Hodgkin's lymphoma=21). The primary end-point of the study was the successful mobilization of a target cell dose of 2x10(6) CD34(+) cells/kg in lymphoma patients receiving ifosfamide, epirubicin and etoposide (IEV) chemotherapy and a fixed dose (6 mg) of pegfilgrastim given as single subcutaneous injection. RESULTS: Following chemotherapy, all patients had grade 4 neutropenia that lasted a median of 1.5 days (1-3). Pegfilgrastim treatment was well tolerated and only 2/25 patients required pain-control medication. CD34+ cells were mobilized in all patients. The median (range) peak value of peripheral blood CD34+ cells after IEV chemotherapy and pegfilgrastim was 141x10(6)/L (12.8-386) and occurred almost invariably on day +14 (13-16). Twenty-three of the 25 patients underwent a single standard volume leukapheresis to collect a median of 8.7x10(6) CD34(+) cells/kg (1.78-17.3). Twenty four/25 patients (96%) reached the target cell dose of 2x10(6) CD34(+) cells/kg. High concentrations of circulating CD34+ cells (> 50x10(6)/L) were observed for several days after the achievement of the peak value. All the study patients were transplanted with their pegfilgrastim-mobilized CD34(+) cells and showed a rapid and sustained engraftment after high-dose chemotherapy. INTERPRETATION AND CONCLUSIONS: Our results show that pegfilgrastim as an adjunct to chemotherapy is a predictable and highly effective mobilization regimen in pretreated lymphoma patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Quimioterapia Adyuvante , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/métodos , Células Madre Hematopoyéticas/efectos de los fármacos , Linfoma/terapia , Adulto , Anciano , Antígenos CD34/biosíntesis , Protocolos de Quimioterapia Combinada Antineoplásica , Femenino , Filgrastim , Movilización de Célula Madre Hematopoyética/instrumentación , Células Madre Hematopoyéticas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Polietilenglicoles , Proteínas Recombinantes , Acondicionamiento Pretrasplante
12.
Dig Liver Dis ; 47(12): 1059-66, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26427587

RESUMEN

BACKGROUND: Bone marrow stem/progenitor cells seem to be effective in liver regeneration after tissue injury. AIM: To evaluate the feasibility and safety of the mobilization and reinfusion of CD133+ stem/progenitor cells in patients with end-stage liver disease. METHODS: Autologous CD133+ stem/progenitor cells, mobilized with granulocyte-colony stimulating factor, were collected by leukapheresis and reinfused at increasing doses through the hepatic artery starting from 5×10(4)/kg up to 1×10(6)/kg. RESULTS: 16 subjects with Model for End-stage Liver Disease (MELD) score between 17 and 25 were enrolled, 14 mobilized an adequate number of CD133+ stem/progenitor cells and 12 were reinfused. No severe adverse events related to the procedure were reported. MELD score significantly worsened during mobilization in Child Turcotte Pugh-C patients. A significant improvement of liver function was observed 2 months after reinfusion (MELD 19.5 vs. 16; P=0.045). Overall, 5 patients underwent liver transplantation within 12 months from reinfusion and 2 died because of progressive liver failure. CONCLUSIONS: CD133+ stem/progenitor cells reinfusion in patients with end-stage liver disease is feasible and safe. A worsening of liver function was observed during mobilization in Child Turcotte Pugh-C patients. The temporary improvement of MELD score after reinfusion suggests that stem cells therapy may be a "bridge to transplant" approach for these patients.


Asunto(s)
Antígenos CD , Enfermedad Hepática en Estado Terminal/terapia , Glicoproteínas , Trasplante de Células Madre Hematopoyéticas , Péptidos , Células Madre/citología , Antígeno AC133 , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética , Humanos , Italia , Leucaféresis , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estudios Prospectivos
13.
Haematologica ; 88(5): 522-8, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12745271

RESUMEN

BACKGROUND AND OBJECTIVES: In this work we examine the characteristics and outcome of patients with Hodgkin's disease (HD) treated with high-dose therapy (HDT) and autologous transplantation at our Institute between 1982 to 2000. DESIGN AND METHODS: A retrospective analysis was performed examining patients' characteristics, prior chemotherapy regimens, pre-transplant disease status, HDT regimen, source of stem cells, time for hematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and relapse-free survival (RFS). RESULTS: Ninety-seven patients with HD were treated and had estimated 10-year OS and RFS rates of 32% and 60%, respectively. Disease status (sensitive vs. refractory) before HDT was the most powerful predictive parameter for OS and RFS in both univariate and multivariate analyses. The rate of transplant-related mortality in the whole cohort was only 1% whereas the rate of second malignancies was 3%. INTERPRETATION AND CONCLUSIONS: Our results confirm that HDT with autologous transplantation is associated with a durable RFS in a remarkable proportion of HD patients and that the procedure has a very low global early and late toxicity.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/radioterapia , Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Trasplante de Médula Ósea , Niño , Terapia Combinada , Femenino , Enfermedad de Hodgkin/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Recurrencia , Estudios Retrospectivos , España , Análisis de Supervivencia , Resultado del Tratamiento
15.
Br J Haematol ; 139(3): 415-24, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17910631

RESUMEN

Fifteen multiple myeloma (MM) patients who had failed maintenance therapy after tandem autologous stem cell transplantation underwent anti-idiotype (Id) vaccination with dendritic cells (DCs). CD14(+)-derived DCs were loaded with the autologous Id as whole protein (=6) or Id-derived class I-restricted peptides (=9) and keyhole limpet hemocyanin (KLH). Vaccination consisted of three subcutaneous (sc) and two intravenous injections of increasing DC doses at 2 weeks interval. DC therapy was well tolerated. Most patients developed both humoral and T-cell responses to KLH, suggesting immunocompetence. Eight of 15 patients developed an Id-specific T-cell proliferative response, 8/15 increased interferon-gamma-secreting T cells and 4/15 showed an Id-positive delayed-type hypersensitivity test. Anti-Id cytotoxic T-lymphocyte precursors increased after DC vaccination in 2/2 evaluable patients. A more robust T-cell response was observed after sc DC injections and increased Id-specific T-cell proliferation was found up to 1 year after vaccination. VDJ-derived peptides were as effective as the whole protein in stimulating T-cell responses. Clinically, 7/15 patients have stable disease after a median follow-up of 26 months, one patient achieved durable partial remission after 40 months, and seven patients progressed. In conclusion, sc injections of cryopreserved Id-pulsed DCs were safe and, in contrast with intravenous administrations, induced anti-MM T-cell responses.


Asunto(s)
Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/trasplante , Idiotipos de Inmunoglobulinas/inmunología , Mieloma Múltiple/terapia , Adulto , Anciano , Anticuerpos Antineoplásicos/biosíntesis , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/administración & dosificación , Femenino , Hemocianinas/inmunología , Humanos , Inmunidad Celular , Región de Unión de la Inmunoglobulina/inmunología , Región Variable de Inmunoglobulina/inmunología , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Fragmentos de Péptidos/inmunología , Resultado del Tratamiento , Vacunación/efectos adversos , Vacunación/métodos
16.
Biol Blood Marrow Transplant ; 13(10): 1224-32, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17889360

RESUMEN

We assessed the capacity of positively selected autologous CD133(+) hematopoietic stem cells (HSCs) to reconstitute lymphomyelopoiesis in chronic lymphocytic leukemia (CLL) patients receiving myeloablative chemotherapy. Ten resistant/relapsed CLL patients underwent HSC mobilization with chemotherapy and granulocyte-colony stimulating factor (G-CSF). Positive selection of circulating CD133(+) HSCs was performed by immunomagnetic technique. Highly purified HSCs were reinfused after busulphan/melphalan myeloablative treatment. A median number of 4.2 x 10(6) CD34(+) cells/kg and of 3.14 x 10(6) CD133(+) cells/kg were collected. Immunomagnetic selection resulted in the reinfusion of a median number of 2.45 x 10(6) CD133(+) cells/kg (median purity: 94.8%; median recovery: 84%) and 2.4 x 10(6) CD34(+) cells/kg (median purity: 93%; median recovery: 71%). HSC selection resulted in a median T cell and CD19(+)/CD5(+) cell depletion of 3.85 log and 2.8 log, respectively. At the molecular level, however, 7 of 8 valuable purified HSC fractions were contaminated by leukemic cells. All CLL patients showed rapid and sustained myeloid engraftment after reinfusion of purified CD133(+) cells. Immunologic reconstitution was comparable to that routinely observed in patients reinfused with unmanipulated leukapheresis products and no late infectious complications were observed. With a median follow-up of 28 months for transplanted patients, 5 patients are in clinical complete remission, 3 are in partial remission, and 1 is in progression. In conclusion, the reinfusion of highly purified CD133(+) HSCs allowed the rapid and sustained recovery of hematopoiesis after myeloablative treatment in resistant/relapsed CLL patients. However, the purging potential of positive selection of CD133(+) cells is not adequate to achieve tumor-free autografts.


Asunto(s)
Antígenos CD/sangre , Glicoproteínas/sangre , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Linfocítica Crónica de Células B/terapia , Recurrencia Local de Neoplasia/terapia , Péptidos/sangre , Células Madre Pluripotentes/trasplante , Trasplante Autólogo/métodos , Antígeno AC133 , Purgación de la Médula Ósea , Separación Celular , Enfermedad Crónica , Femenino , Supervivencia de Injerto , Movilización de Célula Madre Hematopoyética/métodos , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Terapia Recuperativa/métodos , Acondicionamiento Pretrasplante/métodos
17.
Buenos Aires; s.n; 2020. 11 p.
No convencional en Español | LILACS, InstitutionalDB, BINACIS, UNISALUD | ID: biblio-1354490

RESUMEN

El propósito de este escrito es realizar un relato de experiencia del Equipo de Psicopedagogía del Hospital de Niños "Ricardo Gutiérrez" (HNRG) en tiempos de pandemia. Esta coyuntura, como agentes de salud pública, implicó el desafío de encontrar nuevas maneras de acompañar trayectorias de aprendizaje, así como propiciar espacios de salud mental para la comunidad. Se comenzará realizando una breve contextualización de las prácticas previas a la pandemia para luego profundizar en las. nuevas modalidades que se han construido como equipo. (AU)


Asunto(s)
Aislamiento Social , Atención Hospitalaria/métodos , Atención Hospitalaria/organización & administración , Pandemias , COVID-19 , Capacitación en Servicio/métodos , Capacitación en Servicio/tendencias , Internado y Residencia/métodos , Internado y Residencia/tendencias
18.
Buenos Aires; s.n; 2018. 75 p. ilus.
No convencional en Español | LILACS | ID: biblio-1009802

RESUMEN

Ateneo del equipo de residentes psicopedagogas del Centro de Salud y Acción Comunitaria Nº 13, de la Ciudad de Buenos Aires, donde se reflexiona sobre la labor clínica, y el trabajo psicopedagogo en espacios preventivo-promocionales. En la primer parte, se desarrolla el marco teórico respecto del concepto de lenguaje desde el cual se posicionan las residentes, distinguiendo respecto de los conceptos de lengua, habla y lenguaje y su implicancia en el campo de la Psicopedagogía. Se mencionan los factores constitutivos del lenguaje, se describen brevemente algunas alteraciones del lenguaje de los niños, y se abordan las relaciones entre aprendizaje y lenguaje, desplegando su relación con el pensamiento y los aspectos ligados a la compresión lingüística. Finalmente a la luz de los conceptos centrales trabajados en el escrito, se intenta, a través de viñetas y recortes clínicos, reflejar posibles modos de intervención desde la tarea como psicopedagogas.


Asunto(s)
Rehabilitación de los Trastornos del Habla y del Lenguaje , Educación Compensatoria , Lenguaje Infantil , Patología del Habla y Lenguaje , Desarrollo del Lenguaje , Aprendizaje , Centros Comunitarios de Salud , Internado no Médico
19.
Buenos Aires; s.n; 2018. 50 p. graf..
No convencional en Español | LILACS | ID: biblio-1009917

RESUMEN

Ateneo de los residentes de Psicopedagogía del Hospital de Niños Dr Ricardo Gutiérrez, de la Ciudad de Buenos Aires, donde a partir de la práctica psicopedagógica con niños y adolescentes con patología orgánica se desarrollan cuatro ejes temáticos para describir algunas de las patologías o condiciones con las cuales se han ido encontrando en su labor cotidiana. Se relatan algunas viñetas clínicas que surgen de la experiencia en el Consultorio Interdisciplinario de Espina Bífida, con el fin de reflejar la intervención y los aportes de la psicopedagogía en ese campo. Se presenta el caso de una paciente que presentó un cuadro de Encefalitis Autoinmune por anticuerpos contra el receptor NMDAR, patología que despertó un gran interés al interior del equipo y que debido a su creciente recurrencia en los últimos tiempos, convoca a ampliar el conocimiento en ese campo, que aún se encuentra poco investigado. A continuación, se caracterizan dos patologías genéticas a través de casos de Agustín y Matías, considerando la importante incidencia de diversas condiciones genéticas en la población con la cual trabajamos. A partir de los casos clínicos seleccionados, no solo perseguimos el fin de describir y caracterizar algunos cuadros específicos, sino que a través de los mismos buscaremos plasmar los pilares fundamentales sobre los cuales asentamos nuestra mirada e intervención frente a pacientes que exigen un abordaje complejo, integral e interdisciplinario.


Asunto(s)
Anomalías Congénitas/psicología , Anomalías Congénitas/rehabilitación , Anomalías Congénitas/terapia , Disrafia Espinal/terapia , Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Disostosis Mandibulofacial/terapia , Síndrome de Noonan/terapia , Instituciones de Atención Ambulatoria , Internado no Médico
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