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1.
Br J Haematol ; 196(4): 1018-1030, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34750806

RESUMEN

We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adulto , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
2.
Biol Blood Marrow Transplant ; 22(10): 1808-1815, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27470290

RESUMEN

There is at present little data to guide the choice of conditioning for patients with lymphoma undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT). In this study, we compared the outcomes of patients undergoing RIC SCT who received fludarabine and melphalan (FluMel), the standard RIC regimen used by the Spanish Group of Transplantation, and fludarabine and busulfan (FluBu), the standard RIC regimen used by the Dana-Farber Cancer Institute/Brigham and Women's Hospital. We analyzed 136 patients undergoing RIC SCT for lymphoma with either FluBu (n = 61) or FluMel (n = 75) conditioning between 2007 and 2014. Median follow-up was 36 months. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 13% with FluBu and 36% with FluMel (P = .002). The cumulative incidence of nonrelapse mortality (NRM) at 1 year was 3.3% with FluBu and 31% with FluMel (P < .0001). The cumulative incidence of relapse at 1 year was 29% with FluBu and 10% with FluMel (P = .08). The 3-year disease-free survival rate was 47% with FluBu and 36% with FluMel (P = .24), and the 3-year overall survival rate was 62% with FluBu and 48% with FluMel (P = .01). In multivariable analysis, FluMel was associated with a higher risk of acute grades II to IV GVHD (HR, 7.45; 95% CI, 2.30 to 24.17; P = .001) and higher risk of NRM (HR, 4.87; 95% CI, 1.36 to 17.44; P = .015). The type of conditioning was not significantly associated with relapse or disease-free survival in multivariable models. However, conditioning regimen was the only factor significantly associated with overall survival: FluMel conditioning was associated with a hazard ratio for death of 2.78 (95% CI, 1.23 to 6.27; P = .014) compared with FluBu. In conclusion, the use of FluBu as conditioning for patients undergoing SCT for lymphoma was associated with a lower risk of acute GVHD and NRM and improved overall survival when compared with FluMel in our retrospective study. These results confirm the differences between these RIC regimens in terms of toxicity and efficacy and support the need for comparative prospective studies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma/terapia , Acondicionamiento Pretrasplante/mortalidad , Acondicionamiento Pretrasplante/métodos , Adulto , Busulfano/uso terapéutico , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Linfoma/mortalidad , Masculino , Melfalán/uso terapéutico , Persona de Mediana Edad , Tasa de Supervivencia , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
3.
Int J Sports Med ; 36(4): 292-6, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25429550

RESUMEN

Circulating progenitor cells (CPC) are bone marrow-derived cells that are mobilized into the circulation. While exercise is a powerful mediator of hematopoiesis, CPC levels increase, and reports of their activation after different types of exercise are contradictory. Moreover, few studies have compared the possible effects of different training programs on CPC concentrations. 43 physically active healthy male subjects (age 22±2.4 years) were assigned to 4 different training groups: aerobic, resistance, mixed and control. Except for the control group, all participants trained for 6 weeks. Peripheral blood samples were collected through an antecubital vein, and CPC CD34(+) was analyzed on different days: pre-training, post-training, and 3 weeks after finishing the training period. While no significant differences in CPC were observed either within or between the different training groups, there was a tendency towards higher values post-training and large intra- and intergroup dispersion. We detected an inverse linear relationship between pre-training values and % of CPC changes post-training (p<0.001). In the CPC values 3 weeks after training this inverse relationship was maintained, though to a lower extent (p<0.001). No changes in CPC CD34(+) were detected after 6 weeks of different training groups, or after 3 weeks of follow-up.


Asunto(s)
Ejercicio Físico/fisiología , Educación y Entrenamiento Físico/métodos , Células Madre/metabolismo , Antígenos CD34 , Endotelio Vascular/fisiología , Humanos , Masculino , Entrenamiento de Fuerza/métodos , Adulto Joven
4.
Rev Esp Quimioter ; 34(2): 115-119, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33586407

RESUMEN

OBJECTIVE: To determine the indications, success rate and adverse effects of ceftaroline fosamil treatment in a tertiary hospital. METHODS: In total, 84 cases from February 2018 to December 2019 were retrospectively analysed. No exclusion criteria were applied. RESULTS: Eighty-four patients, with a median age of 70 years, of which, 6.7% (56) were male, were treated with ceftaroline fosamil for a median of 14 days. Most indications were off-label, including 29 endocarditis (34.5%), 14 bacteraemia (16.6%), 5 Central nervous system (CNS) infections (6%) and 19 osteoarticular infections (22.6%). Staphylococcus aureus was the most frequently isolated microorganism, including 28 methicillin-sensitive S. aureus (MSSA; 33.3%) and 14 methicillin-resistant S. aureus (MRSA; 16.7%), followed by coagulase-negative Staphylococcus (23, 27.4%). The main reason for ceftaroline fosamil prescription was the failure of previous treatment (41.7% of cases). Treatment was successful in 60/84 patients (71.4%) and failed clinically or microbiologically in 14 (16.7%). Eight patients died for a reason not related to the infection and two were found to have a non-infectious condition. Twenty-two of thirty-five (62.8%) patients prescribed ceftaroline because of failure of previous treatment improved, including eight endocarditis and seven bacteraemia. Adverse effects were reported in five patients (5.9%) including neutropenia, thrombocytopenia, transaminases elevation and creatinine elevation; all except one were mild and all resolved after discontinuation of treatment. CONCLUSIONS: Ceftaroline fosamil is a well-tolerated cephalosporine, effective against multi- resistant gram-positive and many gram-negative microorganisms. Our experience suggests that it is effective as a rescue or first-line therapy in other indications than those currently approved.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Anciano , Antibacterianos , Cefalosporinas , Humanos , Masculino , Prescripciones , Estudios Retrospectivos , Staphylococcus aureus , Centros de Atención Terciaria , Ceftarolina
5.
Medicine (Baltimore) ; 100(51): e27597, 2021 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-34941026

RESUMEN

ABSTRACT: Current data on the frequency and efficacy of linezolid (LNZ) in infective endocarditis (IE) are based on small retrospective series. We used a national database to evaluate the effectiveness of LNZ in IE.This is a retrospective study of IE patients in the Spanish GAMES database who received LNZ. We defined 3 levels of therapeutic impact: LNZ < 7 days, LNZ high-impact (≥ 7 days, > 50% of the total treatment, and > 50% of the LNZ doses prescribed in the first weeks of treatment), and LNZ ≥ 7 days not fulfilling the high-impact criteria (LNZ-NHI). Effectiveness of LNZ was assessed using propensity score matching and multivariate analysis of high-impact cases in comparison to patients not treated with LNZ from the GAMES database matched for age-adjusted comorbidity Charlson index, heart failure, renal failure, prosthetic and intracardiac IE device, left-sided IE, and Staphylococcus aureus. Primary outcomes were in-hospital mortality and one-year mortality. Secondary outcomes included IE complications and relapses.From 3467 patients included in the GAMES database, 295 (8.5%) received LNZ. After excluding 3 patients, 292 were grouped as follows for the analyses: 99 (33.9%) patients in LNZ < 7 days, 11 (3.7%) in LNZ high-impact, and 178 (61%) in LNZ-NHI. In-hospital mortality was 51.5%, 54.4%, and 19.1% respectively. In the propensity analysis, LNZ high-impact group presented with respect to matched controls not treated with LNZ higher in-hospital mortality (54.5% vs 18.2%, P = .04). The multivariate analysis showed an independent relationship of LNZ use with in-hospital mortality (odds ratio 9.06, 95% confidence interval 1.15--71.08, P = .03).Treatment with LNZ is relatively frequent, but most cases do not fulfill our high-impact criteria. Our data suggest that the use of LNZ as definitive treatment in IE may be associated with higher in-hospital mortality.


Asunto(s)
Antibacterianos/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Linezolid/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Anciano , Endocarditis/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Endocarditis Bacteriana/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Infecciones Estafilocócicas/diagnóstico , Staphylococcus aureus/aislamiento & purificación , Resultado del Tratamiento
6.
J Exp Med ; 187(11): 1885-92, 1998 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-9607928

RESUMEN

The efficacy of thalidomide (alpha-phthalimido-glutarimide) therapy in leprosy patients with erythema nodosum leprosum is thought to be due to inhibition of tumor necrosis factor alpha. In other diseases reported to respond to thalidomide, the mechanism of action of the drug is unclear. We show that thalidomide is a potent costimulator of primary human T cells in vitro, synergizing with stimulation via the T cell receptor complex to increase interleukin 2-mediated T cell proliferation and interferon gamma production. The costimulatory effect is greater on the CD8+ than the CD4+ T cell subset. The drug also increases the primary CD8+ cytotoxic T cell response induced by allogeneic dendritic cells in the absence of CD4+ T cells. Therefore, human T cell costimulation can be achieved pharmacologically with thalidomide, and preferentially in the CD8+ T cell subset.


Asunto(s)
Linfocitos T CD8-positivos/efectos de los fármacos , Citocinas/biosíntesis , Mitógenos/farmacología , Talidomida/farmacología , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Células Presentadoras de Antígenos/inmunología , Complejo CD3/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , División Celular , Células Cultivadas , Pruebas Inmunológicas de Citotoxicidad , Células Dendríticas/inmunología , Enterotoxinas/inmunología , Fijadores , Glutaral , Humanos , Superantígenos/inmunología
7.
Bone Marrow Transplant ; 55(2): 419-430, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31551517

RESUMEN

This multicenter phase I trial was designed to evaluate the safety and efficacy of bortezomib (Bz) as part of both the conditioning regimen and the graft-versus-host disease (GvHD) prophylaxis. Patients received fludarabine, melphalan and Bz (days -9 and -2). GVHD prophylaxis consisted of Bz (days +1, +4, and +7), sirolimus (Siro) from day -5 and tacrolimus (Tk) from -3 (except the first five patients that did not receive Tk). Twenty-five patients with poor prognostic multiple myeloma were included. Eleven out of the 19 patients had high-risk features. Out of the 21 patients evaluable at day +100, 14 were in CR (67%) and 7 (33%) in PR. Cumulative incidence (CI) of nonrelapse mortality at 1 year was 24%. CI of grades 2-4 and 3-4 acute GvHD was 35% and 10%, respectively; CI of chronic GvHD was 35% and 55% at 1 and 2 years, respectively. Overall and event free survival at 2 years were 64% and 31%, respectively. Bz as part of the conditioning regimen and in the combination with Siro/tacrolimus for GvHD prophylaxis is safe and effective allowing an optimal disease control early after transplant and reducing the risk of GvHD.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Bortezomib/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Mieloma Múltiple/terapia , Tacrolimus , Acondicionamiento Pretrasplante
8.
Leukemia ; 21(4): 633-41, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17268512

RESUMEN

The aim of this study was to identify immunobiological subgroups in 133 infant acute lymphoblastic leukemia (ALL) cases as assessed by their immunophenotype, immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement pattern, and the presence of mixed lineage leukemia (MLL) rearrangements. About 70% of cases showed the pro-B-ALL immunophenotype, whereas the remaining cases were common ALL and pre-B-ALL. MLL translocations were found in 79% of infants, involving MLL-AF4 (41%), MLL-ENL (18%), MLL-AF9 (11%) or another MLL partner gene (10%). Detailed analysis of Ig/TCR rearrangement patterns revealed IGH, IGK and IGL rearrangements in 91, 21 and 13% of infants, respectively. Cross-lineage TCRD, TCRG and TCRB rearrangements were found in 46, 17 and 10% of cases, respectively. As compared to childhood precursor-B-ALL, Ig/TCR rearrangements in infant ALL were less frequent and more oligoclonal. MLL-AF4 and MLL-ENL-positive infants demonstrated immature rearrangements, whereas in MLL-AF9-positive leukemias more mature rearrangements predominated. The immature Ig/TCR pattern in infant ALL correlated with young age at diagnosis, CD10 negativity and predominantly with the presence and the type of MLL translocation. The high frequency of immature and oligoclonal Ig/TCR rearrangements is probably caused by early (prenatal) oncogenic transformation in immature B-lineage progenitor cells with germline Ig/TCR genes combined with a short latency period.


Asunto(s)
Reordenamiento Génico , Proteína de la Leucemia Mieloide-Linfoide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Regulación Neoplásica de la Expresión Génica , Frecuencia de los Genes , Genes de Inmunoglobulinas , N-Metiltransferasa de Histona-Lisina , Humanos , Inmunofenotipificación , Reacción en Cadena de la Polimerasa , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Translocación Genética
9.
An Pediatr (Barc) ; 69(3): 244-50, 2008 Sep.
Artículo en Español | MEDLINE | ID: mdl-18775270

RESUMEN

INTRODUCTION: Attention deficit disorder and hyperactivity (ADDH), is a condition that affects the normal development of children. The symptoms include difficulty of controlling physical activity, inattention and learning disorders. The ADDH must be diagnosed in accordance with the clinical findings defined in the DSM IV. OBJECTIVE: To describe the epidemiology and clinical characteristics of children diagnosed with ADDH in our hospital. MATERIAL AND METHODS: Biannual observational study. Variables evaluated were: age, sex, personal and family medical history, symptoms, therapy and treatment response. RESULTS: There 83 participants (87 % Male and 13 % Female), of which 32.5 % were diagnosed during the study. Ages ranged from 3-8 years (84 %). There was a family history related to ADDH in 38 % of patients, and personal history of prematurity, acute foetal distress, small for gestational age, convulsions were reported. Association of hyperactivity and attention deficit was found in 65 % of participants. Other related symptoms were cognitive disorder (62 %), language disabilities (41 %) and motor disorders (35 %). Treatment was on-going in 65 % of the patients, 27.7 % of them having adverse effect. Evolution with therapy was favourable in 61 %. CONCLUSIONS: These findings suggest that ADDH is one of the most common childhood psychiatric disorders, mainly affecting boys. There is usually a family history. Failure in school was one of the principal conditions. Association between attention deficit and hyperactivity, mainly hyperactivity, is the most common presentation. Other disorders such as motor and language disabilities are also common in these patients. Methylphenidate showed favourable outcomes in 61 % of the patients studied.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Estudios Retrospectivos
10.
Bone Marrow Transplant ; 52(8): 1138-1143, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28346415

RESUMEN

For patients with AML, the best alternative donor remains to be defined. We analyze outcomes of patients who underwent myeloablative umbilical cord blood or haploidentical hemopoietic stem cell transplantation (HSCT) in Spain. Fifty-one patients underwent single umbilical cord blood transplantation supported by a third party donor (Haplo-Cord) between 1999 and 2012, and 36 patients received an haploidentical HSCT with post-transplant cyclophosphamide (PTCY-haplo) between 2012 and 2014 in GETH centers. The Haplo-Cord cohort included a higher proportion of patients with high disease risk index and use of TBI in the conditioning regimen, and hematopoietic cell transplantation-age Comorbidity Age Index was higher in PTCY-haplo patients. Cumulative incidence of neutrophil engraftment was 97% in the Haplo-Cord and 100% in the PTCY-haplo group, achieved in a median of 12 and 17 days, respectively (P=0.01). Grade II-IV acute GvHD rate was significantly higher in the PTCY-haplo group (9.8% vs 29%, P=0.02) as well as chronic GvHD rates (20% vs 38%, P=0.03). With a median follow-up of 61 months for the Haplo-Cord group and 26 months for the PTCY-haplo cohort, overall survival at 2 years was 55% and 59% (P=0.66), event-free survival was 45% vs 56% (P=0.46), relapse rate was 27% vs 21% (P=0.79), and non-relapse mortality was 17% vs 23% (P=0.54), respectively. In this multicenter experience, Haplo-Cord and PTCY-haplo HSCT offer valid alternatives for patients with AML. Neutrophil engraftment was faster in the Haplo-Cord cohort, with similar survival rates, with higher GvHD rates after haploidentical HSCT.


Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Ciclofosfamida/uso terapéutico , Leucemia Mieloide Aguda/terapia , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anciano , Trasplante de Células Madre de Sangre del Cordón Umbilical/mortalidad , Supervivencia sin Enfermedad , Femenino , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/mortalidad , Adulto Joven
12.
Bone Marrow Transplant ; 52(3): 438-444, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27819684

RESUMEN

HLA-matched related or unrelated donors are not universally available. Consequently, patients can be offered hematopoietic stem cell transplantation (HSCT) from alternative donors, including mismatched unrelated donors (MMURD), known to cause a higher incidence of acute GVHD (aGVHD) and chronic GVHD. In vivo T-cell-depletion strategies, such as antithymocyte globulin (ATG) therapy, significantly decrease the risk of GVHD. We performed a multicenter, retrospective study comparing tacrolimus (TAC) and sirolimus (SIR) with or without ATG in 104 patients (TAC-SIR=45, TAC-SIR-ATG=59) who underwent MMURD HSCT. Use of ATG was associated with a lower incidence, albeit not statistically significant, of grades 2-4 aGVHD (46% vs 64%, P=0.09), no difference in grades 3-4 aGVHD (10% vs 15%, P=0.43), a trend for a lower incidence of moderate/severe chronic GVHD (16% vs 37%, P=0.09) and more frequent Epstein-Barr virus reactivation (54% vs 18%, P=0.0002). There were no statistically significant differences in 3-year overall survival (OS) (TAC-SIR-ATG=40% (95% confidence interval (CI)=24-56%) vs TAC-SIR=54% (95% CI=37-70%), P=0.43) or 3-year cumulative incidence of relapse/progression (TAC-SIR-ATG=40% (95% CI=28-58%) vs TAC-SIR=22% (95% CI=13-39%), P=0.92). An intermediate Center for International Blood & Marrow Transplant Research disease risk resulted in a significantly lower non-relapse mortality and better OS at 3 years. Our study suggests that addition of ATG to TAC-SIR in MMURD HSCT does not affect OS when compared with TAC-SIR alone.


Asunto(s)
Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Sirolimus/administración & dosificación , Trasplante de Células Madre , Tacrolimus/administración & dosificación , Donante no Emparentado , Enfermedad Aguda , Adolescente , Adulto , Anciano , Aloinjertos , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Antígenos HLA , Humanos , Depleción Linfocítica , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Linfocitos T
13.
Leukemia ; 19(2): 214-6, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15618957

RESUMEN

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a detoxification enzyme that protects cells against oxidative stress and toxic quinones. A polymorphism (C609T) in the gene produces in the heterozygous individuals (C/T) a reduction and in those homozygous for the variant allele (T/T) the abolishment of NQO1 protein activity. To assess whether NQO1 inactivating polymorphism (CT/TT) was a possible risk factor for infant acute lymphoblastic leukemia (iALL), we investigated the distribution of NQO1 genotype in 50 iALL patients, 32 with MLL gene rearrangements (MLL+) and 18 without (MLL-). As controls, 106 cases of pediatric ALL (pALL), and 147 healthy subjects were also studied. Compared to normal controls, the frequency of the low/null activity NQO1 genotypes was significantly higher in the iALL MLL- (72 vs 38%, P=0.006; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.43-12.49), while no differences were observed in iALL MLL+ (44 vs 38%, P=0.553; OR 1.26, 95% CI 0.58-2.74). Similar results were observed when pALL were used as control. Our results indicate that only the iALL patients without MLL rearrangements had a significantly higher frequency of NQO1 genotypes associated with low/null activity enzyme, suggesting a possible role for NQO1 gene as an MLL-independent risk factor, in the leukemogenic process of this subtype of iALL.


Asunto(s)
Proteínas de Unión al ADN/genética , Reordenamiento Génico , NAD(P)H Deshidrogenasa (Quinona)/genética , Polimorfismo Genético/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proto-Oncogenes/genética , Factores de Transcripción/genética , Regulación Neoplásica de la Expresión Génica/genética , Genotipo , N-Metiltransferasa de Histona-Lisina , Humanos , Lactante , Proteína de la Leucemia Mieloide-Linfoide , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Valores de Referencia
14.
Bone Marrow Transplant ; 51(6): 819-24, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26950379

RESUMEN

Previous reports ascribe a modulating capacity of the immune response to Helicobacter pylori (HP). Our hypothesis was to demonstrate in a prospective study that HP infection could have a protective effect against development of gastrointestinal GvHD in patients receiving allogeneic hematopoietic cell transplantation (HCT). Presence of HP before transplant was determined using C(13) urea breath test. Seventy-nine patients receiving an allogeneic HCT were included and 93.7% of them received PBSC; in 51.9%, the donor was unrelated. Acute gastrointestinal GvHD was diagnosed in 51.9% (n=41). In the multivariable analysis, HP infection was associated with a lower frequency of gastrointestinal GvHD (odds ratio (OR)=0.19 (95% confidence interval (CI): 0.05-0.67); in contrast, an unrelated donor was associated with a higher frequency of gastrointestinal GvHD (odds ratio=5.4 (95% confidence interval: 1.6-18.2). One year overall survival (OS) was 74%. In the multivariate Cox proportional-hazards regression analysis, stages 0-II gastrointestinal GvHD (hazards ratio (HR)=0.19), reduced intensity conditioning (HR=0.04) and tacrolimus-sirolimus GvHD prophylaxis (HR=0.06) were all associated with a better OS. In summary, HP infection could have a role in decreasing gastrointestinal GvHD in patients receiving allogeneic HCT from peripheral blood including related and unrelated donors.


Asunto(s)
Enfermedades Gastrointestinales/etiología , Enfermedad Injerto contra Huésped/diagnóstico , Helicobacter pylori/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Femenino , Enfermedades Gastrointestinales/microbiología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sirolimus/uso terapéutico , Tasa de Supervivencia , Tacrolimus/uso terapéutico , Acondicionamiento Pretrasplante/métodos
15.
Bone Marrow Transplant ; 51(10): 1307-1312, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27159177

RESUMEN

Relapsed or refractory Hodgkin lymphoma (advanced HL) still remains a therapeutic challenge. Recently, unmanipulated haploidentical related donor transplant with reduced conditioning regimen (HAPLO-RIC) and post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has became a promising rescue strategy potentially available to almost every patient. This paper reports our multicenter experience using an IV busulfan-based HAPLO-RIC regimen and PT-Cy in the treatment of 43 patients with advanced HL. Engraftment occurred in 42 patients (97.5%), with a median time to neutrophil and platelet recovery of 18 and 26 days. Cumulative incidences of grades II-IV acute GvHD and chronic GvHD were 39% and 19%, respectively. With a median follow-up of 25.5 months for survivors, 27 patients are alive, with 22 of them disease free. Cumulative incidences of 1-year non-relapse mortality and relapse at 2 years were 21% and 24%, respectively. The estimated 2-year event-free survival (EFS) and overall survival (OS) were 48% and 58%, respectively. CR prior to HAPLO-RIC correlated with better EFS (78.5% vs 33.5%; P=0.015) and OS (86% vs 46%; P=0.044). Our findings further confirm prior reports using HAPLO-RIC in advanced HL in a multicenter approach employing an IV busulfan-based conditioning regimen.


Asunto(s)
Busulfano/uso terapéutico , Enfermedad de Hodgkin/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Ciclofosfamida/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Terapia Recuperativa/métodos , Terapia Recuperativa/mortalidad , España , Análisis de Supervivencia , Trasplante Haploidéntico/efectos adversos , Trasplante Haploidéntico/mortalidad , Adulto Joven
16.
Leukemia ; 10(11): 1823-5, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8892687

RESUMEN

Despite improved survival in childhood acute lymphoblastic leukemia (ALL), its recurrence and the recognition of extramedullary dissemination continue to be crucial issues in the management of affected patients. We report the case of a boy with ALL who presented with two skin nodules during maintenance therapy. As histological examination of the routinely stained sections and the study of the immunophenotype of the skin biopsy were not conclusive, molecular analysis was carried out. By means of the heteroduplex analysis of the amplified T cell receptor (TCR) gene products we assessed the clonality of the skin lymphoid infiltrate and showed the same pattern of TCR gamma recombination of the bone marrow at diagnosis. The patient was treated with allogeneic bone marrow transplantation and survives disease-free after 3 years. Since cutaneous relapse in ALL occurs rarely, molecular analysis can be helpful and conclusive in defining the nature of a skin infiltrate.


Asunto(s)
ADN de Neoplasias/análisis , Sondas Moleculares , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Neoplasias Cutáneas/diagnóstico , Adolescente , ADN de Neoplasias/genética , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Humanos , Masculino , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/secundario
17.
Leukemia ; 13(1): 32-7, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10049057

RESUMEN

Juvenile myelomonocytic leukemia (JMML) is a malignant hematopoietic disorder of early childhood with excessive proliferation of the myeloid and monocytic lineage. Deregulation of the RAS signal transduction pathway is thought to play a key role in its pathogenesis. We examined peripheral blood or bone marrow cells of 36 children with JMML for activating point mutations in codons 12, 13 and 61 of the NRAS and KRAS proto-oncogenes by allele-specific restriction assay, single-strand conformation polymorphism and/or direct sequencing. Codons 12, 13 and 61 of HRAS were examined in 26 of these patients. We detected RAS mutations in six cases (17%) located at N12 (n = 2), N13 (n = 3) and K13 (n = 1). In addition, we performed clonality studies on different cell lineages in four of these patients applying the RAS mutation, the karyotype and X-chromosome inactivation patterns as clonal markers. Erythroid cells carried mutant RAS, indicating clonal origin. In EBV B cell lines, one of three patients studied harbored a RAS mutation, while the other two patients had polyclonal B cells with wild-type RAS. T lymphocytes were examined in one patient; they were polyclonal and had wild-type RAS. It is likely that JMML is a heterogeneous disease with respect to clonal involvement of different lineages.


Asunto(s)
Genes ras , Leucemia Mielomonocítica Crónica/genética , Mutación Puntual , Polimorfismo Conformacional Retorcido-Simple , Sustitución de Aminoácidos , Trasplante de Médula Ósea , Células Cultivadas , Niño , Preescolar , Codón , Eritroblastos/patología , Granulocitos/patología , Humanos , Lactante , Leucemia Mielomonocítica Crónica/sangre , Leucemia Mielomonocítica Crónica/mortalidad , Leucemia Mielomonocítica Crónica/terapia , Linfocitos/patología , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas p21(ras)/genética , Proto-Oncogenes , Cromosoma X
18.
Transplant Proc ; 37(9): 3664-6, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16386498

RESUMEN

A retrospective analysis of data from January 1996 to June 2004 was performed to evaluate the transmission of bacterial infections from organ donors to recipients. Donors were classified according to blood culture results: group 1 with negative blood culture (n = 216), and group 2 with positive blood cultures (n = 52). The age, cause of death, temperature, leukocytes, and number of organs procured were similar in both groups. Donors of group 2 had significantly more days in the intensive care unit (ICU): group 1 (3.14 +/- 3) versus group 2 (4.39 +/- 3.38 days P = .038). Fifty-one percent of group 1 and 52% of group 2 received antibiotic treatment, in most cases because of the suspected presence of a respiratory infection. In 22 donors the organisms that yielded in the blood culture were considered potentially pathogenic/contaminants (subgroup 2A) and in 30 donors the organisms were considered pathogenic (subgroup 2B). The demographic profiles of these two subgroups were similar. During the first month after transplantation, kidney and liver recipients were closely monitored. Recipients received wide-spectrum antimicrobial prophylaxis. Ten of 61 renal recipients developed infectious diseases. In nine cases (four in subgroup 2A and five in subgroup 2B) there were urinary infections. One recipient of subgroup 2B developed prostatitis. Six of 34 hepatic recipients developed infectious diseases. Four of the six cases (four in group 2A and five in group 2B) developed catheter infections and two cases of peritoneal infections. We could not find any case where a bacterial blood isolate from a donor matched a positive culture in the corresponding recipient. A longer stay of a donor in the ICU resulted in the more pronounced growth of organisms in blood cultures, as expected. In our experience, organs obtained from a donor with a positive blood culture may be transplanted safely, probably due to the low virulence of the organisms as well as the polymicrobial therapy routinely given to the recipients.


Asunto(s)
Bacteriemia , Infecciones Bacterianas/transmisión , Trasplante de Riñón/estadística & datos numéricos , Trasplante de Hígado/estadística & datos numéricos , Donantes de Tejidos/estadística & datos numéricos , Antibacterianos/uso terapéutico , Bacterias/aislamiento & purificación , Humanos , Unidades de Cuidados Intensivos
19.
Dis Aquat Organ ; 65(2): 153-7, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16060268

RESUMEN

Oocysts of an unidentified coccidian are reported in this study to parasitize the gills of the oyster Crassostrea rizophorae (Mollusca, Bivalvia) collected near the city of Recife (Itamaracá Island, 07 degrees 38' 00" S, 34 degrees 48' 06" W), Brazil. Oocysts appeared as light and dense forms, both containing rod-shaped, bacteria-like hyperparasites (BL). Both light and dense oocysts were spherical, 4.3 to 4.7 pm in diameter, but denser oocysts had irregular contours. Both forms consisted of a thick dense wall (approximately 165 nm thick) consisting of 3 layers. The outermost, a dense and irregular layer about 25 nm thick, possessed numerous bead-like structures and some slender conical projections (up to 1.5 microm long). The inner layer of the wall was formed by a dense and homogenous layer about 125 nm thick. Between these 2 layers, a thin light layer about 12 nm thick was present. Uninucleated sporocysts occupied the internal space of the oocyst and contained some rod-shaped BL and mitochondria surrounded by numerous ribosome-like particles. The dense forms of the oocysts showed the same structures described in the lighter forms and appeared to be the final maturation form of the oocysts. Free sporozoites were occasionally observed among oocysts.


Asunto(s)
Coccidios/microbiología , Branquias/parasitología , Oocistos/ultraestructura , Ostreidae/parasitología , Animales , Brasil , Coccidios/ultraestructura , Microscopía Electrónica
20.
An Pediatr (Barc) ; 63(6): 558-60, 2005 Dec.
Artículo en Español | MEDLINE | ID: mdl-16324624

RESUMEN

INTRODUCTION: The occurrence of benign seizures in association with viral gastroenteritis without dehydration or fever is well recognized in Asia, but it is virtually unknown in other parts of the world. This is a benign process that does not lead to a greater risk of epilepsy or developmental deterioration. CASE REPORTS: We describe two infants who were admitted to our department over a 1-year period with acute convulsions and mild gastroenteritis. The seizures were brief and did not recur after the first day. In both cases the outcome was excellent. CONCLUSIONS: This entity does not appear exclusively in Asia and its frequency may have been underestimated in Spain. This diagnosis should be borne in mind in patients with gastroenteritis and seizures to avoid intensive and/or prolonged antiepileptic treatment.


Asunto(s)
Gastroenteritis/complicaciones , Convulsiones/complicaciones , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Remisión Espontánea , Infecciones por Rotavirus/diagnóstico
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