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FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.
Assuntos
Leucemia Mieloide Aguda , Mutação , Proteínas Nucleares , Nucleofosmina , Tirosina Quinase 3 Semelhante a fms , Idoso , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Proteínas Nucleares/genética , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/administração & dosagemRESUMO
Efficacy and toxicity of anthracycline treatment in acute myeloid leukemia (AML) is mediated by reactive oxygen species (ROS). NADPH oxidase is the major endogenous source of ROS and a key mediator of oxidative cardiac damage. The impact of NADPH oxidase polymorphisms (CYBA:rs4673, NCF4:rs1883112, RAC2:rs13058338) was evaluated in 225 adult de novo AML patients. Variant alleles of NCF4 and RAC2 were related to higher complete remission (P=0.035, P=0.016), and CYBA homozygous variant showed lower overall survival with recessive model (P=0.045). Anthracycline-induced cardiotoxicity was associated to NCF4 homozygous variant (P=0.012) and CYBA heterozygous genotype (P=0.027). Novel associations were found between variant allele of CYBA and lower lung and gastrointestinal toxicities, and a protective effect in nephrotoxicity and RAC2 homozygous variant. Moreover, RAC2 homozygous variant was related to delayed thrombocytopenia recovery. This study supports the interest of NADPH oxidase polymorphisms regarding efficacy and toxicity of AML induction therapy, in a coherent integrated manner.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/genética , NADPH Oxidases/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Indução de Remissão/métodos , Estudos Retrospectivos , Proteínas rac de Ligação ao GTP/genética , Proteína RAC2 de Ligação ao GTPRESUMO
Three new HLA class I alleles, HLA-A*02:620, HLA-B*27:150 and HLA-B*07:05:01:02, were described in the Spanish Caucasoid population.
Assuntos
Alelos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Genes MHC Classe I/imunologia , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Humanos , Espanha , População Branca/genéticaRESUMO
The polymorphism rs16754 of the WT1 gene has been described as a possible prognostic marker in different acute myeloid leukemia (AML) cohorts; however, it is not supported by all the studies. We performed the first meta-analysis evaluating the effect of this polymorphism upon the effectiveness of standard AML therapy. Fourteen cohort studies were included (3618 patients). Patients with the variant allele showed a significant higher overall survival (OS) at 5 years (OR:1.24, 95% CI: 1.06-1.45, P=0.007, with dominant model). WT1 did not influence complete remission, but a higher disease-free survival was observed with the variant allele. In the subgroup analysis, Caucasians, pediatric and patients treated with idarubicin and etoposide carrying the variant allele showed consistent results in OS, whereas patients with cytogenetically normal AML did not show differences. To verify the effect of this polymorphism upon other outcomes, studies in larger and multiracial populations are needed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Proteínas WT1/genética , Antraciclinas/administração & dosagem , Estudos de Coortes , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Estudos de Associação Genética , Humanos , Leucemia Mieloide Aguda/genética , Estudos Observacionais como Assunto , Polimorfismo de Nucleotídeo Único , Análise de SobrevidaRESUMO
The external ear is accessible to direct examination; the clinical history and otoscopy are sufficient to diagnose and treat most diseases of the external ear. We aim to describe the normal anatomy of the external ear, specify the indications for imaging tests, and review the clinical and radiological manifestations of the most common diseases affecting the external ear. We classify these diseases according to their origin into congenital, inflammatory, infectious, or traumatic disease or benign bone tumors or malignant tumors. Imaging does not play an important role in diseases of the external ear, but in certain clinical scenarios it can be crucial for reaching a concrete diagnosis and establishing the best treatment. Computed tomography is the first-choice technique for most diseases. Magnetic resonance imaging complements computed tomography and makes it possible to differentiate among different tissue types and to evaluate the extension of disease accurately.
Assuntos
Otopatias/diagnóstico por imagem , Orelha Externa/anatomia & histologia , Orelha Externa/diagnóstico por imagem , Radiografia , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. PATIENTS AND METHODS: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.
Assuntos
Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Síndrome de Lise Tumoral/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Seguimentos , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Síndrome de Lise Tumoral/sangue , Ácido Úrico/sangue , Adulto JovemRESUMO
The ABCB1 gene encodes for P-glycoprotein (P-gp), an efflux pump for a variety of xenobiotics. The role of ABCB1 polymorphisms in acute myeloid leukemia (AML) outcomes of standard chemotherapy (cytarabine plus anthracyclines) remains controversial. A systematic search was made of studies evaluating the association between ABCB1 polymorphisms 1236C>T, 2677G>T/A and 3435C>T and effectiveness variables. We found seven cohort studies (1241 patients) showing a significantly higher overall survival (OS) among carriers of the variant allele of 1236C>T at year 4 (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.07-2.01), 2677G>T/A at years 4-5 (OR: 1.37, 95% CI: 1.01-1.86) and 3435C>T at years 3 (OR: 1.41, 95% CI: 1.03-1.94) and 4-5 (OR: 1.42, 95% CI: 1.05-1.91). In the subgroup analysis according to ethnicity, Caucasians carrying variant allele showed consistent results in OS. ABCB1 influence upon complete remission could not be demonstrated. Future studies based on larger populations and multiethnic groups should help clarify the effect of P-gp polymorphisms upon other outcomes.
Assuntos
Antraciclinas/uso terapêutico , Citarabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Polimorfismo Genético/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Resultado do Tratamento , Adulto JovemRESUMO
Many therapeutic applications of magnetic nanoparticles involve the local administration of nanometric iron oxide based materials as seeds for magnetothermia or drug carriers. A simple and widespread way of controlling the process using x-ray computed tomography (CT) scanners is desirable. The combination of iron and bismuth in one entity will increase the atenuation of x-rays, offering such a possibility. In order to check this possibility core-shell nanocrystals of iron oxide@bismuth oxide have been synthesized by an aqueous route and stabilized in water by polyethylene glycol (PEG), and we have evaluated their ability to generate contrast by CT and magnetic resonance imaging (MRI) to measure the radiopacity and proton relaxivities using phantoms. High-resolution scanning transmission electron microscopy (STEM) revealed that the material consists of a highly crystalline 8 nm core of maghemite and a 1 nm shell of bismuth atoms either isolated or clustered on the nanocrystal's surface. The comparison of µCT and MRI images of mice acquired in the presence of the contrast shows that when local accumulations of the magnetic nanoparticles take place, CT images are more superior in the localization of the magnetic nanoparticles than MRI images, which results in magnetic field inhomogeneity artifacts.
RESUMO
In recent years, improving water use efficiency has been one of the most important challenges for the agricultural sector. However, such improvements have led to the installation of pressurized irrigation systems which generally require more energy to operate, especially in plantations on sloping and mountainous lands. Thus, the reduction of energy use in these systems has also become a major issue. Irrigation network sectoring has been proposed as one of the most effective energy saving measures. Typically, however, the potential benefits of this management strategy have been evaluated by means of theoretical approaches in networks that were originally designed to supply water on demand and not after water application in real irrigation districts designed following sectoring strategies. In this work, this measure is applied to an irrigation district devoted to olive grove production in a mountainous area that was designed according to this management strategy. With this aim, the WEBSO (Water and Energy Based Sectoring Operation) algorithm, which was developed in a previous work, has been modified in order to take into account the specific characteristics of the irrigation district and its actual management, as well as to analyze sensitivity to several irrigation water depths in terms of both energy demand and yields. An economic analysis of the potential benefits of this management strategy is also carried out. The results show that this measure has lead to a nearly 30% reduction in energy consumption, while increasing farmers' profits by 13% compared to traditional on-demand operations.
Assuntos
Agricultura/métodos , Conservação de Recursos Energéticos/métodos , Olea , Abastecimento de Água/análise , Agricultura/economia , Algoritmos , Conservação de Recursos Energéticos/economia , Produtos Agrícolas , Modelos Teóricos , Espanha , Abastecimento de Água/economiaRESUMO
OBJECTIVES: To use the mDIXON-Quant sequence to quantify the fat fraction of adrenal lesions discovered incidentally on CT studies. To analyze the relation between the signal loss between in-phase and out-of-phase T1-weighted sequences and the fat fraction in mDIXON-Quant. To compare the sensitivity and specificity of the two methods for characterizing adrenal lesions. MATERIAL AND METHODS: This prospective descriptive study included 31 patients with incidentally discovered adrenal lesions evaluated with 3T MRI using in-phase and out-of-phase T1-weighted sequences and mDIXON-Quant; the fat fraction of the adrenal lesions was measured by mDIXON-Quant and by calculating the percentage of signal loss between in-phase and out-of-phase T1-weighted sequences. RESULTS: The percentage of signal loss was significantly higher in the group of patients with adenoma (61.3% ± 20.4% vs. 5.1% ± 5.8% in the group without adenoma, p<0.005). The mean fat fraction measured by mDIXON-Quant was also higher for the adenomas (26.9% ±10.8% vs. 3.4% ± 3.0%, p<0.005).The area under the ROC curve was 0.99 (0.96 - 1.00) for the percentage of signal loss and 0.98 (0.94 - 1.00) for the fat fraction measured by mDIXON-Quant. The cutoffs obtained were 24.42% for the percentage of signal loss and 9.2% for the fat fraction measured by mDIXON-Quant. The two techniques had the same values for diagnostic accuracy: sensitivity 96% (79.6 - 99.9), specificity 100% (39.8 - 100.0), positive predictive value 100% (85.8 - 100.0), and negative predictive value 80% (28.4 - 99.5). CONCLUSION: The fat fraction measured by the modified Dixon technique can differentiate between adenomas and other adrenal lesions with the same sensitivity and specificity as the percentage of signal loss between in-phase and out-of-phase T1-weighted sequences.
Assuntos
Doenças das Glândulas Suprarrenais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tecido Adiposo/diagnóstico por imagem , Idoso , Feminino , Humanos , Achados Incidentais , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Chronic graft-versus-host disease (cGVHD) is the most important cause of late non-relapse mortality after allogeneic hematopoietic stem cell transplantation. Sclerodermatous cGVHD is usually steroid refractory and remains a therapeutic challenge. Activating antibodies against the PDGFR have been reported in patients with sclerodermatous cGVHD. These antibodies induce PDGFR phosphorylation and lead to fibrosis. There is increasing evidence of successful treatment of sclerodermatous cGVHD with imatinib, a tyrosine kinase inhibitor. OBJECTIVE: To evaluate the response of cutaneous sclerodermatous cGVHD to imatinib. MATERIALS AND METHODS: Retrospective study of 18 patients with sclerodermatous cGVHD refractory to immunosuppressants treated with imatinib in a single center. Evaluation of treatment response was performed by clinicians' assessment and patients' subjective response at one, 3, 6, 9, 12 and 18 months after initiation of imatinib. Response was assessed as complete, partial, significant, no change or progression. Tapper off steroids was complete, partial or not possible. RESULTS: In our series, 4 (22%) patients achieved complete response, 9 (50%) patients partial response, 2 (11%) patients significant response, 2 (11%) patients had no change and one (6%) patient progressive disease at last follow-up. Mean time from initiation of imatinib to any degree of response was 2,75 months (range 1-9 months). CONCLUSIONS: This study provides further evidence of the role of imatinib for the treatment of steroid refractory sclerodermatous cGVHD.
Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Esclerodermia Localizada/tratamento farmacológico , Adolescente , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Esclerodermia Localizada/etiologia , Resultado do Tratamento , Adulto JovemRESUMO
Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk- and age-adapted protocol (Programa Español de Tratamientos en Hematología (PETHEMA)/HOVON LPA2005), with dose reduction of consolidation chemotherapy. Patients aged ⩾60 years reported to the PETHEMA registry and were treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimens according to three consecutive PETHEMA trials that were included. We compared the long-term outcomes of the LPA2005 trial with the preceding PETHEMA trials using non-age-adapted schedules (LPA96&LPA99). From 1996 to 2012, 389 older patients were registered, of whom 268 patients (69%) were eligible. Causes of ineligibility were secondary APL (19%), and unfit for chemotherapy (11%). Median age was 67 years, without relevant differences between LPA2005 and LPA96&LPA99 cohorts. Overall, 216 patients (81%) achieved complete remission with no differences between trials. The 5-year NRM, cumulative incidence of relapse, disease-free survival and overall survival in the LPA2005 vs the LPA96&99 were 5 vs 18% (P=0.15), 7 vs 12% (P=0.23), 87 vs 69% (P=0.04) and 74 vs 60% (P=0.06). A less intensive front-line regimen with ATRA and anthracycline monochemotherapy resulted in improved outcomes in older APL patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Idoso , Antraciclinas/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão/métodos , Fatores de Risco , Resultado do Tratamento , Tretinoína/administração & dosagemRESUMO
Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.
Assuntos
Inibidor de Quinase Dependente de Ciclina p15/genética , Deleção de Genes , Genes p16 , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteína Supressora de Tumor p14ARF/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , PrognósticoRESUMO
Autoimmune hemolytic anemia (AIHA) after allogeneic hematopoietic stem cell transplantation (HSCT) is still not well characterized. The aim of this study was to analyze the incidence and risk factors for the development of AIHA, as well as its prognosis and response to treatment in a series of patients undergoing allogeneic HSCT at a single institution. Between 1996 and 2004, 272 adult patients with a variety of malignant hematopoietic disorders underwent allogeneic HSCT. Direct antiglobulin testing was performed in routine pretransfusion compatibility testing or after clinical suspicion of AIHA. Twelve patients developed AIHA after HSCT at a median time of 147 days (range, 41-170). The 3-year cumulative incidence of AIHA was 4.44%. Eight cold antibodies and four warm antibodies were detected. Multivariate analysis shows that HSCT from unrelated donors (P=0.02) and the development of chronic extensive graft-versus-host disease (GVHD) (P=0.0004) were the only independent factors associated with AIHA. Two patients are still alive. AIHA was never the primary cause of death but added morbidity in patients with other concomitant complications. Patients undergoing HSCT from unrelated donors and those who develop chronic extensive GVHD are especially predisposed for this complication.
Assuntos
Anemia Hemolítica Autoimune , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Adulto , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/etiologia , Anemia Hemolítica Autoimune/mortalidade , Autoanticorpos/sangue , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplante HomólogoRESUMO
Hematopoietic stem cell transplantation is usually performed without considering the ABO compatibility between donor and recipient. There are few studies analyzing ABO matching impact on transfusion outcome of umbilical cord blood transplantation (UCBT) recipients. The aim of this study was to analyze factors influencing transfusion outcome, highlighting the ABO matching between donor and recipient. This study has reviewed data from 318 patients who underwent single unit UCBT at la Fe University Hospital from January 2000 to December 2014. There were no differences between RBC and platelet (PLT) requirements or RBC and PLT transfusion independence according to ABO matching between donor and recipient. RBC and PLT requirements were statistically correlated (ρ=0,841, P<0.001). A total of 170 and 188 patients achieved RBC and PLT independence, respectively, within 180 days after UCBT. Persistence of recipient isoagglutinins was detected in 6.8% of patients with major ABO incompatibility at median of 176 days (103-269) after UCBT. Autoimmune haemolytic anemia was diagnosed in 15 patients, 12 of them due to cold antibodies. In conclusion, ABO matching has not influenced transfusion requirements of patients undergoing UCBT.
Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Neoplasias Hematológicas/terapia , Adolescente , Adulto , Idoso , Aloenxertos , Tipagem e Reações Cruzadas Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Ciclofosfamida/uso terapêutico , Leucemia Mieloide Aguda/terapia , Transplante Haploidêntico/métodos , Adolescente , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/mortalidade , Adulto JovemRESUMO
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.
Assuntos
Bussulfano/uso terapêutico , Doença de Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Adolescente , Adulto , Ciclofosfamida/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença de Hodgkin/complicações , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Espanha , Análise de Sobrevida , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/mortalidade , Adulto JovemRESUMO
We evaluated the use of CD34+ selected allogeneic peripheral blood as a source of hematopoietic progenitors for allogeneic transplantation in 11 patients with aplastic anemia (AA). The median age was 17 years (range, 6--9), and the median time between diagnosis and transplant 1 month (range, 1--4). Conditioning consisted of cyclophosphamide (50 mg/kg per day) on days--7 to--4 and antithymocyte globulin (30 mg/kg per day) on days--4 to--2 in nine patients. Total lymphoid irradiation was added to the preparative regimen for two. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and prednisone. Median doses of CD34+ and CD3+ cells infused were 3.91 x 10(6) and 0.3 x 10(6)/kg, respectively. The median time taken to achieve a neutrophil count >0.5 x 10(9)/l was 12 days and to recover a platelet count >20 x 10(9)/l, 13 days. Two patients developed acute GVHD grade I--II and one developed limited chronic GVHD. There were two treatment-related deaths. At a median follow-up of 44 months (range, 4--3), nine patients were alive with sustained and complete engraftment. This is a promising procedure in patients with AA, resulting in a rapid hematopoietic recovery, a low transplant-related mortality, and a low incidence of GVHD.
Assuntos
Anemia Aplástica/terapia , Antígenos CD34 , Transplante de Células-Tronco de Sangue Periférico/métodos , Adolescente , Adulto , Anemia Aplástica/complicações , Anemia Aplástica/mortalidade , Complexo CD3 , Criança , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade , Humanos , Cinética , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Pré-Medicação , Radioterapia Adjuvante , Irmãos , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do TratamentoRESUMO
PURPOSE: Compressed sensing is a technique used to accelerate magnetic resonance imaging (MRI) acquisition without compromising image quality. While it has proven particularly useful in dynamic imaging procedures such as cardiac cine, very few authors have applied it to functional magnetic resonance imaging (fMRI). The purpose of the present study was to check whether the prior image constrained compressed sensing (PICCS) algorithm, which is based on an available prior image, can improve the statistical maps in fMRI better than other strategies that also exploit temporal redundancy. METHODS: PICCS was compared to spatiotemporal total variation (TTV) and k-t FASTER, since they have already demonstrated high performance and robustness in other MRI applications, such as cardiac cine MRI and resting state fMRI, respectively. The prior image for PICCS was the average of all undersampled data. Both PICCS and TTV were solved using the split Bregman formulation. K-t FASTER algorithm relies on matrix completion to reconstruct the undersampled k-spaces. The three algorithms were evaluated using two datasets with high and low signal-to-noise ratio (SNR)-BOLD contrast-acquired in a 7 T preclinical MRI scanner and retrospectively undersampled at various rates (i.e., acceleration factors). The authors evaluated their performance in terms of the sensitivity/specificity of BOLD detection through receiver operating characteristic curves and by visual inspection of the statistical maps. RESULTS: With high SNR studies, PICCS performed similarly to the state-of-the-art algorithms TTV and k-t FASTER and provided consistent BOLD signal at the ROI. In scenarios with low SNR and high acceleration factors, PICCS still provided consistent maps and higher sensitivity/specificity than TTV, whereas k-t FASTER failed to provide significant maps. CONCLUSIONS: The authors performed a comparison between three reconstructions (PICCS, TTV, and k-t FASTER) that exploit temporal redundancy in fMRI. The prior-based algorithm, PICCS, preserved BOLD activation and sensitivity/specificity better than TTV and k-t FASTER in noisy scenarios. The PICCS algorithm can potentially reach an acceleration factor of ×8 and still provide BOLD contrast in the ROI with an area under the curve over 0.99.