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1.
Eur J Haematol ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32243655

RESUMO

INTRODUCTION: Inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms. OBJECTIVE: The aim of this study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017. METHODS: In this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed. RESULTS: Sixty-one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One and 4-year CIR were 52% and 56%. One and 4-year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, p=0.017). CONCLUSION: Inv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.

2.
Iran J Kidney Dis ; 14(2): 81-94, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32165592

RESUMO

Diabetic nephropathy (ND) is the leading cause of end-stage renal disease and oxidative stress (OS) has been recognized as a key factor in the pathogenesis and progression. Hyperglycemia, reactive oxygen species, advanced glycation end products, arterial pressure, insulin resistance, decrease in nitric oxide, inflammatory markers, and cytokines, among others; are involved in the presence of OS on ND. This revision focus on diverse studies in experimental and human models with diabetes and DN that has been demonstrated beneficial effects of different dietary antioxidant as resveratrol, curcumin, selenium, soy, catechins, α-lipoic acid, coenzyme Q10, omega-3 fatty acids, zinc, vitamins E and C, on OS and the capacity for antioxidant response. Therefore, this interventions could have a positive clinical impact on DN.

3.
Leukemia ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152464

RESUMO

The treatment of acute myeloid leukemia (AML) is adjusted according to cytogenetic risk factors and molecular markers. Cytarabine remains the main drug to treat AML, and several studies have explored the prognostic relevance of the genotype of cytarabine metabolizing enzymes in AML. Glucuronidation has been identified to be relevant in the cytarabine clearance, but there are still few data concerning the clinical impact of genetic polymorphisms known to condition the activity of UDP-glucuronosyl transferases in AML patients. Here we report the association between the UGT1A1 rs8175347 genotype and the clinical outcome of 455 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy. Patients with the UGT1A1*28 homozygous variant (associated to a lower UGT1A1 activity) had a lower overall survival (OS) (25.8% vs. 45.5%; p: 0.004). Multivariate analysis confirmed this association (p: 0.008; HR: 1.79; 95% CI: 1.16-2.76). Subgroup analysis showed the negative effect of the UGT1A1*28 homozygous genotype on OS in women (14.8% vs. 52.7%; p: 0.001) but not in men. This lower OS was associated with longer neutropenia after consolidation chemotherapy and with higher mortality without previous relapse, suggesting an association between a low glucuronidation activity and mortal toxic events.

4.
Br J Haematol ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32020596

RESUMO

Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a poor-risk entity, commonly associated with FLT3-ITD (internal tandem duplication). Allogeneic stem-cell tranplantation (allo-SCT) is recommended, although studies analysing the outcome of allo-SCT in this setting are lacking. We selected 195 patients with t(6;9) AML, who received a first allo-SCT between 2000 and 2016 from the EBMT (European Society for Blood and Marrow Transplantation) registry. Disease status at time of allo-SCT was the strongest independent prognostic factor, with a two-year leukaemia-free survival and relapse incidence of 57% and 19% in patients in CR1 (first complete remission), 34% and 33% in CR2 (second complete remission), and 24% and 49% in patients not in remission, respectively (P < 0·001). This study, which represents the largest one available in t(6;9) AML, supports the recommendation to submit these patients to allo-SCT in CR1.

5.
Int J Infect Dis ; 91: 17-21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31669141

RESUMO

BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver from HBsAg-negative subjects. Our aim was to determine OBI frequency in serum and genomic DNA in patients undergoing renal transplant and their cognate donors in a selected population from Western Mexico. METHODS: Blood samples were obtained from 94 donors and their cognate recipients (188 participants) before kidney transplantation. Identification of HBV DNA was carried-out by nested (S-region) and semi-nested (Pol-region) PCR in both genomic and serum DNA samples from 188 participants at pre-surgical stage and from a subset of 73 recipients at three-month follow-up. RESULTS: HBV-DNA was not detected in either genomic or serum DNA samples from recipients or donors prior to transplantation. After three-months of follow-up, 2 out of 73 (2.7%, 95% CI: 0.9-11.9%) recipients were positive to HBV-DNA (Pol-region) in genomic DNA samples using a high sensitivity Taq DNA polymerase. CONCLUSIONS: OBI incidence in recipients of kidney transplant may be higher than previously recognized. Detection of HBV-DNA was higher in genomic DNA than in serum samples using a high sensitivity Taq DNA polymerase. To the best of our knowledge, this is the first report regarding this specific topic in Mexicans.

6.
Gynecol Endocrinol ; 36(2): 93-95, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31389272

RESUMO

To evaluate numerous publications that question the bone and extraosseous benefits of vitamin D diet supplementation based on results, which often transcend to public opinion, but are not well interpreted. This may have negative consequences on compliance of patients under vitamin D supplementation. Critical appraisal of several articles on vitamin D supplementation and its relationship with fractures, falls, cardiovascular diseases, and cancer incidence. Such publications have certain limitations (i.e. patients excluded because of a diagnosis of osteoporosis, or at a higher risk for fractures and falls, or because they have a vitamin D deficiency, etc.), and conclusions and/or subsequent recommendations should be approached with caution. Our research shows that patients with osteoporosis, vitamin D deficiency, and at high risk of fractures and falls should not discontinue vitamin D supplementation (often associated with calcium). It is becoming increasingly evident that patients with hypovitaminosis D are those that gain a maximal benefit from vitamin D supplementation.

7.
Leukemia ; 34(1): 128-137, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31409921

RESUMO

Large differences in patient and transplant backgrounds make it difficult to identify consistent prognostic factors of unrelated cord blood transplantation (UCBT) among different populations. Thus, we performed a collaborative study between Eurocord/ALWP-EBMT and JSHCT/JDCHCT. Adults with acute leukaemia who underwent a single UCBT were eligible. In total, 3764 and 1027 patients of the JSHCT/JDCHCT and Eurocord/ALWP-EBMT registries, respectively, were included. The median ages of the Japanese and European cohorts were 51 and 38 years, respectively. Three or more HLA mismatches were more frequently observed in the Japanese cohort. The median total nucleated cell (TNC) counts were 2.58 and 3.51 × 107/kg in the Japanese and European cohorts, respectively. Anti-thymocyte globulin was used in only 2% of the Japanese cohort compared with 65% of the European cohort. The 3-year overall survival (OS) was 41% in JSHCT/JDCHCT and 33% in Eurocord/ALWP-EBMT. In the multivariate analysis, TNC dose and HLA matching had no significant effect on OS in either cohort, whereas year of transplantation, age, and refined disease risk index affected OS in both cohorts. Despite considerable differences in characteristics between the Japanese and European cohorts, we observed similar prognostic factors affecting UCBT outcomes in adult patients with acute leukaemia in both registries.

8.
Haematologica ; 105(3): 741-753, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31248974

RESUMO

One-third of diffuse large B-cell lymphoma patients are refractory to initial treatment or relapse after rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy. In these patients, CXCR4 overexpression (CXCR4+) associates with lower overall and disease-free survival. Nanomedicine pursues active targeting to selectively deliver antitumor agents to cancer cells; a novel approach that promises to revolutionize therapy by dramatically increasing drug concentration in target tumor cells. In this study, we intravenously administered a liganded protein nanocarrier (T22-GFP-H6) targeting CXCR4+ lymphoma cells in mouse models to assess its selectivity as a nanocarrier by measuring its tissue biodistribution in cancer and normal cells. No previous protein-based nanocarrier has been described as specifically targeting lymphoma cells. T22-GFP-H6 achieved a highly selective tumor uptake in a CXCR4+ lymphoma subcutaneous model, as detected by fluorescent emission. We demonstrated that tumor uptake was CXCR4-dependent because pretreatment with AMD3100, a CXCR4 antagonist, significantly reduced tumor uptake. Moreover, in contrast to CXCR4+ subcutaneous models, CXCR4- tumors did not accumulate the nanocarrier. Most importantly, after intravenous injection in a disseminated model, the nanocarrier accumulated and internalized in all clinically relevant organs affected by lymphoma cells with negligible distribution to unaffected tissues. Finally, we obtained antitumor effect without toxicity in a CXCR4+ lymphoma model by administration of T22-DITOX-H6, a nanoparticle incorporating a toxin with the same structure as the nanocarrier. Hence, the use of the T22-GFP-H6 nanocarrier could be a good strategy to load and deliver drugs or toxins to treat specifically CXCR4-mediated refractory or relapsed diffuse large B-cell lymphoma without systemic toxicity.

9.
Blood ; 135(5): 371-380, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31826241

RESUMO

Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (≥0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 NPM1/FLT3-ITD genotypes differed significantly with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after 1 or 2 induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly among ELN risk groups, with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate-, and adverse-risk groups, respectively (P < .001). A multivariate Cox model for OS using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.

10.
Ann Hematol ; 99(1): 157-165, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31844931

RESUMO

Haploidentical related (Haplo) and umbilical cord blood (UCB) donors are the main "alternative donor" options for allogeneic hematopoietic stem cell transplantation (HCT) for patients without identical donor. At our institution, UCB was the main alternative donor type until 2013, when HaploHCT was introduced as the preferred procedure. A common myeloablative conditioning regimen was used, based on thiotepa, busulfan, and fludarabine. We analyze the outcomes of 47 patients (61%) who received a single UCB transplantation (UCBT) and 30 patients (39%) who received a HaploHCT with post-transplant cyclophosphamide. No differences were found in the rate of neutrophil engraftment, whereas platelet recovery was earlier with HaploHCT. NRM was higher after UCBT at 3 months and 3 years (13% and 13% vs. 23% and 45% in HaploHCT and UCBT, respectively; p < 0.001 for both time points). The 3-year relapse incidence was 35% after HaploHCT vs. 17% after UCBT, respectively (p = 0.13). The 100-day incidence of grade 3-4 acute GVHD (3% vs. 11%) and the 3-year moderate-to-severe chronic GVHD (4% vs. 15%) did not differ between HaploHCT and UCBT, respectively (p > 0.2). There was a trend for higher overall survival at 1 and 3 years in HaploHCT recipients (69% vs. 45% and 64% vs. 38%, respectively; p = 0.055 for both time points). Despite the small sample sizes, multivariate analysis adjusted for patient age and disease status at transplant showed a better 3-year OS in HaploHCT recipients, mostly due to a lower NRM (p < 0.001). Our results support the use of HaploHCT when feasible when an identical donor is not available.


Assuntos
Bussulfano/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Antígenos HLA , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico , Tiotepa/administração & dosagem , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Adulto , Idoso , Aloenxertos , Feminino , Neoplasias Hematológicas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vidarabina/administração & dosagem
11.
Artigo em Inglês | MEDLINE | ID: mdl-31700138

RESUMO

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31636397

RESUMO

In many healthcare settings, benchmarking for complex procedures has become a mandatory requirement by competent authorities, regulators, payers and patients to assure clinical performance, cost-effectiveness and safe care of patients. In several countries inside and outside Europe, benchmarking systems have been established for haematopoietic stem cell transplantation (HSCT), but access is not universal. As benchmarking is now integrated into the FACT-JACIE standards, the EBMT and JACIE established a Clinical Outcomes Group (COG) to develop and introduce a universal system accessible across EBMT members. Established systems from seven European countries (United Kingdom, Italy, Belgium, France, Germany, Spain, Switzerland), USA and Australia were appraised, revealing similarities in process, but wide variations in selection criteria and statistical methods. In tandem, the COG developed the first phase of a bespoke risk-adapted international benchmarking model for one-year survival following allogeneic and autologous HSCT based on current capabilities within the EBMT registry core dataset. Data completeness, which has a critical impact on validity of centre comparisons, is also assessed. Ongoing development will include further scientific validation of the model, incorporation of further variables (when appropriate) alongside implementation of systems for clinically meaningful interpretation and governance aiming to maximise acceptance to centres, clinicians, payers and patients across EBMT.

14.
Haematologica ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601686

RESUMO

Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation derives from preclinical models where the depletion of uric acid led to improved survival and reduced graft-versus-host disease. In a clinical pilot trial, peri-transplant uric acid depletion reduced acute graft-versus-host disease incidence. This prospective international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with allogeneic stem cell transplantation outcome. We included patients with acute leukemia, lymphoma or myelodysplastic syndrome receiving a first matched sibling allogeneic stem cell transplantation from peripheral blood, regardless of conditioning. We compared outcomes between patients with high and low uric acid levels with univariate- and multivariate analysis using a cause-specific Cox model. Twenty centers from 10 countries reported data on 366 allogeneic stem cell transplantation recipients. There were no significant differences in terms of baseline co-morbidity and disease stage between the high- and low uric acid group. Patients with uric acid levels above median measured before start of conditioning did not significantly differ from remaining in term of acute graft-versus-host disease grades II-IV incidence (HR=1.5, CI=1-2.4, p=0.08). However, they had significantly shorter overall survival (HR=2.8, CI=1.7-4.7, p<0.0001) and progression free survival (HR=1.6, CI=1.1-2.4, p=0.025). Non-relapse mortality was significantly increased in allogeneic stem cell transplantation recipients with high uric acid levels (HR=2.7, CI=1.4-5.0, p=0.003). Finally, the incidence of relapse after allogeneic stem cell transplantation was increased in patients with higher uric acid levels (HR=1.6, CI=1-2.5, p=0.04). We conclude that high uric acid levels before the start of conditioning correlate with increased mortality after allogeneic stem cell transplantation.

15.
Leuk Res ; 85: 106197, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31541945

RESUMO

The role of histone deacetylase inhibitors in the treatment of acute myeloid leukemia (AML) is not well characterized. The current study evaluated the safety and efficacy of panobinostat in combination with idarubicin and cytarabine in newly diagnosed patients aged ≤65 years with primary or secondary high-risk AML based on cytogenetic classification. Treatment included fixed dose idarubicin (12 mg/m2/d, IV; day 1-3) and cytarabine (100 mg/m2/d, continuous IV infusion; day 1-7) and escalating oral doses of panobinostat at 15 mg, 20 mg, and 25 mg, thrice weekly starting at week 2 of a 28-day cycle. Forty-six patients were enrolled (primary AML [n = 36], secondary AML [n = 10]). The median age was 55 years. The most common all-grade AEs were diarrhea (54.3%), nausea (39.1%), vomiting, and decreased appetite (each, 21.7%), stomatitis (19.6%), and fatigue (17.4%). The overall response rate was 60.9%, 43.5% achieved a complete remission (CR), and 17.4% achieved CR with incomplete count recovery. The event-free survival at 1-year was 78.3%. Panobinostat in combination with idarubicin and cytarabine demonstrated tolerable safety and efficacy in younger patients with high-risk AML. The recommended phase 2 dose of panobinostat in this combination was 20 mg. ClinicalTrials.gov registry no: NCT01242774, and European Trial Registry EudraCT no: 2009-016809-42.

16.
Int J Hematol ; 110(4): 406-410, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31317515

RESUMO

Advanced cutaneous T cell lymphoma (CTCL) patients have a dismal prognosis, especially those relapsing or progressing after systemic therapy. No curative therapies are available, but some new agents have prolonged disease-free survival time with a good toxicity profile. Allogeneic stem cell transplantation (allo-SCT) offers the longest disease-free survival, potentially representing the best therapeutic option for eligible patients. In the present article, we discuss current evidence about allo-SCT for CTCL patients, timing, and new therapeutic options before allo-SCT, taking into account some considerations that may impact clinical outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T/terapia , Neoplasias Cutâneas/terapia , Intervalo Livre de Doença , Medicina Baseada em Evidências , Humanos , Linfoma de Células T/mortalidade , Micose Fungoide , Recidiva Local de Neoplasia , Seleção de Pacientes , Síndrome de Sézary , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo
17.
Transpl Infect Dis ; 21(5): e13139, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271696

RESUMO

PURPOSE: Solid organ transplant recipients are highly susceptible to Toxoplasma gondii infection. We aimed to describe the 12-month follow-up risk of seroconversion in renal transplant recipients. METHODOLOGY: Anti-T gondii antibodies were investigated in donors and recipients of renal transplants. In donors, anti-T gondii were evaluated before transplantation. In recipients, anti-T gondii were monitored over a 12-month period to evaluate potential seroconversion or reactivation. IgG and IgM anti-T gondii antibodies were investigated through enzyme immunoassay and Western blot. Molecular diagnosis was performed on peripheral blood leukocytes using PCR to amplify fragments corresponding to the T gondii B1 gene and the repetitive 529-bp element. RESULTS: The basal frequency of seropositive IgG anti-T gondii antibodies was higher in donors than in recipients (38.4% vs 25.2%; P = .03). During the 12-month follow-up, the accumulated seroconversion to IgG and IgM antibodies was 3/99 (3.0%), and the accumulated reactivation was 11/99 (11.0%). None of the samples exhibited positivity to T gondii DNA. CONCLUSIONS: This study showed that there is an increased risk of seroconversion or reactivation in renal transplant recipients over a 12-month follow-up. Our data suggest that prophylaxis with trimethoprim and sulfamethoxazole effectively prevented toxoplasmosis, since neither T gondii DNA nor clinical toxoplasmosis was detected.


Assuntos
Anticorpos Antiprotozoários/sangue , Doadores de Tecidos/estatística & dados numéricos , Toxoplasmose/diagnóstico , Transplantados/estatística & dados numéricos , DNA de Protozoário , Seguimentos , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Transplante de Rim , Estudos Longitudinais , México , Soroconversão , Toxoplasma/genética
18.
Eur J Haematol ; 103(3): 208-214, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211880

RESUMO

INTRODUCTION: Increased levels of Wilms' tumor (WT1) mRNA have been used to establish risk categories in patients with acute myeloid leukemia (AML). Raised values of WT1 have been associated with progression in myelodysplastic syndrome (MDS). METHODS: We retrospectively analyzed the available bone marrow (BM) samples from 115 patients with myeloid neoplasms obtained before and during treatment with 5-azacytidine. A threshold of 100 copies in BM was used to define risk groups: group 1: patients with WT1 levels always below < 100 copies; group 2: cases with initial WT1 levels greater than 100 copies but with a conversion to sustained levels below 100; and group 3: cases with follow-up WT1 levels greater than 100. RESULTS: Twenty patients were included in group 1, 17 in group 2, and 78 in group 3. Survival analysis showed statistically significant differences in terms of OS between groups (p: 0.016). Patients in group 2 showed the best 5-year overall survival (OS). In multivariate analysis, only the cytogenetic risk category and receiving an allogeneic hematopoietic stem cell transplantation (HCT) independently predicted the survival. CONCLUSIONS: Further studies are needed to assess whether BM WT1 levels could be useful to predict the survival of patients with myeloid neoplasms treated with 5-azacytidine.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Células da Medula Óssea/metabolismo , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genética , Proteínas WT1/genética , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/farmacologia , Terapia Combinada , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/patologia , Transplante Homólogo , Resultado do Tratamento , Proteínas WT1/metabolismo
19.
Leuk Lymphoma ; 60(10): 2404-2414, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30997844

RESUMO

Most myelodysplastic syndromes (MDS)-patients receive multiple red blood cell transfusions (RBCT). Transfusions may cause iron-related toxicity and mortality, influencing outcome after allogeneic HSCT. This prospective non-interventional study evaluated 222 MDS and CMML patients undergoing HSCT. Overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence (RI) at 36 months were 52%, 44%, 25%, and 31%, respectively. Age, percentage of marrow blasts and severe comorbidities impacted OS. RFS was significantly associated with RBCT burden prior to HSCT (HR: 1.7; p = .02). High ferritin levels had a significant negative impact on OS and RI, but no impact on NRM. Administration of iron chelation therapy prior to HSCT did not influence the outcome, but early iron reduction after HSCT (started before 6 months) improved RFS significantly after transplantation (56% in the control group vs. 90% in the treated group, respectively; p = .04). This study illustrates the impact of RBCT and related parameters on HSCT-outcome. Patients with an expected prolonged survival after transplantation may benefit from early iron reduction therapy after transplantation.

20.
Hematol Rep ; 11(1): 7841, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30915203

RESUMO

Within T-cell lymphomas (TCL) there are 2 entities expressing gamma-delta TCR: hepatosplenic gamma-delta T-cell lymphoma (HSGDTL) and the primary cutaneous gamma-delta T-cell lymphoma (PCGDTL). PCGDTL is a rare form of Tcell lymphoma with specific tropism for skin that have a dismal prognosis. Although even rarer, there have been reports of TCL with loss of expression of the TCR, which have been termed peripheral TCL TCR-silent type. We report the case of a cutaneous TCR-silent type lymphoma associated to a clonal plasma cell proliferation with an ominous outcome that led to a lot of discussion in its classification. Due to the aggressiveness of the disease and the scant evidence about therapy in this strange entity the outcome was fatal. We report a unique case of a TCR-silent cutaneous TCL with an exceptional histopathology, prolonged clinical evolution and a subsequent plasma cell clonal expansion.

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