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  • 1
    Publication Date: 2019-11-13
    Description: Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare disease characterized by a severe deficiency of the enzymatic activity of ADAMTS13 caused by autoantibodies, with an incidence of 3-4 x106inhabitants per year according to the few published data available. Accurate estimates of the incidence of aTTP are important to assess the resources required for current treatments and to anticipate the need to develop new treatments. The aim of this study was to determine the actualincidence of aTTP in Spain, as well as its diagnosis, management, and associated complications. Material and methods:A cross-sectional surveywascarried out among hematologists working in Spanish hospitals by means of an email that was sent to all members of the three main hematological scientificsocieties of Spain. All participants were asked to report the number of patients over the age of 16 years with a de novodiagnosis and relapses examined between Jan 2015 and Dec 2017. They were also asked about the number of patients that were known and alive in each hospital without having experienced any episode during such period. The population area of each participating hospital was consideredto calculate the incidence and prevalence of the disease. We also estimated the hospitalization service, mean hospital stay, percentage of ADAMTS13 activity at diagnosis and during follow-up, initial management, refractory cases and exacerbations (as defined by Scully et al.), treatment-related complications, and sequelae of aTTP. The median, interquartile ranges, and percentages were used for the descriptive analysis. Given that no personal data were treated, this study did not require the approval of a Research Ethics Committee. Results:A response was received from 42 centers (Figure 1). All hospitals except a private one belonged to the Spanish public health system, which provides health coverage to the entire Spanish population.A total of 203 episodes were reported (138 new episodes). The calculated population of the participating centers was nearly 21 x 106inhabitants. The incidence was 2.25 x106inhabitants per year, and the prevalence 19 x106inhabitants. Six patients died before they could start treatment (all but one in first episodes) and five were sent to other hospitals; thus, a total of 192 episodes were eventually treated. Table 1 and 2 show the data of the enzymatic activity of ADAMTS13 and the ADAMTS13 inhibitor at diagnosis, as well asthe complications. Plasma exchange (PEX) was performed by the Hematology and Nephrology Departments of 29 (70.7%) and 12 (29.3%) hospitals, respectively. The median hospital stay was 14 days (IQR: 10-20). Seventy-five episodes (39.1%) required admission to the intensive care unit with a median stay of 4 days (IQR: 3-7). During first-time episodes, a median of 12 PEX procedures (IQR: 8-19) were performed per patient, whereas in the case of relapses, a median of 9 (7-10) PEX procedures were carried out per patient. One plasma volume (PV) was used in the PEX procedures performed in 34% of the episodes, while 1.5 PVs were used in 56% of the episodes, and other PVs were used in the remaining 9.8%. The median duration of the PEX procedures was 121 minutes (IQR: 118-180). PEX and corticosteroids were the initial treatments administered in 98.4% of the episodes. Rituximab was used as a first-line treatment for new episodes in 18 of the 127 patients (14.1%), as a second-line treatment in 34 patients (26.6%), and as a prophylactic treatment (followingremission) in 4 patients (3.5%). In addition to the 6 early deaths, 9 patients died despite receiving the treatment (15 of 203 episodes, accounting for a mortality rate of 7.3%). Refractoriness to the PEX + corticoids was observed in 31 episodes of the 192 ones treated (16.1%), and at least one exacerbation (26.5%) took place in 51 episodes. Conclusion.Wecalculated the incidence ofclinically diagnosed aTTP associated with a severe ADAMTS13 deficiency inalmost half of the Spanish population which provided a high accuracy to our findings. These data are concordant with those published previously in other countries. Despite the currently available therapies, considerable rates of refractoriness and mortality still persist.Our data will be very useful for estimating the budget invested in this pathology and proposing standards for the diagnosis and treatment of this disease in our region. Disclosures Pascual Izquierdo: Novartis: Consultancy; Sanofi: Consultancy. De La Rubia:AMGEN: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Mingot-Castellano:Novartis: Consultancy; Novonordisk: Consultancy; Roche: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Amgen: Consultancy; CSL Behring: Consultancy; Sobi: Consultancy.
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  • 2
    Publication Date: 2016-12-02
    Description: Introduction: 30% of Hodgkin Lymphoma (HL) patients are refractory or relapse (RR) after first line therapy. Salvage chemotherapy followed by high-dose chemotherapy and with Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) can cure many patients, but those who are transplanted with active disease detectable by PET-CT have a very poor prognosis. Therefore, the current challenge in HL is to improve the results of the pre-transplant chemotherapy. We and others have demonstrated that the addition of Brentuximab Vedotin (BV) to chemotherapy can produce very good results. Objectives: We conducted a phase II trial to assess response rate with combined Brentuximab vedotin and ESHAP chemotherapy [BRESHAP] as 2nd line therapy for RRHL prior to APBSCT (ClinicalTrials.gov #NCT02243436). Methods: Primary efficacy endpoint was the proportion of complete responses (CR) pre-APBSCT. A prior phase I step was carried out to establish the appropriate dosis. Final treatment consisted of Brentuximab Vedotin (1.8 mg/m2/day IV, D1), Etoposide (40 mg/m2/day IV, D1-4), Solumedrol (250 mg/day IV, D1-4), High dose AraC (2 g/m2 IV, D5) and cisPlatin (25 mg/m2/day IV, D1-4). Results: Patients with relapsed or refractory classical HL (cHL) after one prior line of therapy were eligible. 66 patients were included in the trial. There were 35 females and 31 males, with a median age of 36 years (18-66). At inclusion, 40 patients were considered primary refractory, 16 as early relapses (complete remission -CR- shorter than 1 year) and 10 as late relapses. Currently, all patients have completed the pre-transplant therapy. During that period, there were 22 Severe Adverse Events (SAEs) reported in 15 patients: Fever in 13 occasions (neutropenic in seven, and non-neutropenic in six), hypomagnesemia and gastrointestinal alterations (n=2) and pneumothorax, skin lesions, left ventricular function reduction and pulmonary embolism [PE](n=1). There were 2 deaths: non-neutropenic abdominal sepsis and PE. Grade 3-4 hematologic toxicity presented in 22 cases: neutropenia (n=18), thrombocytopenia (n=12), and anemia (n=5). Grade 3-4 extrahematologic adverse events present in ≥5% of cases were non-neutropenic fever (n=8) and hypomagnesemia (n=3). All patients except three underwent stem cell mobilization after the 1st (n=15), 2nd (n=36) or 3rd (n=12) cycle using subcutaneous G-CSF 5 mcg/Kg/12 h. for 5 days. All patients collected 〉2·10e6/Kg peripheral blood CD34+ cells in all cases (median 5.75, range 2.12-33.4). The number of harvesting procedures was one in 47 patients, two in 13, three in 2 and four in 1. The transplant has been done in 61 patients, with data are available from 47: all engrafted with a median of 9&10 days for neutrophil and platelet recovery, respectively. No major events were registered during transplant period, except for one patient who died at day +110 due to pneumonia. Overall pre-transplant response was 96%, including a 70% and 26% complete and partial remission rates, respectively. Of these forty-seven patients, 37 (80%) were in metabolic CR after transplant and 3 (7%) in PR; six patients were considered as non-responders (13%) and went out of the trial. At a mean follow-up of 11 months, 7 patients have progressed, rendering a projected progression free survival of 87% at one year. Six patients have already died: three due to progression, and the three already mentioned above (PE, abdominal sepsis and pneumonia). With a mean follow-up of 11 months, the projected overall survival was 90% at one year (cause specific, 96%). Conclusions: BRESHAP is a highly effective regimen for remission induction prior to transplant in patients with refractory or relapsed Hodgkin lymphoma. The addition of BV to the conventional chemotherapy did not resulted in a higher toxicity for the pre- and post-transplant periods and it did not hamper the collection of PBSC. Disclosures No relevant conflicts of interest to declare.
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  • 3
    Publication Date: 2014-12-06
    Description: Type 2-diabetes (T2D) is thought to be a relevant risk factor for multiple myeloma (MM), but the relationship between both traits is still not well understood. Thus, we decided to conduct a population-based case-control study in a population of 1420 MM patients (705 women and 715 men) and 1858 controls (916 women and 942 men) to evaluate whether 58 genome-wide association studies (GWAS)-identified common variants for T2D influence the risk of developing MM. Logistic regression analyses showed that carriers of the KCNQ1rs2237892T allele or CDKN2A-2Brs2383208G/G, IGF-1rs35767T/T and MADDrs7944584T/T genotypes had an increased risk of MM (OR=1.32, 95%CI 1.01-1.71, P=0.039; OR=1.86, 95%CI 1.12-3.11, P=0.016; OR=2.13, 95%CI 1.35-3.37, P=0.001 and OR=1.33, 95%CI 1.06-1.67, P=0.014, respectively) whereas those carrying the KCNJ11rs5215C, KCNJ11rs5219T and THADArs7578597C alleles or the FTOrs8050136A/A and LTArs1041981C/C genotypes showed a decreased risk for the disease (OR=0.85, 95%CI 0.73-0.99, P=0.38; OR=0.84, 95%CI 0.72-0.99, P=0.034; OR=0.81, 95%CI 0.68-0.98, P=0.032; OR=0.78, 95%CI 0.64-0.95, P=0.013; and OR=0.76, 95%CI 0.58-0.99, P=0.042, respectively). The associations of these T2D-related variants with an increased or decreased risk of MM were due to non-diabetogenic alleles, which suggests a non-diabetogenic mechanism underlying the effect of these variants to determine the risk of the disease. A gender-stratified analysis also revealed a significant gender effect modification for ADAM30rs2641348, and NOTCH2rs10923931 SNPs (Pinteraction=0.001 and 0.0004 and Phet=0.19 and 0.60, respectively), which also underlies the importance of considering gender as a factor modifying the risk for MM. Men harbouring the ADAM30rs2641348C and NOTCH2rs10923931T alleles had a decreased risk of MM (OR=0.71, 95%CI 0.54-0.94, P=0.015 and OR=0.66, 95%CI 0.50-0.86, P=0.0019) whereas an opposite but not significant effect was observed in women. Finally, SNP-SNP interaction analysis revealed overall significant two- and three-locus interaction models to increase the risk of MM (FAM148Brs11071657-KCNJ11rs5219, and SLC30A8rs13266634-KCNJ11rs5219-FTOrs8050136; P=0.01 and 0.001, respectively) whereas a significant four-locus model was also found to increase the risk of MM in men (FADS1rs174550-TSPAN8rs7961581-PROX1rs340874-KCNJ11rs5219, P=0.001). Although further studies in independent populations are warranted to replicate these findings, these results suggest that TD2-related variants may influence the risk of developing MM, likely through non-diabetogenic mechanisms. Abstract 2044. Table 1. Demographical characteristics of IMMEnSE cases and controls. CASES CONTROLS Region* Gender M/F (Total) Mean Age (± STD) Gender M/F (Total) Mean Age (± STD) Control type Italy 117/107 (224) 62.60±9.90 127/105 (232) 58.75±10.92 General population Poland 173/198 (371) 62.35±10.39 124/226 (350) 50.68±19.43 Blood donors Spain 139/133 (272) 63.06±11.04 218/192 (410) 63.12±11.94 Hospitalized subjects France 42/33 (75) 55.80±9.04 95/89 (184) 44.07±15.22 Blood donors Portugal 32/35 (67) 65.79±11.16 52/42 (94) 60.88±07.88 Blood donors Hungary 49/87 (136) 65.83±11.19 50/51 (101) 73.18±10.10 Hospitalized subjects Denmark 163/112 (275) 55.20±07.32 276/211 (487) 43.26±11.84 General population Total 715/705 (1420) 61.06±10.57 942/916 (1858) 53.56±16.45 Table 2. Selected type-2 diabetes-related polymorphisms Gene name dbSNP rs# Gene name dbSNP rs# ADAM30 rs2641348 JAZF1 rs864745 ADAMTS9 rs4607103 KCNJ11 rs5215 ADCY5 rs11708067 rs5219 ADRA2A rs10885122 KCNQ1 rs2237897 ARAPI, CENTD2 rs1552224 rs2074196 BCL11A rs10490072 rs2237892 CDC123 rs12779790 rs2237895 CDKAL1 rs7754840 KCNQ1OT1 rs231362 CDKN2A-2B rs564398 LTA rs1041981 rs10811661 MADD rs7944584 rs2383208 MCR4 rs12970134 COL5A1 rs4240702 MTNR1B rs1387153 CRY2 rs11605924 NOTCH2 rs10923931 DCD rs1153188 PKN2 rs6698181 EXT2 rs1113132 PPARG rs1801282 FADS1 rs174550 PRC1 rs8042680 FAM148B rs11071657 PROX1 rs340874 FLJ39370 rs17044137 RBMS1 rs7593730 FTO rs8050136 SLC2A2 rs11920090 G6PC2 rs560887 SLC30A8 rs13266634 GCK rs1799884 TCF2 rs7501939 GCKR rs1260326 TCF7L2 rs7903146 HHEX rs1111875 TCF7L2 rs12255372 HMGA2 rs1531343 THADA rs7578597 HNF1A, TCF1 rs7957197 TP53INP1 rs896854 IGF1 rs35767 TSPAN8 rs7961581 IGF2BP2 rs4402960 VEGFA rs9472138 IL13 rs20541 WFS1 rs734312 IRS1 rs2943641 rs10010131 Disclosures No relevant conflicts of interest to declare.
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  • 4
    Publication Date: 2015-12-03
    Description: The development of the NCCN International Prognostic Index (NCCN-IPI) for patients with DLBCL treated in the rituximab era improves discrimination when compared to the original IPI model. The aim of the present study is to validate the results of the NCCN-IPI in a large independent series of patients in a different geographical area. Materials & Methods. This nation-wide retrospective study includes 2156 patients with de novo DLBCL diagnosed in 20 (mostly) large academic Spanish centers within the Grupo Español de Linfomas y Transplante de Médula Osea (GELTAMO) network between 1998 to July 2014. Patients had to be ≥ 18 years-old, treated with rituximab plus chemotherapy (R-CHOP or variants and also more intense treatments) and a minimum of 1 year of follow-up; all histological subtypes of DLBCL and primary extranodal cases were acceptable, with the only exclusion of primary testicular or CNS sites. In the whole series the scoring of the IPI and NCCN-IPI indexes were used and 5-year Overall Survival (5y-OS) estimated with the Kaplan-Meier method and compared with the log-rank test. Results. Debugging the database resulted in a final working series that included 1885 patients. The demographics of the series were comparable to the NCCN series: NCCN/GELTAMO male gender(%) 54 vs 50.4, Age(y) 57 vs 60, LDH〉1(%) 50 vs 54.7, Ann Arbor stage III-IV (%) 59 vs 62.5, ECOG PS≥2(%) 11 vs 30, extranodal disease(%) 36 vs 40.7. The IPI scoring (1760 patients) significantly separated the four risk groups, low (LR, 33.6% of the patients), low/intermediate (LI, 22.7%), intermediate/high (HI, 25.1%) and high (HR, 18.6%) with significantly different (p
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  • 5
    Publication Date: 2019-11-13
    Description: Introduction: Classical Hodgkin lymphoma (cHL) is highly curable with front-line multi-agent chemotherapy with or without radiotherapy. The treatment landscape is rapidly evolving, with a continued focus on optimizing available therapies in order to improve outcomes and minimize toxicity. Randomized controlled trials provide valuable insights into new treatments and outcomes; however, real-world data describing treatment effectiveness, safety, and health-related quality of life (HRQoL) are limited. This analysis was conducted to understand patient-reported outcomes (PROs) in patients who were treated for newly diagnosed cHL across a range of academic and community settings. Methods: Study CA209655 is an ongoing, prospective, observational study (NCT02856646) at ~80 US oncology practices with a target enrollment of 500 patients and a planned follow-up of ≤ 5 years. Eligible patients are ≥ 18 years old with histologically confirmed cHL and are treatment naive or within ± 2 weeks of beginning any line of therapy at time of enrollment. HRQoL is a secondary endpoint and evaluated using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire. The FACT-Lym combines a generic cancer-related core consisting of the FACT-General (FACT-G; 27 items) that assesses physical (PWB; 7 items), social/family (SWB; 7 items), emotional (EWB; 6 items), and functional well-being (FWB; 7 items), and a 15-item disease-specific lymphoma subscale (LymS) that assesses lymphoma-specific symptoms. PROs were assessed using questionnaires at baseline (BL), every 3-6 months for ≤ 2 years, and annually thereafter. All patients with BL and ≥ 1 post-BL assessment were included in the PRO analysis. Completion rates and changes from BL scores were evaluated descriptively and analyzed based on published estimates for clinically important differences and individual responder definitions (Hlubocky et al. Lymphoma 2013; Carter et al. Blood 2008; Yost and Eton. Eval Health Prof 2005). High scores indicate better health/functioning for all scales/subscales. Results: Of 278 enrolled patients at data cutoff (Feb 2019), 226 (81%) were treatment naive; for those, the most common index therapy was chemotherapy (n = 210; 93%). The most common index chemotherapies were ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; n = 187, 83%) and AAVD (adriamycin, brentuximab, vinblastine, dacarbazine; n = 10, 5%). Only patients receiving index chemotherapy were included in the full analysis set. In all, 89% (87/210) of patients had BL and ≥ 1 post-BL assessment and were included in the PRO analysis. PRO completion rate at BL was 97% (204/210) and remained 〉 70% up to 24 months for the expected population. Analysis of PROs was not feasible after 24 months owing to small patient numbers (≤ 10); therefore, PRO analyses were focused on the first 18 months. At BL, mean (SD) scores were: FACT-Lym total, 122 (24); FACT-G, 82 (15); PWB, 21 (6); SWB, 25 (3); EWB, 18 (4); FWB, 18 (6); and LymS, 40 (11). At 3 months there was a deterioration in mean scores from baseline in FACT-G (−3.8) and PWB (−3.0) (Figure A). Clinically meaningful improvement of mean scores was observed starting at 6 months in LymS (+4.4) and at 9 months in FACT-G (+7.1), PWB (+3.1), FWB (+2.8), and FACT-Lym total (+15.6). There were no clinically meaningful improvements in SWB and EWB. Based on individual responder definitions, ≥ 50% of patients had improvements in PWB (Figure B) and FACT-G from 12 months, and FACT-Lym total from 9 months. Conclusions: Initial data from this observational study suggest most patients receive multi-agent cytotoxic chemotherapy as first-line treatment of cHL. Patient-reported PWB initially declined with chemotherapy, but improved with time, and patients had a clinically meaningful improvement in HRQoL by 9 months. The timing of this improvement may be due to discontinuation of chemotherapy due to disease control. Future analyses will evaluate the relationship between improvements in HRQoL and other factors including response, use of immunotherapies versus chemotherapy, and the timing of treatment discontinuation. Study support: Bristol-Myers Squibb. Disclosures Svoboda: Seattle Genetics: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy; Celgene: Research Funding; Kyowa: Consultancy; Kite: Consultancy. Armand:Roche: Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Research Funding; Sigma Tau: Research Funding; Infinity: Consultancy; Genentech: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding. Taylor:Adelphi Values: Employment, Other: I am an employee of Adelphi Values, a consulting firm who has received payment from Bristol-Myers Squibb for statistical data analysis in Bristol-Myers Squibb's trials. Sun:Adelphi Values: Employment. Gajavelli:Bristol-Myers Squibb: Employment. Peterson:Bristol-Myers Squibb: Employment, Equity Ownership. Chen:Bristol-Myers Squibb: Employment.
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  • 6
  • 7
    Publication Date: 2002-04-01
    Description: The p21 is a downstream effector of p53/p73 and belongs to the CIP/KIP family of cyclin-dependent kinase inhibitors (CDKIs). It is, therefore, a potential tumor suppressor gene and probably plays an important role in tumor development. Moreover, reduced expression of p21 has been reported to have prognostic value in several human malignancies. In contrast with other CDKIs, mutational inactivation of p21 is infrequent, but gene inactivation by an alternative mechanism seems to be the general pathway. In this study, we analyzed the methylation status of the p21 promoter region using semiquantitative polymerase chain reaction in 124 patients with acute lymphoblastic leukemia (ALL). We observed p21 hypermethylation in bone marrow cells from 41% (51 of 124) of ALL patients. Hypermethylation within promoter strongly correlated with decreased p21 messenger RNA expression in tumoral cells. Clinical, molecular, and laboratory features and complete remission rate did not differ significantly between hypermethylated and normally methylated patients. Estimated disease-free survival (DFS) and overall survival at 7 and 9 years, respectively, were 59% and 65% for healthy patients and 6% and 8% for hypermethylated patients (P = .00001 andP = .006). Multivariate analysis of potential prognostic factors demonstrated that p21 methylation status was an independent prognostic factor in predicting DFS (P = .0001). Our results indicate that the p21 gene is subject to methylation regulation at the transcription level in ALL and seems to be an important factor in predicting the clinical outcome of these patients.
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  • 8
    Publication Date: 2014-12-06
    Description: Objective :To evaluate the prognostic significance of RELamplification, expression and c-Rel activation in DLBCL patients and to identify potential mechanisms for impact of c-Rel activation on patient survival. Patients and Design : The study cohort consists 460 de novo DLBCL patients (median follow-up, 46.8 moths) treated with R-CHOP. We assessed the nuclear expression/activation of c-Rel and other NF-κB subunits by immunohistochemistry, REL gene amplification by fluorescence in situ hybridization, and gene expression profiling using Affymetrix GeneChips array. Correlations between expression of nuclear c-Rel, REL mRNA, and expression of TP53, MDM2, MDM4, MYC, BCL2, AKT1, NFKB1, RELA, NFKB2, and RELB, both at the mRNA and protein levels were analyzed using t-tests. The prognostic significance of c-Rel activation, REL mRNA expression, and REL amplification was evaluated in the overall cohort, and different subgroups stratified by COO, status of TP53 mutation (wide type/WT, or mutated/MUT) and expression, Myc, Bcl-2 overexpression, and nuclear expression of other NF-κB subunits. Results :Nuclear c-Rel expression was observed in 29.6% of DLBCL patients and did not correlate with REL mRNA levels (P=0.95) and COO (P=0.77). In contrast, REL mRNA was significantly higher in germinal center B-like (GCB) subtype (P
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  • 9
    Publication Date: 2015-12-03
    Description: In recent years, the role of tumor microenvironment in neoplasm initiation and malignant evolution has been increasingly recognized. However, the bone marrow mesenchymal stem/stromal cell (BMMSC) contribution to disease progression remains poorly explored. We had previously performed a microarray analysis of myelodysplastic syndrome (MDS) patient-derived BMMSC (MDS-BMMSC) and found an underexpression of HAI-2/SPINT2, an endogenous inhibitor of the hepatocyte growth factor (HGF) activator. This gene has been described as methylated in various cancer types and has been associated with disease progression. Despite of being related to the pathogenesis of several neoplasms, the role of HAI-2/SPINT2 has not yet been fully elucidated in hematological diseases, such as MDS and acute myeloid leukemia (AML). Thus, the aim of this study was to evaluate HAI-2/SPINT2 expression in derived BMMSC and total bone marrow (BM) of healthy donors (HD), MDS and AML patients as well as in BMMSC treated with 5-Azacitidine (Aza), a DNA methyltransferase (DNMT) inhibitor. To achieve this, we collected BM hematopoietic cells and plastic-adherent BMMSC from aspirates of HD, MDS and AML patients. BMMSC were expanded to passage 4 and defined as CD73+/CD90+/CD105+/CD45-/CD34-/CD31-/HLA-DR-. A total of 29 HD and 121 patients at diagnosis (MDS=72 [low-risk=46, high-risk=26], AML with myelodysplastic related changes (AML-MRC)=17 and de novo AML=32) were included. HAI-2/SPINT2 mRNA was significantly decreased in MDS- (0.34[0.01-2.06];P
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  • 10
    Publication Date: 2019-11-13
    Description: Introduction Patients with AML are inmmunocompromised because of the disease itself and the use of chemotherapy, increasing endemic opportunistic infections. The main complication is secondary infectious diseases, which we have to consider TB. In cancer patients infected with TB frequently manifest more atypical. Clinical signs and symptoms include lung disease which is still the most commonly involved site, extra pulmonary tuberculosis is not uncommon. Even that we're in an endemic country we still have some delay in the diagnosis of such disease. Objective To characterize the clinical and factors that contributes to the delay on the diagnosis of tuberculosis in patients with AML. Methods We did a chart review of patients with the diagnosis of TB and AML in the Instituto Nacional de Cancerologia, Mexico City, from January 2014 to July 2019. We analyze the clinical presentation of and the time to diagnosis TB in those patients. Results We analyze a cohort of 5 patients, three male and two female with a median age of 44 years old. The majority of patients were on induction chemotherapy. The main clinical presentation was persistent fever that begins in the nadir of chemotherapy. We observed a median of days for the diagnosis of tuberculosis of 37 days (9-82), the diagnosis was made by histopathology supported by special stains, and were required at least two biopsies for the diagnosis. One patient has pulmonary tuberculosis, one nodal presentation, two have a hepatosplenic presentation, and in the last patient was conclude latent TB. Just in one patient was available the microbiological identification, Mycobaterium bovis. Four patients started the approved treatment in Mexico, intensive phase with rifampicin, pyrazinamide, ethambutol and isoniazid. One patient develop Drug induce liver injury (DILI) so she couldn't continue the first line treatment and have to receive the second line which it is not standardize. After the initiation of the treatment, patients went out of fever and improve their condition. The patients were followed during the maintenance phase with rifampicin, and isoniazid. All of the patients are alive at the moment of the study. Conclusion: Febril neutropenia is a common complication in patients with AML, and in patients with persistent fever, tuberculosis should be include in the differential diagnosis. In México we have limited access to all the diagnostic tools available in our center. Culture is not always a way to identify TB, most of our patients were diagnosed by biopsy, median number of procedures were 3. Patient number 5 was followed by the infectology service after the whole protocol of culturing TB were concluded with no evidence of the disease and they decide to stop the treatment, and they manage the patient as latent TB. The availability of the techniques is the main factor which contributes to the diagnosis delay of TB. After the treatment was started, patients have a significant clinical improvement. Disclosures No relevant conflicts of interest to declare.
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