Survival analysis of patients with brain metastases at initial breast cancer diagnosis over the last decade.

PURPOSE: There have been significant advances in the treatment of metastatic breast cancer (BC) over the past years, and long-term outcomes after a diagnosis of brain metastases are lacking. We aimed to identify predictors of brain metastases at initial breast cancer diagnosis, describe overall survival (OS) in the past decade, and identify factors associated with OS after brain metastases diagnosis. METHODS: We evaluated patients with de novo stage IV BC using the Surveillance, Epidemiology and End Results database from 2010 to 2019. Multivariate logistic regression was conducted to assess predictors of brain metastases at initial breast cancer diagnosis. OS was estimated using the Kaplan-Meier method and log rank test was used to compare differences between groups. Cox regression was used to assess associations between several variables and OS. RESULTS: 1,939 patients with brain metastases at initial breast cancer diagnosis were included. Factors associated with this presentation were grade III/IV tumors, ductal histology, hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-positive subtype, and extracranial metastases. Patients with HR-positive/HER2-positive disease had the longest OS (median 18 months) and 12.2% were alive at 8 years. Factors associated with shorter OS included older age, lower income, triple-negative subtype, higher grade, and visceral metastases. CONCLUSION: Over the last decade, the median OS of patients with brain metastases at initial breast cancer diagnosis remained poor; however, a substantial minority survive 5 or more years, with rates higher in patients with HER2-positive tumors. In addition to tumor subtype, OS varied according to age, extracranial metastases, and sociodemographic factors.

A multicentre ambispective observational study into the incidence and clinical management of aplastic anaemia in Spain (IMAS study).

Aplastic anemia (AA) is a rare, life-threatening hematological disease, with a poorly defined incidence. As the data available on AA varies substantially worldwide, a multicenter, ambispective, observational study was carried out between 2010 and 2019 to assess the incidence, clinical management and survival of AA at seven Spanish hospitals. The incidence of AA was 2.83 per million inhabitants per year, consistent with that reported previously in Europe, with a median age at diagnosis of 61 years-old (range 12-86), and a similar number of males and females. The initial diagnosis was severe or very severe AA in 55.8% of cases and 93.7% required transfusion. The most frequent first line therapy was anti-thymocyte globulin (ATG) plus cyclosporin A (CsA, 44.2%), followed by other CsA-based regimes (46.3%), with hematopoietic stem cell transplantation an infrequent 1st line therapy. The 6-month response rate was 68.2%, which then increased over a median follow-up of 3.9 years. The 5-year overall survival (5OS) was 73.6%, similar in severe (78.6%) and very severe AA patients (74.6%) but lower in moderate AA (MAA) patients (68.4%). The 5OS was 100% in 0-25 year-old patients but dropping to 58.3% in patients ≥ 60 years-old. At the last contact, 75.8% of the patients were alive. In conclusion, the incidence, characteristics and management of AA in our study are consistent with that reported previously. In terms of survival, although the global long-term OS rate was good, there is room for improvement, particularly in older patients. Finally, what appears to be a worse long-term survival of MAA patients, as reported previously, reinforces the importance of not underestimating this condition when diagnosed as MAA.

Efficacy of neoadjuvant chemotherapy in male breast cancer compared with female breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is standard for many females with breast cancer (FBC). The efficacy of NAC in male breast cancer (MaBC) is unclear. The aim of this study was to compare proportions of pathologic complete response (pCR) between MaBC and FBC by tumor subtype (TS). METHODS: MaBC and FBC treated with NAC between 2010 and 2016, with known TS, were evaluated from the National Cancer Database. Proportions of pCR (ypT0/Tis ypN0) were compared between sexes within TS by Fisher test. Multivariable logistic regression assessed the independent association of sex with pCR. Overall survival (OS) was estimated by Kaplan-Meier. RESULTS: A total of 385 MaBC and 68,065 FBC were included. Median time from initiation of NAC to surgery was 143 days in MaBC and 148 days in FBC. Proportions of pCR in MaBC and FBC by TS were: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-): 4.9% vs 9.7%, p = .01; HR+/HER2+: 16.1% vs 33.6%, p < .001; HR-/HER2+: 44.0% vs 53.2%, p = .42; and HR-/HER2-: 21.4% vs 32.1%, p = .18, respectively. FBC had twice the odds of pCR than MaBC (adjusted odds ratio, 2.0; 95% CI, 1.5-2.8; p < .001). Five-year OS for MaBC with pCR vs not was 90% vs 64.7%; p = .02. Five-year OS for FBC with pCR vs not was 91.9% vs 75.3%; p < .01. CONCLUSIONS: Proportions and odds of pCR to NAC were numerically lower in MaBC compared with FBC for each TS and statistically significant for HR+/HER2- and HR+/HER2+. The independent association of sex with pCR was confirmed in multivariable analysis. pCR is prognostic in both MaBC and FBC.

Peri-event plasma PCSK9 and hsCRP after an acute myocardial infarction correlate with early deterioration of left ventricular ejection fraction: a cohort study.

BACKGROUND: It is important to identify patients at increased risk of worsening of left ventricular ejection fraction (LVEF) after a myocardial infarction (MI). We aimed to identify the association of various potential biomarkers with LVEF impairment after an MI in South American patients. METHODS: We studied adult patients admitted to a University Hospital and diagnosed with an acute MI. Plasma concentrations of high-sensitivity C-reactive protein (hsCRP), proprotein convertase subtilisin/kexin type 9 (PCSK9), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and heart-type fatty-acid-binding protein (FABP3) were determined in samples drawn shortly after the event. Participants had a follow-up visit at least 45 days after the event. The primary endpoint was defined as any decline in LVEF at follow-up relative to baseline. RESULTS: The study included 106 patients (77.4% men, 22.6% women), mean age was 64.1, mean baseline LVEF was 56.6, 19% had a prior MI. We obtained a follow-up evaluation in 100 (94.4%) of participants, mean follow-up time was 163 days. There was a significant correlation between baseline PCSK9 and hsCRP (r = 0.39, p < 0.001). Baseline hsCRP concentrations were higher in patients who developed the endpoint than in those who did not (32.1 versus 21.2 mg/L, p = 0.066). After multivariate adjustment, baseline PCSK9, male sex and age were significantly associated with impairment in LVEF. The absolute change in LVEF was inversely correlated with baseline hsCRP (standardized coefficient = - 0.246, p = 0.004). CONCLUSION: High plasma levels of PCSK9 and hsCRP were associated with early decreases in LVEF after an MI in Latin American patients.

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group.

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.

The prognostic significance of metastatic pattern in stage IV male breast cancer at initial diagnosis: a population-based study.

PURPOSE: Metastatic pattern (MP) is a prognostic factor in women with breast cancer. However, the prognostic significance of MP in male breast cancer patients remains unknown. METHODS: Using the SEER database, we gathered demographic information and disease characteristics for men diagnosed with de novo metastatic breast cancer from 2010 to 2017. Metastases to bone, brain, liver, and lung were used to define MP (bone-only, visceral, bone and visceral [BV], or other). Statistical analyses were performed to identify associations between overall survival (OS) and MP, as well as other patient and tumor features. We used multivariate logistic regression to evaluate factors associated with sites of metastases. RESULTS: We included 250 patients. MP distribution was bone = 38.8%, visceral = 14.8%, BV = 33.2%, and other = 13.2%. Median OS for each was bone = 33 months, visceral = 23 months, BV = 20 months, and other = 46 months (p = 0.046). Patients with brain metastases had significantly shorter OS compared with no brain metastases (median OS = 9 months vs. 30 months; p < 0.001). Compared with other subtypes, triple negative had the shortest OS (median 9 months, p < 0.001). Logistic regression modeling revealed that compared with HR+/HER2- breast cancers, HR-/HER2+ had higher odds of liver metastases and triple negative had higher odds of brain metastases. Patients younger than 50 years had a significantly greater risk of developing brain metastases. CONCLUSIONS: MP and tumor subtype can predict OS outcomes in men with metastatic breast cancer at diagnosis. Brain metastases confer very poor prognosis.

Tumor subtypes and survival in male breast cancer.

PURPOSE: Male breast cancer is an uncommon disease, and population-based information regarding prognostic factors is limited. Most cases are hormone receptor (HR) positive; however, the association of tumor subtype with overall survival (OS) and breast cancer-specific survival (BCSS) is unclear. METHODS: Using SEER data, we identified men with invasive breast cancer between 2010 and 2017 with known HR and HER2 status. We examined tumor subtypes by patient characteristics and performed multivariate Cox proportional hazards analyses to determine the associations of each variable with OS and BCSS. RESULTS: We included 2389 men with a median follow-up of 43 months (IQR 19-68). Median age was 66 years. Tumor subtype distribution was 84.1% HR+/HER2-, 12.7% HR+/HER2+ , 0.8% HR-/HER2+, and 2.3% triple-negative (TN). In univariate analysis, OS at 5 years was 76.5% for HR+/HER2-, 65.1% for HR+/HER2+ , 84.2% for HR-/HER2+, and 48.1% for TN (p < 0.0001). Of all subtypes, TN had the worst BCSS (p < 0.0001). Stage, tumor subtype and race were significantly associated with OS and BCSS in multivariate analysis. Adjusted Cox hazard ratios for OS by tumor subtype with HR+/HER2- as reference were 1.55 for HR+/HER2+ (p = 0.001), 1.1 for HR-/HER2+ (p = 0.888), and 3.59 for TN (p < 0.001). CONCLUSION: We observed significant differences in survival outcomes by tumor subtype. Poor outcomes among men with HER2+ and TN disease suggest possible under-treatment, aggressive tumor biology, and/or more advanced disease at presentation. Studies to better understand the inferior survival for men with these subtypes are warranted and will likely require international collaboration.

Twenty-year risks of breast cancer-specific mortality for stage III breast cancer in the surveillance, epidemiology, and end results registry.

PURPOSE: We aimed to report the 20-year risk of breast cancer-specific mortality (BCSM), report the risk of BCSM conditional on having survived 5 years, and identify factors associated with late deaths in stage III breast cancer. METHODS: Using Surveillance, Epidemiology, and End Results data, we included women with stage III breast cancer diagnosed from 1990 to 2005. We excluded women with unknown hormone receptor (HR) status, women who did not undergo resection of the primary tumor or axillary nodes, or unknown cause of death. We estimated risks of BCSM using cumulative incidence function and used Fine and Gray regression to identify factors associated with late deaths. RESULTS: Final sample was 36,500 patients with 14 years of median follow-up. For each stage subgroup, the risk of BCSM at 20 years was significantly higher for HR-negative vs HR-positive tumors (IIIA: 49.8% vs 43.2%, P < 0.0001; IIIB: 60.9% vs 47.6%, P < 0.0001; IIIC: 68.7% vs 63.1%, P < 0.0001). Compared with the risks of non-BCSM, the risks of BCSM at 20 years were four times higher in stage IIIC HR-positive disease and seven times higher in stage IIIC HR-negative disease. Risks of BCSM conditional on having survived 5 years depended on tumor size, nodal status, race, and tumor grade for HR-positive disease and depended on tumor size, nodal status, and age for HR-negative disease. CONCLUSIONS: In stage III breast cancer, the risk of BCSM at 20 years is very high and remains important even beyond the first 5 years in both HR-positive and HR-negative disease. Late BCSM depends on traditional clinicopathologic factors.

Factors associated with late risks of breast cancer-specific mortality in the SEER registry.

PURPOSE: Most reports describing the risk of late relapse in breast cancer (BC) have been based on selected patients enrolled into clinical trials. We examined population-based long-term risks of BC-specific mortality (BCSM), the risks of BCSM conditional on having survived 5 years, and factors associated with late BCSM. METHODS: Using SEER, we identified women diagnosed with BC (T1-T2, N0-N2, M0) between 1990 and 2005 with known hormone receptor (HR) status. Kaplan-Meier analyses determined cumulative risks of BCSM. We performed Fine and Gray regression stratified by HR status. RESULTS: We included 202,080 patients (median follow-up of 14.17 years). Of all BC deaths, the proportion that occurred after 5 years was 65% for HR-positive vs 28% for HR-negative (p < 0.001) BC. In HR-positive BC, the cumulative risks of BCSM during years 5-20 were 9.9%, 21.9%, and 38% for N0, N1, and N2 disease. For HR-negative BC, the risks were 7.9%, 12.2%, and 19.9%, respectively. For T1a/b, N0, HR-positive BC, the risk of BCSM was 6 times lower than the risk of non-BCSM. In N2, HR-positive BC, the risk of BCSM was 43% higher than the risk of non-BCSM. In adjusted Fine and Gray models stratified by HR status, the risks of BCSM conditional on having survived 5 years for both HR-positive and HR-negative depended on T-N status, age, and year of diagnosis. In HR-positive, the risks also depended on race and grade. CONCLUSION: The risks of BCSM beyond 5 years, although different, remain important for both HR-positive and HR-negative BC. Strategies to prevent early and late recurrences are warranted.

Defibrotide in hematopoietic stem cell transplantation: A multicenter survey study of the Spanish Hematopoietic Stem Cell Transplantation Group (GETH).

BACKGROUND: Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT. METHODS: This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON). RESULTS: Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%). CONCLUSIONS: Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

Assessment of the association between cytomegalovirus DNAemia and subsequent acute graft-versus-host disease in allogeneic peripheral blood stem cell transplantation: A multicenter study from the Spanish hematopoietic transplantation and cell therapy group.

The potential role of active CMV infection in promoting acute Graft-versus-Host Disease (aGvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. We further addressed this issue conducting a retrospective, observational, multicenter study of 632 patients subjected to allogeneic peripheral blood HSCT at 20 Spanish centers. Monitoring of CMV DNA load in plasma or whole blood was performed by real-time PCR assays. Cumulative incidence of CMV DNAemia was 48.9% (95% CI, 45%-52.9%), of any grade aGvHD, 45.6; 95% (CI, 41.3%-50.1%), and of grade II-IV aGvHD, 30.7 (95% CI, 24.9%-36.4%). Overall, development of CMV DNAemia at any level resulted in an increased risk of subsequent all grade (HR, 1.38; 95% CI, 1.08 - 1.76; P = .009) or grade II-IV (HR, 1.58; 95% CI, 1.22 - 2.06; P = .001) aGvHD. The increased risk of aGvHD linked to prior occurrence of CMV DNAemia was similar to the above when only clinically significant episodes were considered for the analyses (HR for all grade aGvHD, 1.48; 95% CI, 1.13 - 1.91; P = .041, and HR for grade II-IV aGvHD, 1.53; 95% CI. 1.13-1.81; P = .04). The CMV DNA doubling time in blood was comparable overall in episodes of CMV DNAemia whether followed by aGvHD or not. Whether CMV replication is a surrogate risk marker of aGvHD or it is causally involved is an important question to be addressed in future experimental research.

Biomarkers as a Prognostic Factor in COPD Exacerbation: A Cohort Study.

The acute exacerbations of COPD (AECOPD) are one of the main causes of hospitalization and morbimortality in the adult population. There are not many tools available to predict the clinical course of these patients during exacerbations. Our goal was to estimate the clinical utility of C Reactive Protein (CRP), Mean Platelet Volume (MPV), eosinophil count and neutrophil/lymphocyte ratio (NLR) as in-hospital prognostic factors in patients with AECOPD. A prospective cohort study was conducted in patients who consulted three reference hospitals in the city of Medellín for AECOPD and who required hospitalization between 2017 and 2020. A multivariate analysis was performed to estimate the effect of biomarkers in the two primary outcomes: the composite outcome of in-hospital death and/or admission to the ICU and hospital length-of-stay. A total of 610 patients with a median age of 74 years were included; 15% were admitted to the ICU and 3.9% died in the hospital. In the multivariate analysis adjusted for confounding variables, the only marker significantly associated with the risk of dying or being admitted to the ICU was the NLR > 5 (OR: 3; CI95%: 1.5; 6). Similarly, the NLR > 5 was also associated to a lower probability of being discharged alive from the institution (SHR: 0.73; CI95%: 0.57; 0.94) and, therefore, a longer hospital stay. It was found that a neutrophil/lymphocyte ratio greater than 5 is a strong predictor of mortality or ICU admissions and a longer hospital stay in patients hospitalized with AECOPD.

Predicting Survival after Allogeneic Hematopoietic Cell Transplantation in Myelofibrosis: Performance of the Myelofibrosis Transplant Scoring System (MTSS) and Development of a New Prognostic Model.

Accurate prognostic tools are crucial to assess the risk/benefit ratio of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with myelofibrosis (MF). We aimed to evaluate the performance of the Myelofibrosis Transplant Scoring System (MTSS) and identify risk factors for survival in a multicenter series of 197 patients with MF undergoing allo-HCT. After a median follow-up of 3.1 years, 47% of patients had died, and the estimated 5-year survival rate was 51%. Projected 5-year risk of nonrelapse mortality and relapse incidence was 30% and 20%, respectively. Factors independently associated with increased mortality were a hematopoietic cell transplantation-specific comorbidity index (HCT-CI) ≥3 and receiving a graft from an HLA-mismatched unrelated donor or cord blood, whereas post-transplant cyclophosphamide (PT-Cy) was associated with improved survival. Donor type was the only parameter included in the MTSS model with independent prognostic value for survival. According to the MTSS, 3-year survival was 62%, 66%, 37%, and 17% for low-, intermediate-, high-, and very high-risk groups, respectively. By pooling together the low- and intermediate-risk groups, as well as the high- and very high-risk groups, we pinpointed 2 categories: standard risk and high risk (25% of the series). Three-year survival was 62% in standard-risk and 25% in high-risk categories (P < .001). We derived a risk score based on the 3 independent risk factors for survival in our series (donor type, HCT-CI, and PT-Cy). The corresponding 5-year survival for the low-, intermediate-, and high-risk categories was 79%, 55%, and 32%, respectively (P < .001). In conclusion, the MTSS model failed to clearly delineate 4 prognostic groups in our series but may still be useful to identify a subset of patients with poor outcome. We provide a simple prognostic scoring system for risk/benefit considerations before transplantation in patients with MF.

PD-1 genotype of the donor is associated with acute graft-versus-host disease after HLA-identical sibling donor stem cell transplantation.

Programmed death 1 (PD-1) activation triggers an immune checkpoint resulting in inhibition of T cells that leads to peripheral tolerance. Some PD-1 polymorphisms have been described and associated with the development of autoimmune diseases or cancer predisposition, but there are few data concerning the relevance of such polymorphisms on the clinical outcome after allogeneic hematopoietic stem cell transplant (alloHSCT). We analyzed the distribution of the SNPs PD-1.1G/A (rs36084323) and PD-1.3G/A (rs11568821) genotypes of the donor in a cohort of 1485 alloHSCT from HLA-identical sibling donors. We found an increased risk of grades II to IV graft-versus-host disease (GvHD) in patients receiving grafts from donors homozygous for the G allele at the rs36084323 SNP (P = 0.033; hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.1 to 4.8) and also from donors homozygous for the A allele at the rs11568821 position (P < 0.001; HR 4.5, 95%CI 2.0 to 10.1). In contrast, the PD-1 genotype of the donor did not show association with overall survival or relapse incidence. These results suggest that the PD-1 genotype of the donor plays an important role for the development of acute GvHD after alloHSCT from HLA-identical sibling donors.

First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001-2012.

The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti-thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n = 492), or between 2009 and 2012 (n = 463). The median age of the patients was 21 years (range 1-84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (P = .007).The actuarial 10-year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders (P < .0001). The 10-year survival of nonresponders at 6 months, undergoing a subsequent transplant (n = 110), was 64%, vs 60% for patient not transplantated (n = 266) (P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis-treament and severity of the disease, remain strong predictors of response and survival.

Donor CTLA-4 Genotype Modulates the Immune Response to Minor Histocompatibility Antigen Mismatches.

Minor histocompatibility antigen (miHA) mismatches have been related to graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, but this association remains controversial due to the lack of consistency in the results obtained by different groups. The CTLA-4 genotype of the donor has been reported to be relevant in the appearance of acute GVHD. We explored the effect of the donor's CTLA-4 genotype in the incidence of acute GVHD associated with HA-1, HA-8, or H-Y miHA mismatches in a large cohort of 1295 patients receiving an allogeneic transplant from an HLA-identical sibling donor. The incidence of acute GVHD was higher if the donor and recipient were mismatched for HA-1, HA-8, or H-Y, but only when the donor had the CTLA-4 rs231775 AA genotype (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.27 to 3.75; P = .005; HR, 2.11, 95% CI, 1.06 to 4.18; P = .033; and HR, 1.50; 95% CI, 1.05 to 2.15; P = .025, respectively). In contrast, this increased risk of developing acute GVHD was not found when the donor presented the CTLA-4 rs231775 AG or GG genotypes. We conclude that the immune response to specific miHA mismatches is modulated by the CTLA-4 genotype of the donor.

Autologous Stem Cell Transplantation for Follicular Lymphoma: Favorable Long-Term Survival Irrespective of Pretransplantation Rituximab Exposure.

High-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) has contributed to modify the natural history of follicular lymphoma (FL); however, an overall survival (OS) benefit has been demonstrated at relapse only after a rituximab-free chemotherapy regimen. A total of 655 patients with FL were reported to the Spanish GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) registry and underwent first ASCT between 1989 and 2007. A total of 203 patients underwent ASCT in first complete response (CR1), 174 in second complete response (CR2), 28 in third complete response (CR3), 140 in first partial response (PR1), 81 in subsequent PR, and 29 with resistant/refractory disease; 184 patients received rituximab before ASCT. With a median follow-up of 12 years from ASCT, median progression-free survival (PFS) and overall survival (OS) were 9.7 and 21.3 years, respectively. Actuarial 12-year PFS and OS were 63% (95% confidence interval [CI], 58%-68%) and 73% (95% CI, 68%-78%), respectively, for patients in CR (with a plateau in the curve beyond 15.9 years), 25% (95% CI, 19%-28%) and 49% (95% CI 42%-56%), respectively, for patients in PR, and 23% (95% CI, 8%-48%) and 28% (95% CI, 9%-45%), respectively, for patients with resistant/refractory disease (P < .001). In patients who received rituximab before ASCT, the estimated 9-year PFS and OS from ASCT were 59.5% (95% CI, 51%-67%) and 75% (95% CI, 68%-83%), respectively. Interestingly, for patients who underwent transplantation in CR ≥2 or PR ≥2 who had received rituximab before ASCT (n = 90), 9-year PFS and OS were 61% (95% CI, 51%-73%) and 75% (95% CI, 65%-80%), respectively, with no relapses occurring beyond 5.1 years after ASCT. The cumulative incidence of second malignancies in the global series was 6.7% at 5 years and 12.8% at 10 years. This analysis strongly suggests that ASCT is a potentially curative option for eligible patients with FL. In the setting of relapse, it is of especial interest in pretransplantation rituximab-sensitive patients with FL.

Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis.

PURPOSE: To analyze the prognostic influence of metastatic pattern (MP) compared with other biologic and clinical factors in stage IV breast cancer at initial diagnosis (BCID) and evaluate factors associated with specific sites of metastases (SSM). METHODS: We evaluated women with stage IV BCID with known metastatic sites, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2013. MP was categorized as bone-only, visceral, bone and visceral (BV), and other. Univariate and multivariate analyses determined the effects of each variable on overall survival (OS). Logistic regression examined factors associated with SSM. RESULTS: We included 9143 patients. Bone represented 37.5% of patients, visceral 21.9%, BV 28.8%, and other 11.9%. Median OS by MP was as follows: bone 38 months, visceral 21 months, BV 19 months, and other 33 months (P < 0.0001). Univariate analysis showed that higher number of metastatic sites had worse prognosis. In multivariate analysis, older age (hazard ratio 1.9), black race (hazard ratio 1.17), grade 3/4 tumors (hazard ratio 1.6), triple-negative (hazard ratio 2.24), BV MP (hazard ratio 2.07), and unmarried patients (hazard ratio 1.25) had significantly shorter OS. As compared with HR+/HER2- tumors, triple-negative and HR-/HER2+ had higher odds of brain, liver, lung, and other metastases. HR+/HER2+ had higher odds of liver metastases. All three subtypes had lower odds of bone metastases. CONCLUSIONS: There were substantial differences in OS according to MP. Tumor subtypes have a clear influence among other factors on SSM. We identified several prognostic factors that could guide therapy selection in treatment naïve patients.

Modified lateral tarsal strip for involutional entropion and ectropion surgery.

PURPOSE: Our purpose was to assess our outcomes in involutional lower eyelid ectropion and entropion surgery after horizontal eyelid tightening by a modified tarsal strip technique. METHODS: A prospective study of 88 eyelids with ectropion and 96 with entropion was performed. Patients were randomly distributed into two groups: the control group included 90 eyelids (46 entropion and 44 ectropion) and the other group of 94 eyelids (50 entropion and 44 ectropion). The control group was treated with a conventional tarsal strip, whereas the second group underwent the same surgery except for a modified suture placement of the tarsal strip different in patients with ectropion and entropion. The mean follow-up was 5.4 years. Horizontal eyelid laxity, orbicularis muscle and lower eyelid retractors function were measured prior and after surgery. Recurrence rate was also evaluated. RESULTS: Recurrent entropion occurred in eight eyelids (17.4 %) treated with conventional tarsal strip, while only two eyelids (4 %) showed recurrence after surgery in the group treated with the modified technique. Recurrence ectropion was only found in one eyelid (2.3 %) in the control group. Pathological horizontal laxity was present in all patients at the baseline study. After surgery, the horizontal laxity improved in both groups, we found significant differences in the patients treated with the modified technique (P=0.04). CONCLUSIONS: The modified suture placement of the tarsal strip reported in this work improves the lower eyelid stability and prevents future recurrences after surgery. This modified technique is useful for the management of patients with entropion and moderate eyelid dysfunction retractors without other surgical procedures.

Attenuation of the physiological response to infection on adults over 65 years old admitted to the emergency room (ER).

It has been considered that the elderly have clinical manifestations different from the ones observed in middle-age adults during an injury event. This hypothesis has not been extensively explored in sepsis and bacterial infections. Secondary analysis of two prospective studies including 2611 patients over 18 years of age admitted to the emergency room with confirmed or probable bacterial infections and sepsis. The outcome measures were heart rate, respiratory rate, systolic blood pressure, temperature, Glasgow Coma Scale, creatinine, PaO2/FiO2 and platelets daily during the first week. Compared to survivors younger than 65, the deceased under 65 had an average heart rate of 12.5 beats per minute per day higher (95% CI 9.32; 15.61), while patients over 65 who died barely had an average 5.7 beats per minute per day higher than the same reference group (95% CI 3.45; 8.06). The systolic blood pressure had a significant decreased in those who died younger than 65, compared to survivors with the same age, in both cohorts (-5.2 mmHg, 95% CI -8.17; -2.23 and -8.5 mmHg, 95% CI -13.48; -3.54, respectively), while those older than 65 who died had a nonsignificant increase (+1.6 mmHg, 95% CI -1.33; 4.62 and +0.1, 95% CI -6.48; 6.72, respectively) compared to the same reference group. The behavior of most clinical and laboratory variables suggests a less pronounced response of subjects above 65 years of age who died 28 days after being diagnosed with sepsis.