Geriatric assessment in hematology scale predicts treatment tolerability in older patients diagnosed with hematological malignancies: The RETROGAH study.

INTRODUCTION: The GAH (Geriatric Assessment in Hematology) scale is a psychometrically valid tool aimed at identifying older patients with hematological malignancies at higher risk of treatment-related toxicity. Our objective in this study was to determine the weights for each dimension of the GAH scale and the cut-off point to reliably predict treatment tolerability in this population, estimated by a weighted receiver operating characteristic (ROC) analysis and quantified by the area under the curve (AUC). MATERIAL AND METHODS: The RETROGAH was a retrospective cohort study including 126 patients who had previously participated in the GAH study. Patients were ≥ 65 years old with newly diagnosed myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), multiple myeloma (MM), or chronic lymphoid leukemia (CLL) and treated with standard front-line therapy within three months after having completed the GAH scale. RESULTS: The optimal cut-off value of the GAH total score to discriminate patients at higher risk of treatment toxicity was 42, with 68.5% sensitivity and 55.8% specificity. Using this value, 66.1% of patients evaluated were found to develop some type of toxicity. The AUC was 0.6259 (95% CI: 0.512-0.739; p = 0.035). DISCUSSION: The GAH scale not only would enable clinicians to individualize therapy based on individual risk of toxicity but also discriminate patients that will benefit most from intensive treatments from those requiring an adapted approach. While futures studies in clinical practice may improve the model and overcome its limitations, the GAH scale should not be used alone when making treatment decisions.

Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure without the need for immunotherapy.

OBJECTIVE/BACKGROUND: Patients with follicular lymphoma (FL) with early therapy failure (ETF) within 2 years of frontline therapy have poor overall survival (OS). We recently reported the results of autologous stem cell transplantation (ASCT) in patients from the Grupo Español de Linfomas y Trasplantes de Médula Ósea (GELTAMO) registry treated with rituximab prior to ASCT and with ETF after first-line immunochemotherapy, leading to 81% 5-year OS since ASCT. We explored whether ASCT is also an effective option in the pre-rituximab era-that is, in patients treated in induction and rescued only with chemotherapy. METHODS: ETF was defined as relapse/progression within 2 years of starting first-line therapy. We identified two groups: the ETF cohort (n = 87) and the non-ETF cohort (n = 47 patients receiving ASCT but not experiencing ETF following first-line therapy). RESULTS: There was a significant difference in 5-year progression-free survival between the ETF and non-ETF cohorts (43% vs. 57%, respectively; p = .048). Nevertheless, in patients with ETF with an interval from first relapse after primary treatment to ASCT of <1 year, no differences were observed in 5-year progression-free survival (48% vs. 66%, respectively; p = .44) or in 5-year OS (69% vs. 77%, p = .4). Patients in the ETF cohort transplanted in complete remission showed a plateau in the OS curves, at 56%, beyond 13.7 years of follow-up. CONCLUSION: ASCT may be a curative option for ETF in patients who respond to rescue chemotherapy, without the need for immunotherapy or other therapies, and should be considered as an early consolidation, especially in patients with difficult access to rituximab.

Progression-free survival at 2 years post-autologous transplant: a surrogate end point for overall survival in follicular lymphoma.

Overall survival (OS) is the gold-standard end point for studies evaluating autologous stem cell transplantation (ASCT) in follicular lymphoma (FL), but assessment may be elusive due to the lengthy disease course. We analyzed the validity of two earlier end points, proposed in the setting of first-line chemo-/immunotherapy, as surrogates for OS-progression-free survival (PFS) status at 24 months (PFS24) and complete response at 30 months (CR30) post-ASCT. We also have investigated the clinical features of patients with early progression after ASCT. Data were available for 626 chemosensitive FL patients who received ASCT between 1989 and 2007. Median follow-up was 12.2 years from ASCT. In the PFS24 analysis, 153 (24%) patients progressed within 24 months and 447 were alive and progression-free at 24 months post-ASCT (26 who died without disease progressions within 24 months were excluded). Early progression was associated with shorter OS (hazard ratio [HR], 6.8; P = 0.00001). In the subgroup of patients who received an ASCT in the setting or relapse after being exposed to rituximab, the HR was 11.3 (95% CI, 3.9-30.2; P < 0.00001). In the CR30 analysis, 183 of 596 (31%) response-evaluable patients progressed/died with 30 months post-ASCT. The absence of CR30 was associated with shorter OS (HR, 7.8; P < 0.00001), including in patients with prior rituximab (HR, 8.2). PFS24 and CR30 post-ASCT are associated with poor outcomes and should be primary end points. Further research is needed to identify this population to be offered alternative treatments.

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.

PINK1-linked parkinsonism is associated with Lewy body pathology.

Phosphatase and tensin homolog-induced putative kinase 1 gene mutations have been associated with autosomal recessive early-onset Parkinson's disease. To date, no neuropathological reports have been published from patients with Parkinson's disease with both phosphatase and tensin homolog-induced putative kinase 1 gene copies mutated. We analysed the coding region of phosphatase and tensin homolog-induced putative kinase 1 gene in a large Spanish family with six members with parkinsonism. The phenotype was characterized by an early-onset (mean: 31.6, standard deviation: 9.6 years, range: 14-45 years), slowly progressive levodopa-responsive parkinsonism, initial gait impairment and psychiatric symptoms. We identified two segregating pathogenic phosphatase and tensin homolog-induced putative kinase 1 mutations that were either in homozygous or heterozygous compound state in all affected family members. We found an exon 7 deletion (g.16089_16383del293; c.1252_1488del) and a novel+1U1-dependent 5' splice-site mutation in exon 7 (g.16378G>A; c.1488+1G>A). Leukocyte-derived messenger RNA analysis showed that both mutations caused exon 7 skipping and c.1488+1G>A also lead to an in-frame transcript with a 33 base-pair deletion (p.L485_R497del) resulting from activation of a 5' cryptic exon 7 splice site. Single photon emission computed tomography quantification of striatal dopamine transporter binding (123I-Ioflupane) revealed a posterior-anterior gradient similar to that of idiopathic Parkinson's disease, but there was no correlation between striatal reduced uptake and disease duration. Post-mortem neuropathological examination of an early-onset Parkinson's disease carrier of two heterozygous compound phosphatase and tensin homolog-induced putative kinase 1 mutations showed neuronal loss in the substantia nigra pars compacta, Lewy bodies and aberrant neurites in the reticular nuclei of the brainstem, substantia nigra pars compacta and Meynert nucleus, but the locus ceruleus and the amygdala were spared. This is the first neuropathological report of the brain from an early-onset phosphatase and tensin homolog-induced putative kinase 1-linked parkinsonism showing that mutated phosphatase and tensin homolog-induced putative kinase 1 protein induces Lewy body pathology. Unbalanced preservation of the locus ceruleus may well play a role in the slow evolution of motor symptoms and, probably, in the psychiatric symptoms often encountered in Parkinson's disease associated with phosphatase and tensin homolog-induced putative kinase 1 mutation.

Prevalence and correlates of hepatitis C virus infection among street-recruited injection drug users in San Juan, Puerto Rico.

Throughout the world, injection drug users (IDUs) are the group at highest risk for hepatitis C virus (HCV) infection. IDUs residing in the island of Puerto Rico and Puerto Rican IDUs residing in the U.S. mainland have been shown to be at very high risk of infection with HIV. However, the extent to which HCV infection has spread among IDUs in Puerto Rico is not yet known. The aims of this study were to estimate seroprevalence of HCV and to identify the correlates associated with HCV transmission. The sample was drawn through street outreach strategies and was comprised of 400 injection drug users not in treatment, living in the San Juan metropolitan area. HCV and HIV infection were detected by enzyme-linked immunosorbent assay and the results were confirmed by Western blot. Information on sociodemographics, drug use patterns, and risk behaviors was obtained through structured interviews. Bivariate analyses and multivariate logistic regression were used to assess covariates of infection with HCV. The prevalence of HCV infection was 89%. After controlling for sociodemographic characteristics, HCV infection was positively associated with increasing years of injection, injecting in a shooting gallery, tattooing in prison, and self-reported STD infection. Notably, IDUs who had initiated drug injection within the year prior to the study interview had an HCV infection rate of 57%. This study indicates that more aggressive educational programs are urgently needed to reduce the spread of HCV infection among IDUs in Puerto Rico.

Drug treatment disparities among Hispanic drug-using women in Puerto Rico and New York City.

This paper reports findings on 334 out-of-treatment drug users in Puerto Rico and 617 in New York City, at the 6-month follow-up interview of a Longitudinal Survey. Main outcomes were health care and drug treatment utilization since baseline, assessed by asking participants if they had received physical or mental health services (including HIV medications), and if they had been in methadone maintenance, inpatient or outpatient drug treatment, or drug treatment while incarcerated. Chi-square tests were used to evaluate associations between gender and the various correlates. Logistic regression was used to calculate the contribution of each variable in predicting use of drug treatment. The analysis suggests that women in both sites were likely to suffer from disparities in both health care and drug treatment utilization when compared with men, albeit women in New York utilized more drug treatment resources and were more embedded in the immediate family than their female peers in Puerto Rico. Further research to specify the impact of contextual factors at the organizational and community levels, among members of the same ethnic group residing in different sites, may prove valuable in identifying the health needs and the factors that impede or facilitate drug-using women in obtaining the most appropriate treatment. Findings from these studies can help in developing appropriate public health policy and science-based drug treatment programs to eliminate disparities such as the ones detected in this study.

[Primary cutaneous diffuse large B-cell lymphoma of the leg according to the new WHO-EORTC classification. Two cases]. / Linfoma primario cutáneo B de célula grande difuso tipo piernas según la nueva clasificación de la OMS-EORTC. Dos casos.

Primary cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders characterized by skin involvement with no evidence of systemic disease at the time of diagnosis. Their clinical behavior is generally indolent, and only occasionally is the development of extracutaneous disease observed. Since the 1980s, primary cutaneous B-cell lymphomas have been considered a specific group of lymphomas, differentiated from both T-cell lymphomas and from secondary cutaneous B-cell lymphomas. Both the EORTC and the WHO have proposed alternative classifications for these entities, with significant discrepancies that were finally resolved through the development of a new classification (WHO-EORTC classification for cutaneous lymphomas), which standardizes criteria that had previously been different. We present two new cases of primary cutaneous diffuse large B-cell lymphoma of the leg according to the new classification.

Biofilm: the microbial "bunker" for intravascular catheter-related infection.

Catheter-related infection in cancer patients remains an important health-care problem with major financial implications. During the last few years a better understanding of the pathogenesis of catheter-related infections and the interaction between microorganisms and catheter surfaces has emerged. Recently the influence of biofilm formation in catheter-related infections has been established. The development of biofilm by the colonizing microbes permits attachment of the organisms to the vascular access device and confers resistance to antibiotics and host defense mechanisms. Strategies to overcome the development of biofilm are being developed to prevent catheter- and other medical device-related infections.

AIDS risk behavior patterns among intravenous drug users in Puerto Rico and the United States

En este análisis se entrevistaron y analizaron 385 usuários de droga intravenosas reclutados en varios vecindarios del área metropolitana de San Juan. Los usuarios de drogas intravenosas (UDI), independientemente de raza, grupo étnico o medio ambiente geográfico, continúan practicando conductas de riesgo para el contagio del virus de inmuodeficiencia humana (VIH). En general los UDI incluídos en este análisis son jóvenes. Sin embargo, se encontró que los grupos de puertorriqueños e hispanos tenían un nivel de escolaridad menor al de los blancos y negros de los Estados Unidos. El hecho de que casi la mitad de los UDI puertorriqueños reidiendo en los Estados Unidos Continentales reportaran actividades ilegales como fuente de ingreso, sorprendió a los investigadores. Tal y como fuera hipotetizado, casi la mitad de los UDI puertorriqueños en la isla informaron vivir con sus padres. Los UDI en la isla de Puerto Rico continúan practicando conductas de riesgo, se inyectan drogas y utilizan los "hospitalillos" con más frecuencia y son menos propensos a desinfectar las agujas y a utilizar condone que los UDI puertorriqueños, blancos y los negros que residen en los Estados Unidos. Los UDI son el grupo de mayor riesgo para el contagio del síndrome de inmunodeficiencia adquirida (SIDA) entre los puertorriqueños que residen en Puerto Rico y en Estados Unidos. Los UDI son también el grupo con mayor riesgo de contagio heterosexual y la mayor fuente de contagio perinatal de la enfermedad. Por lo tanto, los recursos para prevenir el SIDA en Puerto Rico son más necesarios entre los UDI, donde el 44.5% de los sujetos han obtenido resultados positivos en la prueba del VIH