Effectiveness of azacitidine in unselected high-risk myelodysplastic syndromes: results from the Spanish registry.

The benefit of azacitidine treatment in survival of high-risk myelodysplastic syndromes (MDS) patients compared with conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival (OS) between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and acute myeloblastic leukemia (AML) progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8-16) months for azacitidine-treated patients and 12.2 (11-14.1) for patients under CCT (P=0.41). In a multivariate model, age, International prognostic scoring system and lactate dehydrogenase were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86-1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend toward a better survival was observed in azacitidine-treated patients (median survival 13.3 (11-18) months) compared with CCT (median survival 8.6 (5-10.4) months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory.

Results of allogeneic stem cell transplantation in the Spanish MDS registry: prognostic factors for low risk patients.

Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics.

Auditory event-related potentials in 50 melancholic patients: increased N100, N200 and P300 latencies and diminished P300 amplitude.

BACKGROUND: To investigate whether there are some differences in Event-Related Potentials (ERP) between melancholic patients and healthy controls. To establish whether there is a relationship between abnormalities of ERP and severity of depression and psychomotor retardation. METHOD: Melancholic depressed patients (N=50) and normal comparison subjects (N=31) were assessed for latencies and interlatencies of N100, N200, N400, latency and amplitude of P300. The ERPs were studied with an 'oddball paradigm' in the auditory modality. Severity of depression was measured by the Hamilton Depression Rating Scale (HDRS) and psychomotor retardation with the Depressive Retardation Rating Scale (DRRS). RESULTS: The melancholic group showed a significantly higher latency in N100 (P<0.001), N200 (P<0.001) and P300 (P<0.001) and a significantly lower P300 amplitude (P<0.001) than healthy controls. No other differences were found either in the latencies of the N400 or in their interlatencies. HDRS and DRRS do not have any significant correlations with amplitude or latency measures. LIMITATIONS: The subjects of this study are inpatients, with a severe subcategory of depression and high average age. It is difficult to generalize these findings. CONCLUSIONS: The principal finding of this study is the increase in three of the four latencies measured (N100, N200 and P300) and in the decreased P300 amplitude in melancholic patients compared to normal controls. There is no association between these abnormalities and clinical variables.

Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies.

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 x 10(7)/kg (range, 1.01 x 10(7)/kg to 4.96 x 10(7)/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 x 10(9)/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 x 10(9)/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P =.01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.

Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study.

OBJECTIVE: The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex for patients with obsessive-compulsive disorder (OCD) was studied under double-blind, placebo-controlled conditions. METHOD: Patients were randomly assigned to 18 sessions of real (N=10) or sham (N=8) rTMS. Treatments lasted 20 minutes, and the frequency was 1 Hz for both conditions, but the intensity was 110% of motor threshold for real rTMS and 20% for the sham condition. RESULTS: No significant changes in OCD were detected in either group after treatment. Two patients who received real rTMS, with checking compulsions, and one receiving sham treatment, with sexual/religious obsessions, were considered responders. CONCLUSIONS: Low-frequency rTMS of the right prefrontal cortex failed to produce significant improvement of OCD and was not significantly different from sham treatment. Further studies are indicated to assess the efficacy of rTMS in OCD and to clarify the optimal stimulation characteristics.

Donor age-related differences in PBPC mobilization with rHuG-CSF.

BACKGROUND: Data on the administration of rHuG-CSF to normal donors <18 years old are very limited. STUDY DESIGN AND METHODS: The results of rHuG-CSF administration to 61 donors <18 years old (Group A) were retrospectively evaluated and compared with results from 353 donors > or = 18 years old (Group B) who are included in the Spanish National Donor Registry. The mean age (range) in Group A and B was 14 (1-17) and 38 (18-71) years, respectively (p<0.001). The mean dose of rHuG-CSF was 10 microg per kg per day (range, 9-16) during a mean of 5 days (range, 4-6). Central venous access was placed more frequently in younger donors (25% vs. 6%; p<0.001). RESULTS: The mean number of CD34+ cells collected was 7.6 and 6.9 x 10(6) per kg of donor's body weight in Group A and B, respectively. Fifty-six percent of Group A donors needed only one apheresis to achieve > or = 4 x 10(6) CD34+ cells per kg versus 39 percent of Group B donors (p = 0.01). Side effects were more common in Group B (71% vs. 41%; p<0.001). CONCLUSION: The administration of rHuG-CSF to donors <18 years old leads to CD34+ cell mobilization in a pattern similar to that observed in adults. Greater age was associated with a more frequent requirement for more than one apheresis to achieve a similar number of CD34+ cells.

Potenciales evocados cognitivos en el trastorno obsesivo-compulsivo, trastorno depresivo mayor con melancolía y controles sanos / Event related potentials in obsessive-compulsive disorder, major depressive disorder with melancholia and healthy controls

Objetivo: Determinar la existencia de posibles diferencias en los potenciales evocados cognitivos (PPEE) entre pacientes obsesivos, melancólicos y controles. Investigar la influencia de la sintomatología depresiva comórbida sobre los PPEE en los pacientes con trastorno obsesivo-compulsivo (TOC). Métodos: Se estudian las latencias N100, N200, P300, N400 y la amplitud P300, utilizando un oddball-paradigm auditivo, en 47 obsesivos, 80 depresivos melancólicos y 88 controles. Resultados: La amplitud media de la P300 fue significativamente menor entre los melancólicos (-X = 9,6, DE = 4,2) respecto los obsesivos (-X = 14,3, DE = 6,3) y controles (-X = 17,3, DE = 4,8), manteniéndose las diferencias al controlar la edad como covariante. Al controlar la edad, los melancólicos presentaron una mayor latencia de las ondas N100, N200 y P300 respecto a obsesivos y controles. Los pacientes con TOC presentaron valores intermedios, obteniendo significaciones sólo para una mayor latencia N100 y una menor amplitud P300 respecto a los controles. Entre los obsesivos, los que presentaron puntuaciones más patológicas (y más cercanas a los melancólicos) fueron los que tenían puntuaciones más altas en el test de Hamilton de depresión, siendo este hecho independiente de la edad y del subtipo de TOC. En cambio, entre los melancólicos, la gravedad de la depresión no se relacionaba con el grado de alteración en los PPEE. Conclusiones: Este estudio apoyaría la hipótesis de que las alteraciones en los PPEE en pacientes con TOC son secundarias al nivel de depresión comórbido y no a la sintomatología obsesiva primaria. Sin embargo, estas alteraciones parecen ser cualitativamente diferentes entre pacientes obsesivos respecto a los melancólicos (AU)

Administration of recombinant human granulocyte colony-stimulating factor to normal donors: results of the Spanish National Donor Registry. Spanish Group of Allo-PBT.

A Spanish National PBPC Donor Registry has recently been established for short- and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 microg/kg/day (4-20) and 5 days (4-8), respectively. Donors underwent a median of two aphereses (range, 1-5). Adverse effects consisted mainly of bone pain (90.2%), headache (16.9%) and fever (6. 1%), but no donor discontinued rhG-CSF prematurely due to toxicity. Side-effects were more frequent in donors receiving >10 microg/kg/day than in those with lower doses (82.8% vs 61.8%; P = 0. 004). A significant decrease between baseline and post-apheresis platelet counts was the most important analytical finding (229 x 10(9)/l vs 140 x 10(9)/l; P < 0.0001), with a progressive reduction in platelet count with each apheresis procedure. One donor developed pneumothorax that required hospitalization due to central venous line placement. The mean CD34+ cell dose collected was 6.9 x 10(6)/kg (range, 1.3-36), with only 14 donors (2.9%) not achieving a minimum target of CD34+ cells of 2 x 10(6)/kg. No definitive information about potential long-term side effects is yet available. However, we hope this National Registry will serve as a useful basis for better monitoring of the efficiency and side-effects of cytokine administration in healthy people.

Tomato Mosaic Tobamovirus, Causal Agent of a Severe Disease of Pepino (Solanum muricatum).

Pepino (Solanum muricatum Aiton), a vegetatively propagated herbaceous crop from the Andes, is esteemed for its edible, juicy, and fragrant fruits. Its cultivation as a crop for diversification is increasing in many frost-free areas throughout the world (2). In 1994, a severe viruslike disease, previously undescribed, was observed on pepino plants in Valencia, Spain. The disease has continued to cause economic losses in pepino plantings in subsequent years. Symptoms, which are exacerbated at temperatures above 30°C, include dark and light green mosaic predominantly in young leaves, leaf puckering and distortion, short internodes, fruit deformation, delay in ripening, and yield reduction. Samples from affected plants were analyzed by enzyme-linked immunosorbent assay (ELISA). All samples displaying viruslike symptoms reacted positively with antiserum made against tomato mosaic tobamovirus (ToMV) but not with antisera made against alfalfa mosaic alfamovirus, cucumber mosaic cucumovirus, potato Y potyvirus, tobacco mosaic tobamovirus, tomato spotted wilt tospovirus, or tomato yellow leaf curl bigeminivirus. A leaf extract from diseased plants was heated at 72°C for 10 min. This treatment inactivates most plant viruses but does not eliminate infectivity of ToMV (1). Inoculation of a collection of pepino clones resulted in the development of symptoms in most clones. Symptomatic clones were also ELISA-positive for ToMV. A few clones showed a hypersensitive reaction, which consisted of the development of necrotic lesions in the inoculated area. New growth on these clones was asymptomatic and ELISA-negative for ToMV. These results clearly point to a causal relationship between ToMV infection and the observed disease. The initial source of the infection should be eliminated from commercial plantings, as ToMV is easily transmitted when the pepino plants are trellised and pruned. Special care must also be taken to ensure that mother plants from which cuttings are taken are free from this virus. In addition, ToMV is usually found in meristematic tissues, even after thermotherapy and chemotherapy treatments are applied, making the regeneration of virus-free plants from infected clones by meristem tip culture difficult. Therefore, it seems that the best strategy against this disease is the development of resistant cultivars. References: (1) H. Laterrot. Ann. Amélior. Plant. 23:287, 1973; (2) J. Prohens et al. Econ. Bot. 50:355, 1996.