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Biomedical subjects

A León

Publications and source records attributed to A León.

At least 37 records · Page 2Linked to original sources
PubMed2002

Low transplant-related mortality after second allogeneic peripheral blood stem cell transplant with reduced-intensity conditioning in adult patients who have failed a prior autologous transplant.

Standard allogeneic stem cell transplantation (SCT) has been associated with a high transplant-related mortality (TRM) in patients who have failed a prior autologous SCT (ASCT). Reduced-intensity conditioning (RIC) regimens may reduce the toxicities and TRM of traditional myeloablative transplants. We report 46 adults who received a RIC peripheral blood SCT from an HLA-identical sibling in two multicenter prospective studies. The median interval between ASCT and allograft was 16 months, and the patients were allografted due to disease progression (n = 43) and/or secondary myelodysplasia (n = 4). Conditioning regimens consisted of fludarabine plus melphalan (n = 41) or busulphan (n = 5). The 100-day incidence of grade II-IV acute graft-versus-host disease (GVHD) was 42% (24% grade III-IV), and 10/30 evaluable patients developed chronic extensive GVHD. Early complete donor chimerism in bone marrow and peripheral blood was observed in 35/42 (83%) patients, and 16 evaluable patients had complete chimerism 1 year post transplant. With a median follow-up of 358 days (450 in 29 survivors), the 1-year incidence of TRM was 24%, and the 1-year overall (OS) and progression-free survival were 63% and 57%, respectively. Patients who had chemorefractory/ progressive disease, a low performance status or received GVHD prophylaxis with cyclosporine A alone (n = 32) had a 1-year TRM of 35% and an OS of 46%, while patients who had none of these characteristics (n = 32) had a 1-year TRM of 35% and an OS of 46% while patients who had none of these characteristics (n = 14) had a TRM of 0% and an OS of 100%. Our results suggest that adult patients who fail a prior ASCT can be salvaged with a RIC allogeneic PBSCT with a low risk of TRM, although patient selection has a profound influence on early outcome.

Adult↗
PubMed2002

Toxicity of a GM3 cancer vaccine in Macaca fascicularis monkey: a 12-month study.

GM3 is a ganglioside that has been biochemically identified as dominating the cell surface of several human tumours, but is also found on human normal cells at much lower density. Since GM3 is widely distributed in essentially all types of animal cells, there is a conflict with the concepts of tumour-associated antigen, immunogen, and toxicity. We have designed a GM3-based cancer vaccine for the treatment of human breast and melanoma tumours. Prior to the Phase I clinical trial, we carried out a 12-month dose repeated toxicity study in five male Macaca fascicularis monkeys. Four male monkeys were treated with placebo in a similar way. During the study, no differences were observed between control and treated monkeys related to daily clinical observations (other than local damage) including rectal temperature, blood pressure, respiratory and cardiac rates, weight gain, biochemical and hematological parameters (with the exception of transitory pathological changes), and anti-DNA and anti-nuclear antibodies, although treated monkeys consistently developed both IgM- and IgG-specific anti-GM3 antibodies. Sixty per cent of treated monkeys developed moderate local reactions at the injection site, which disappeared without sequels. We concluded that this GM3 cancer vaccine overcame in monkeys the natural tolerance to GM3 ganglioside evidenced by a strong immune response, while the local reactions elicited-were transitory without apparent important systemic toxicity effects.

Adjuvants, Immunologic↗
PubMed2001

Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group.

PURPOSE: To analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin's disease (HD) undergoing autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: Detailed records from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis. Most patients received high-dose chemotherapy without radiation for conditioning (n = 443). The graft consisted of bone marrow (n = 244) or peripheral blood (n = 250). RESULTS: The 100-day mortality rate was 9%. The 5-year actuarial TTF and OS rates were 45.0% (95% confidence interval [CI], 39.5% to 50.5%) and 54.5% (95% CI, 48.4% to 60.6%), respectively. In multivariate analysis, the presence of active disease at transplantation, transplantation before 1992, and two or more lines of therapy before transplantation were adverse prognostic factors for outcome. Sixteen patients developed a secondary malignancy (5-year cumulative incidence of 4.3%) after transplantation. Adjuvant radiotherapy before transplantation, the use of total-body irradiation (TBI) in the conditioning regimen, and age > or = 40 years were found to be predictive factors for the development of second cancers after ASCT. CONCLUSION: ASCT achieves long-term disease-free survival in HD patients. Disease status before ASCT is the most important prognostic factor for final outcome; thus, transplantation should be considered in early stages of the disease. TBI must be avoided in the conditioning regimen because of a significantly higher rate of late complications, including secondary malignancies.

Adolescent↗
PubMed2001

Study of binding and neutralising antibodies to interferon-beta in two groups of relapsing-remitting multiple sclerosis patients.

Interferon (IFN)-beta is generally considered an effective treatment for multiple sclerosis (MS); however, some patients do not respond to this therapy, possibly due to the production of neutralising antibodies (NAB) which can prevent the biological effect of IFN-beta. We compared the two types of IFN-beta, the glycosylated IFN-beta1a and the non-glycosylated IFN-beta1b, as their chemical differences may entail differing immunogenic capacities. We studied 22 relapsing-remitting MS patients treated with IFN-beta1a and 31 treated with IFN-beta1b for 1 year, using the same assay and criteria, to compare the two types of IFN-beta in their ability to induce binding and neutralising antibodies and examined the correlation of the findings with the clinical data. Binding antibodies to IFN-beta1a and IFN-beta1b were determined by enzyme-linked immunosorbent assay. A bioassay was used to detect and quantify the NABs to IFN-beta, measuring the capacity of NABs to block the antiviral resistance induced by IFNs. Binding antibodies were found in 32 % of those treated with IFN-beta1a and in 52 % of those treated with IFN-beta1b; NABs were found in 14% and 24 %, respectively. Both groups showed a significant decrease in relapse rate during the first year of treatment. These results demonstrate that the IFN-beta1b molecule is more immunogenic than the IFN-beta1a molecule. This may be due to the non-glycosylated, chemical structure of the former, which can produce aggregates and enhance antibody production. No association was found between the presence of NABs and the clinical status of the patients.

Adult↗
PubMed2001

Autologous stem cell transplantation for clinically aggressive non-Hodgkin's lymphoma: the role of preparative regimens.

We investigated the impact of the most commonly used preparative regimens on the outcome of 395 patients with diffuse large cell lymphoma (DLCL), consecutively reported to the registry of the Spanish GEL/TAMO. Among them, 139 (35%) were autografted in 1st CR, 86 (22%) in 2nd/3rd CR, 124 (31%) had chemosensitive disease and 46 (12%) had chemoresistant disease. Conditioning consisted of chemotherapy-only in 348 patients (BEAM, 164; BEAC, 145; and CBV, 39) and radiochemotherapy with CY and TBI in 47. Median times to granulocyte, platelet recovery and to discharge were significantly shorter in the chemotherapy-only group. Early transplant-related mortality was significantly higher when using CY-TBI. After a median follow-up of 28 months, overall survival (OS) at 8 years of patients conditioned with BEAM or BEAC (58% (95% CI 50-66%)) was more favorable than with CBV (40% (95% CI 24-56%)), and significantly better than with CY-TBI (31% (95% CI 18-44%)). Multivariate analysis revealed that patients conditioned with chemotherapy-only regimens had improved OS, disease-free (DFS) and relapse-free survival (RFS) when compared to those conditioned with CY-TBI. Status at transplant was also a powerful prognostic indicator. We conclude that preparative regimens consisting of chemotherapy-only seem more efficacious than CY-TBI as conditioning for DLCL, because of faster engraftment and greater anti-lymphoma effect, as indicated by improved OS, DFS and RFS.

Adolescent↗
PubMed2001

Reduced-intensity conditioning reduces the risk of severe infections after allogeneic peripheral blood stem cell transplantation.

We compared the occurrence of severe infections following 71 reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplants (PBSCT) and 123 standard myeloablative PBSCT (MINI and STAND groups, respectively) from HLA-identical siblings. The probability of 1-year infection-related mortality (IRM) was 19% in the STAND group and 10% in the MINI group (log-rank, P = 0.3). On multivariate analysis the only significant variable associated with a higher risk of IRM was the development of moderate-to-severe GVHD (P = 0.005). The probability of developing CMV infection was 39% in the STAND group and 21% in the MINI group (P = 0.03) (43% and 21%, respectively, in seropositive donor/recipient pairs, P = 0.01), and the probability of developing CMV disease was 9.5% and 1%, respectively (P = 0.05) (11% and 1%, respectively, in seropositive donor/recipient pairs, P = 0.03). Multivariate analysis of CMV infection identified four variables associated with a higher risk: CMV positive serostatus (P = 0.05), STAND transplant group (P = 0.02), the development of moderate-to-severe GVHD (P < 0.001) and a dose of CD34(+) cells infused below 6 x 10(6)/kg (P = 0.01). Invasive fungal infections and pneumonias of unknown origin did not differ between groups, and neither did other severe non-CMV viral infections and bacterial infections. Our results suggest that RIC allogeneic PBSCT may decrease the risk of dying from an opportunistic infection and reduces the occurrence of CMV infection and disease. Overall, the development of GVHD (acute or chronic) is an important risk factor for these complications. Other infections continue to pose a significant threat to recipients of RIC allografts, stressing that prophylactic and supportive measures are an important aspect in their care.

Adolescent↗
PubMed2001

Pretreatment characteristics and clinical outcome of acute promyelocytic leukaemia patients according to the PML-RAR alpha isoforms: a study of the PETHEMA group.

Of 167 newly diagnosed acute promyelocytic leukaemia patients, 83 patients were long (L)-form (50%), eight variable (V)-form (5%) and 76 short (S)-form (45%). The V-form and S-form groups presented a significantly higher percentage of patients with white blood cell counts > 10 x 10(9)/l (P < 0.05). The S-form cases displayed a significantly higher number of cases with M3v microgranular features (P = 0.005) and CD34 expression (P < 0.0001). There were no differences between the three isoforms in complete remission (CR) rate (overall CR 90%), but the 3-year disease-free survival was lower for V-form cases than it was for L- and S-form cases (62% vs. 94% and 89%, P = 0.056). We conclude that the V-form and S-form types are associated with some negative prognostic features at diagnosis. However, our data were only able to demonstrate an association with adverse prognosis in the V-form type and, moreover, as the number of cases was limited, needs to be confirmed in large, uniformly treated series.

Adolescent↗
PubMed2001

Study of radiation induced cancers in a breast screening programme.

It is demonstrated that screening mammography programmes reduce breast cancer mortality considerably. Nevertheless, radiology techniques have an intrinsic risk, the most important being the late somatic effect of the induction of cancer. This study was carried out in order to evaluate the risk to the population produced by the Comunidad Valenciana Breast Screening Programme. All the calculations are carried out for two risk models, UNSCEAR 94 and NRPB 93. On the one hand, screening series detriments are investigated as a function of doses delivered and other parameters related to population structure and X ray equipment. On the other hand the radiation induced cancer probability for a woman who starts at 45 years and remains in the programme until 65 years old is calculated as a function of mammography units' doses and average compression breast thickness. Finally, risk comparison between a screening programme starting at 45 years old and another one starting at 50 years old is made.

Aged↗
PubMed2001

[Hepatitis C virus in a group of hematological and oncohematological patients].

BACKGROUND: Little information is available in Chile about hepatitis C virus (HCV) in hematological and oncohematological patients. AIM: To evaluate the prevalence of hepatitis C virus markers in a group of hematological and oncohematological pediatric patients seen at Valdivia Regional Hospital. PATIENTS AND METHODS: Antibodies against virus C, determined by ELISA and viral RNA, determined using RT-polymerase chain reaction, were measured in 54 blood samples from children with hematological diseases (34 with Acute Lymphoblastic Leukaemia, 4 with Hodgkin Diseases, 4 with Haemolytic Anemia, 5 with Sarcomas, 2 with Non-Hodgkin Lymphoma, 2 with Thrombocytopenic Purpura, 1 with an Ependimoma, one with a Wilms Tumor and 1 with a Von Willebrand Disease). RESULTS: All samples were negative for antibodies against hepatitis C virus. Viral RNA was found in four children, all with a diagnosis of acute lymphoblastic leukemia and who received chemotherapy and multiple transfusions. CONCLUSIONS: The prevalence of Viral RNA for hepatitis C virus in oncohematological patients in our study is high and associated with the use of chemotherapy and multiple transfusions.

Adolescent↗
PubMed2001

[Acute mountain sickness at 3500 and 4250 m. A study of symptom, incidence and severity].

BACKGROUND: Acute Mountain Sickness (AMS) refers to signs and symptoms associated with hypobaric hypoxia. Its reported incidence is highly variable. AIM: To determine the incidence of AMS symptoms and severity at 3,500 and 4,250 m above sea level. SUBJECTS AND METHODS: A population of 362 soldiers without former exposure to altitude was studied. AMS symptoms, were assessed by an extensively used standard questionnaire (Lake Louise), applied 36-72 hours after exposure to high altitude. RESULTS: A group of 200 recruits ascended to Putre (3,500 m) and a second group (162) ascended to Alto Pacollo (4,250 m). The incidence of AMS was 28% and 60% respectively (p < 0.05). Headaches and sleeping difficulties were the most frequent symptoms at both altitudes. Furthermore, severe digestive problems and dizziness were described in a high proportion of individuals at both 3,500 and 4,250 m. CONCLUSIONS: The prevalence of AMS in this study is similar to that reported elsewhere at equivalent altitudes.

Acute Disease↗
PubMed2001

Gemcitabine and carboplatin for patients with advanced non-small cell lung cancer.

The survival of patients with advanced non-small cell lung cancer remains poor. Cisplatin-based chemotherapy produces a modest benefit in survival compared with that observed with best supportive care. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a novel nucleoside antimetabolite, is active and well tolerated. The combination of gemcitabine/cisplatin has shown a significant improvement in response rate and survival over cisplatin alone. Phase III trials comparing gemcitabine/cisplatin with older combinations such as cisplatin/etoposide or mitomycin/ifosfamide/cisplatin have shown a higher activity for gemcitabine/cisplatin; however, the best way to combine these drugs remains unclear. In addition, the 3-week schedule has obtained a higher dose intensity with less toxicity and similar efficacy as the 4-week schedule. The role of carboplatin in combination with new drugs is still under evaluation. Gemcitabine/carboplatin seems to be a good alternative, with the advantage of ambulatory administration and lower nonhematologic toxicity. The 4-week schedule has produced frequent grade 3/4 neutropenia and thrombocytopenia in some studies. The 3-week schedule, using gemcitabine on days 1 and 8 and carboplatin on day 1, is a convenient and well-tolerated regimen. The toxicity profile is acceptable without serious symptoms. This schedule could be considered a good option as a standard regimen. Semin Oncol 28 (suppl 10):4-9.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Familial and isolated primary hyperparathyroidism. Case report].

Familial hyperparathyroidism can be a part of a type 1 or 2 multiple endocrine neoplasia syndrome, can be associated to mandibular fibromas or can appear as an isolated disease. We report a family with 11 members affected by a primary hyperparathyroidism, all with a history of kidney stones and without evidences of other endocrine tumors. Not knowing the familial history of the disease, only one adenoma was resected in four cases and in all, the disease recidivated. Two were operated again, performing a total parathyroidectomy and heterologous autotransplantation of parathyroid tissue in the forearm. The presentation form of primary hyperparathyroidism in this family, is similar to other reported cases. It is more aggressive, is diagnosed at a lower age has a higher incidence of recurrence and multiglandular involvement than the sporadic disease.

Adult↗
PubMed2000

Synthesis and characterization of mixed-ligand oxorhenium complexes with the SNN type of ligand. Isolation of a novel ReO[SN][S][S] complex.

A new series of mixed-ligand oxorhenium complexes 4-9, with ligands 1-3 (L1H2) containing the SNN donor set and monodentate thiols as coligands (L2H), is reported. All complexes were synthesized using ReOCl3(PPh3)2 as precursor. They were isolated as crystalline products and characterized by elemental analysis and IR and NMR spectroscopy. The ligands 1 and 2 (general formula RCH2CH2NHCH2CH2SH, where R = N(C2H5)2 in 1 and pyrrolidin-1-yl in 2) act as tridentate SNN chelates to the ReO3+ core, leaving one open coordination site cis to the oxo group. The fourth coordination site is occupied by a monodentate aromatic thiol which acts as a coligand. Thus, three new "3 + 1" [SNN][S] oxorhenium complexes 4-6 (general formula ReO[RCH2CH2NCH2CH2S][SX], where R = N(C2H5)2 and X = phenyl in 4, R = N(C2H5)2 and X = p-methylphenyl in 5, and R = pyrrolidinlyl and X = p-methylphenyl in 6) were prepared in high yield. Complex 4 adopts an almost perfect square pyramidal geometry (tau = 0.07), while 6 forms a distorted square pyramidal geometry (tau = 0.24). In both complexes 4 and 6, the basal plane is formed by the SNN donor set of the tridentate ligand and the S of the monodentate thiol. On the other hand, the ligand 3, [(CH3)2CH]2NCH2CH2NHCH2CH2SH, acts as a bidentate ligand, probably due to steric hindrance, and it coordinates to the ReO3+ core through the SN atoms, leaving two open coordination sites cis to the oxo group. These two vacant positions are occupied by two molecules of the monodentate thiol coligand, producing a novel type of "2 + 1 + 1" [SN][S][S] oxorhenium mixed-ligand complexes 7-9 (general formula ReO[[(CH3)2CH]2NCH2CH2NHCH2CH2S][SX][SX], where X = phenyl in 7, p-methylphenyl in 8, and benzyl in 9). The coordination sphere about rhenium in 7 and 8 consists of the SN donor set of ligand 3, two sulfurs of the two monodentate thiols, and the doubly bonded oxygen atom in a trigonally distorted square pyramidal geometry (tau = 0.44 and 0.45 for 7 and 8, respectively). Detailed NMR assignments were determined for complexes 5 and 8.

Journal Article↗
PubMed2000

A factorial design for optimizing a flow injection analysis system.

The use of a factorial design for the response exploration of a flow injection (FI) system is described and illustrated by FI spectrophotometric determination of paraquat. Variable response (absorbance) is explored as a function of the factors flow rate and length of the reaction coil. The present study was found to be useful to detect and estimate any interaction among the factors that may affect the optimal conditions for the maximal response in the optimization of the FI system, which is not possible with a univariate design. In addition, this study showed that factorial experiments enable economy of experimentation and yield results of high precision due to the use of the whole data for calculating the effects.

Analysis of Variance↗
PubMed2000

Conditioning regimens in autologous stem cell transplantation for multiple myeloma: a comparative study of efficacy and toxicity from the Spanish Registry for Transplantation in Multiple Myeloma.

High-dose chemoradiotherapy conditioning regimens for autologous stem cell transplantation (ASCT) are generally held to give similar results in multiple myeloma (MM), but no specific comparative study has been published. We addressed this issue by comparing the main high-dose chemoradiotherapy regimens used in the Spanish Registry. Patient cohorts included 315 cases treated with 200 mg/m2 melphalan (MEL200), 127 patients with 140 mg/m2 melphalan plus total body irradiation (MEL140 + TBI) and 121 cases with 12 mg/kg busulphan plus 140 mg/m2 melphalan (BUMEL). After ASCT, granulocyte and platelet recovery time was similar in all conditioning groups. There were no differences in transplant-related mortality. All regimens yielded a similar response in reference to pre-ASCT MM status, although BUMEL produced a slightly better overall response when compared with the other regimens (97% vs. 89% and 92%, P = 0.003). The 5-year overall survival (OS) with BUMEL was 47% [95% confidence interval (CI) 26-68] compared with 43% (CI 31-54) for MEL140 + TBI and 37% (CI: 18-56) for MEL200. The median survival for the BUMEL group was 64 months compared with 45 and 37 months for the MEL200 and MEL140 + TBI groups respectively. These differences were non-significant (P = 0.2). The median event-free survival (EFS) was better for BUMEL (32 months) than for MEL200 (22 months) or for MEL140 + TBI (20 months). The differences in EFS between BUMEL and the other conditioning regimens reached statistical significance (P = 0.01). Nevertheless, the adjusted multivariate analysis for OS and EFS revealed that the conditioning regimens had no independent prognostic value. We concluded that three different conditioning regimens, commonly used for ASCT in MM, have a similar antimyeloma effect. However, the trend for better results observed in our series with BUMEL requires a prospective trial.

Busulfan↗
PubMed2000

Remission status defined by immunofixation vs. electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients.

We have retrospectively analysed 344 multiple myeloma (MM) patients (202 de novo patients) treated in a non-uniform way in whom high-dose therapy and autologous stem cell transplantation (ASCT) response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF). Patients in complete remission (CR) by EP were further subclassified as CR1 when IF was negative and CR2 when it remained positive. Partial responders (PR) were also subclassified as PR1 (very good PR, > 90% reduction in M-component) or PR2 (50-90% reduction). CR1 patients showed a significantly better event-free survival (EFS) [35% at 5 years, 95% confidence interval (CI) 17-53, median 46 months] and overall survival (OS) (72% at 5 years, CI 57-86, median not reached) compared with any other response group (univariate comparison P < 0.00000 to P = 0. 004). In contrast, comparison of CR2 with PR1 and with PR2 did not define different prognostic subgroups (median EFS 30, 30 and 26 months respectively, P = 0.6; median survival 56, 44 and 42 months respectively, P = 0.5). The non-responding patients had the worst outcome (5-year OS 8%, median 7 months). Multivariate analysis confirmed both the absence of differences among CR2, PR1 and PR2 and the highly discriminatory prognostic capacity of a three-category classification: (i) CR1 (ii) CR2 + PR1 + PR2, and (iii) non-response (EFS P < 0.00000; OS P < 0.00000; both Cox models P < 0.00000). In the logistic regression analysis, the factors significantly associated with failure to achieve CR1 were the use of two or more up-front chemotherapy lines, status of non-response pre-ASCT and inclusion of total body irradiation (TBI) in the preparative regimen. Tandem transplants or the use of multiple agents (busulphan and melphalan) in the preparative regimen resulted in a higher CR1 level; none of the biological factors explored influenced the possibility of achieving CR1. These results confirm that, in MM patients undergoing ASCT, achieving a negative IF identifies the patient subset with the best prognosis; accordingly, therapeutic strategies should be specifically designed to achieve negative IF.

Electrophoresis↗