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Biomedical subjects

J F Tomás

Publications and source records attributed to J F Tomás.

At least 19 recordsLinked to original sources
PubMed2007

Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention.

To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally, age <or=40 and male gender were favorable variables for survival, whereas molecular response predicted longer leukemia-free survival. In conclusion, early institution of salvage therapy at molecular failure, before onset of hematological relapse, is beneficial in APL. Moreover, given the poor outcome of HEMrel managed with ATRA and HDAC, use of alternative therapeutic strategies in this setting is warranted.

Adolescent↗
PubMed2005

Relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: outcome and prognostic factors: the Chronic Myeloid Leukemia Subcommittee of the GETH (Grupo Español de Trasplante Hemopoyético).

In order to analyze the outcome of patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT), we investigated data from 107 patients reported to the Spanish Registry, GETH. In all, 93 (87%) patients were treated after relapse; 36 out of 49 that failed to achieve a response received a second relapse-treatment, and seven a third one. At the last follow-up, the number of patients in molecular or cytogenetic remission was 29 and 13, respectively. Overall survival and progression-free survival after relapse were 53.6% (95% CI: 42.9--64.2) and 52% (95% CI: 41-63) at 5 years, respectively. In multivariate analysis, survival was significantly related to CML phase at relapse (cytogenetic or chronic phase vs advanced phases) and time from transplant to relapse (<1 vs >or=1 year). Patients with no adverse factors had a better survival compared with patients with one or two adverse features (65 vs 35 vs 0%, respectively). We conclude that a significant proportion of CML patients that relapse after transplantation can regain complete and long-lasting remissions with one or more salvage therapies. Disease stage at relapse and time from transplant to relapse should be taken into account when comparing results of different salvage treatments.

Adolescent↗
PubMed2005

Advantages of flow cytometry immunophenotyping for the diagnosis of central nervous system non-Hodgkin's lymphoma in AIDS patients.

BACKGROUND: Neurological disorders are common in HIV-infected patients. Central nervous system (CNS) lymphoma should always be considered because it is an important cause of morbidity and mortality. OBJECTIVES: To investigate the clinical utility of flow cytometry immunophenotyping (FCI) in diagnosing or discarding leptomeningeal involvement in HIV-infected patients and to compare its sensitivity with that of conventional cytological methods. METHODS: Fifty-six cerebrospinal fluid (CSF) samples from 29 HIV-infected patients were independently evaluated by flow cytometry and cytology. The description of an aberrant immunophenotype was the criterion used to define the malignant nature of any CSF cell population. RESULTS: FCI and cytology gave concordant results for 48 of the 56 CSF samples studied: 37 were negative for malignancy and 11 had evidence of CNS lymphoma. Discordant results were obtained for eight CSF samples, and the accuracy of the FCI findings could be demonstrated for four CSF samples described as positive for malignancy according to the FCI criteria. CONCLUSIONS: A high level of agreement was found between the results obtained using the two methods, but FCI gave at least 25% higher sensitivity than conventional cytomorphological methods for the detection of malignant cells. This advantage suggests that, in case of negative flow cytometry results, disorders other than non-Hodgkin's lymphoma should be strongly considered.

Adult↗
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↗
PubMed2001

Report of three cases of circulating heparin-like anticoagulants.

Clinically significant endogenous circulating heparin-like anticoagulant activity has been associated with hematological malignancies, liver damage, and other pathological conditions. The source of high plasma concentrations of endogenous heparin-like anticoagulants is poorly understood. We report three cases of circulating heparin-like anticoagulants in three patients with hematological malignancies: CLL, multiple myeloma, and T-prolymphocytic leukemia. The severity of bleeding in our patients ranged from severe epistaxis and deep-site hematoma to bleeding of biopsy site and occasional ecchymosis.

Aged↗
PubMed2001

Atypical chronic graft-versus-host disease following interferon therapy for chronic myeloid leukaemia relapsing after allogeneic BMT.

We report a 54-year-old woman who received interferon alpha for haematological relapse of Ph-positive CML, 7 years after allogeneic BMT from an HLA-identical brother. Eighteen months after relapse, cytogenetic and molecular remission was achieved. She received interferon therapy for 25 months and it was discontinued when she developed skin lesions on her face and trunk, dysphagia and fever with respiratory failure and bilateral patchy airspace consolidation of the lung without microbiologic findings. Histologic features showed discoid lupus erythematosis, oesophagitis with pseudomembranes and a mixed pattern of lymphocytic bronchiolitis involving the alveoli and interstitial spaces all compatible with chronic GVHD. The patient was commenced on immunosuppressive therapy with complete clinical and radiological resolution. The available evidence supports an atypical presentation of chronic GVHD and suggests a role for interferon alpha in the pathogenesis of GVHD. To the best of our knowledge, this is the first case reported of severe chronic GVHD occurring during the course of interferon therapy for relapsed CML.

Antineoplastic Agents↗
PubMed2001

Expression of factor VII in the liver of patients with liver disease: correlations with the disease severity and impairment in the hemostasis.

Factor VII (FVII) plasma levels in patients with liver disease may be below the normal range. However, no data are available on FVII expression in liver biopsies from patients with liver diseases other than cirrhosis. We have analyzed the expression of FVII by in situ hybridization in liver biopsies from 50 patients in comparison with the procoagulant activity of FVII, and with the plasma levels as activated FVII (FVIIa) and FVII antigen. The level of FVIIa was significantly lower in stage 4 liver fibrosis patients than in the remaining ones (P < 0.05). The percentage of hepatocytes expressing FVII was significantly lower in stage 4 liver fibrosis patients (4.1+/-1.3%) than in stage 3 (22.7+/-6.1%), stage 2 (31.5+/-6.1%), stage 1 (43.7+/-8.2%) and stage 0 patients (63.8+/-4.4%) (P < 0.001). These percentages correlated inversely in a statistically significant way with the histological activity index and the liver function tests. We have demonstrated that the FVIIa plasma levels in patients with chronic liver disease other than cirrhosis may be below the normal range in the absence of blood coagulation impairment. The percentage of hepatocytes expressing FVII decreases as the severity of liver damage increases.

Adult↗
PubMed2000

Long-term liver dysfunction after allogeneic bone marrow transplantation: clinical features and course in 61 patients.

This retrospective study has aimed at determining the prevalence, aetiology and clinical evolution of chronic liver disease (CLD) after allogeneic bone marrow transplantation (BMT). A total of 106 patients who had been transplanted in a single institution and who had survived for at least 2 years after BMT were studied. The prevalence of CLD was 57.5% (61/106). In 47.3% of cases more than one aetiopathogenic agent coexisted. The causes of CLD were iron overload (52.4%), chronic hepatitis C (47.5%), chronic graft-versus-host disease (C-GVHD) (37.7%), hepatitis B (6.5%), non-alcoholic steatohepatitis (NASH) (4.9%), autoimmune hepatitis (AIH) (4.9%) and unknown two (3.3%). Twenty-three patients with iron overload underwent venesections which were well tolerated. An improvement in liver function tests (LFTs) was observed in 21 (91%) patients. All six patients with siderosis as the only cause of CLD normalized LFT as well as three patients with HCV infection. Clinical evolution was satisfactory for patients with GVHD, AIH, NASH and hepatitis B. At the last visit 23 patients continued with abnormal LFTs, and 19 of them were infected by the HCV. A sustained biochemical and virologic response was achieved in only one case out of six patients with CHC who received interferon. We have found that CLD is a common complication in long-term BMT survivors. The aetiology is often multifactorial, iron overload, CHC and C-GVHD being the main causes. The CLD followed a rather 'benign' and slow course in our patients as none of them developed symptoms or signs of liver failure and we did not observe an increase in morbidity or mortality in these patients, but a longer follow-up is necessary in HCV infected patients based on the natural history of this infection in other populations.

Adolescent↗
PubMed2000

Measurement of the procoagulant activity of factor VII in patients with liver cirrhosis and normal prothrombin activity: evaluation of the bleeding risk.

Patients with liver cirrhosis and diminished prothrombin activity (PA) have decreased levels of factor (F)VII coagulation activity (FVII:C) and an increased bleeding tendency. Whether this is also true of cirrhotic patients with normal PA is unknown. This study measured FVII:C levels in such patients and investigated the correlation between altered FVII:C levels and bleeding tendency. Fifteen of 41 patients (37%) had decreased FVII:C levels. Of these, the Child-Pugh score of liver function was A (n = 9), B (n = 5) and C (n = 1), compared to A (n = 25) and B (n = 1) in patients with normal FVII:C values (chi2 = 8.88, P = 0.012). Bleeding time was significantly prolonged in 9/15 patients (60%) with impaired FVII:C activity, compared to 3/26 (12%) patients with normal FVII:C values (relative risk: 5.2, 95% CI: 1.7-16.6; P = 0.003). In conclusion, liver cirrhosis patients may show impaired FVII:C levels despite normal PA. In those with decreased FVII:C activity, prolonged bleeding time is hypothesized to arise from an alteration in platelet activation due to FVII deficiency and diminished platelet count. Bleeding risk should be evaluated, regardless of platelet count, before these patients are subjected to invasive diagnostic or surgical procedures.

Adult↗
PubMed2000

Unrelated donor bone marrow transplantation as treatment for chronic myeloid leukemia: the Spanish experience. The Chronic Myeloid Leukemia Subcommittee of the GETH. Grupo Español de Trasplante Hemopoyético.

BACKGROUND AND OBJECTIVE: To analyze the results of unrelated bone marrow transplantation (UDBMT) as treatment for chronic myeloid leukemia (CML) in Spain. DESIGN AND METHODS: Eighty-seven consecutive UDBMT performed in 9 centers between October 1989 and February 1998 were evaluated. This represents more than 95% of UDBMT for CML performed in adult transplant centers in Spain during this period. The patients' median age was 31.5 years (range, 12-49). The median interval from CML diagnosis to UDBMT was 30 months (range, 3-160). Seventy-nine percent of transplants were performed during the first chronic phase (1CP). RESULTS: Actuarial probability of survival and disease-free survival at 4 years for the whole series was 24% (95% confidence interval [CI]: 14%-34%) and 20% (CI: 10%-30%), respectively. The cumulative incidence of relapse and transplant-related mortality (TRM) was 7% (CI: 4%-10%) and 71% (CI: 60%-82%), respectively. The main causes of death were graft failure (n=7), infection (n=23), and graft-versus-host disease (GvHD) (n=25). The actuarial probability of acute GvHD grade II-IV and grade III-IV was 56% (CI:46%-66%) and 36% (CI: 26%-36%), respectively. The cumulative incidence of extensive chronic GvHD was 18% (CI: 9%-27%). Univariate analyses showed that the pre-transplant factor with the highest influence on survival was disease status at transplant (30% in 1CP vs. 0% in advanced phases; p=0.0001). Other pre-transplant factors influencing survival among patients in 1CP were: patient's age (older than 30 years 11% vs. 48%), interval diagnosis-transplantation (longer than 2 years 17% vs. 55%), donor type (HLA, B, DRB1 identical 32% vs. 25%), CMV serologic status (donor and recipient negative 63% vs. 24%), year of transplantation (before 1995 19% vs. 40%), and conditioning regimen (cyclophosphamide plus total body radiation 40% vs. 16%). The main risk factors had a cumulative effect on survival. Thus, probability of survival ranged from 66% (CI: 39%-93%) in patients in 1CP, under 40 years of age, transplanted from an HLA, A, B, DRB1 identical donor during the first two years after diagnosis, to 0% in those with three or more risk factors. INTERPRETATION AND CONCLUSIONS: This experience shows that UDBMT used to have a high TRM that has progressively decreased along the years. At the present time, the results are encouraging, particularly when UDBMT is performed under favorable conditions.

Actuarial Analysis↗
PubMed1999

Induction of hyperacute graft-vs-host disease after donor leukocyte infusions.

BACKGROUND: Infusions of leukocytes obtained from the original bone marrow donor is a new approach for treating patients who have a relapse of leukemia after allogeneic bone marrow transplantation. Up to 90% of patients who achieved remission developed graft-vs-host disease (GVHD). However, any description of the clinical and histologic features in these cases is lacking. OBSERVATIONS: We describe 2 patients in whom a severe, peculiar, hyperacute, fatal GVHD developed after treatment with donor leukocyte infusions and interferon alfa. The patients had not received any additional chemotherapy or GVHD prophylaxis. In both patients, the eruption started with the appearance of erythematous plaques at the interferon alfa injection sites, and a generalized maculopapular eruption subsequently developed. The clinical lesions evolved from acute to lichenoid within several days. The histologic examination also demonstrated unusual findings and showed features of both acute and chronic lichenoid GVHD. CONCLUSIONS: Donor leukocyte infusions without GVHD prophylaxis may provoke a severe fatal hyperacute GVHD. In the cases presented herein, we discuss the significance of the rapid clinical evolution from acute to lichenoid and the combination of histologic features of both acute and chronic GVHD in the biopsy specimens.

Acute Disease↗
PubMed1999

Identification of a novel GB type C virus/hepatitis G virus subtype in patients with hematologic malignancies.

The existence of four GB C virus/hepatitis G virus (GBV-C/HGV) subtypes has been reported. The subtype was determined in 16 multitransfused GBV-C/HGV infected patients prior to bone marrow transplantation by comparing the 5' untranslated region (5' UTR) sequence with 39 available sequences. Phylogenetic and bootstrap analyses were carried out with PHYLIP package 3.5c. In the samples with undefined subtype, the whole 5' UTR was cloned and sequenced. Comparison of distances showed that the isolates from 12/16 and 4/16 patients belonged theoretically to subtypes 2a and 2b, respectively. The phylogenetic tree and bootstrap analyses confirmed this result in only 11/16 samples. Analysis of the entire 5' UTR from the remaining five samples with undefined GBV-C/HGV subtype revealed genomic variability within the isolates from each patient and between the isolates of different patients. Evolutionary distances, phylogenetic tree, and bootstrap showed that the isolates from these samples were grouped in a separate branch, different from the published subtypes. In conclusion, a novel GBV-C/HGV subtype was found in a group of multitransfused patients with GBV-C/HGV infection.

5' Untranslated Regions↗