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D Carrera

Publications and source records attributed to D Carrera.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis.

Fluorescence in situ hybridization (FISH) has become a powerful technique for prognostic assessment in multiple myeloma (MM). However, the existence of associations between cytogenetic abnormalities compels us to re-assess the value of each abnormality. A total of 260 patients with MM at the time of diagnosis, enrolled in the GEM-2000 Spanish transplant protocol, have been analyzed by FISH in order to ascertain the independent influence on myeloma prognosis of IGH translocations, as well as RB and P53 deletions. Survival analyses showed that patients with t(4;14), RB or P53 deletions had a significantly shorter survival than patients without these abnormalities. However, patients with RB deletions without other abnormalities in FISH analysis, displayed a similar outcome to those patients without genetic changes by FISH (46 vs 54 months, P=0.3). In the multivariate analysis the presence of t(4;14), RB deletion associated with other abnormalities, age >60 years, high proportion of S-phase cells and advanced stage of the disease according to the International Staging System retained their independent prognostic influence. In summary, RB deletion as a sole abnormality does not lead to a shortening in the survival of MM patients, whereas t(4;14) confers the worst prognosis in MM patients treated with high-dose chemotherapy.

Adult↗
PubMed2006

Neuropharmacological profile of an ethanol extract of Ruta chalepensis L. in mice.

The effects of an ethanol extract of the aerial parts of Ruta chalepensis on the central nervous system (CNS) and LD(50) determination were studied in mice. A crude extract was given systemically and its effects were tested on pentylenetetrazole (PTZ)-induced seizures, sodium pentobarbital-induced hypnosis, exploratory activity, anxiety and nociception. Results from the experimental models tested showed: (1) a delay in the onset of seizures and a dose-dependent suppression in the tonic phase and mortality induced by PTZ; (2) a prolongation of the time of sodium pentobarbital-induced hypnosis; (3) a significant attenuation in the anxiety-response and (4) a reduction in the licking time and shaking behavior in the formalin-induced nociception test. The sedative-hypnotic potentiation, anxiolytic, anticonvulsant and antinociceptive effects suggest that Ruta chalepensis induces a depressant activity on the CNS.

Animals↗
PubMed2005

Subdermal re-injection: a method to increase surgical detection of the sentinel node in breast cancer without increasing the false-negative rate.

PURPOSE: The aim of this study was to evaluate in breast cancer whether subdermal (SB) re-injection improves surgical detection (SD) of the sentinel node (SN) in patients with negative lymphoscintigraphy on peritumoral (PT) injection, without increasing the false-negative (FN) rate. METHODS: Group I comprised 261 patients with invasive breast cancer >3 cm and clinically negative axilla treated with primary chemotherapy. Axillary lymphadenectomy was performed in all of these patients. Group IA comprised 201 patients with PT injection, while group IB comprised 60 patients with SB injection in the tumour quadrant. Group II comprised 652 patients with breast cancer <3 cm; in 73 of these patients with negative lymphoscintigraphy, SB re-injection was performed. For lymphoscintigraphy, 37-55 MBq (99m)Tc-albumin nanocolloid in 1 ml was used for PT injection, and 18 MBq in 0.2 ml for SB injection. Five-minute images were obtained 2 h p.i. for PT injection and 20-30 min p.i. for SB injection. SD was performed 4 or 24 h p.i. Lymphoscintigraphic (LD), surgical and internal mammary (IM) detection rates were calculated. In group I, FN, negative predictive value (NPV) and accuracy (A) were calculated. Statistical analysis was performed using the chi-square test. RESULTS: In percentages, results were as follows: Group IA: SD: 84.1, FN: 13.6, NPV: 88.9, A: 78.6, IM: 14.5*. Group IB: SD: 90, FN: 0, NPV: 100, A: 90, IM: 1.7* (*p<0.025). Group II: PT injection only: LD: 82.4, SD: 94; PT injection+SB re-injection: LD: 90, SD: 98.5. SD was 97.8** in patients with positive lymphoscintigraphy and 58.5** when lymphoscintigraphy was negative (**p<0.001). CONCLUSION: For correct staging, including extra-axillary drainage, peritumoural injection should first be performed. When the SN is not visualised, and only in those cases, SB re-injection should be performed, which increases the SD rate without increasing the FN rate.

Adult↗
PubMed2005

Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse.

PURPOSE: To analyse outcome and prognostic factors for overall survival (OS) and time to treatment failure (TTF) in 357 patients with Hodgkin's lymphoma (HL) undergoing an autologous stem cell transplantation (ASCT) after a first relapse and reported to the The Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GEL/TAMO) Cooperative Group. METHODS: Two hundred and twenty males and 137 females with a median age of 29 years were autografted in second remission (n=181), first sensitive relapse (n=148) and first resistant relapse (n=28). RESULTS: Five-year actuarial TTF and OS were of 49% +/- 3% and 57% +/- 3%. Advanced stage at diagnosis, complementary radiotherapy before ASCT, a short first complete response (CR) and detectable disease at ASCT adversely influenced TTF. Year of transplant < or =1995, bulky disease at diagnosis, a short first CR, detectable disease at ASCT and > or =1 extranodal areas involved at ASCT were adverse factors for OS. CONCLUSIONS: ASCT constitutes a therapeutic option for HL patients after a first relapse. Promising results are observed in patients with low tumour burden at diagnosis, autografted after a long CR and without detectable disease at ASCT. Innovative approaches should be pursued for patients with risk factors at relapse.

Adolescent↗
PubMed2003

Autologous stem cell transplantation for primary refractory Hodgkin's disease: results and clinical variables affecting outcome.

BACKGROUND: Patients with primary refractory Hodgkin's disease (PR-HD) have a dismal prognosis when treated with conventional salvage chemotherapy. We analyzed time to treatment failure (TTF), overall survival (OS) and clinical variables influencing the outcome in patients undergoing autologous stem cell transplantation (ASCT) for PR-HD and reported to the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO). PATIENTS AND METHODS: Sixty-two patients, 41 males and 21 females with a median age of 27 years (range 13-55) were analyzed. Forty-two patients (68%) had advanced stage at diagnosis, 47 (76%) presented with B symptoms and 29 (47%) with a bulky mediastinal mass. Seventy-five percent of the patients had received more than one line of therapy before ASCT. Thirty-three patients received bone marrow as a source of hematopoietic progenitors, and 29 peripheral blood. Six patients were conditioned with high-dose chemotherapy plus total-body irradiation and 56 received chemotherapy-based protocols. RESULTS: One-year transplantation-related mortality was 14% [95% confidence interval (CI) 6% to 23%]. Response rate at 3 months after ASCT was 52% [complete remission in 21 patients (34%), partial remission in 11 patients (18%)]. Actuarial 5-year TTF and OS were 15% (95% CI 5% to 24%) and 26% (95% CI 13% to 39%), respectively. The presence of B symptoms at ASCT was the only adverse prognostic factor significantly influencing TTF [relative risk (RR) 1.75, 95% CI 0.92-3.35, P = 0.08]. The presence of B symptoms at diagnosis (RR 2.08, 95% CI 0.90-4.79, P = 0.08), MOPP-like regimens as first-line therapy (RR 3.84, 95% CI 1.69-9.09, P = 0.001), bulky disease at ASCT (RR 2.79, 95% CI 0.29-6.03, P = 0.009) and two or more lines of therapy before ASCT (RR 2.24, 95% CI 0.95-5.27, P = 0.06) adversely influenced OS. CONCLUSIONS: In our experience, although overall results of ASCT in PR-HD patients are poor, one-quarter of the patients remain alive at 5 years. Despite this, other therapeutic strategies should be investigated in this group of patients to improve the outcome.

Adolescent↗
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↗
PubMed2000

Are myeloma patients with renal failure candidates for autologous stem cell transplantation?

INTRODUCTION: Renal function is one of the most important prognostic factors in multiple myeloma (MM). Patients with renal failure are generally excluded from high dose therapy even though they display a poor prognosis with conventional chemotherapy schemes. The aim of this study was to analyze the outcome of MM patients with renal insufficiency undergoing autologous stem cell transplantation (ASCT), including the evaluation of the quality of PB stem cell collections, kinetics of engraftment, transplant-related mortality, response to high dose chemotherapy and survival. MATERIALS AND METHODS: From a total of 566 valuable patients included in the MM Spanish ASCT registry, three groups of patients were defined: group BA, patients with abnormal renal function at diagnosis but normal at transplant (73 cases); group BB, patients with abnormal function both at diagnosis and at transplant (14 cases); and group AA (control group, 479 cases), patients who constantly had normal renal function. RESULTS AND CONCLUSION: Patients from groups BA and BB presented with a significantly higher number of adverse prognostic factors, reflecting that we were dealing with high tumor MM cases, as compared with patients from group AA. The number of mononuclear cells, CD34+ cells and CFU-GM cells collected in patients with non-reversible renal insufficiency was similar to those harvested in MM patients with normal renal function. Moreover, neutrophil and platelet engraftments were identical in patients with and without renal failure (days +11 and +12, respectively). By contrast, transplant-related mortality (TRM) was significantly higher in group BB patients (29%) than in groups BA (4.1%) and AA (3.3%). In multivariate analysis only three variables showed independent influence on TRM: poor performance status (ECOG 3), hemoglobin <9.5 g/dl and serum creatinine > or =5 mg/dl. The response to high dose therapy was independent of renal function. Interestingly, 43% of patients from group BB showed an improvement in renal function (creatinine < 2 mg/dl) after transplant. The three-year overall survival from transplantation was 56, 49 and 61% for the BB, BA and AA groups, respectively, with a statistically significant difference favoring group AA (P<0.01). PFS did not differ significantly between the three groups of patients. In multivariate analysis the only unfavorable independent prognostic factors for overall survival were poor performance status either at diagnosis or at transplant, high beta(2)-microglobulin levels, and no response to transplant. According to these results, ASCT is an attractive alternative for MM patients with renal insufficiency, and it should not constitute a criterion for exclusion from transplant unless patients display poor performance status and very high creatinine levels (>5 mg/dl).

Adult↗
PubMed1997

Autologous stem cell transplantation for poor prognosis Hodgkin's disease in first complete remission: a retrospective study from the Spanish GEL-TAMO cooperative group.

Although more than 50% of Hodgkin's disease patients are cured with conventional chemotherapy, many will relapse and eventually die from their disease. Many efforts have been made to identify poor prognostic factors that could be useful in selecting high-risk patients in 1st CR who may benefit from high-dose chemo/radiotherapy. However, the role of early transplantation in 1st CR remains unclear. We have retrospectively analyzed the results obtained with this procedure in 22 hospitals belonging to the Spanish GEL/TAMO cooperative group. Twenty-seven patients, of whom 19 were males, underwent autologous transplantation for Hodgkin's disease in 1st CR between January 1987 and January 1996. Remission had been achieved after one (n = 22) or two (n = 5) lines of treatment. Twenty-four patients had advanced stage disease, 12 patients bulky mediastinal disease, nine bone marrow involvement and 18 had extranodal disease. Peripheral blood was used as the source of hematopoietic stem cells in 15 patients, BM in nine, and both in three. All but three patients received chemotherapy-based conditioning regimens (16 CBV, four BEAM and four BEAC), while three were conditioned with CY and TBI. There were no transplant-related deaths. Median (range) times to recover >0.5 x 10(9)/l neutrophils and >50 x 10(9)/l platelets were 14 (8-56) days and 16 (8-240) days, respectively. With a median follow-up of 30 (8-66) months, 21 patients are alive and in continuous CR. Four patients who relapsed after transplant at 8, 17.5, 22 and 26 months achieved a second CR with conventional chemotherapy; one patient relapsed 92 months post-transplant and died 5 months afterwards. Another patient died 30.5 months post-transplant from a secondary malignancy. In conclusion, high-dose therapy in poor prognosis Hodgkin's disease in 1st CR was well tolerated with no transplant-related mortalities. Although the follow-up of this series is relatively short, our results seem promising. Nevertheless, late relapses can occur, and the role of this procedure vs conventional treatment in very high-risk patients should be assessed in prospective randomized studies.

Adolescent↗
PubMed1992

[Features of chronic myeloid leukemia at diagnosis. Study of a series of 134 cases].

PURPOSE: To analyse the clinico-biological features of 134 patients with chronic myelogenous leukaemia (CML) at presentation. MATERIAL AND METHODS: The series is comprised of 134 patients from the Asturias Central Hospital and other hospital of the region, diagnosed of CML with conventional criteria between 1970 and 1989. A retrospective study was carried out revising the clinical records and the clinico-biological data at diagnosis. Cytogenetic studies were available in 62 cases. The statistical analysis was based upon descriptive statistics and comparison of means and proportions by the chi square and Student's tests. Univariate study was also performed for several variables. RESULTS: The mean age of the group was 50 years, ranging between 2 and 81. The M/F ratio was 76/58. The commonest symptoms at onset were those secondary to hypermetabolism and splenomegaly, 8% of the patients being asymptomatic. Splenomegaly was present in 73.8% of the patients and hepatomegaly in 37.6%. The median white cell count was 132 x 10(9)/L. Absolute basophilia and eosinophilia were seen in 83% and 78% of the cases, respectively. Anaemia was found in 47.4% of the patients, usually mild, and 39% of them had nucleated red cells in peripheral blood. The median platelet count was 400 x 10(9)/L. Thrombocytosis was found in 48% of the cases, while 11% had thrombocytopenia. The mean number of blast cells in the bone marrow was 1.72%. The histopathologic study of the bone marrow revealed decreased red cells in 94.5% of the patients and decreased megakaryocytes in 29.5%; these last were increased in 50% of the patients. Increased reticulin fibres were found in 38.5% of the bone marrow samples. In addition to the Ph' chromosome, which was present in 51 patients, chromosomal abnormalities were seen in 15.6% of the cases in the chronic phase and in 69.2% in the terminal stages of the disease. Positive correlation could be established between the white cell count and the size of spleen (p < 0.001) and liver (p < 0.05), and there was a negative correlation between white blood cell count and haemoglobin rate and platelet count (p < 0.05 for both). CONCLUSIONS: (1) The analysis of this series shows that the CML cases in this region have similar characteristics to those in other western world communities (2). The mean age of this group is somewhat higher than in other series, which should be re-evaluated after discarding the Ph'-negative cases. (3) There seems to be positive correlation between leucocyte count and spleen and liver enlargement, and negative correlation between leucocyte count and haemoglobin and platelet count.

Adolescent↗
PubMed1992

[Low-grade non-Hodgkin's lymphomas. Study of 73 cases].

PURPOSE: To analyse the clinico-biologic features at diagnosis and the response to therapy and survival of a group of patients with low-grade non-Hodgkin's lymphoma (NHL). MATERIAL AND METHODS: The study comprises 73 NHL patients diagnosed between 1974 and 1989 in the Covadonga Hospital and classified as low-grade in accordance with the international Working Formulation. The first-line treatment regimens used were cyclophosphamide-vincristine-prednisone (CVP), chlorambucil-prednisone (CBL-PRED), radiotherapy, and other combinations. The statistical study was performed by comparative statistics (Student's tests, chi-square), univariate analysis (Cox Mantel method) and multivariate analysis (Cox proportional risks); the BMDP pack was used for the study. RESULTS: The median age of the group was 63 years. Stages III and IV were seen at first in 75% of the patients, and 22% of the series had extranodal involvement. CVP was used in 69% of the cases, 7.6 received CBL-PRED, 11% were given radiotherapy, and other combinations were given to 11% of the patients. As a whole, responses were seen in 46 cases (73%), of whom complete remission (CR) was achieved in 49% and partial remission (PR) or minor responses (MR) were attained in 24% of instances. The factors influencing upon CR were: stage (p less than 0.0005), B-symptoms (p 0.004), splenomegaly (p less than 0.801), platelet count and haemoglobin rate (p less than 0.01). The total survival at 10 years was 53%, and the disease-free survival for those attaining CR was 48%, with disease-free median of 81 months. The univariate analysis was influenced in a negative fashion by the following: peripheral blood lymphocyte count below 2 x 10(9)/L, B-symptoms (p less than 0.002), bulky tumoural mass (p less than 0.007), advanced stage (p less than 0.003) and, chiefly, response to treatment (p less than 0.0001). The 10-year survival of the patients achieving CR was 86%, that of both types of response (PR and MR) was 20%, and it was 0% for the failures. CONCLUSIONS: 1) Patients in low stages have high possibilities of curation with radiotherapy. 2) CVP for advanced stages provides moderate percentage of response, with CR rate lower than 50%. It is necessary to select those patients with unfavourable prognostic factors in order to use aggressive treatment to achieve CR. 3) Patients attaining CR have better prognosis in spite of the frequent relapses (63% at 10 years).

Adult↗
PubMed1992

Autologous bone marrow transplantation in 22 adult patients with lymphoblastic lymphoma responsive to conventional dose chemotherapy.

In order to clarify the role of autologous bone marrow transplantation in adult lymphoblastic lymphoma (LBL) patients we have conducted a retrospective multi-institutional Spanish survey. Twenty-two adult patients, 20 males, two females, age 14-52 years (median 25.5) with LBL were treated with high-dose chemoradiotherapy and autologous bone marrow support. Fourteen cases were transplanted in first complete remission (CR1) and eight with other chemosensitive status (four later CR, two partial remissions and two sensitive relapses). From the 14 cases transplanted in CR1, four had previous bone marrow involvement and one meningeal infiltration; eight cases were Ann-Arbor stage IV and fulfilled accepted high-risk criteria for relapse. The conditioning regimen consisted of cyclophosphamide (60 mg/kg x 2) and total body irradiation (9-12 Gy) in 16 cases and high dose chemotherapy in six. The procedure-related mortality was 9% (7% in CR1 patients). The actuarial 2-year overall survival for CR1 patients was 85% at a median follow-up of 19 months. Disease-free survival (DFS) was 77%. In patients with less favourable disease status the 2-year overall and DFS were 73% and 50% respectively. In this study the DFS in CR1 patients was not influenced by bone marrow involvement or high-risk criteria predictive for relapse. These results support the effectiveness of this procedure, mainly for patients in CR1.

Adolescent↗
PubMed1988

Allogeneic bone marrow transplantation versus intensification chemotherapy for acute myelogenous leukaemia in first remission: a prospective controlled trial.

In 1982 we began a prospective controlled trial to assess the effectiveness of allogeneic bone marrow transplantation and intensive post-remission chemotherapy for patients with acute myelogenous leukaemia in first complete remission. Fourteen patients, 3-45 years of age, who had an HLA-identical sibling donor, received bone marrow transplantation. Twenty-five patients who either lacked an HLA-identical sibling or were over 45 years of age received intensive consolidation chemotherapy including high-dose cytosine arabinoside with or without adriamycin. The actuarial rate of continued complete remission (CCR) at 3 years was significantly higher in the transplantation group than in the chemotherapy group: 70% (95% confidence interval 35-91%) compared with 10% (95% confidence interval 2-30%); P = 0.01. However, the actuarial rate of CCR was not significantly different between the transplantation group and patients under 45 years in the chemotherapy group: 70% (95% confidence interval 35-91%) compared with 17% (95% confidence interval 4-45%), 0.1 greater than P greater than 0.05. The actuarial probability of leukaemia relapse was significantly lower in the transplantation group than in the chemotherapy group: 10% (95% confidence interval 4-21%) compared with 88% (95% confidence interval 70-96%), 0.005 greater than P greater than 0.001. There was no significant difference between both groups if we compare only the patients who died of non-leukaemic causes: 22% (95% confidence interval 9-42%) versus 25% (95% confidence interval 7-59%), P = NS. In summary, this study shows that allogeneic bone marrow transplantation is a better anti-leukaemic treatment than is intensive consolidation chemotherapy in patients with AML in first complete remission.

Adolescent↗
PubMed1978

Effect on platelet functions of derivatives of cyclic nucleotides.

Derivatives of cyclic nucleotides were evaluated for their ability to inhibit platelet aggregation and the release reaction. Derivatives substituted in position 8 (mainly 8-Br-cyclic GMP) were more active than 3'-5' cyclic AMP, and their relative potency in inhibiting platelet aggregation and 14C-serotonin release was comparable to that of N62-0'-dibutyryl-cyclic AMP. Compounds substituted in position 6 or 2'-0 were not effective. The active compounds, which were also tested for their ability to stimulate platelet adenylate cyclase or to inhibit cyclic AMP phosphodiesterase, did not modify the intracellular levels of cyclic AMP. Since previous animal experiments have shown that these derivatives cause less side effects than cyclic AMP and its dibutyryl derivative in animals, it is suggested that modification of the cyclophosphate molecule might make it possible to find compounds active only on platelet function without interfering with other biological systems.

Blood Platelets↗