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Biomedical subjects

M Tormo

Publications and source records attributed to M Tormo.

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↗
PubMed2006

Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)].

Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level >0.1% at the end of treatment than in patients with < or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of >10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR >10 compared to 21% for patients with RQ-PCR levels < or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.

Acute Disease↗
PubMed2005

Adverse prognostic impact of CD36 and CD2 expression in adult de novo acute myeloid leukemia patients.

BACKGROUND AND OBJECTIVES: A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytometry. DESIGN AND METHODS: Two hundred and sixty-six bone marrow (BM) samples from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were studied by multiparametric flow cytometry. Immunophenotyping studies were performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells was analyzed using triple stainings with fluorochrome-conjugated combinations of monoclonal antibodies. RESULTS: CD2 was positive in 21 cases (8%); an associated inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS) rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)- patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+ patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+ (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2; p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS. CONCLUSIONS: CD2+ patients had a very poor OS when CD2/inv(16)+ cases were excluded. CD36 and CD2 expression at diagnosis can provide prognostically important information in adult de novo AML.

Acute Disease↗
PubMed2005

Impact of different strategies of second-line stem cell harvest on the outcome of autologous transplantation in poor peripheral blood stem cell mobilizers.

The optimal approach to obtain an adequate graft for transplantation in patients with poor peripheral blood stem cell (PBSC) mobilization remains unclear. We retrospectively assessed the impact of different strategies of second-line stem cell harvest on the transplantation outcome of patients who failed PBSC mobilization in our institution. Such patients were distributed into three groups: those who proceeded to steady-state bone marrow (BM) collection (group A, n = 34); those who underwent second PBSC mobilization (group B, n = 41); those in whom no further harvesting was carried out (group C, n = 30). PBSC harvest yielded significantly more CD34+ cells than BM collection. Autologous transplantation was performed in 30, 23 and 11 patients from groups A, B and C, respectively. Engraftment data and transplantation outcome did not differ significantly between groups A and C. By contrast, group B patients had a faster neutrophil recovery, required less platelet transfusions and experienced less transplant-related morbidity, as reflected by lower antibiotics needs and shorter hospital stays. In conclusion, remobilization of PBSC constitutes an effective approach to ensure a rapid hematopoietic engraftment and a safe transplantation procedure for poor mobilizers, whereas unprimed BM harvest does not provide any clinical benefit in this setting.

Adult↗
PubMed2005

Guillain-Barré syndrome associated with cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation.

The association between cytomegalovirus (CMV) infection and the development of Guillain-Barré syndrome (GBS) in the setting of allogeneic hematopoietic stem cell transplantation (alloSCT) has been reported only occasionally. We describe here a 23-year-old patient diagnosed with acute myelogenous leukemia who underwent a partially HLA-mismatched alloSCT and soon after developed GBS along with a CMV infection. Serum autoantibodies to several ganglioside antigens were concomitantly detected. Despite therapy with ganciclovir and plasma exchanges, the patient's clinical condition rapidly deteriorated, and he died 3 weeks later with persisting CMV antigenemia. Although a coincidental association cannot be excluded, it could be speculated that a pathogenetic link exists between the 2 disorders. In this sense, molecular mimicry between viral antigens and neural host tissues could be postulated as the hypothetical mechanism underlying the triggering of the autoimmune disease in the present case.

Adult↗
PubMed2004

Alternative reversed-phase high-performance liquid chromatography method to analyse organic acids in dairy products.

A RP-HPLC method for the analysis of oxalic, citric, formic, succinic, orotic, uric, pyruvic, acetic, propionic, lactic and butyric acids in dairy products with a simple treatment of the sample has been developed. A gradient programme pumping phosphate buffer at pH 2.20 and acetonitrile was used to separate the compounds on a C18 column. Various parameters affecting analysis have been optimised to take < 18 min with an excellent linearity (R > 0.999). The precision was good (R.S.D. < 5%) and the recovery found close to 100%. Its application to analyse the quality of some dairy products has been investigated.

Acids↗
PubMed2004

Bcl-6 mutation status provides clinically valuable information in early-stage B-cell chronic lymphocytic leukemia.

In B-cell chronic lymphocytic leukemia (B-CLL), somatic mutation of IgVH genes defines a subgroup with favorable prognosis, whereas the absence of IgVH mutations is correlated with a worse outcome. Mutations of the BCL-6 gene are also observed in a subset of B-CLL, but the clinical significance of this molecular alteration remains uncertain. We examined the distribution of IgVH and BCL-6 gene mutations in 95 well-characterized patients with Binet stage A B-CLL, and correlated them with clinical, laboratory, cytogenetic findings and disease progression. Mutations of the BCL-6 gene were observed only in cases harboring mutated IgVH. Unexpectedly, coexistence of IgVH and BCL-6 mutations was correlated with shorter treatment-free interval (TFI) compared to cases harboring only IgVH mutation (median, 55 months vs not reached; P=0.01), resembling the clinical course of unmutated IgVH cases (median TFI, 44 months). As expected, deletions of 17p13 (P53 locus) and 11q22 (ATM locus) were observed in cases with unmutated IgVH, except one patient who showed mutations of both IgVH and BCL-6. No other statistically significant differences were observed among the genetic subgroups. Our data indicate that BCL-6 mutations identify a subgroup of Binet stage A B-CLL patients with a high risk of progression despite the presence of mutated IgVH gene.

Adult↗
PubMed2003

Soluble intercellular adhesion molecule-1 (s-ICAM-1/s-CD54) in diffuse large B-cell lymphoma: association with clinical characteristics and outcome.

BACKGROUND: High serum levels of soluble intercellular adhesion molecule-1(s-ICAM-1/s-CD54) have been associated with adverse clinical features and poor outcome in chronic lymphocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphoma, but their value in the different subtypes of non-Hodgkin's lymphoma has not been well addressed. PATIENTS AND METHODS: Our aim was to study the serum levels of s-ICAM-1 in diffuse large B-cell lymphoma (DLBCL) and to correlate them with clinical characteristics and outcome. We analyzed the serum levels of s-ICAM-1 in a series of 55 patients with DLBCL diagnosed in a single institution. s-ICAM-1 levels were quantified by an immunoenzymatic assay. Median age was 62 years (range 22-96); 29 (53%) were male. Twenty-eight (51%) presented with advanced clinical stage (III/IV), 32 (58%) had extranodal involvement, 28 (51%) had high serum lactate dehydrogenase (LDH) and 23 (43%) had high beta2-microglobulin levels. All patients received anthracycline-containing regimens. Correlation between clinical variables and s-ICAM-1 levels were tested with the Mann-Whitney U-test and survival was plotted by the Kaplan-Meier method, and curves compared with the log-rank test. RESULTS: Serum levels of s-ICAM-1 were significantly increased in patients with DLBCL compared with normal controls (589 +/- 487 versus 279 +/- 65 ng/ml, respectively; P <0.001). Higher levels of s-ICAM-1 were present in patients with B symptoms, advanced stage and increased LDH and beta2-microglobulin. s-ICAM-1 levels also correlated with achievement of a complete response. Patients with s-ICAM-1 over 668 ng/ml had a shorter time to treatment failure (TTF) (3-year TTF, 59% versus 20%, respectively; P = 0.01) and overall survival (OS) (3-year OS, 58% versus 22%, respectively; P = 0.04) than the remainders. When only low and low-intermediate risk patients in the international prognostic index score were considered, those with s-ICAM-1 over 668 ng/ml also had worse TTF and OS. CONCLUSIONS: In DLBCL, s-ICAM-1 levels correlated with high tumor burden and lymphoma dissemination and may contribute to assessment of prognosis.

Adult↗
PubMed2003

Optimization and validation of a rapid method to determine citrate and inorganic phosphate in milk by capillary electrophoresis.

Quantification of phosphate and citrate compounds is very important because their distribution between soluble and colloidal phases of milk and their interactions with milk proteins influence the stability and some functional properties of dairy products. The aim of this work was to optimize and validate a capillary electrophoresis method for the rapid determination of these compounds in milk. Various parameters affecting analysis have been optimized, including type, composition, and pH of the electrolyte, and sample extraction. Ethanol, acetonitrile, sulfuric acid, water at 50 degrees C or at room temperature were tested as sample buffers (SB). Water at room temperature yielded the best overall results and was chosen for further validation. The extraction time was checked and could be shortened to less than 1 min. Also, sample preparation was simplified to pipet 12 microl of milk into 1 ml of water containing 20 ppm of tartaric acid as an internal standard. The linearity of the method was excellent (R2 > 0.999) with CV values of response factors <3%. The detection limits for phosphate and citrate were 5.1 and 2.4 nM, respectively. The accuracy of the method was calculated for each compound (103.2 and 100.3%). In addition, citrate and phosphate content of several commercial milk samples were analyzed by this method, and the results deviated less than 5% from values obtained when analyzing the samples by official methods. To study the versatility of the technique, other dairy productssuch as cream cheese, yogurt, or Cheddar cheese were analyzed and accuracy was similar to milk in all products tested. The procedure is rapid and offers a very fast and simple sample preparation. Once the sample has arrived at the laboratory, less than 5 min (including handling, preparation, running, integration, and quantification) are necessary to determine the concentration of citric acid and inorganic phosphate. Because of the speed and accuracy of this method, it is promising as an analytical quantitative testing technique.

Animals↗
PubMed2002

Rapid simultaneous determination of organic acids, free amino acids, and lactose in cheese by capillary electrophoresis.

A capillary electrophoresis (CE) method for the simultaneous separation of 11 metabolically important organic acids (oxalic, formic, citric, succinic, orotic, uric, acetic, pyruvic, propionic, lactic, and butyric), 10 amino acids (Asp, Glu, Tyr, Gly, Ala, Ser, Leu, Phe, Lys, and Trp), and lactose has been optimized, validated, and tested in dairy products. Repeatability and linearity were calculated for each compound, with detection limit values as low as 0.2 x 10(-2) mM for citric acid and Gly. The method was applied to analyze yogurt and different varieties of commercial cheeses. This method yielded specific CE patterns for different varieties of cheese. Also, it has been shown to be sensitive enough to measure small changes in composition of some of those compounds in fresh cheese stored under accelerated ripening conditions for 2 d at 32 degrees C (e.g., from 1728.3 +/- 45.0 to 1166.7 +/- 4.5 mg/100 g of DM in the case of lactose, or from 23.5 +/- 0.6 to 76.8 +/- 16.7 mg/100 g of DM in the case of acetic acid).

Acetic Acid↗
PubMed2001

Loss of a novel tumor suppressor gene locus at chromosome 8p is associated with leukemic mantle cell lymphoma.

Patients with mantle cell lymphoma (MCL) may present with either nodal or leukemic disease. The molecular determinants underlying this different biologic behavior are not known. This study compared the pattern of genetic abnormalities in patients with nodal and leukemic phases of MCL using comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) for specific gene loci. Although both leukemic and nodal MCL showed similar genomic patterns of losses (involving 6q, 11q22-q23, 13q14, and 17p13) and gains (affecting 3q and 8q), genomic loss of chromosome 8p occurred more frequently in patients with leukemic disease (79% versus 11%, P <.001). Subsequent CGH analysis confirmed the genomic loss of 8p21-p23 in 6 of 8 MCL cell lines. Interestingly, MYC gene amplification was restricted to cases with 8p deletion. These data indicate the presence of a novel tumor suppressor gene locus on 8p, whose deletion may be associated with leukemic dissemination and poor prognosis in patients with MCL.

Chromosomes, Human, Pair 8↗
PubMed2001

[Results of treatment with 2-chlorodeoxyadenosine in refractory or relapsed Langerhans cell histiocytosis. Study of 9 patients].

BACKGROUND: To analyse the results of the treatment with 2-chlorodeoxyadenosine (2CdA) in 9 patients with refractory or relapsed Langerhans cell histiocytosis (LCH) tracted in 8 Spanish hospitals between 1993 and 1999. PATIENTS AND METHOD: In the 9 patients the following data were recorded: age, sex, organ involvement by LCH, first treatment and response, dose, number of cycles and schedule of administration 2CdA, response to 2CdA treatment, toxicity, disease-free survival (DFS) and overall survival (OS). RESULTS: Median age was 25 years (range, 6-63). All patients had multiorganic involvement by LCH, with severe organ dysfunction in 4. 2CdA was administered as second line treatment in 7 cases and as third line in 2. The 2CdA dose was 0.1 mg/kg per day during 5 days in the majority of patients, and interval between cycles was 4 weeks. In 2 cases a complete remission (CR) was achieved and 4 cases attained a partial remission (PR) (overall response rate 66%). The main toxicity was hematologic, with neutropenia grade > 2 in 5 cases and thrombocytopenia > 2 in 5. Four patients had infections, with fatal evolution in one of them. After a median follow-up of 8 months (range 2-17), 2 patients remained in CR (12 months both), 4 in PR (range 2-12 months) and one had active disease (17 months). The other two died due to progressive disease and Aspergillus spp. sepsis, respectively. The actuarial probabilities of DFS and OS were 58% (95% CI, 38-78%) and 71% (95% CI, 54-88%), respectively. CONCLUSIONS: 2CdA is an active drug for patients with refractory or relapsed LCH, and its main toxicity is myelosuppression. The usefulness of 2CdA, isolated or in combination with other drugs, in patients with refractory or relapsed LCH must be assessed in controlled studies.

Adolescent↗
PubMed2001

Identification of two subgroups of mantle cell leukemia with distinct clinical and biological features.

INTRODUCTION: Mantle cell leukemia (MCLeu) has been considered as a leukemic form of mantle cell lymphoma (MCL). However, the presence of certain features rarely observed in MCL, such as transformation to prolymphocytic leukemia (PLL) or indolent clinical course, suggests that MCLeu may represent a distinct disorder. METHODS: Seven cases of MCLeu with t(11;14)(q13;q32) and BCL1-IGH gene rearrangement were ascertained among 140 newly diagnosed chronic B-cell lymphoproliferative disorders with leukemic expression. Comparative genomic hybridization, FISH for specific gene loci, and immunological studies were preformed in them. RESULTS: In comparison with CLL, MCLeu cases had low immunological scores < or =2 with respect to B-CLL (P<0.0001). Expression of CD38 was absent in 43% of MCLeu and in 44% of B-CLL. Comparative genomic hybridization analysis identified genomic imbalances in 86% of MCLeu with a similar pattern than in MCL: gains of 3q, 8q involving MYC gene and 15q, and losses of 6q, 9p, 13q and 17p affecting P53 gene. Differently from MCL and CLL, genomic loss of 8p was frequently detected in MCLeu (83%). Although clinical presentation of MCLeu was indistinguishable from CLL, all patients but one had disease progression within three years. According to the immunologic and genomic profiles, two distinct subgroups of MCLeu were defined: one related to PLL, showing CD38-, deletion of P53, and MYC amplification and another which corresponds to a leukemic form of classical MCL, presenting with CD38+ and normal P53 and MYC status. CONCLUSION: MCLeu and MCL are closely related disorders, as they show similar genomic and molecular patterns. However, the deletion of the short arm of chromosome 8 may represent a specific marker for MCLeu. Two distinct subgroups of MCLeu may also be distinguished according to the immunologic and genomic cell profiles.

ADP-ribosyl Cyclase↗
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

Additional cytogenetic changes do not influence the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with an ATRA plus anthracyclin based protocol. A report of the Spanish group PETHEMA.

BACKGROUND AND OBJECTIVES: To analyze in patients with de novo acute promyelocytic leukemia (APL) treated with an ATRA plus anthracyclin-based protocol if the presence of additional cytogenetic aberrations to the t(15;17) influences: 1. clinical and biological presenting features; 2. disease outcome. DESIGN AND METHODS: One hundred and thirteen patients with newly diagnosed APL enrolled in the APL-96 protocol of the Spanish PETHEMA group were studied by conventional karyotyping, FISH and RT-PCR for the PML-RARa fusion. Treatment was homogeneous in all cases and consisted of anthracyclines and ATRA. RESULTS: Additional chromosome aberrations were observed in 30% of cases. The most frequent secondary changes were +8 (14 cases), and abnormalities of chromosomes 9 or 3 (4 patients each), and of chromosomes 1 and 8 (3 cases each). No clinical, biological, morphological, immunophenotypic or molecular differences were observed between the group of APLs with t(15;17) alone and the group of patients with additional changes. Patients with additional changes had a higher rates of complete remission (CR) and 4-year disease-free survival (DFS) (97%, and 97%, respectively) than patients with t(15;17) alone (CR, 70% and DFS, 84%) but these differences were not statistically significant. INTERPRETATION AND CONCLUSIONS: Patients with APL and additional cytogenetic abnormalities do not show different clinical, biological, morphological or molecular features as compared to patients with t(15;17) alone. The prognosis of patients with APL and t(15;17) alone and those with additional changes is similar in both groups. This study indicates that there is no rationale for administering more intensive treatment in APL patients with additional cytogenetic abnormalities receiving ATRA plus anthracycline-based chemotherapy.

Adolescent↗