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Biomedical subjects

M C Cañizo

Publications and source records attributed to M C Cañizo.

At least 19 recordsLinked to original sources
PubMed1997

Sequential intravenous-oral ciprofloxacin plus amoxycillin/clavulanic acid shortens hospital stay in infected non severe neutropenic patients.

The objective of this study was to determine the efficacy and safety of the combination ciprofloxacin plus amoxicillin/clavulanic acid as an empirical treatment of infection in hematologic patients without severe neutropenia. These drugs allowed us to carry out a sequential therapy, first intravenously and later orally, so that the patient could be discharged as soon as there was a response. Serum concentrations of ciprofloxacin were monitored in this study. Forty seven of the sixty-six patients included (71%) responded to the treatment with no differences between the dosages of ciprofloxacin employed (600-900 mg daily in two or three divided doses). In the patients who responded, the signs and symptoms of infection lasted only three days, which could allow a short hospital stay (median of six days). In the first pre and post-dose serum samples, ciprofloxacin concentrations were significantly higher when the drug was administered every 8 h. Nevertheless, 72 h after the beginning of treatment, they had leveled out in either 8 and 12 h schemes. The toxicity of the treatment was very light, with only four cases with adverse effects, grades I and II. This data suggests that the employed combination is effective and safe and can considerably decrease costs incurred through the admission of hematologic patients with serious infections but without severe neutropenia.

Administration, Oral↗
PubMed1995

DNA aneuploidy in acute myeloblastic leukemia is associated with a high expression of lymphoid markers.

In the present study the DNA cell content of 205 de novo acute myeloblastic leukemia (AML) patients is analyzed at flow cytometry in order to determine both the incidence of DNA aneuploidy in AML patients and the clinical and biological characteristics of AML aneuploid cases. All technical procedures were performed in accordance with the proposed guidelines of the DNA Cytometric Consensus Conference. Our results show that the incidence of DNA aneuploidy is quite low (4.8%), with most cases (n = 8) hyperdiploid and only a small proportion (n = 2) hypodiploid. No major differences were detected between the aneuploid and diploid cases with respect to the clinical and prognostic disease characteristics. Regarding the immunophenotype of the blast cells, the aneuploid cases displayed both a higher incidence of immature myeloblastic phenotype and a greater expression of lymphoid-associated antigens. In summary, our results show that AML patients display a quite low incidence of DNA aneuploidy and that despite the fact that these cases do not display particular clinical characteristics, they show an association with the expression of lymphoid-related markers.

Adult↗
PubMed1995

Gene rearrangement in acute non-lymphoblastic leukaemia: correlation with morphological and immunophenotypic characteristics of blast cells.

The presence of Ig and TCR gene rearrangement has been reported to occur in ANLL. However, most of the studies have been performed in short series of patients and, in general, not all rearranging genes have been included. We have investigated the configuration of immunoglobulin (Ig) and T-cell receptor loci (TCR) in a series of 160 untreated patients with de novo acute non-lymphoblastic leukaemia (ANLL) and correlated the results with the morphological and immunophenotypic characteristics of blast cells. IGH gene rearrangement was detected in 16/160 cases analysed (10%) and IGK was rearranged in half of them. The incidence of cases displaying TCRB, TCRG and TCRD rearrangements was 5.6%, 13.8% and 13%, respectively. Concomitant recombinatorial events including different Ig and/or TCR genes were frequently detected. Gene rearrangement was not related to the stage of cell differentiation within the myeloid lineage assessed both by morphological and immunophenotypic criteria. Regarding the correlation with the presence of lymphoid related markers, the only relevant association was between the expression of CD7 antigen and TCRG and TCRD gene rearrangement. Our results show that the incidence of gene rearrangement in ANLL may be slightly higher than previously suspected, and that it is not associated with early stages of cell differentiation nor to the expression of lymphoid markers.

Antigens, CD↗
PubMed1993

Immunophenotypic characterisation of acute leukaemia after polycythemia vera.

AIMS: To analyze the immunophenotype of blast cells in patients with acute leukaemia after polycythemia vera, together with the most relevant clinical and haematological disease characteristics. METHODS: The immunophenotype was analysed in nine patients by immunofluorescence flow cytometry using a panel of 15 monoclonal antibodies. The DNA content of blast cells was determined using Vindelov's technique. RESULTS: The most relevant clinical and haematological disease characteristics included: the presence of enlarged spleen and liver by 56% and 67%, respectively; a moderate degree of leucocytosis with thrombocytopenia while haemoglobin was normal in 50% of patients. All patients received alkylating agents or hydroxyurea, or both. Interestingly, the chronic phase in patients receiving this latter drug was shorter. All cases showed a myeloid phenotype, four of them reactive only to early myeloid antigens (CD13/33); in the remaining cases the blast cells displayed granulomonocytic (CD14+, CD15+), erythroid (CD71 ), or megakaryocytic (CD61+, CD41+) markers. Coexpression of lymphoid related antigens (CD7, TdT, or CD19) was also detected. The morphological assessment of blast cells agreed with the immunophenotyping in five out of the nine cases. Blast cells from all six patients analysed displayed a diploid DNA content and the proportion of S-phase cells ranged from 0.4% to 4%. CONCLUSIONS: These findings suggest a pluripotential stem cell with myeloid commitment as the target cell of acute leukaemia after polycythemia vera.

Adult↗
PubMed1993

Expression of NK and lymphoid-associated antigens in blast cells of acute myeloblastic leukemia.

In the present study, the expression of two NK-associated antigens (CD56 and CD16) together with six 'classically' considered lymphoid-related markers (TDT,CD19,CD10,CD7,CD2,CD4) has been analyzed by appropriate dual combinations in 265 acute myelogenous leukemia (AML) patients. Among the lymphoid markers, CD4 and CD7 were those most frequently expressed by AML blast cells (58% and 21.6%, respectively) while the incidence of positivity for the other markers was lower: CD19 (7.8%), CD10 (10.9%), CD2 (11.4%), and TDT (11.3%). Regarding NK-associated antigens, CD56 was present in 41% of AML cases analyzed whereas CD16 was detected in only 23%. All but one of the CD16+ cases coexpressed the CD56 antigen. The expression of these antigens was not associated with the degree of cell differentiation assessed either by morphological or immunophenotypical criteria, with the exception of the correlation observed between monocytic leukaemias and the expression of the CD4, CD56, and CD16 antigens. Regarding the prognostic value of the markers investigated, CD56 expression was associated with a tendency for a better outcome whereas CD7 was the only antigen that had an adverse influence on the survival of AML patients.

Antigens, CD↗
PubMed1992

Development of acute leukaemia after idiopathic myelofibrosis.

AIMS: To determine the characteristics of blastic transformation of idiopathic myelofibrosis. METHODS: The clinical and haematological features, as well as the morphological characteristics of blast cells, were analysed in nine adults with blast transformation. RESULTS: Most of the patients were male and had enlarged spleens and livers. Five of the patients had normal platelet counts, while all had pronounced anaemia and a moderate degree of leucocytosis. The duration of the acute phase was usually short: 16 (SD 8) weeks. Most myeloid cell lineages--granulocytic, monocytic, and megakaryocytic--were similarly distributed. One patient also had a hybrid (lymphoid-myeloid) phenotype. The morphological assessment of blast cells agreed with immunophenotyping in five out of the nine cases. The onset of the blastic phase was not related to previous treatment. CONCLUSIONS: A pluripotential stem cell with preferential myeloid commitment would be the target cell of blast transformation in idiopathic myelofibrosis. Our immunophenotypic data do not support the concept of a preferential association between megakaryocytic lineage and the acute transformation of idiopathic myelofibrosis. The absence of previous treatment in some cases suggests that this kind of evolution is part of the natural history of idiopathic myelofibrosis.

Acute Disease↗
PubMed1992

Concomitant chronic lymphocytic leukemia (CLL) and acute myeloid leukemia. Complete remission of CLL achieved with high-dose cytosine arabinoside.

The concomitant presentation of acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) is rare with so far only eleven cases reported. In addition, the achievement of complete remission (CR) in CLL is exceptional and generally not assessed by immunophenotypical investigations. We report a case with a simultaneous occurrence of AML and CLL in which, in addition to the complete remission of AML, an eradication of the CLL clone was obtained following high-dose cytosine arabinoside. The immunophenotypic investigation of minimal residual disease showed that less than 1 x 10(-3) CD19+/CD5+ B-cells remained in bone marrow.

Acute Disease↗
PubMed1991

Acute leukemia after a primary myelodysplastic syndrome: immunophenotypic, genotypic, and clinical characteristics.

We studied the nature of blast cells in 41 patients with acute leukemia following a previous primary myelodysplastic syndrome (MDS) by a combined multiparameter analysis including morphologic, immunophenotypic, and molecular genetic (Igs, T-cell receptor (TCR)-beta, -gamma, and -delta and the major breakpoint cluster region [M-bcr]) investigations. In addition, the clinical and hematologic characteristics according to the immunophenotype of blast cells were analyzed. Our results show that, although the granulocytic and/or monocytic lineages are those most commonly involved in these acute leukemias, other cell components, including the megakaryocytic and lymphoid, may be present (12% and 15% of the cases, respectively). Moreover, both morphologic and phenotypic studies show the frequent coexistence of two or three cell populations. Interestingly, in all cases the lymphoblastic component constantly displayed an early B phenotype (CD19+, CD10-, TdT+). Upon analyzing whether the type of MDS conditioned any differences in the immunophenotype of blast cells, we observed that, although the lymphoid lineage may be involved in all MDS subgroups, some differences emerge within the myeloid leukemic transformations. Thus, the refractory anemias with excess of blasts (RAEB) and RAEB in transformation displayed a significantly higher incidence of myeloblastic and megakaryoblastic transformations, while in the RA, RA with ring sideroblasts and chronic myelomonocytic leukemia, the granulo-monocytic phenotype predominated. In addition, our results show that the clinical and hematologic characteristics of these patients may be partially related to the immunophenotype of the blast cells. Ig heavy chain gene rearrangements were found in two of 19 patients analyzed (11%), one with a hybrid leukemia (lymphoid-myeloid) and the other with a granulo-monocytic phenotype. Two other hybrid transformations analyzed were in germline configuration. Gamma and delta gene rearrangements were found in 21% and 37% of these acute transformation, respectively. The TCR-beta and M-bcr were in germline configuration in all 19 cases studied. In summary, immunophenotype and molecular studies point to a pluripotent stem cell with preferential myeloid commitment as the target cell of leukemias following a primary MDS.

Acute Disease↗
PubMed1991

Immunophenotypic, genomic and clinical characteristics of blast crisis of chronic myelogenous leukaemia.

We have studied phenotypic and clinical features in a consecutive series of 45 patients with chronic myelogenous leukaemia (CML) in blast crisis (BC). In addition, in 22 of these patients we have analysed the genotypic characteristics including immunoglobulin, T-cell receptor (TCR) and major breakpoint cluster region (M-bcr) gene organization. The granulomonocytic and megakaryoblastic lineages are the most commonly involved in these BC of CML (33% and 33% of cases, respectively); only 18% of our cases displayed a lymphoid phenotype. Moreover, both morphological and immunophenotypic studies revealed the frequent coexistence of two or three cell populations, especially when the megakaryoblast component is involved. The lymphoid BC displayed the highest incidence of complete remissions although this was not associated with a longer survival. Only minor differences between the different myeloid subgroups were observed. Immunoglobulin heavy chain (IgH) gene rearrangement was found in five of the six lymphoid BC and in one myeloid BC. Only one case showed k light chain gene rearrangement. In all but one myeloid BC the TCR-beta gene was in germline configuration. The TCR-gamma gene was rearranged in all lymphoid and one myeloid BC, while TCR-delta gene rearrangement was detected in 67% and 16% of the lymphoid and myeloid BC, respectively. Most of the lymphoid BC (4/5) had the M-bcr breakpoint in subregion 3, while the myeloid BC had the breakpoint either in subregion 2 or 3. No differences between the different myeloid phenotypic subgroups were observed in relation to breakpoint.

Antigens, CD↗
PubMed1991

[Phenotypic changes in refractory and relapse acute lymphoblastic leukemias].

Out of a group of 220 acute lymphoblastic leukaemias (ALL) with phenotypic study at diagnosis, 18 were selected on which sequential studies were performed due to relapse (15 cases) or to lack of achievement of complete remission (primary resistant ALL, 3 cases). The purpose of this study was to analyse the incidence and characteristics of the possible antigenic changes with regard to the diagnosis. Along with the classic markers, a panel comprised of 20 monoclonal antibodies against lymphoid and myeloid antigens was used. Major phenotypic changes (acquisition of myeloid antigens CD13 and CD33) were found only in one case amongst the relapsing ALL (7%). Seven other patients (47%) showed minor phenotyping changes, including: 1) acquisition or loss of antigens (2 cases); 2) changes in more then 50% of any antigen's expression (4 cases); 3) both (1 case). These results might suggest that antigenic changes are rather frequent in relapsing ALL; however, none of such changes modified in our experience the phenotypic diagnosis so any change of this last should be regarded as an exceptional event. The majority of these antigenic changes consisted of the loss of maturation antigens (CD20) or acquisition of early markers (TdT, HLA-DR) or activation markers (CD38); this would mean that the relapsing blast cells show a functional status of activation and proliferation, with a phenotype more immature than that of the diagnosis, thus explaining the poorer prognosis of the patients in relapse. No phenotypic changes were found in the primary resistant ALL, which may indicate the persistence of the original cell clone without any alteration.

Adult↗
PubMed1990

Bone marrow biopsy in myelodysplastic syndromes: morphological characteristics and contribution to the study of prognostic factors.

Ten characteristics of bone marrow (BM) biopsies in paraffin sections, obtained at diagnosis from patients with myelodysplastic syndromes (MDS) classified according to the FAB criteria, were analysed to identify both the most relevant morphologic data and any possible influence on survival. Agreement between two observers was obtained for 94% of the data. BM cellularity was increased in 63% of the cases and was higher in refractory anaemia with excess of blasts (RAEB). RAEB in transformation (RAEB-t) and chronic myelomonocytic leukaemia (CMML) (P = 0.001). Dysmegakaryopoiesis and dyserythropoiesis were present respectively in 83% and 72% of the cases, with slight differences among the FAB subtypes. Abnormal localization of immature precursors (ALIP) was found in more than half of the cases and somewhat more frequently seen in the RAEB + RAEB-t + CMML group (P = 0.07). Eosinophilia, plasmacytosis and reticulin fibrosis were evident in 26%, 18% and 47% of the cases respectively. Cellularity (P = 0.006), eosinophilia (P = 0.009) and, to some extent, dysmegakaryopoiesis (P = 0.07) bore a certain relationship with survival on univariate analysis. The presence of ALIP was not seen to affect the outcome. Multivariate analysis showed that the cellularity and presence of dysmegakaryopoiesis, in BM biopsy, added significant independent prognostic information to that achieved with age, platelet count and proportion of blast cells in BM aspirate, three variables with proven prognostic value in MDS patients. Using a regression model including these five characteristics we have stratified the patients into low, intermediate and high-risk groups with different survivals (P = 0.00001). The present findings show that BM biopsy is able to provide both morphological characteristics and information about the prognosis of survival, and should thus be included in the initial evaluation of MDS.

Adult↗
PubMed1989

[Prediction of survival in myelodysplastic syndrome. Analysis of 2 scoring systems with prognostic value].

The wide prognostic variability of myelodysplastic syndromes (MDS) complicates decision-making regarding the choice and evaluation of alternative treatments to transfusional and antiinfectious supportive measures. Due to its simplicity the Bournemouth scoring system seems to have achieved wide acceptance for establishing the prognosis in MDS patients. The aims of this study were to examine the Bournemouth system in a series of 370 patients with MDS and to evaluate the capability of the prognostic index recently proposed by our group to better define the outcome predicted by the former. The Bournemouth scoring system identified 3 risk groups, A (0-1 points), B (2-3 points) and C (4 points), in the whole series (p less than 0.0001) and it allowed us to stratify refractory anemia (RA), RA with excess of blasts (RAEB) and RAEB in transformation (RAEB-t) patients into two distinct prognostic groups (p = 0.03 and p = 0.01, respectively). This scoring system did not show a significant value in RA with ringed sideroblasts (RARS) and chronic myelomonocytic leukemia (CMML) patients (p greater than 0.05). Our prognostic index clearly segregated patients in the whole series into low- (0-1 points), intermediate- (2-3 points) and high-risk (4-5 points) groups (p less than 0.00001) as well as stratifying ARSA (p = 0.0005), CMML (p less than 0.0001) and RAEB and RAEB-t patients (p less than 0.00001) into different prognostic subset, although it failed to demonstrate a significant predictive value in RA patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients.

Therapy planning in patients with myelodysplastic syndromes (MDSs) is complicated by its high prognostic heterogeneity. Forty-one patient and disease characteristics at onset of 370 patients with MDS were analyzed to identify significant prognostic factors for survival and transformation to acute myeloblastic leukemia (AML), and to develop and validate a regression model for predicting survival. Multivariate regression analysis showed that the total bone marrow percentage of blast cells, age, platelet count, WBC count, and hemoglobin level were the characteristics more significantly associated with survival in the overall series. The bone marrow percentage of type I blast cells was the most important factor predicting transformation into AML. Proportional hazards regression analysis in a randomly selected training sample of 240 patients demonstrated that the combination of total bone marrow percentage of blast cells, platelet count, and age had the strongest predictive relation to survival length. The resulting regression models, continuous and categorized, were validated in the remaining test sample of 130 patients by demonstrating its capability of segregating patients into low-, intermediate-, and high-risk groups, with distinctively different survival curves (P less than .0001). A scoring system derived from the categorized model also had a great prognostic value (P less than .0001). These regression models and the simpler scoring system may be accurately used for decision-making regarding therapy in MDS patients.

Female↗
PubMed1989

Prognostic value of immunological markers in acute myeloblastic leukemia.

In order to investigate the prognostic value of immunologic markers together with the most relevant clinical and hematological disease characteristics in acute myeloblastic leukemia (AML), the reactivity of blast cells from 102 patients with AML was analyzed with a panel of twenty monoclonal antibodies. The univariate analysis showed that five parameters had an adverse effect on both complete remission (CR) and survival: advanced age (greater than 60 years), anemia (hemoglobin concentration (Hb) less than 10g/dl), the expression of the antigens detected by the anti-megakaryocytic antibodies (CDw41/CDw42), the monocytic antibodies (CD14), and the CD9 (FMC56, FMC8) antigen. In addition, the failure to obtain CR had a significant adverse effect on survival (p less than 0.0001). Multivariate analysis showed that only age and Hb had a significant influence on CR while for predicting survival the most important independent prognostic factors were: CR, age, number of platelets and reactivity with the CD9 antibody. These results show that immunological markers could represent a valuable tool in the assignment of risk categories in AML patients.

Age Factors↗
PubMed1988

Clinical and immunological findings in large B-cell chronic lymphocytic leukemia.

In order to define the characteristics of B-CLL cases in which the predominant cell population is composed of large lymphocytes, we studied 97 patients with B-CLL, comparing the cell morphological features with the clinical and biological findings and the immunological phenotype of the proliferating cells. Multivariant analysis showed that there were three significantly different morphological groups: Typical CLL, large lymphocyte CLL (LLL), and CLL with prolymphocytes (CLL/PL). The LLL group showed a greater incidence of lymphadenopathies (P less than 0.05) and higher percentages of both mu + delta + cells (P less than 0.01) and Fmc/7+ cells (P less than 0.001) than in typical CLL. The main differences between LLL and CLL/PL were the peripheral blood lymphocyte count and the percentage of Fmc/7+ cells (P less than 0.002)--both higher in the CLL/PL group--and the percentage of mouse rosette-forming cells (P less than 0.01)--lower in CLL/PL. Further studies including functional assays and survival analyses could contribute to elucidating whether these groups are different entities or a single disease with marked heterogeneity.

Antibodies, Monoclonal↗
PubMed1988

Leukemias with megakaryoblastic involvement: clinical, hematologic, and immunologic characteristics.

The clinical, hematologic, and phenotypic features of 28 patients with acute leukemia with megakaryocytic involvement (AMKL) were analyzed. The prevalence of this type of leukemia in the entire series was 11.6%, with a higher incidence among patients with acute transformation of a previous myeloproliferative disorder (MPD) (24%) than among the transformed myelodysplastic syndrome (13%) patients. The incidence in the "de novo" ANLL was 8% and 16% among secondary leukemias. The presence of bone marrow fibrosis together with low WBC and normal or increased platelet counts despite a severe anemia are the most relevant features in these patients who otherwise displayed an apparently poor prognosis. Megakaryoblasts were morphologically recognized more frequently in the acute transformations of MPD than in de novo ANLL. Only two cases were considered pure AMKL, and in the remaining 26 patients, megakaryoblasts coexisted with other granulomonocytic and/or erythroid populations. Antiglycoprotein IIIa (anti-GPIIIa) (C17) and anti-GPIIb/IIIa (CDw41-, J15-) antibodies are probably the best markers for AMKL, although the monoclonal antibody against GPIX (FMC25) was also positive in a majority of cases but in a lower percentage of cells. On the other hand, megakaryoblasts were generally negative for granulocytic or monocytic markers (CD13, CD14, CD15); the expression of HLA-DR antigens in these cells was variable. Our present results indicate that megakaryoblastic involvement is more common than previously recognized. This is true not only in acute transformed leukemias but also in de novo ANLL. Although the diagnosis of these cases should be based on megakaryocytic markers, it is often possible to suspect a diagnosis according to certain clinical and hematologic features.

Adult↗