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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
PubMed2005

CD34 + cell dose and outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation.

While in bone marrow allogeneic transplantation the infusion of high doses of progenitor stem cells has a favourable impact on outcome, due to a faster hematopoietic and immune recovery, in the peripheral blood allo-setting the infusion of a high number of CD34 cells increases the risk of extensive chronic graft vs. host disease (cGVHD). This higher incidence of extensive cGVHD has an adverse impact on outcome due to a higher transplant related mortality, specially among patients receiving T-cell depleted allogeneic transplantation with myeloablative conditioning. By contrast, patients undergoing reduced intensity conditioning regimen may benefit from increasing higher CD34 + cell doses, especially those categorized as high risk according to disease status at transplant. Thus, the source of progenitors cells, type of conditioning and GVHD prophylaxis, among other factors, may influence the effect of the progenitor cell dose on outcome after allogeneic transplant.

Antigens, CD34↗
PubMed2004

Results of autologous transplantation in lymphoma are not improved by increasing the dose of etoposide in the BEAM regimen: a single-centre sequential-cohort study.

We have undertaken a retrospective sequential-cohort analysis of 131 lymphoma patients treated with the BEAM regimen and autologous stem cell transplantation, to compare BEAM at standard doses (sBEAM; n = 67 from May 1990 to April 1995) and BEAM with escalated etoposide dose from 800 to 1600 mg/m(2) (eBEAM; n = 64 from May 1995 to June 1999). Transplant-related mortality and incidence of secondary malignancies were similar in both groups. Disease progression was significantly lower in indolent lymphoma (IL) patients receiving eBEAM (7 vs 43%), although survival was comparable due to a higher toxic mortality in the eBEAM group. The 5-year event-free survival and overall survival were better in Hodgkin's disease (HD) patients treated with eBEAM (70 and 77%, respectively) compared to sBEAM (58 and 69%, respectively), but the difference was not statistically significant. In aggressive lymphomas, no difference was detected between groups. Our results indicate that while escalation of the etoposide doses in the BEAM conditioning regimen does not appear to improve outcome, encouraging results in IL and HD may warrant further studies.

Adolescent↗
PubMed2004

Quality of life assessment in patients undergoing reduced intensity conditioning allogeneic as compared to autologous transplantation: results of a prospective study.

The aim was to analyze quality-of-life (QOL) during the first year post transplant in 47 patients undergoing reduced-intensity conditioning (RIC) allotransplantation, and to compare these with a similar subgroup of patients receiving autologous stem cell transplantation (ASCT). We used self-reported questionnaires. Each answer scored from 0 (not at all) to 4 (very much), with higher scores indicating worse functioning. Mean value of physical categories among RIC transplants ranged between 1.23 and 0.77 indicating that patients scored very low for physical symptoms. Patients undergoing ASCT had higher scores in questionnaires performed early after transplant and then gradually improved (P < 0.001). Overall, when we compared physical functioning scores, allo-RIC did significantly better (P = 0.049). Nevertheless, while allo-RIC scores were significantly better for the first three questionnaires, ASCT patients did better in the last two questionnaires. These findings are in accordance with the toxicities observed in both subgroups which are lower in the RIC group early after transplant. No significant differences were observed between either subgroup for any of the functional, social/ family, psychological distress and satisfaction with doctor/nurse relationship items. We have observed similar QOL among patients undergoing RIC-allo as compared to ASCT although GVHD remains an important 'event' in QOL.

Adolescent↗
PubMed2001

Differences in genetic changes between multiple myeloma and plasma cell leukemia demonstrated by comparative genomic hybridization.

To analyze the genomic differences between multiple myeloma (MM) and plasma cell leukemia (PCL), a total of 30 cases were studied by comparative genomic hybridization (CGH). In five cases with a low proportion of plasma cells (PC) in bone marrow, an enrichment of PC was performed by using immunomagnetic beads conjugated with the monoclonal antibody B-B4. In 24 out of the 25 MM (96%) and in all five PCL (100%) patients DNA copy number changes were identified by CGH analysis; in the MM case without chromosomal imbalances, the immunomagnetic enrichment of PC had failed. The most recurrent changes in MM patients were gains at chromosomes 15q (48%), 11q (44%), 3q (40%), 9q (40%) and 1q (36%). By contrast, all PCL patients showed gains in 1q. Losses of chromosomal material were significantly more frequent in PCL than in MM patients (P = 0.03): losses on 13q in 80% of PCL vs 28% of MM; and on chromosome 16 in 80% vs 12%, respectively. In addition, PCL patients showed losses of 2q and 6p that were not present in MM. The CGH data show differences in chromosomal imbalances between MM and PCL.

Aged↗
PubMed1999

Clinical significance of CD34+ cell dose in long-term engraftment following autologous peripheral blood stem cell transplantation.

The number of CD34+ cells has been described as the best parameter for predicting the quality of engraftment in peripheral blood progenitor cell (PBPC) transplantation in the early post-transplant period. In this study we have determined the optimal number of CD34+cells in order to maintain engraftment in the long term in a series of 100 patients receiving autologous PBPC transplantation. Based on our previous experience on the speed of early hematopoietic recovery, four subgroups of patients were established: patients infused less than 0.75 x 106/kg CD34+ (n = 9), 0.75 to 1.25 (n = 24), 1.25 to 2.0 (n = 37) and more than 2.0 (n = 30). These groups were designated as low, intermediate-low, intermediate-high and high CD34 groups, respectively. Transitory loss of neutrophil engraftment was observed in 67%, 30%, 16% and 6% of patients in the four mentioned CD34 groups respectively, with statistically significant differences between the different groups. Significant differences were also observed between the low CD34 group and the rest of the groups as regards platelet and red blood cell transfusion requirements, fever episodes, days of hospitalization and antibiotic requirements throughout the first year. Our results show that the dose of CD34+ cells influences engraftment also in the late post-transplant period, and correlates with transfusion and antibiotic requirements, fever episodes and days of hospitalization during the first year post-transplant.

Anti-Bacterial Agents↗
PubMed1999

Extensive characterization of the immunophenotype and pattern of cytokine production by distinct subpopulations of normal human peripheral blood MHC II+/lineage- cells.

Dendritic cells (DC) represent the most powerful professional antigen-presenting cells (APC) in the immune system. The aim of the present study was to analyse, on a single-cell basis by multiparametric flow cytometry with simultaneous four-colour staining and a two-step acquisition procedure, the immunophenotypic profile and cytokine production of DC from 67 normal whole peripheral blood (PB) samples. Two clearly different subsets of HLA-II+/lineage- were identified on the basis of their distinct phenotypic characteristics: one DC subset was CD33strong+ and CD123dim+ (0.16 +/- 0.06% of the PB nucleated cells and 55.9 +/- 11. 9% of all PB DC) and the other, CD33dim+ and CD123strong+ (0.12 +/- 0.04% of PB nucleated cells and 44.53 +/- 11.5% of all PB DC). Moreover, the former DC subpopulation clearly showed higher expression of the CD13 myeloid-associated antigen, the CD29 and CD58 adhesion molecules, the CD2, CD5 and CD86 costimulatory molecules, the CD32 IgG receptor and the CD11c complement receptor. In addition, these cells showed stronger HLA-DR and HLA-DQ expression and a higher reactivity for the IL-6 receptor alpha-chain (CD126) and for CD38. In contrast, the CD123strong+/CD33dim+ DC showed a stronger reactivity for the CD4 and CD45RA molecules, whereas they did not express the CD58, CD5, CD11c and CD13 antigens. Regarding cytokine production, our results show that while the CD33strong+/CD123dim+ DC are able to produce significant amounts of inflammatory cytokines, such as IL-1beta (97 +/- 5% of positive cells), IL-6 (96 +/- 1.1% of positive cells), IL-12 (81.5 +/- 15.5% of positive cells) and tumour necrosis factor-alpha (TNF-alpha) (84 +/- 22.1% of positive cells) as well as chemokines such as IL-8 (99 +/- 1% of positive cells), the functional ability of the CD123strong+/CD33dim+ DC subset to produce cytokines under the same conditions was almost null. Our results therefore clearly show the presence of two distinct subsets of DC in normal human PB, which differ not only in their immunophenotype but also in their functionality, as regards cytokine production.

AC133 Antigen↗
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↗