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Biomedical subjects

J M Rodríguez-Fernández

Publications and source records attributed to J M Rodríguez-Fernández.

7 recordsLinked to original sources

Hemopoietic stem cell transplantation in childhood: reduction in mortality and improvement of survival over the years.

Stem cell transplantation (SCT) is an effective treatment for life-threatening hematologic and nonhematologic pediatric diseases. Reducing transplant-related mortality (TRM), a major complication of SCT, to improve long-term survival, therefore, is one of the main objectives of transplantation teams. We analyzed TRM and overall survival (OS) over the years in children undergoing SCT in our center. From June 1998 to October 2002, 156 consecutive children, 105 boys and 51 girls, median age 10 years (range, 2-18), with different diagnoses underwent SCT (100 autologous and 56 allogeneic). OS and TRM were analyzed in 2 different periods (June 1989-December 1998 and January 1999-October 2002) and grouped according to the different SCT modalities. The median follow-up was 18 months (range, 1-160). Autologous TRM showed a statistically significant improvement within 1999-2002 (0%) compared with 1989-1998 (12.2%) (P < .05). There were no statistical differences for allogeneic SCT. OS was 34% in the first period and 80.4% in the second period (P < .01), the improvement being for both autologous and allogeneic SCT. In our study, TRM decreased significantly for those children receiving autologous SCT in recent years. OS was significantly better in the latter period (1999-2002), both globally and for each SCT modality.

Adolescent↗

Bone marrow processing using the fenwal CS-3000 plus blood cell separator: results of 99 procedures.

BMT is used as an established therapy for patients with malignant and nonmalignant diseases. Many techniques for ex vivo treatment have been developed, but these techniques must be preceded by BM processing. We report our experience in processing 99 BM using the Fenwal CS-3000 Plus cell separator using the 1-special program. Ninety-nine procedures were performed in BM harvested from 73 patients and 26 healthy donors. The number of nucleated cells (NC), mononuclear cells (MNC), RBC, platelets, colony-forming units-granulocyte-macrophage (CFU-GM), CD34+ cells, relative purity of MNC and PMN, and volume were determined in the unprocessed BM and in the final product. BM processing resulted in NC, MNC, CFU-GM, and CD34+ cell recoveries of 31%, 82.2%, 117.6%, and 97.8%, respectively. RBC, PMN, platelets, and volume removal, respectively, were 96%, 92%, 37.2%, and 85.1%. In pediatric patients, the volume reduction was significantly lower than in adult patients (79.6% versus 88.8%). No other significant differences were found between pediatric and adult results. We conclude that BM processing with the Fenwal CS-3000 Plus cell separator provides a product that can undergo further ex vivo treatments or cryopreservation.

Adult↗

Chronic lymphocytic leukemia with two cellular populations: a biphenotypic or biclonal disease.

A case of CLL with two different cellular populations is reported. A 50-year-old man was evaluated for persistent absolute lymphocytosis. A peripheral blood smear revealed numerous small lymphocytes (83% of white blood cells counted). Frequent Grumpecht shadows were present, too. On bone marrow aspirate smears lymphocytes comprised 85% of the total cells counted, and the bone marrow biopsy showed a mixed nodular-interstitial infiltration pattern. The immunophenotypic study showed two different leukemic populations. The first one (comprising 79% leukemic cells) was CD5+, CD19+, CD10-, CD20+, CD18-, CD22-, CD23+ +, lambda dim, and FMC7-. The second population (comprising 21% leukemic cells) was CD5+, CD19+, CD10-, CD20+, CD18+, CD22+, CD23+, lambda+ +, and FMC7+. Gene rearrangement studies detected the germline and one rearranged band in Jk blot with each restriction endonuclease. In the Jh blot the germline and two rearranged bands were detected with EcoRI and BamHI and three rearranged bands with HindIII. The JBI/JBII blot detected only the germline band. The detection of three rearranged bands was interpreted as evidence of the presence of at least two monoclonal populations of cells with the same light chain restriction.

Clone Cells↗

Repopulation of circulating T, B and NK lymphocytes following bone marrow and blood stem cell transplantation.

A variety of T, B and natural killer (NK) cell subsets defined by surface markers were analyzed by double immunofluorescence flow cytometry in the peripheral blood of patients following autologous bone marrow transplantation (ABMT, n = 14), autologous peripheral blood stem cell transplantation (PBSCT, n = 10) and allogeneic bone marrow transplantation (allo-BMT, n = 6). Patients following ABMT were divided in 2 groups, those who did not received G-CSF post-transplant (ABMT, n = 6) and those who did (ABMT + G, n = 8). All patients following PBSCT or allo BMT received G-CSF. In all the groups prolonged significant decreases with respect to normal numbers were observed for the T CD3+, CD2+ and CD25+ subsets, more profound for the CD4+ subset but less for the CD8+ subset, especially following PBSCT (only decreased at 1 month). A significant expansion of the CD3+CD57+ and CD8+CD57+ phenotypes was noticed between 9 and 12 months following ABMT, the group of longer follow-up. Long-lasting expansion of the NK-like CD3+CD56+ and CD3+CD16+ subsets was also observed. The B CD19+ and CD20+ subsets had a significant overexpression from 4 months after ABMT, showing a normally balanced Igk+:Ig1+ ratio. Concordantly, the HLA-DR+ and HLA-DQ+ subsets showed significant increases. The NK CD56+ and CD16+ subsets had a faster recovery than the T or B subsets in all the groups. However, the CD3-CD56+, CD3-CD16+, CD16+CD56+, CD3-CD8+, and especially the CD3-CD57+, CD16+CD57+, and CD56+CD57+ subsets had a slower recovery than the global CD56+, CD16+, or CD57+ subsets. The biological and clinical implications of these findings are discussed.

B-Lymphocyte Subsets↗

Natural killer cytotoxicity and lymphocyte subpopulations in patients with acute leukemia.

We have studied lymphocyte subpopulations and the NK cytotoxicity of the PBMC from acute leukemia patients in complete remission after chemotherapy or ABMT and from normal donors. We have found a positive linear correlation between the percentage of subpopulations with CD3-CD16+, CD3-CD56+ and CD3-CD8+ phenotypes and the percentage of NK cytotoxicity. The slopes of the regression lines in the two groups of patients were lower than in normal donors, indicating a decreased ability of these cells to operate. The percentages of these subpopulations represent parameters for estimating the percentage of NK cytotoxicity both in normal donors and in patients with acute leukemia.

Acute Disease↗

Lymphokine-activated killer cytotoxicity and lymphocyte subpopulations in patients with acute leukemia.

In this report we investigated lymphokine-activated killer (LAK) cytotoxicity and lymphocyte subpopulations of peripheral blood mononuclear cells (PBMCs) of patients with acute leukemia in complete remission after chemotherapy or autologous bone marrow transplantation (ABMT) and of normal donors. A positive linear correlation was found between the percentage of spontaneous LAK activity and that of lymphocyte subpopulations with phenotypes CD56+, CD3-CD8+ CD3-CD56+ and CD3-CD57+ in both groups of patients. A 3-day culture with IL-2 produced an up-regulation in the expression of the CD25, CD69, and HLA-DR markers proportional to the LAK cytotoxicity levels generated in the culture. Determination of percentages of spontaneous and in vitro generated LAK activity as well as of the above mentioned phenotypic markers contribute to the analysis of the process of LAK activation in patients with acute leukemia and may also be useful in those cases in which immunotherapy with IL-2 and/or LAK cells is anticipated.

Acute Disease↗

Bone marrow histologic pattern--the best single prognostic parameter in chronic lymphocytic leukemia: a multivariate survival analysis of 329 cases.

In previous studies, the prognostic value of bone marrow (BM) histologic patterns in chronic lymphocytic leukemia (CLL) has been demonstrated. In order to investigate whether such a value is independent of other prognostic parameters, a multivariate survival analysis (Cox's regression model) was undertaken in a series of 329 CLL patients in whom a BM had been performed. The following binary variables were included in the analysis: age (more than 60 years), lymphadenopathy (more than two areas involved), splenomegaly, hepatomegaly, absolute lymphocyte count (more than 30,000 microL), anemia (hemoglobin less than 10 g/dL), thrombocytopenia (less than 100,000 microL), and BM pattern (diffuse v nondiffuse). Three variables entered the regression at significant level: BM pattern (P less than .001), anemia (P less than .001), and hepatomegaly (P = .03). The model was also tested by expressing the variables in a continuous way when possible. Again, BM pattern entered first in the regression (P less than .001), followed by the hepatomegaly (P = .002), hemoglobin level (P = .02), and lymphadenopathy (P = .04). When both the binary and the continuous models were tested separately in 227 patients with BM as initial staging procedure and in 102 patients in whom this was performed later during the course of the disease, in all instances, BM pattern entered first in the regression at a highly significant level. BM histologic pattern appears to be a better single prognostic parameter than any one of the variables employed in current clinical staging systems. A combined clinicopathologic system incorporating the BM pattern, together with the usual clinical variables, is presented.

Actuarial Analysis↗