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Biomedical subjects

J Sierra

Publications and source records attributed to J Sierra.

At least 91 records · Page 5Linked to original sources
PubMed2000

Tuberculosis after hematopoietic stem cell transplantation: incidence, clinical characteristics and outcome. Spanish Group on Infectious Complications in Hematopoietic Transplantation.

A national survey of tuberculosis after hematopoietic stem cell transplant (SCT) was undertaken to study incidence, clinical presentation and outcome. Twenty confirmed cases were found among 8,013 patients (eight in 5,147 autologous and 12 in 2,866 allogeneic SCT). The estimated incidence in cases/10(5) patients/year (95% CI) was 101 (56.5-145) for the whole group, 71.1 (21.8-120) in autologous and 135.6 (58.9-212) in allogeneic transplants. Compared with the general population, tuberculosis was more frequent after allogeneic (RR 2.95) but not after autologous SCT. Tuberculosis after SCT is a late infection (median 324 days post transplant), predominately affects the lungs (80% of the cases), appears to respond well to treatment but has a high mortality (25%) in allogeneic recipients. It can also complicate the post-transplant management as antituberculosis drugs frequently decrease the serum levels of cyclosporine causing an aggravation of GVHD. Graft-versus-host disease, corticosteroid treatment and total body irradiation appear to be associated with tuberculosis in allogeneic recipients. No obvious factors were associated with tuberculosis in autologous transplants. Finally, we found that the published literature on tuberculosis after solid and SCT has overestimated its incidence due to the direct translation of tuberculosis frequency into incidence.

Adult↗
PubMed2000

Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience.

Between 1985 and 1998, 161 patients with primary acute myeloid leukemia (AML) received T-replete bone marrow transplantation (BMT) from unrelated donors in Seattle. Median age was 30 (range 1-55) years. Conditioning for BMT consisted of cyclophosphamide and total body irradiation in 154 (96%) cases and graft-versus-host disease prophylaxis was the standard methotrexate and cyclosporine combination in 134 (83%) cases. Median post-transplant follow-up was 2.9 years. Leukemia-free survival (LFS) at 5 years was 50+/-12% for transplants during first complete remission (n = 16), 28+/-8% during second CR (n = 40), 27+/-17% during subsequent CR (n = 8), 7+/-3% during relapse (n = 81) and 19+/-10% during primary induction failure (n = 16). The cumulative incidences of relapse were 19%, 23%, 25%, 44% and 63%, for the five groups, respectively. Transplantation during remission, a marrow cell dose above 3.5 x 10(8)/kg, and cytomegalovirus seronegative status before BMT in both patient and donor were favorable prognostic factors. Adults in any CR who received a marrow cell dose above 3.5 x 10(8)/mg had a LFS of 54+/-9% at 5 years. These data extend our previous findings on the association between a high marrow cell dose and improved survival and support the use of unrelated donor BMT for treatment of patients with high risk AML when a family match is not available.

Acute Disease↗
PubMed2000

No impact of high-dose cytarabine on the outcome of patients transplanted for acute myeloblastic leukaemia in first remission. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

High-dose cytarabine is currently used in combination with anthracycline in the treatment of acute myeloblastic leukaemia (AML). Moreover, high-dose cytarabine has been reported to produce long-term disease-free survival in a proportion of patients, especially in certain subtypes of AML. However, it remains unknown whether the outcome of patients undergoing allogeneic or autologous stem cell transplantation is influenced by previous treatment with high-dose cytarabine. To this end, 1672 patients with AML in first remission who were reported to the Acute Leukaemia Working Party registry of the European Group for Blood and Marrow Transplantation (EBMT) and who were transplanted between 1980 and 1995 were analysed according to the dose intensity of cytarabine given at induction and/or consolidation. Autologous stem cell transplantation (ABMT) was performed in 846 patients and allogeneic bone marrow transplantation (BMT) in 826 patients. This study shows that the dose of cytarabine (Ara-C) given at induction and/or consolidation did not influence the relapse incidence in patients subsequently allografted or autografted. In addition, it did not give any advantage in terms of overall outcome. Therefore, high-dose (HD) Ara-C may not be needed for patients who have a planned stem cell transplantation (SCT) as post-remission therapy. Nevertheless, HD Ara-C may be utilized in certain subtypes of AML that are believed to be curable by chemotherapy alone.

Adolescent↗
PubMed2000

Feasibility and recent improvement of autologous stem cell transplantation for acute myelocytic leukaemia in patients over 60 years of age: importance of the source of stem cells.

A total of 193 patients with acute myelocytic leukaemia (AML) [147 in first complete remission (CR1)], ranging from 60 years to 75 years of age (median 63 years), were autografted between January 1984 and December 1998. The source of stem cells was peripheral blood (PB) in 128 patients, bone marrow in 51 patients and a combination of both in 14 patients. Total body irradiation (TBI) was used in 34 cases. Ninety-seven per cent of patients had successful engraftment of neutrophils on day 15 (range days 7-71) and of platelets on day 30 (range days 9-894). In patients autografted in CR1, the transplant-related mortality (TRM) was 15 +/- 4%, the relapse incidence (RI) was 58 +/- 5%, the leukaemia-free survival (LFS) was 36 +/- 5% and the overall survival was 47 +/- 5% at 3 years. The source and dose of stem cells were studied in particular; in patients transplanted in CR1, the RI was 44 +/- 11% in those receiving marrow compared with 63 +/- 6% in those receiving PB (P = 0.04). Patients autografted in CR1 who received higher granulocyte-macrophage colony-forming units (CFU-GM) doses (above the median) had a lower RI (47 +/- 11% vs. 79 +/- 9%, P = 0.009). There was a significant improvement in patients transplanted after March 1996; for those in CR1, the RI was 41 +/- 8% vs. 65 +/- 6% (P = 0.01), the LFS was 53 +/- 8% vs. 28 +/- 5% (P = 0.01) and the overall survival was 72 +/- 7% vs. 36 +/- 6% (P = 0.02). By multivariate analyses, significant factors for the outcome were the date of transplant with recent improvement and the source of stem cells, with a lower RI for marrow. Autologous stem cell transplantation (ASCT) is a potential therapeutic approach in patients with AML over 60 years of age; results have improved recently.

Aged↗
PubMed2000

Isolation of CD34+ progenitor cells from peripheral blood by use of an automated immunomagnetic selection system: factors affecting the results.

BACKGROUND: The isolation of CD34+ cells from mobilized peripheral blood is being increasingly used in the setting of allogeneic or autologous hematopoietic cell transplantation. Investigation of variables that may influence the effectiveness of CD34+ cell selection is of interest. STUDY DESIGN AND METHODS: Fifty-one CD34+ cell selections from peripheral blood progenitor cells (PBPCs) (39 allogeneic and 12 autologous) were performed using a magnetic cell separator (Isolex 300i, Baxter), including version 2.0 software. The results obtained were analyzed for different processing variables. The feasibility of transplanting these isolated CD34+ cells was also analyzed. RESULTS: The isolated CD34+ cell fraction had a median purity of 88.9 percent (range, 47.8-98.3). The median recovery of CD34+ cells was 45.1 percent (13.8-76.2), and the median colony-forming unit- granulocyte-macrophage (CFU-GM) content was 17. 2 percent (0.8-58.6). Logarithms of T- and B-cell depletion had median values of 3.7 and 2.8, respectively. The version 2.0 software of the Isolex 300i gave a higher CD34+ cell recovery in the enriched cell fraction (median 57.8%) than did version 1.11 (39.4%) or 1.12 (44.4%) (p = 0.01). The use of recombinant human deoxyribonuclease I during cell processing yielded more CD34+ cells (53% vs. 41%, p = 0. 01) and higher purity (92.8% vs. 87%, p = 0.03). There was a correlation between the percentage of CD34+ cells labeled with the monoclonal antibody 8G12 clone and the percentage of CD34+ cells labeled with the monoclonal antibody used during the processing technique (9C5 clone) in the initial, enriched, and depleted CD34+ cell fractions (R(2) = 0.95; 0.92; 0.78, p< 0.005, respectively). Median times for recovering >0.5 x 10(9) per L of granulocytes and >20 x 10(9) per L of platelets were 13 and 16 days in the allograft patients and 13 and 14 days in the autograft patients. CONCLUSION: CD34+ cells can be highly and effectively isolated from allogeneic and autologous grafts by use of this automated technique, with a high grade of T- and B-cell depletion. These purified CD34+ cell components can engraft normally.

Adult↗
PubMed2000

Expression of transforming growth factor-beta but not tumor necrosis factor-alpha, interferon-gamma, and interleukin-4 in granulomatous lung lesions in tuberculosis.

The expression of transforming growth factor (TGF-beta 1), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were assessed in lung tissues from patients with tuberculosis. Vimentin, a constitutively expressed cellular protein, was present in 12 of 19 tissue sections indicating adequate preservation of tissue proteins in these cases. Immunohistochemical studies for cytokines were done in the vimentin positive sections only. TGF-beta 1 was localized to mononuclear phagocytes of tuberculous lung lesions in 4 of 12 tuberculosis patients. TNF-alpha, IFN-gamma, and IL-4 were absent in sections from all tuberculosis patients. The failure to detect the latter cytokines may indicate that these molecules may not be expressed at the site of disease, or are not a feature of the late stages of tuberculous granulomas. TGF beta-1, although not universally expressed, may be involved in the development and/or consequences of tuberculous granuloma formation. These data substantiate further the role of TGF-beta 1 in the immunopathology of tuberculosis.

Antibodies, Monoclonal↗
PubMed2000

Autologous stem cell transplantation for high-risk Hodgkin's disease: improvement over time and impact of conditioning regimen.

BACKGROUND AND OBJECTIVE: High-dose chemo/radiotherapy with autologous stem cell support is increasingly being used in Hodgkin's disease (HD) patients who do not respond to or who relapse after conventional chemotherapy. In this work we analyze the results of 56 consecutive high-risk HD patients autografted in our institution and the role of possible prognostic factors. DESIGN AND METHODS: There were 34 males and 22 females with a median age of 31 years. At transplantation, 24 patients (43%) were in complete remission and 32 (57%) were autografted while with active disease. Twenty-nine patients were autografted before January 1993. Bone marrow was used as the source of stem cells in 40 patients (71%) and peripheral blood (PB) in 16 (29%). Forty-five patients received chemotherapy-based conditioning regimens (40 CBV and 5 BEAM) while the remaining 11 received cyclophosphamide (Cy) and total body irradiation (TBI). RESULTS: Two bone marrow transplantation (BMT) recipients did not engraft. Hematologic recovery was significantly faster in patients transplanted with PB progenitor cells. Early transplant-related mortality (early TRM) (before day 100 after transplantation) was 9%; it was higher in patients transplanted before January 1993 than in patients transplanted afterwards (14% vs 4%) and in patients receiving TBI (18% vs 7%), although these differences did not reach statistical significance. Overall TRM (before and after day 100) was 14%. TBI-containing regimens significantly increased overall TRM (36% and 9%, p = 0.03). Actuarial 3.5-year overall survival (OS), event-free survival (EFS) and progression-free survival (PFS) were 57%, 58% and 65%, respectively. On multivariable analysis, TBI containing regimens and transplantation before 1993 significantly reduced OS and EFS. INTERPRETATION AND CONCLUSIONS: Our results confirm that high-dose therapy followed by autologous stem cell transplantation is associated with sustained PFS in a remarkable proportion of patients with HD unlikely to be cured with standard chemotherapy. Results improved over time and TBI containing regimens had a negative effect on post-transplant outcome.

Adolescent↗
PubMed2000

Unrelated donor bone marrow transplantation as treatment for chronic myeloid leukemia: the Spanish experience. The Chronic Myeloid Leukemia Subcommittee of the GETH. Grupo Español de Trasplante Hemopoyético.

BACKGROUND AND OBJECTIVE: To analyze the results of unrelated bone marrow transplantation (UDBMT) as treatment for chronic myeloid leukemia (CML) in Spain. DESIGN AND METHODS: Eighty-seven consecutive UDBMT performed in 9 centers between October 1989 and February 1998 were evaluated. This represents more than 95% of UDBMT for CML performed in adult transplant centers in Spain during this period. The patients' median age was 31.5 years (range, 12-49). The median interval from CML diagnosis to UDBMT was 30 months (range, 3-160). Seventy-nine percent of transplants were performed during the first chronic phase (1CP). RESULTS: Actuarial probability of survival and disease-free survival at 4 years for the whole series was 24% (95% confidence interval [CI]: 14%-34%) and 20% (CI: 10%-30%), respectively. The cumulative incidence of relapse and transplant-related mortality (TRM) was 7% (CI: 4%-10%) and 71% (CI: 60%-82%), respectively. The main causes of death were graft failure (n=7), infection (n=23), and graft-versus-host disease (GvHD) (n=25). The actuarial probability of acute GvHD grade II-IV and grade III-IV was 56% (CI:46%-66%) and 36% (CI: 26%-36%), respectively. The cumulative incidence of extensive chronic GvHD was 18% (CI: 9%-27%). Univariate analyses showed that the pre-transplant factor with the highest influence on survival was disease status at transplant (30% in 1CP vs. 0% in advanced phases; p=0.0001). Other pre-transplant factors influencing survival among patients in 1CP were: patient's age (older than 30 years 11% vs. 48%), interval diagnosis-transplantation (longer than 2 years 17% vs. 55%), donor type (HLA, B, DRB1 identical 32% vs. 25%), CMV serologic status (donor and recipient negative 63% vs. 24%), year of transplantation (before 1995 19% vs. 40%), and conditioning regimen (cyclophosphamide plus total body radiation 40% vs. 16%). The main risk factors had a cumulative effect on survival. Thus, probability of survival ranged from 66% (CI: 39%-93%) in patients in 1CP, under 40 years of age, transplanted from an HLA, A, B, DRB1 identical donor during the first two years after diagnosis, to 0% in those with three or more risk factors. INTERPRETATION AND CONCLUSIONS: This experience shows that UDBMT used to have a high TRM that has progressively decreased along the years. At the present time, the results are encouraging, particularly when UDBMT is performed under favorable conditions.

Actuarial Analysis↗
PubMed2000

Combined use of reverse transcriptase polymerase chain reaction and flow cytometry to study minimal residual disease in Philadelphia positive acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: The Philadelphia chromosome in acute lymphoblastic leukemia (Ph+ ALL) is associated with a poor prognosis given the high frequency of chemoresistance and leukemia relapse. Minimal residual disease (MRD) detection before cytogenetic and hematologic relapse could be useful in early therapy. The most suitable methods for detecting MRD in Ph+ ALL are flow cytometry (FC) and reverse transcriptase polymerase chain reaction (RT-PCR). However, since both techniques carry the risk of false-negative results the combined use of these two techniques could overcome this problem. DESIGN AND METHODS: We report our experience using this approach in 47 bone marrow samples obtained from 10 Ph+ ALL patients. Twenty-seven marrow aspirates were taken from patients in clinical remission (CR). The samples were considered positive for MRD by FC when two conditions were met: 1) detection of an abnormal B-cell differentiation pattern and 2) presence of more than 1x10(-3) cells coexpressing CD22/CD34/CD45 or CD66/CD34/CD10. After FC analysis, RNA was purified using standard methods. RESULTS: FC was positive in 23/27 samples in CR (sensitivity 85%). RT-PCR was successfully performed in 23 samples in CR. RT-PCR was positive in 18/23 samples (sensitivity 78%). There were 5 samples with discordant results. FC was positive in 3 samples with a negative RT-PCR and FC was negative in 2 samples with a positive RT. All the 10 patients relapsed and only 1 is currently alive after an allogeneic stem cell transplantation (alloSCT). The median (range) time from MRD detection to relapse in patients treated with chemotherapy was 42 (39-71) days. INTERPRETATION AND CONCLUSIONS: These data suggest that RT-PCR may be negative despite the presence of neoplastic cells identified by their immunophenotypic traits. We conclude that immunologic and molecular techniques can be used in tandem for monitoring MRD in Ph+ ALL.

Adolescent↗
PubMed2000

Bronchoscopy guided by high-resolution computed tomography for the diagnosis of pulmonary infections in patients with hematologic malignancies and normal plain chest X-ray.

BACKGROUND AND OBJECTIVES: High-resolution computed tomography (HRCT) of the chest is able to demonstrate the presence of pulmonary infiltrates in febrile neutropenic patients with normal chest X-rays. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is a safe procedure for the etiological diagnosis of pulmonary infiltrates in oncohematologic patients. The objective of this study was to determine the diagnostic yield and subsequent therapeutic changes of a protected BAL (p-BAL) guided by HRCT in febrile oncohematologic patients unresponsive to broad-spectrum antibiotics with a normal chest X-ray. DESIGN AND METHODS: Twenty-two episodes from 20 oncohematologic patients were included: group A, 9 episodes (8 patients) with no respiratory symptoms and group B, 13 episodes (12 patients) with signs or symptoms of pulmonary infection. HRCT and p-BAL were performed in all episodes within the first 24 hours. RESULTS: HRCT showed abnormalities in all 22 episodes (bilateral abnormalities in 14 of the 22 episodes [64%]) and the most frequent pattern was ground-glass infiltrate (7 out of 22 episodes). An infectious agent was isolated in 12 of the 22 episodes, 5 in group A and 7 in group B with a diagnostic yield of 54%. Antimicrobial therapy was modified in 12 of the 22 episodes (54%): 5 in group A and 7 in group B. In 6 episodes, treatment was changed according to HRCT results and in the remaining 6 due to positive microbiologic results. Modifications in empirical therapy were associated with a favorable response in 44% episodes of group A and in 31% of group B. INTERPRETATION AND CONCLUSIONS: Oncohematologic patients with fever of unknown origin unresponsive to empirical antibiotics and with a normal chest X-ray can be candidates to undergo a HRCT. This subgroup of high-risk patients can benefit from a combined strategy consisting of BAL guided by a previous HRCT.

Adolescent↗
PubMed2000

Leukemic relapse as T-acute lymphoblastic leukemia in a patient with acute myeloid leukemia and a minor T-cell clone at diagnosis.

BACKGROUND AND OBJECTIVES: Lineage classification needs to be established before starting chemotherapy in acute leukemias. In some cases, mixed populations can be found and these are differentiated by antigenic expression patterns. DESIGN AND METHODS: We report the case of a patient with acute myelogenous leukemia whose relapse was classified as T-acute lymphoblastic leukemia (T-ALL). RESULTS: Flow cytometry analysis at diagnosis enabled us to identify a minor T-cell subclone which progressively increased and became dominant at relapse. There were no changes at cytogenetic and molecular levels. INTERPRETATION AND CONCLUSIONS: This case illustrates the usefulness of multiparametric flow cytometry for assessing minor leukemic populations.

Acute Disease↗
PubMed2000

Allogeneic peripheral blood stem cell transplantation with CD34+-cell selection and delayed T-cell add-back in adults. Results of a single center pilot study.

BACKGROUND AND OBJECTIVES: Allogeneic peripheral blood stem cell transplantation with CD34+ cell-selection (CD34+-PBSCT) allows rapid hematologic engraftment with a reduction in graft-versus-host disease (GVHD), although concerns exist regarding the increased risk of tumor relapse associated with T-cell depletion of the graft. Delayed T-cell add-back (TCAB) after such transplants may restore the graft-versus-tumor effect while achieving a reduced early transplant-related mortality due to less GVHD in a group of patients at high risk of early death (i.e., age >= 45 years). DESIGN AND METHODS: Ten patients 45 years of age or older with hematologic malignancies received a CD34+-PBSCT and cyclosporin A (CyA) to prevent acute GVHD, followed by a planned delayed donor TCAB of 107 T-cells/kg to restore the graft-versus-tumor effect. The infused graft included a median of 6.3x106 CD34+ cells/kg and 4.4x104 CD3+ cells/kg. RESULTS: Engraftment was prompt in all cases. Four patients developed acute GVHD after the CD34+-PBSCT and/or chronic GVHD after CyA withdrawal and did not proceed to TCAB, and two patients died early before the planned TCAB. Four patients proceeded to TCAB at a median of day +104 after CD34+-PBSCT (+92 to +150). Two of these patients developed acute GVHD grades I-II (IBMTR Index B) after TCAB and all four developed chronic GVHD, which was extensive in two. With a median follow-up of 611 days (range 499-847) after transplant in the seven survivors, there have been no disease progressions, and all patients show a pattern of complete donor chimerism in bone marrow and peripheral blood. INTERPRETATIONS AND CONCLUSIONS: The results of our pilot study suggest that this protocol produces an acceptable transplant-related morbidity and mortality in patients 45 years and older. However, there may be benefit in infusing CD34+-selected PBSCT with even lower T-cell contents and further delaying the TCAB.

Antigens, CD34↗