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J Sierra

Publications and source records attributed to J Sierra.

At least 181 records · Page 10Linked to original sources
PubMed1994

Different response to recombinant human granulocyte-macrophage colony-stimulating factor in primary and secondary graft failure after bone marrow transplantation.

The efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in graft failure after bone marrow transplantation (BMT) has been evaluated in 25 patients. rhGM-CSF was administered intravenously at a dose of 5 or 10 micrograms/kg. Fourteen patients (seven allogeneic BMT [allo-BMT], seven autologous BMT [ABMT]) were treated for primary bone marrow failure (no granulocyte recovery after BMT), and 11 cases (all allo-BMT) received rhGM-CSF for secondary bone marrow failure (absolute neutrophil count lower than 0.5 x 10(9)/L after a previously sustained granulocyte recovery). Two allo-BMT and three ABMT patients with primary bone marrow failure achieved a granulocyte response to rhGM-CSF. In contrast, nine patients with primary graft failure did not respond to rhGM-CSF (four ABMT, three HLA-identical T-depleted BMT, one minor mismatch BMT, one unrelated BMT). Ten of 11 allo-BMT patients treated for secondary bone marrow failure attained an ANC higher than 0.5 x 10(9)/L, but most became severely neutropenic again at a median time of 4 weeks. The possible cause triggering graft failure (graft-vs.-host disease [GVHD], cytomegalovirus [CMV] infection) remained unsolved in most of these cases. Actuarial probability of survival of the entire series was 16 +/- 9% at 15 months. The severity of graft failure and the presence of other concomitant complications in most of our patients may justify these poor results. In conclusion, rhGM-CSF had less efficacy in patients with primary bone marrow failure than in those with secondary bone marrow failure. In the latter setting, measures addressed to correct the initial cause of graft failure are mandatory.

Adolescent↗
PubMed1993

Magnetic resonance imaging measurements and clinical changes accompanying transtentorial and foramen magnum brain herniation.

Current concepts of brain herniation have depended largely on correlating clinical signs and symptoms with indirect radiographic studies and the results of postmortem neuropathology. This article describes measurements on midsagittal magnetic resonance imaging (MRI) scans that distinctly define normal and abnormal rostral-caudal relationships between the diencephalic-mesencephalic junction and the plane of the tentorial incisura, herein termed the incisural line. We similarly provide quantitative MRI scan measurements relating the cerebellum and the plane of the foramen magnum, termed the foramen magnum line. Measurements from 156 midsagittal and 63 coronal MRI scans performed on 123 normal adults, placed the iter of the aqueduct 0.2 +/- 0.8 mm (mean +/- SD) below the incisural line and the cerebellar tonsils 0.1 +/- 2.1 mm below the foramen magnum line. Defining 2 SD from these norms as abnormal, 23 patients with intracranial mass or obstructive lesions showed 4 distinct patterns of brain herniation, i.e., upward or downward transtentorial shift with or without accompanying cerebellar tonsillar herniation. Five patients with posterior fossa masses demonstrated displacement of the iter above the incisura ranging from 1.6 to 6.3 mm. Eighteen patients with supratentorial masses demonstrated displacement of the iter ranging from 2.0 to 11.0 mm below the incisura. Two-thirds of patients with upward and one-half of those with downward transtentorial shift had concurrent tonsillar herniation. In acute illnesses, MRI scan changes anticipated or confirmed clinical signs of brain herniation. In chronic cases, clinical and MRI scans correlated less well, with MRI sometimes revealing major degrees of anatomical herniation well in advance of clinical abnormalities.

Adolescent↗
PubMed1993

On the reliability of clinical criteria for the diagnosis of hepatic veno-occlusive disease.

Among 217 patients who received an allogeneic (136 cases) or autologous (81 cases) bone marrow transplant, the diagnosis of hepatic veno-occlusive disease (VOD) was established in 38 according to Seattle clinical criteria. Thirty-two underwent a transjugular liver biopsy and measurement of the hepatic venous pressure gradient (HVPG). The study was completed in 30 patients with no serious complications. Hepatic VOD was histologically confirmed in 18 patients (60%); the remaining 12 were classified as non-VOD. An increased HVPG discriminated well between VOD and non-VOD cases. Thus, hemodynamic data can considerably reinforce the accuracy of histological diagnosis. The predictive value of two vs. three clinical data of the Seattle criteria was analyzed. Among the 19 cases fulfilling two clinical data VOD was confirmed in only eight (42%), whereas VOD was proved in ten of 11 cases (91%) (p = 0.02) suspected on the basis of three clinical data. When reliability of the Baltimore clinical criteria was analyzed, the result was identical to that observed when three Seattle clinical data were present. The specificity of the latter classification was high (92%) while its sensitivity was relatively low (56%). In conclusion, clinical criteria are not reliable for either recognizing or excluding the diagnosis of VOD. Thus, a transjugular liver biopsy, associated with hemodynamic evaluation, is strongly recommended when VOD is clinically suspected.

Adolescent↗
PubMed1993

Frozen vs. nonfrozen bone marrow for autologous transplantation in lymphomas: a report from the Spanish GEL/TAMO Cooperative Group.

To investigate the impact of frozen and non-frozen bone marrow on engraftment kinetics and disease outcome, 94 patients with non-Hodgkin's lymphoma (NHL) autografted with frozen marrow (F group) were retrospectively compared with 38 who received marrow stored at 4 degrees C or 10 degrees C (NF group). The major end points of this study were time to hematopoietic recovery and early toxicity; disease response, disease-free survival (DFS), and relapse rate were also analyzed. Upon comparison of the NF and F groups, no significant differences were found in the period of time required to achieve a granulocyte count higher than 0.5 x 10(9)/l (20 and 22 days, respectively, p = 0.47) or a platelet count higher than 20 x 10(9)/l (28 and 27 days, respectively, p = 0.54). In addition, both groups behaved similarly in respect to toxic death (NF group 13%, F group 22%, p = 0.36), response rate (complete remission rate 78% in both groups), DFS (NF group 48%, F group 49%, p = 0.66), and relapse rate (NF group 30, F group 19%, p = 0.37). This study confirms that nonfrozen bone marrow is useful to support patients with NHL treated with myeloablative therapies.

Adolescent↗
PubMed1993

Risk factors for early mortality in allogeneic bone marrow transplantation. A multivariate analysis on 174 leukaemia patients.

Allogeneic bone marrow transplantation in patients with leukaemia is an aggressive therapeutic procedure which implies high early mortality. Current opinion trends attribute the greater part of the procedure toxicity to the preparative regimen. The results of a multivariate analysis on data of 174 leukaemia patients conditioned with total body irradiation (TBI), 10-12 Gy, single dose or fractionated, and lung shielding at 8 Gy, plus chemotherapy: cyclophosphamide 120 mg/kg, before or after TBI, are presented. The variables statistically related with early mortality are age, Karnofsky index (KI) and acute graft-versus-host disease (GvHD). No variable depending on radiotherapy reached the significance level. The relative risk of early mortality for patients older than 26 years, in bad general condition (KI < 90%), or developing acute severe (grades II-IV)GvHD, is 3.99, 5.68, and 6.71, respectively. We conclude that in the range of TBI schedules analysed, radiation therapy is not an important factor in early death, but acute severe GvHD, or recipient's bad general condition are factors to be improved by bone marrow transplantation teams if they want to improve the therapeutic index of the procedure.

Adolescent↗
PubMed1993

Hematological recovery after autologous bone marrow transplantation in acute leukemia: predictive factors.

The kinetics of hematological recovery after autologous marrow transplantation have been studied in 70 patients with acute leukemia (38 acute nonlymphoblastic leukemia [ANNL] and 32 acute lymphoblastic leukemia [ALL]). The incidence of graft failure in this group was 3.2%, and a persistent severe thrombocytopenia was observed in 24% of the cases. Variables influencing engraftment have been studied using univariate and multivariate statistical analysis. Analysis of the entire group showed a correlation between graft colony-forming unit granulocyte-macrophage (CFU-GM) content and granulocyte recovery (p < 0.001). Marrow purging was associated with a delayed engraftment (p < 0.001). In ANLL patients, we found that high cummulated AraC doses before marrow cryopreservation correlated with poor granulocyte recovery after marrow infusion (p < 0.002). Platelet recovery was essentially affected by age, with shorter thrombocytopenia periods in younger patients (p < 0.001). Finally, excluding autotransplants with purged marrows, ALL patients showed better platelet recoveries than ANLL patients (p < 0.005). These findings will be useful to evaluate the risk of delayed engraftment after autologous bone marrow transplantation (ABMT) in patients with acute leukemia.

Acute Disease↗
PubMed1993

Large-cell lymphoma: a study of prognostic factors and assessment of five recently proposed predictive systems.

The main initial and evolutive variables of 133 patients with large-cell lymphoma treated with adriamycin-containing regimens were evaluated for prognostic significance. At the time of analysis, 66 patients had died with the median survival of the series being 48.9 months. Variables associated with poor prognosis in the univariate study were: lymphoma of immunoblastic subtype, advanced Ann Arbor stage, presence of B-symptoms, poor performance status, bulky disease (> or = 10 cm), involvement of two or more extranodal sites, bone marrow infiltration, and high serum LDH levels. In the multivariate analysis, Ann Arbor stage (p < 0.001), bulky disease (p = 0.004), performance status (p = 0.018), and histologic subtype (p = 0.021) retained their prognostic value. After excluding those patients with localized disease (stage I), the Ann Arbor staging system lost prognostic significance in favor of bone marrow infiltration (p = 0.009) and serum LDH (p < 0.001). However, when response to treatment was included in the regression model, it proved to be the most important prognostic factor (p < 0.001), followed by serum LDH (p = 0.004). On the other hand, when the analysis was restricted to complete responders, serum LDH at diagnosis was the only parameter useful to predict survival (p = 0.008). Finally, five recently proposed prognostic classifications were useful to separate different risk-groups of patients when applied to the series.

Aged↗
PubMed1993

[Immunophenotyping study of bone marrow fractions obtained by elutriation in allogeneic bone marrow transplantation].

PURPOSE: Bone marrow transplantation (BMT) is an effective treatment for acute and chronic leukaemias. Lymphocyte depletion of donor bone marrow for preventing GVHD has been associated with a higher incidence of relapse after allogeneic BMT. This association suggests an antileukaemic effect of donor lymphocytes. In vitro studies show that cytotoxic T lymphocytes (CD3+ CD56+) and NK cells (CD3-CD56+) have an antileukaemic effect. To know which specific subpopulation of lymphocytes are depleted by counterflow centrifugation or elutriation, we analysed B, T, NK cells and hematopoietic precursors in the marrow fractions after this procedure. PATIENTS AND METHODS: Eight patients (6 CML, 1 ALL, 1 B-CLL) received an allogeneic BMT with lymphocyte depletion of the bone marrow graft using elutriation. After a Percoll gradient, donor marrow mononuclear cells (MNC) were separated with this method in five fractions (F1 to F5). RESULTS: Lymphocyte depletion of donor marrow was in average of 1.7 log. This depletion was also selective, the last fraction containing higher number of cytotoxic T lymphocytes and NK cells than the other fractions. Recovery of CD34+ cells in the four fractions concerning to post-Percoll marrow was 84%, most of them being in the last fraction. CONCLUSIONS: The use of elutriation for lymphocyte depletion is a good method for graft manipulation with the feasibility to adjust a lymphocyte/Kg. dose. Elutriation may be effective in reducing the incidence and severity of graft versus host disease and preserving the antileukaemic effect.

Adult↗
PubMed1993

Doppler echocardiographic evaluation of the Bioflo pericardial bioprosthesis.

The Bioflo pericardial bioprosthesis was introduced to improve the durability of previous pericardial bioprostheses by means of a protective sheath of bovine pericardium around the stent. It has since been withdrawn from the market. Before its withdrawal, we studied 19 patients with mitral Bioflo valves (three of 25 mm, seven of 27 mm, eight of 29 mm, one of 31 mm) and 21 patients with aortic Bioflo valves (eight of 19 mm, nine of 21 mm, four of 23 mm) between two weeks and six months postoperatively, at which time all were in NYHA functional classes I or II. Standard Doppler echocardiographic measurements were taken to determine the effective orifice area of all valves, the peak and mean diastolic gradients across the mitral valves, and the peak and mean systolic gradients across the aortic valves. The smaller Bioflo valves performed poorly both in absolute terms and in comparison with other valves, presumably due to a reduction in the effective orifice area by the protective sheath. This finding should be borne in mind by the designers of future pericardial bioprostheses.

Adult↗
PubMed1993

Autologous bone marrow transplantation for acute leukemia: results and prognostic factors in 90 consecutive patients.

The results of autologous bone marrow transplantation (ABMT) in acute leukemia (AL) and the prognostic factors for outcome were analyzed in a series of 90 consecutive patients treated at a single institution (mean +/- SD age: 25 +/- 11 years). Diagnosis was: AML (n = 43), ALL (n = 44), acute undifferentiated leukemia (n = 2) and acute bilineage (n = 1). Disease stage at ABMT was: first complete remission (CR1) 46 cases, CR2 33, other stages 11. Conditioning consisted of cyclophosphamide and total body irradiation in 88 patients. The 3 year probability of disease-free survival (DFS) was influenced by disease stage at ABMT: CR1 48%, CR2 28%, CR3 plus CR4 15%. The characteristics associated with a high probability of relapse were: in AML a FAB subtype other than M1 or M3 (p = 0.01) and in ALL an interval between CR1 and ABMT of < 3 months (p = 0.002). A WBC > 15 x 10(9)/l at diagnosis (p = 0.01), splenomegaly at diagnosis (p = 0.002) and time to CR1 > 4 weeks (p = 0.06) increased the risk of relapse in the entire group in CR1. In multivariate analysis, WBC at diagnosis (p = 0.006) and disease stage at ABMT (p = 0.03) independently influenced DFS. This study confirms the encouraging results of ABMT in CR1 but further antileukemia measures are necessary in patients with adverse prognostic features.

Acute Disease↗
PubMed1993

Immunophenotypic characteristics of blast crisis of chronic myeloid leukaemia: correlations with clinico-biological features and survival.

Blast cells from 40 patients with Philadelphia-positive chronic myeloid leukaemia (CML) in blast crisis were analysed by immunophenotypic methods. In 27 cases, BCR gene studies were also performed. By light microscopy morphology and cytochemistry the cases were classified as follows: undifferentiated (n = 7; 17.5%), myeloid (n = 27; 67.5%), and lymphoid (n = 6; 15%). On the basis of the immunological markers, the cases were reclassified as: myeloid (n = 17; 42.5%), megakaryoblastic (n = 17; 42.5%), and lymphoid (n = 6; 15%). The seven cases initially considered as undifferentiated by morphological and conventional cytochemical criteria were classified as myeloid (four cases) and megakaryoblastic (three cases) by marker analysis. The monoclonal antibody anti-myeloperoxidase (anti-MPO) was the most sensitive myeloid associated marker in these cases, being positive in five of them. A significant proportion (27%) of non-lymphoid blast crisis cases were CD7-positive, and myeloid markers were positive in the four lymphoid CML-CB cases studied. Analysis of the clinico-haematological characteristics on the various subgroups of patients showed that patients with lymphoid blast crisis had shorter duration of the chronic phase, more frequent extramedullary blastic involvement, more favourable response to therapy, and longer survival. Finally, a trend for an association between megakaryoblastic involvement of blast crisis and breakpoint localization in the 3' extreme of the M-bcr segment was also noted.

Adolescent↗
PubMed1993

Interstitial pneumonitis after BMT: 15 years experience in a single institution.

Data from 311 patients with hematological malignancies who received an autologous, allogeneic or syngeneic BMT in a single institution were analyzed. Interstitial pneumonia (IPn) was observed in 58 patients. Two years actuarial probability of IPn was 26.8%. In 50% of cases CMV was detected. In 23 patients (39.7%) IPn was considered idiopathic. The median time from BMT to IPn was 63.5 (range 7-720) days. Patients submitted to allogeneic BMT had a significantly higher risk of developing IPn than patients receiving syngeneic or autologous BMT (34.1% vs 16.7% and 4.9%, respectively; p = 0.0006). Among 230 patients receiving allogeneic transplant, factors with a higher risk for IPn in univariate analysis were: age over 20 years, CML, alloimmunized donor, previous splenectomy, acute and chronic GVHD. When the analysis was restricted to patients with a CMV-associated IPn, all factors except alloimmunization maintained their significance. Multivariate analysis showed that only acute GVHD (p < 0.0001) and a diagnosis of CML (p < 0.001) in the whole group of allogeneic transplants, and acute GVHD (p < 0.001) and splenectomy (p < 0.003) in CMV-associated IPn, maintained their significance. These results are discussed within the frame work of the clinical application of BMT.

Adolescent↗
PubMed1993

Transjugular liver biopsy in BMT.

With the aim of evaluating liver disturbances after BMT in 76 patients, the hepatic venous pressure gradient was measured and a transvenous liver biopsy was performed through the jugular vein. Catheterization was successful in 71 patients (93%). In 11 cases the procedure was performed twice, yielding a total number of 82 studies. In five (6%) liver biopsies were non-evaluable. Complications were rare (7%), minor and reversible. As a result of this procedure, the diagnosis was modified in 45%, with both the diagnosis and treatment being modified in 30% of patients. Veno-occlusive disease (VOD) was histologically demonstrated in 15 out of 26 patients (58%) in whom this complication was suspected and in two out of 33 (6%) in whom it was not. Acute GVHD of the liver was confirmed in 15 out of the 35 patients (43%) in whom this complication was suspected and in four of 24 (17%) in whom it was not. The hepatic venous pressure gradient was significantly higher in VOD than in liver GVHD. Whereas 14/17 (82%) patients with VOD had a gradient pressure higher than 9 mmHg, no patient with GVHD had a gradient above this value. We conclude that transjugular liver biopsy is an effective, safe, and useful technique to evaluate BMT related liver dysfunction.

Biopsy↗
PubMed1992

Chronic systemic candidiasis in acute leukemia.

In the past few years a new syndrome of invasive Candida infection, the so-called hepatosplenic or chronic systemic candidiasis (CSC), has been recognized with increasing frequency in neutropenic patients. From January 1985 to December 1990, ten of 305 acute leukemia (AL) patients treated at our institution were diagnosed as having CSC. In contrast, during the same period this type of Candida infection was not observed in any patient with hematological diseases other than AL treated in our center, including 277 patients who underwent bone marrow transplantation. All patients with CSC had fever and hepatomegaly, and five complained of abdominal pain. Seven patients had neutrophilic leukocytosis and six an increased serum alkaline phosphatase activity. Abdominal computed tomography and ultrasound study showed typical lesions in eight and seven patients, respectively. In four patients a laparoscopy-guided needle liver biopsy displayed yellowish nodules on the liver surface, and the histologic study revealed large granulomas with yeasts and pseudohyphae. All patients were given amphotericin B (mean: 4.6 g, range: 1-12.5 g) and 5-fluorocytosine, and five received fluconazole. No patient died as a direct consequence of CSC and in six the infection resolved. Finally, once controlled, the infectious complication did not preclude subsequent intensive antileukemic therapy, including bone marrow transplantation.

Adolescent↗
PubMed1992

The value of detecting surface and cytoplasmic antigens in acute myeloid leukaemia.

The immunophenotype of leukaemia cells from 60 patients with acute myeloid leukaemia (AML) was analysed with the APAAP technique using a panel of anti-myeloid and lymphoid associated monoclonal antibodies (McAb). Cells from all cases, including three with negative cytochemical features, were labelled by at least one of the anti-myeloid McAb CD13, anti-myeloperoxidase (anti-Mpo), and/or CD14. The most sensitive marker was CD13, since it was positive in 90% of cases. In two out of three AML cases defined as M0-AML, CD13 was expressed in the cytoplasm but not on the membrane; in these three cases peroxidase (Mpo) was not detected by conventional cytochemistry, but could be demonstrated in all of them using the McAb anti-Mpo. The simultaneous expression of CD14 and CD68 McAb was often confined to the M4 and M5 FAB AML subtypes (92% cases) as compared to the others: M1, M2, M3 (18% cases). Lymphoid antigens were rarely positive (TdT+: 13%, CD7+: 15%, CD19+: 5%) and none of the AML cases were CD3+ or CD10+. By contrast, CD4 was expressed in blasts from 44% of cases and this was not restricted to AML with a monocytic component (M4, M5) but also found in other subtypes. There were no significant differences in the clinical or prognostic features according to the positivity or negativity with TdT and CD4. By contrast, expression of CD7 was associated with refractoriness to the treatment or short complete remission duration, although the number of patients is too small to draw firm conclusions. Our findings support the clinical and diagnostic relevance of immunophenotypic studies in AML.

Acute Disease↗