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Biomedical subjects

J Passweg

Publications and source records attributed to J Passweg.

52 records · Page 3Linked to original sources

Correction of spurious blood cell counts in a patient with cryoglobulinemia reversed by the use of citrate-anticoagulated blood.

Cryoglobulins may interfere with automated cell counting when proteins precipitate or blood cells aggregate. This results in spurious platelet or leukocyte counts, false values for red blood cell parameters and abnormal scattergrams. Usually it can be reversed by warming blood specimens to 37 degrees C. We describe the case of a 63-year-old woman with autoimmune disease in whom the diagnosis of cryoglobulinemia was suspected due to typical changes in blood cell counts. Artifacts were resistant to warming of the sample to 37 degrees C in both EDTA- and heparin-anticoagulated blood specimens. In contrast, the use of citrate as anticoagulant allowed correct measurements. This case underlines the role of assessment of blood counts in the detection of cryoglobulinemia. Correct measurements of automated blood counts in cryoglobulinemia may depend on the use of alternative anticoagulants.

Anticoagulants↗

[Optimizing plasma cell content in bone marrow aspirates].

Bone marrow samples used for flow cytometric analysis of plasma cells frequently provide a low plasma cell content. Regularly, samples used for flow cytometry are provided by second step aspiration while the first aspirate is used for cytologic examination. We investigated whether the use of secondary aspirates leads to a systematic underestimation of the bone marrow plasma cell content as a consequence of an increased blood contaminant. To test the hypothesis, plasma cell (CD38bright) percentages were established by flow cytometry in 13 pairs of primary/secondary aspirates. In all cases we found lower plasma cell contents in secondary as compared to primary aspirates (p = 0.0015). Median plasma cell counts in secondary aspirates were 57% lower compared to primary aspirates. We conclude that the use of secondary aspirates leads to systematic underestimation of the bone marrow plasma cell content.

Bone Marrow↗

[Immunophenotype of blast crisis in chronic myeloid leukemia].

The blast crisis in chronic myeloid leukaemia (CML) is morphologically well defined. The aim of this report was to analyze whether immunophenotyping can divide CML blast crises into subtypes as is done in acute de novo leukaemia, and whether a specific CML pattern exists. Between 1991 and 1997 we reevaluated all the immunophenotypes of patients with CML blast crises with special regard to immunological subclassification, expression of CD34, presence of aberrant markers and number of immunological clusters. Twenty-nine CML blast crises were analyzed. Seventeen were myeloid, 11 lymphoid and one biphenotypic. The blast crises were divided into subtypes as de novo acute leukaemias: of the 17 myeloid blast crises 6 were undifferentiated, 5 differentiated and 6 had monocytic differentiation. In the lymphoid blast crises there were no pro-B, 8 common-B and 3 mature-B. No T-lymphoid blast crises were observed. In 26/29 analyses (90%) CD34 was expressed in the blasts. In 17/29 analyses (59%) one or two aberrant markers were found. In summary, immunophenotyping is important in distinguishing between myeloid and lymphoid blast crises. A subclassification, as in acute leukaemias, is possible. We found no specific immunophenotypic CML pattern. A study directly comparing immunophenotyping of CML blast crises with acute de novo leukaemia is planned.

Adolescent↗

Blood and marrow transplantation activity in Europe 1996. European Group for Blood and Marrow Transplantation (EBMT).

Transplant activity by members of the European Group for Blood and Marrow Transplantation (EBMT) and related European teams is reported for 1996 by indication, donor type and stem cell source. Bearing in mind reports from previous years, the annual numbers of transplants for each indication, transplant rates for each participating country, changes in transplant rates by indication and changes in donor types and stem cell sources are described. A total 14,593 blood or marrow transplants, performed in Europe by 382 teams from 31 countries, were reported in 1996. Of these, 4393 (30%) were allogeneic and 10,200 (70%) were autologous transplants. Of the autologous transplants, 978 (10%) were bone marrow derived, 9222 (90%) from peripheral blood stem cells or combined bone marrow and peripheral blood stem cell transplants. Of the allogeneic transplants, 3252 (74%) were bone marrow and 1141 (26%) were peripheral blood stem cell transplants. Main indications in 1996 were leukemias with 4961 transplants (34%), 70% allogeneic and 30% autologous; lymphomas with 5505 transplants (38%), 6% allogeneic and 94% autologous; solid tumours with 3484 transplants (24%), 1% allogeneic and 99% autologous; non-malignant disorders with 643 transplants (4%), 92% allogeneic and 8% autologous. There are major differences between countries. Transplant rates per 10m inhabitants per country ranged from 0 to >500 (median 202 per 10 m inhabitants). The most pronounced increase since 1990 for new indications in autologous transplants was observed in multiple myeloma and carcinoma of the breast. These data reflect recent changes and present status of blood and marrow transplantation in Europe. They provide a basis for patient counselling and health care planning.

Bone Marrow Transplantation↗

Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia.

In a single-centre study the feasibility and efficacy of repeated antilymphocyte globulin (ALG) for patients with severe aplastic anaemia (SAA) not responding to an initial ALG treatment or relapsing after initial response to ALG was evaluated. 139 consecutive patients with newly diagnosed SAA were treated with ALG between 1976 and 1995. 89 patients responded to a first course; 50 patients did not become transfusion independent. Of the 89 responders, 66 remained in remission, 23 relapsed. 43 patients received a second or subsequent course of ALG for failure to respond (n = 25) or relapse (n = 18) and were given a total of 53 courses. Acute reactions in the multiply exposed patients occurred during the first ALG treatment in 11 (26%) and during subsequent exposures in 16/53 courses (30%; P > 0.2). Incidence of serum sickness was 63% (27/43) after the initial course compared to 57% (30/53) after subsequent courses (P > 0.2), but clinical signs of serum sickness occurred earlier after repeated (median 6 d) as compared to initial exposure (13d; P = 0.008). Transfusion-independent haemopoiesis was achieved in 27/43 (63%) and survival probabilities for the 43 patients receiving multiple courses of ALG was 52 +/- 8% at 10 years. The probability of developing a late clonal disorder was 53 +/- 10% after multiple, as compared to 34 +/- 7% after single exposure (P = 0.15). No difference in results was observed between patients retreated for failure to first ALG or for relapse. ALG of the same species can be repeated without increased risks of side-effects in patients with SAA. A second or subsequent course of ALG from the same source can be effective when the first course has failed.

Adolescent↗

Association of donor-derived host-reactive cytolytic and helper T cells with outcome following alternative donor T cell-depleted bone marrow transplantation.

Recipients of marrow from alternative donors (unrelated or HLA-mismatched related donors) have a higher incidence of post-transplant complications compared to recipients of marrow from HLA-identical siblings. HLA disparity undetected by routine typing techniques has been suggested as one cause for the increased complications observed. Limiting dilution analysis (LDA) of donor-derived, host-reactive T cell precursor frequency prior to transplant has been proposed as a surrogate indicator of underlying HLA disparity which might be used to predict transplant outcome and aid in donor selection. We compared results of LDA of host-reactive IL-2 producing helper T lymphocytes (HTLp) and/or cytolytic T lymphocytes (CTLp) in 77 alternative marrow donor/recipient pairs with transplant outcome using univariate and multivariate analysis. All donor grafts were depleted ex vivo of mature T cells. Median patient age was 15 years (1-53). Donor selection was based on serologic typing for HLA class I and high resolution oligotyping for HLA-DRB1-DRB5, and HLA-DQB1. HLA-A and HLA-B locus antigens were retrospectively defined by one dimensional isoelectric focusing (IEF). Cox proportional hazards regression models were used to assess the impact of frequency and estimated cell dose of CTLp and HTLp on outcome. The CTLp assay was most sensitive to HLA-A and HLA-B locus disparity detected by serology or IEF. The HTLp assay detected class I disparity but was most strongly reactive in the presence of HLA-DRB1 disparity. Univariate analysis indicated a significant association of CTLp frequency and dose with severe (grades 3-4) acute graft-versus-host disease (GVHD), and of CTLp dose with chronic GVHD. Both assays were associated with survival and neither assay was associated with relapse. After adjustment for other significant covariables including known HLA disparity, the association of CTLp with acute GVHD was lost, however, CTLp frequency and CTLp dose remained associated with survival and HTLp frequency was associated with chronic GVHD. These data support the hypothesis that post-BMT complications may be influenced not only by T cell dose but by the alloreactive potential of the cells infused. LDA of alloreactive potential was useful in detecting disparity and in predicting survival or chronic GVHD in recipients of alternative donor TCD marrow grafts.

Adolescent↗

Effect of T cell subset dose on outcome of T cell-depleted bone marrow transplantation.

T cell depletion using the murine monoclonal antibody (moAb) T10B9 is unique in that the T cell receptor (TCR)gamma delta bearing subset is relatively spared compared to the TCR alpha beta + subset. We evaluated the probabilities of engraftment, acute and chronic graft-versus-host disease (GVHD), relapse, and survival in 273 recipients of marrow T cell depleted using T10B9. Sixty-two patients received marrow from an HLA-identical sibling, 54 patients received partially matched related donor marrow and 157 patients received unrelated donor marrow. Limiting dilution analysis (LDA) was used to estimate total clonable T cell dose in all patients and a modified LDA using moAb-coated immunomagnetic beads was used to estimate TCR alpha beta +, CD4+, and CD8+ T cells in a subset of patients. TCR gamma delta + cell dose was estimated by flow cytometry. Cox proportional hazards regression models were used to assess the impact of T cell subset dose/kg of body weight on outcome. We found a significant association of TCR gamma delta + T cell dose (P = 0.004), but not TCR alpha beta + T cell dose or total clonable T cell dose, with the probability of engraftment. TCR alpha beta +, CD4+, CD8+ and total clonable T cell dose were significantly associated (P < 0.001) with the risks of grade 2-4 acute GVHD in recipients of marrow from related donors but not in recipients of marrow from unrelated donors. Neither total clonable T cell dose nor any T cell subset dose was found to be significantly associated with chronic GVHD, relapse or survival. The results confirm preclinical studies showing TCR gamma delta + T cells promote engraftment. TCR gamma delta + T cells are not associated with an increased risk of acute GVHD while TCR alpha beta T cells are associated with acute GVHD but not engraftment in recipients of marrow grafts T cell depleted using T10B9. These findings support the hypothesis that T cell subsets differentially contribute to alloengraftment and GVHD.

Adolescent↗

Monoclonal gammopathy after intense induction immunosuppression in renal transplant patients.

OBJECTIVES: Incidence and risk factors of post-transplant monoclonal gammopathy were studied in renal transplant patients who received their grafts between 1982 and 1992 (n = 390 grafts). Immunoelectrophoresis was performed at annual intervals after transplantation. RESULTS: Forty-six cases of clonal gammopathy were detected: 35 monoclonal, 11 bi- or triclonal, with a predominance of IgG and kappa light-chain subtypes (IgG, 39; IgA, 3; IgM, 4; kappa, 35; lambda, 19). Gammopathy was incidence of gammopathy was 10.7%, much higher than expected for a group of similar age from the general population. Thirty of the 46 gammopathies appeared within the first 2 years of transplantation. Gammopathy never progressed to multiple myeloma during follow-up (median 1 year; (range 0-10)); one patient subsequently developed Kaposi sarcoma. The 2-year incidence of gammopathy was much higher in patients transplanted in 1989-1991 (23/142) than in 1982-1988 (7/248) (P < 0.0001). This coincided with the use of quadruple induction immunosuppression (cyclosporin A+azathioprine+prednisone plus either ATG-fresenius (ATG-F) or OKT3) since 1989. The risk for acquiring gammopathy within 2 years of transplantation was 14.7% (95% CI 9.2, 20.3%) in patients receiving quadruple induction therapy, but only 3.0% (CI 1.2, 6.1%) without such therapy (P < 0.0001). The risk for patients receiving quadruple immunosuppression with OKT3 was 24.5%, significantly greater than with ATG-F (11.8%, P < 0.05). Discriminant analysis revealed that the type of immunosuppression, but not age or year of transplantation, were independent risk factors for gammopathy. CONCLUSION: Monoclonal gammopathy frequently occurs after renal transplantation. Risks are higher for patients receiving quadruple induction immunosuppression, particularly if it includes OKT3. Follow-up of these patients is warranted for the early detection of malignant transformation.

Antilymphocyte Serum↗

[Hydroxyurea, erythrocyte volumes and hemoglobin F].

Hydroxyurea is used in the treatment of sickle cell anemia and beta-thalassemia major to increase the content of hemoglobin F (HbF) and presumably ameliorate clinical symptoms. Under therapy with hydroxyurea an increase of the mean corpuscular volume (MCV) of the erythrocytes can be observed. To evaluate a possible estimation of the content of HbF using the increase of MCV under treatment with hydroxyurea, we measured MCV and HbF during therapy with hydroxyurea. The median MCV before therapy was 87.8 fl (range 74.3-95.7) and under hydroxyurea 104.1 fl (81.0-139.5), and the median HbF 1.8% (0.1-5.4). Although both MCV and HbF increased under treatment with hydroxyurea, a linear correlation between these two parameters was not detectable. Therefore, MCV cannot replace the measurement of HbF.

Erythrocyte Indices↗

[Late idiopathic pneumopathy following bone marrow transplantation].

4 of the 198 patients treated by bone marrow transplantation in Basel, Switzerland, with a follow-up of more than one year after therapy, developed a severe restrictive pneumopathy. In none of the 4 patients could an infectious pathogen be isolated, but all of them had signs of a chronic graft-versus-host disease. The 4 cases are described in detail.

Adolescent↗

Comparison of fluconazole with oral polyenes in the prevention of fungal infections in neutropenic patients. A prospective, randomized, single-center study.

The goal of this prospective randomized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole (400 mg daily) (group A) with oral nystatin plus miconazole inhalations (group B) in the prevention of fungal infections on a hemato-oncological isolation Ward. Of 157 patients admitted to the isolation ward during the study period only 90 (57%) were eligible for randomization; 22 (14%) had a fungal infection at admission. Of the 90 randomized patients, 89 were evaluable, 43 in group A and 46 in group B. The age, sex, diagnosis, planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups. Oral thrush and mucocutaneous candidiasis were prevented in all patients of both groups, and 29 patients (32%: 17 in group A, 12 in group B) were discharged after successful prophylaxis (NS). Empiric amphotericin B was given according to predetermined criteria to 45 patients (51%: 23 group A, 22 group B; NS). Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days (0-45 days, range) of neutropenia below 0.5 x 10(9) granulocytes/l in group A and 7.5 days (0-26, range) in group B (P < 0.05). The duration of successful prophylaxis was significantly longer in group A (26 days median) than in group B (21 days, median) (P < 0.05). Systematic fungal infection was documented in 3 patients (1 group A, 2 group B; NS).

Adolescent↗

[How long should cyclosporin be administered following bone marrow transplantation?].

After organ transplantation, life-long immunosuppression is mandatory to prevent rejection. This is not the case after allogeneic bone marrow transplantation (BMT). The mechanisms of tolerance are little understood and there is little data about the required duration of immunosuppression. In a retrospective study we analyzed the use of cyclosporine A (CyA) treatment in all BMT patients who where transplanted in Basel from 1979 to 1991. 243 patients with a median age of 26 (2-49) years received CyA to prevent graft-versus-host-disease (GvHD) and rejection. 206 patients had leukemia, 26 severe aplastic anemia and 10 a lymphoproliferative disorder. All were treated according to a common CyA regimen with initial parenteral administration followed by oral treatment for a year; after 1988 treatment duration was reduced to 6 months. Drug dosage was adjusted according to clinical symptoms, plasma levels and toxicity. At relapse of the original disease CyA was always withdrawn. Three months after BMT 96% were still on CyA. After 6 months 79%, after 1 year 61%, after 2 years 29%, after 3 years 18%, after 4 years 15%, after 5 years 8% and after 8 years 2% of patients were still taking CyA. All 20 patients who are still alive 10 years after BMT are off CyA. CyA was administered parenterally for a median of 31 (5-147) days. Oral treatment started at day 25 (4-28). The oral dose was reduced 5 (1-20) times, increased once (1-75) and finally discontinued after a median time lapse of 1 year (14d-8y).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Isolation ward: initial experiences after 4 years].

UNLABELLED: Since October 1988 there has been an isolation ward at Basle Cantonal Hospital. Its purpose is to treat patients with high dose chemotherapy and bone marrow transplantation under protective isolation and by standardized criteria. The isolation ward has two sub-units, viz. the reverse isolation for neutropenic patients (8 single room units) and the LAF unit (5 laminar airflow units) for allogeneic bone marrow transplantation (BMT). Up to July 1992, 287 patients (152 males and 133 females) required 527 hospitalizations. The median age was 41 (5-82) years in the reverse isolation unit and 28 (4-61) years in the LAF unit. Bed occupation was 90% and 82% throughout the period. 71% of patients were from the Basle area and the rest from elsewhere in Switzerland or from other countries. DIAGNOSIS: acute leukemias (112); myelodysplastic or myeloproliferative syndromes (52); severe aplastic anemia or agranulocytosis (46); lymphoproliferative syndromes (50); solid tumors (28). Indications for hospitalisation: BMT (107); complications after BMT (infections, GvHD) (63); chemotherapy on protocols of SAKK (105); other chemotherapies (64); antilymphocyte globulin or growth factor treatment (27); splenectomies (18); neutropenic fever (62); patient work-up (59); terminal care (20). Patients in reverse isolation were hospitalized for a median 17 (1-142) days; in the LAF unit for 52 (1-121) days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Use of salivary levels to predict clearance of caffeine in patients with cystic fibrosis.

The quantification of liver function is possible using the approach of salivary caffeine clearance. Hepatopathy sometimes complicates cystic fibrosis (CF), thus suggesting the use of this diagnostic tool in CF as well. Since in CF some compounds are poorly absorbed or abnormally metabolized, and the function of salivary glands or renal tubuli partly impaired, caffeine was measured in urine, blood, and saliva after a single oral dose of 3 mg/kg in CF patients. The urinary excretion rate of caffeine was normal in five CF patients. The caffeine levels in plasma or saliva, measured 4 to 5 h and 16 to 17 h after caffeine intake, were normal in 34 nonhepatopatic CF patients. The calculated salivary caffeine clearance was comparable in the 34 nonhepatopatic CF patients (1.88 +/- 0.46 ml/min/kg) and in the control group (1.88 +/- 0.44 ml/min/kg). In CF patients, no correlation was found between caffeine clearance and body weight, height, relative underweight, dosage of pancreatic enzymes, or Chrispin-Norman x-ray score. The salivary caffeine clearance was reduced in seven hepatopathic CF patients (1.32 +/- 0.63 ml/min/kg, p less than 0.01); nevertheless, the salivary caffeine clearance was reduced (boundary line at 1.1 ml/min/kg) in three CF patients with proven liver cirrhosis but not in four with hepatosplenomegaly and altered liver tests. These data indicate an unaltered caffeine metabolism in CF and open the way for the use of this diagnostic procedure in CF as well. This test might be valuable in CF patients with clinical or laboratory findings suggesting liver involvement.

Adolescent↗