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Biomedical subjects

I Schwarzinger

Publications and source records attributed to I Schwarzinger.

At least 73 records · Page 4Linked to original sources
PubMed1995

Kinetics of minimal residual disease during induction/consolidation therapy in standard-risk adult B-lineage acute lymphoblastic leukemia.

We have compared the kinetics of minimal residual disease (MRD) by simultaneous polymerase chain reaction (PCR) monitoring with oligonucleotides for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 (CDR3) and the T-cell receptor gamma chain gene (TCR gamma), as well as clone-specific CDR3 sequences in adult patients (aged 17-51 years) with acute lymphoblastic leukemia (ALL) who entered a complete hematological remission (CR) after chemotherapy with the German multicenter ALL (GMALL) protocol. The sensitivities were one in 10(2-3) for the CDR3- and TCR gamma-PCR and one in 10(5-6) for a two-step, seminested CDR3/clone-specific PCR. At diagnosis, 7/7 patients were CDR3 positive and four were TCR gamma positive in their bone marrow (BM). At the end of induction therapy (after 2 months) 4/6 tested positive for CDR3, 2/6 for TCR gamma, and 5/6 for clone-specific rearrangements. At the end of consolidation treatment (after 7 months) only 1/7 remained positive for CDR3, 2/7 for TCR gamma, and 5/7 for clone-specific rearrangements. After an observation period of 18-36 months, 4/7 patients were still in CR and all were PCR negative by the clone-specific method during or after maintenance therapy. Two patients died in leukemic relapse; one patient relapsed but is still alive. All three of these patients remained PCR positive throughout the course of their disease. Clonal evolution in the IgH locus was found in one of these patients. We conclude that the molecular response to chemotherapy in adult B-lineage ALL is slow, even in patients without risk factors other than age. As in childhood ALL, most patients with long-term CR convert to PCR negativity approximately 18 months after the start of chemotherapy. The data also suggest the existence of early clone-specific PCR negativity in a small proportion of long-term survivors. The predictive value of this observation will now have to be confirmed in a larger study.

Adolescent↗
PubMed1995

Evaluation of a total hematology analysis system (Sysmex HS-430). Benefits for large laboratories by reducing manual work load and optimizing screening efficacy for pathologic samples.

In this study, the authors evaluated a closed tube total hematology analysis system, Sysmex HS-430 (HS), which consists of two automated hematology analyzers, Sysmex NE-8000, the reticulocyte analyzer, Sysmex R-3000, and a slide preparation unit integrated in an automated sample transport system (TOA Medical Electronics, Kobe, Japan). The suitability of the system was compared with a conventional hematology system (CS) consisting of two single standing Coulter STKS analyzers (Hialeah, FL), one automated reticulocyte counter Sysmex R-1000, and the manual blood smear preparation. Evaluation was performed following the concept suggested by the Austrian-German societies for Clinical Chemistry and Laboratory Medicine that includes the evaluation of personnel supply. Eight consecutive series with a total of 4,896 samples were analyzed on both systems. Evaluation revealed that the analysis time per series was 238 minutes on the HS-430 and 359 minutes on the CS. The mean analyzer down times because of technical reasons were 36 minutes on the HS and 32 minutes on the CS. The down time because of "nontechnical" reasons was 31 minutes on the HS-430, but 173 minutes on the CS, which was mainly because of discontinuous sample loading of analyzers of the CS. The average direct technical time effort for complete blood cell count (CBC) analyses, reticulocyte counts, and blood smear preparations per series was 23 minutes on the HS and 245 minutes on the CS. In summary, these data show that an automated system like the HS-430 saves 222 minutes of manual activities arising in a large routine hematology laboratory with a mean throughout of 612 samples per day. Furthermore, the system improves intralaboratory turnaround times, avoids human errors by automated sample identification, and guarantees more safety for laboratory staff by minimizing the contact with potential biohazards.

Blood Cell Count↗
PubMed1995

PCR-monitoring of minimal residual leukaemia after conventional chemotherapy and bone marrow transplantation in BCR-ABL-positive acute lymphoblastic leukaemia.

We report the results of consecutive tests in nine BCR-ABL-positive ALL patients by one-step and two-step (nested primer) reverse transcriptase-polymerase chain reaction (RT-PCR). Six patients could be tested in complete haematological remission (CHR). One patient remained one-step positive; four patients became one-step negative, but remained two-step positive; only one patient became two-step negative. In five patients the haematological relapse was preceded by one-step positivity by 1.5-5 weeks. In two patients who received autologous BMT in CHR, BCR-ABL was still detectable by two-step PCR, whereas allogeneic BMT was able to transiently reduce BCR-ABL below the two-step detection level. Our results show that one-step combined with two-step RT-PCR analysis gives valuable information about the efficacy of treatment and the dynamics of the leukaemic clone.

Adult↗
PubMed1994

Effect of hydroxyethyl starch on the activity of blood coagulation and fibrinolysis in healthy volunteers: comparison with albumin.

OBJECTIVE: The aim of this study was to investigate whether hydroxyethyl starch of medium molecular weight (200 daltons), compared with albumin, has specific effects on blood coagulation and fibrinolysis. DESIGN: A prospective, randomized, double-blind, crossover trial. SETTING: Laboratory at a university hospital. PATIENTS: Ten healthy male volunteers, 23 to 39 yrs old, with no history of hypersensitivity, who had normal physical examinations, and were free of a bleeding disorder. All patients did not ingest any medications for > or = 2 wks before or during the study period. INTERVENTION: Each volunteer received either 500 mL of hydroxyethyl starch (6% wt/vol, average molecular weight 200 kilodaltons, molar substitution 0.5 [ratio hydroxyethyl groups/glucose units] in 0.9% sodium chloride; average molecular weight of 200 kilodaltons) or a control of 500 mL of human albumin (5% albumin solution). After a washout period of 4 wks, subjects crossed over to the alternate treatment. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken immediately before infusion and 20, 45, 75, 105, 165, 285, 405, and 1485 mins after the infusion started. Hematocrit, the blood coagulation parameters fibrinogen, activated partial thromboplastin time, factor VIII:C, thrombin-antithrombin III complexes, and the fibrinolytic parameters fibrin-split product D-Dimer, tissue type plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor, and plasmin-antiplasmin complexes were measured. Except for factor VIII:C levels, which were significantly lower in the hydroxyethyl starch group, no other significant differences in the plasma levels of the parameters mentioned were detected between hydroxyethyl starch and albumin infusions. In one volunteer, who had a low initial factor VIII:C level of 51%, a decrease to 28% at 165 mins during hydroxyethyl starch infusion was found (corresponding albumin value at 165 mins was 41%). CONCLUSIONS: a) Medium molecular weight hydroxyethyl starch has a specific lowering effect on factor VIII:C concentrations; this phenomenon may be hazardous to patients who need full hemostatic competence and who receive medium molecular weight hydroxyethyl starch (e.g., as a plasma expander). b) Medium molecular weight hydroxyethyl starch does not specifically influence the activity of the fibrinolytic system.

Adult↗
PubMed1994

PML-RAR alpha PCR positivity in the bone marrow of patients with APL precedes haematological relapse by 2-3 months.

We report the results of serial tests in three patients with hyperleucocytotic AML M3 by haematological methods, coagulation assays and PCR analyses following treatment with ATRA and chemotherapy. All three patients became PCR negative in bone marrow and peripheral blood (sensitivity level 1 in 10(5) cells) after one cycle of ATRA + chemotherapy. However, they relapsed haematologically 6-9 months after achieving complete haematological remission. The haematological relapse was preceded by PCR positivity in the bone marrow by 3 months. Platelet counts decreased already during CHR, but dropped below normal levels only at the time of relapse. Coagulation parameters were not helpful for early prediction of relapse. Our results demonstrate that PCR analysis in the bone marrow is the best way to monitor patients with APL. However, in hyperleucocytotic patients, PCR negativity does not seem to indicate long-term remission.

Base Sequence↗
PubMed1994

AML1/ETO fusion mRNA can be detected in remission blood samples of all patients with t(8;21) acute myeloid leukemia after chemotherapy or autologous bone marrow transplantation.

The chromosomal translocation t(8;21)(q22;q22) in acute myeloid leukemia (AML) can be detected by a reverse transcription-polymerase chain reaction (RT-PCR) for the chimeric AML1/ETO transcript. We have evaluated the clinical relevance of this method for monitoring and detection of minimal residual disease (MRD) in seven patients who reached a complete hematological remission (CHR) after chemotherapy or autologous bone marrow transplantation (ABMT). Peripheral blood (PB) samples of five patients in first continuous complete remission (CCR) were still PCR-positive at a frequency of 1 in 10(5) cells after 7, 8, 8, 10 or 66 months. Chemotherapy led to a reduction from first- to second-step PCR-positivity in three serially monitored patients. AML1/ETO mRNA was also detected in the PB of two patients in CCR, 10 or 12 months after ABMT. PB and bone marrow (BM) showed identical results in all samples tested simultaneously. AML1/ETO fusion transcripts were neither found in the PB and BM of a healthy individual, nor in the PB of a patient after allogeneic BMT for cytogenetically proven t(8;21)-leukemia. Our results indicate the presence of cells carrying the AML1/ETO rearrangement in the PB and BM of all patients in CHR after chemotherapy or ABMT for t(8;21)-positive AML. While this finding raises interesting questions about the biology of acute leukemia, it limits the value of the AML/ETO RT-PCR for the prediction of impending relapse.

Adult↗
PubMed1994

Modulation of pyrogen-induced upregulation of endothelial cell adhesion molecules (CAMs) by interleukin-4: transcriptional mechanisms and CAM-shedding.

The pyrogens interleukin 1 (IL-1), tumor necrosis factor (TNF), and bacterial lipopolysaccharides (LPS) are known to increase endothelial cell (EC) adhesiveness for leukocytes by stimulating surface expression of various adhesion molecules. IL-4, a product of activated T-cells, was shown to affect pyrogen-mediated regulation of EC adhesion molecule surface expression. In the present study, we investigated the effect of IL-4 on pyrogen-induced upregulation of the cell adhesion molecules (CAMs) ICAM-1 (intercellular cell adhesion molecule-1), ELAM-1 (endothelial leucocyte adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1) in cultured human umbilical vein EC (HUVEC). Surface expression of adhesion molecules was quantified by flow cytometry, HUVEC mRNA content was estimated by Northern blot analysis, and ICAM-1 antigen in conditioned media was measured by ELISA. Incubation of HUVEC with IL-1 (100 U/ml), TNF (500 U/ml), and LPS (10 micrograms/ml) caused significant increase in ICAM-1, ELAM-1, and VCAM-1 surface expression; IL-1 caused about an eightfold increase in ICAM-1 expression, about a 13-fold increase in ELAM-1 surface expression, and about a fourfold increase in VCAM-1 expression. Coincubation of pyrogens with IL-4 (500 U/ml) differentially influenced their proadhesive effects on the HUVEC surface. In the presence of IL-4, IL-1-induced ICAM-1 upregulation was reduced, ELAM-1 upregulation was not significantly influenced by IL-4, and induction of VCAM-1 was enhanced by IL-4.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Early detection of hematopoietic engraftment after bone marrow and peripheral blood stem cell transplantation by highly fluorescent reticulocyte counts.

At present, the appearance of neutrophils in the peripheral blood is considered to be the earliest sign of hematopoietic regeneration after myeloablative chemoradiotherapy. We studied erythroid regeneration in 27 allogeneic and 21 autologous marrow recipients using an automated reticulocyte counter employing a flow cytometric technique. Thereby, reticulocytes can be divided into a high, moderate and low fluorescent fraction according to RNA content. Marrow ablation caused an immediate and rapid fall in highly fluorescent reticulocytes (HFR) to zero in all patients. HFR reappeared after a median time of 7 days after allogeneic and 11 days after autologous marrow grafting. This was 7 and 2 days earlier than the appearance of first neutrophils. In allogeneic marrow recipients given erythropoetin after marrow infusion the median time to reach HFR of 0.2 and 0.5 x 10(9)/l was significantly shorter than time to reach similar absolute neutrophil counts (ANC). In allogeneic marrow recipients treated with G-CSF time to rise of HFR and ANC was almost exactly the same. Thus, automated flow cytometric reticulocyte counting allows early detection of hematopoietic regeneration and may be of clinical value for the early diagnosis of inadequate marrow function after marrow transplantation and the monitoring of erythroid regeneration under cytokine administration.

Adolescent↗
PubMed1994

Recipient-specific donor cytotoxic T lymphocytes enhance engraftment of unrelated, DLA non-identical canine marrow.

Resistance to canine marrow grafts from unrelated DLA non-identical donors can be overcome by infusion of viable donor peripheral blood leukocytes or thoracic duct cells in addition to the marrow. The mechanisms by which these cells enhance engraftment are unknown but are likely to include a graft-versus-host reaction. The current study investigated whether recipient-specific, donor alloreactive cytotoxic lymphocytes mediating a graft-versus-host reaction could abrogate resistance to canine marrow grafts. To this purpose, cytotoxic donor lymphocytes (CTL) specific for recipient DLA antigens were generated in vitro and expanded in culture by exogenous interleukin-2 (IL-2). Two groups of dogs were studied. All were given 9.2 Gy total body irradiation followed by 3.7 x 10(8) marrow cells/kg from an unrelated DLA non-identical donor on day 0 and 1.2 x 10(8) host-specific CTL/kg on days 1 and 2. Dogs in group 2 were given, in addition, subcutaneous injections of recombinant human IL-2, 10,000 U/kg twice daily on days 1 through 10 post-grafting. Ten of 16 dogs in the two groups showed hematopoietic engraftment regardless of whether they received in vivo IL-2. Engraftment in current dogs was significantly better than that in 47 controls given marrow alone (p = 0.001), although it was worse than that in 64 dogs given marrow and an order of magnitude higher number of viable mononuclear cells obtained from the peripheral blood (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Rapid achievement of PML-RAR alpha polymerase chain reaction (PCR)-negativity by combined treatment with all-trans-retinoic acid and chemotherapy in acute promyelocytic leukemia: a pilot study.

The reverse transcriptase-polymerase chain reaction (RT-PCR) for the fusion transcript of PML-RAR alpha can be used to detect minimal residual disease (MRD) in acute promyelocytic leukemia (APL). We have applied a semi-quantitative two-step PCR assay (sensitivity: step 1 = 1 in 10(3) cells; step 2 = 1 in 10(6) cells) to monitor the dynamics of MRD after combined therapy with all-trans-retinoic acid (ATRA) and chemotherapy (CT) in 5 patients in whom complete clinical remission (CR) was achieved. The patients received an induction treatment with ATRA for 47, 40, 38, 14 or 10 days. In three patients ATRA was followed by CT. Two patients with hyperleukocytosis at diagnosis or after ATRA received an overlapping CT starting from day 3 or 7. Four of the five patients became two-step PCR-negative in their bone marrow within 43 to 82 days after onset of therapy. Two-step PCR-negatively was achieved with ATRA plus one course of CT in these four patients who are still in continuous complete remission after 19, 18, 7 and 5 months. One of these patients did not even receive consolidation CT because of congestive heart failure. The fifth patient remained second-step PCR-positive and relapsed after 5 months. Our results indicate that the combined regimen can rapidly reduce MRD below a detection limit of 1 in 10(6) cells within 1-3 months and that these results can even by achieved by a short course of ATRA together with only one cycle of CT.

Aged↗
PubMed1993

Hypergranular acute lymphoblastic leukemia (ALL). Report of a case and review of the literature.

We report a case of adult acute lymphoblastic leukemia (ALL) with myeloid-like hypergranulation of blast cells. Like most of the "granular" ALLs described in the literature, the blast cells had L2 morphology and exhibited a common-ALL immunologic phenotype. The clinical findings at diagnosis were unremarkable. Cytogenetic analysis showed a 46XY karyotype. Molecular genetic analysis revealed T-cell receptor (TCR) gamma and immunoglobulin heavy chain rearrangements; no rearrangement was found at the TCR beta gene locus. The polymerase chain reaction (PCR) for the BCR-ABL translocation was negative. The clinical course of the patient was uncomplicated. On standard ALL treatment protocol he achieved complete remission (CR) within 4 weeks, and he is currently disease free 8 months after diagnosis. The case contributes well-documented data to the characterization of adult "granular" ALL, with special regard to changes at the molecular genetic level.

Adult↗
PubMed1993

Granulocyte colony-stimulating factor (rh G-CSF) as an adjunct to interferon alpha therapy of neutropenic patients with hairy cell leukemia.

Six patients with hairy cell leukemia (HCL) and neutropenia (median neutrophil count 563/microliters, range 30-1200) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 5 micrograms/kg by daily subcutaneous injection as an adjunct to interferon-alpha (IFN-a) therapy, in order to ameliorate neutropenia. Five of six patients responded to G-CSF with normalization of neutrophil counts (> 1800/microliters) within 2-11 days and a median neutrophil count of 5211/microliters (range 4312-10160) at the end of G-CSF therapy. In three of these patients, infections resolved when neutropoiesis recovered. In one patient with very severe neutropenia (30/microliters), in whom myeloid progenitors were not detectable, G-CSF therapy failed to restore granulopoiesis. Cessation or interruption of G-CSF after 2-5 weeks of therapy resulted in a rapid decline of neutrophil counts to lower or subnormal levels (median value 1478/microliters, range 770-2739) within 1 week, suggesting that the improvement of granulopoiesis was dependent on G-CSF and not due to IFN-a therapy. G-CSF may be a useful adjunct to IFN-a therapy in patients with HCL in order to manage or prevent neutropenic complications in the early phase of treatment.

Adult↗
PubMed1992

Recurrent, isolated factor X deficiency in myeloma: repeated normalization of factor X levels after cytostatic chemotherapy followed by late treatment failure associated with the development of systemic amyloidosis.

We describe the case of a 64-year-old woman with isolated severe factor X deficiency associated with kappa light chain myeloma. At the time of diagnosis there was no evidence for amyloidosis. Complete remission (CR) of myeloma as well as normalization of factor X levels were achieved after cytostatic chemotherapy. Subsequently, factor X deficiency recurred twice without any evidence for relapse of myeloma. The first time factor X normalized again following cytostatic treatment, the second time, however, factor X deficiency was refractory to chemotherapy. Finally, relapse of myeloma became evident associated with rapidly progressing, systemic amyloidosis, which was fatal within a few months. Initially, factor X infusion studies showed a normal recovery, but when amyloidosis became overt the recovery decreased to 0%. We assume that factor X deficiency was due to a binding of factor X to kappa light chains associated with the proliferation of the malignant myeloma cell clone.

Amyloidosis↗
PubMed1992

Prognostic impact of karyotype and immunologic phenotype in 125 adult patients with de novo AML.

One hundred-twenty-five adult patients with de novo acute myeloid leukemia (AML) were treated according to a standard 7 + 3 induction regimen. Karyotype and immunological phenotype of blasts examined prior to treatment were correlated with each other, with response to treatment and duration of survival. The following monoclonal antibodies (mAbs) were used for immunological phenotyping: VIM-D5 (CD15), MY7 (CD13), MY9 (CD33), VIM-2 (CDw65), VIM-13 (CD14), 63D3 (CD14), VID-1 (anti HLA-DR), WT1 (CD7), CLB-Ery3 (antiblood group H antigen), C17-27 (CD61), and an antiserum against TdT. Despite a considerable overlap between the individual groups, patients with specific aberrations as defined by the MIC classification (n = 39) showed distinct, characteristic, myeloid or myelomonocytic immunophenotypes. In M2/t(8;21) there was a significant association with negativity to CD13, in M3/t(15;17) with negativity to CD15 and HLA-DR, whereas in M4/inv(16) expression of blood group H antigen was unexpectedly found. The response to therapy, as well as rate of complete remission as duration of survival, was better in patients with M2/t(8;21), M3/t(15;17), and M4Eo/inv(16) as compared to all other patients and significantly worse in patients with M5a/t/del(11)(q23). In 35 patients with normal karyotype and 16 patients with cytogenetic anomalies not presently associated with FAB subtypes the expected correlations of rather immature myeloid immunologic phenotypes with M1 and M2 morphology and CD14 expression in monoblastic leukemias was found. Remission rate and survival were significantly worse in 19 patients with complex nonrandom aberrations, where blast cell expression of blood group H antigen and of TdT were significantly increased.

Adolescent↗
PubMed1992

MACOP-B treatment in patients with Ki-1-positive large-cell anaplastic lymphoma.

Nine adult patients with Ki-1-positive large-cell anaplastic lymphoma were treated with MACOP-B. Two suffered from relapsed disease and had previously received chemotherapy; a third patient had received a single dose of 100 mg/m2 cisplatin before initiation of MACOP-B. The stage of lymphoma was determined according to the Ann Arbor Conference criteria and was II in one, III in two and IV in six patients. All patients had constitutional symptoms. Five patients had achieved complete remission 4 weeks after termination of the protocol and there were two partial remissions. One patient died of massive pulmonary embolism during the 4th week of treatment; another patient, who had received MACOP-B as salvage therapy, died of progressive lymphoma 1 month after completion of the regimen. Maximal observed toxicities according to WHO were mucositis grade 3 (n = 3) and there were three cases with thromboembolic complications, including a fatal pulmonary embolism in a young patient. However, MACOP-B appears an effective, fairly well-tolerated and feasible therapy for patients with Ki-1-positive large-cell anaplastic lymphoma.

Adult↗
PubMed1991

Coincidence of acquired factor-X deficiency and disseminated intravascular coagulation in patients with acute nonlymphoblastic leukemia.

Systematic clotting studies were performed in 157 patients with de novo acute nonlymphoblastic leukemia (ANLL) prior to treatment. Sixteen patients had disseminated intravascular coagulation (DIC). Three of the patients with DIC (two with M3, one with M5 leukemia) had a marked isolated factor-X deficiency (factor X:C 21%, 33%, and 41%, respectively). Another four patients had a mild isolated factor-X deficiency (factor X:C 55%-68%). In these seven patients the remaining liver-synthesized clotting factors (factors II, VII, IX, V) as well as serum albumin and cholinesterase were within the normal range. Liver disease or vitamin-K deficiency could therefore be excluded. In none of the 141 patients without DIC was a marked isolated factor X deficiency observed; two patients had moderately reduced factor X:C levels but normal liver-synthesized proteins. Induction treatment led to the control of DIC with an almost parallel increase of fibrinogen and factor X up to normal in all patients with factor-X deficiency who achieved complete remission. In one patient, recurrence of leukemia was associated with reoccurrence of DIC and marked factor-X deficiency. We conclude that there is a coincidence of isolated factor-X deficiency and DIC in some patients with ANLL. In some patients, this factor-X deficiency may be severe enough to contribute to the bleeding tendency.

Adult↗
PubMed1991

Hepatic and splenic abscesses--a common complication of intensive chemotherapy of acute myeloid leukemia (AML). A prospective study.

In order to determine the frequency of hepatosplenic abscesses in AML patients during chemotherapy and to evaluate the clinical and laboratory characteristics of this complication we performed a prospective study over a 28-month period. Fifty-five consecutive patients with de novo AML or relapse who received intensive chemotherapy underwent regular ultrasound examinations. In 16 patients (29.1%) hepatic and/or splenic abscesses were detected sonographically. Histopathological evidence for abscess formation was obtained in five of these 16 patients. In three patients granulation tissue and in one patient necrotizing granulomas were found. Causative micro-organisms were proven in only three patients: Candida hyphae were demonstrated in one patient, gram-positive cocci in another. Bacteria and fungi were seen in the tissue specimen of the third patient. Patients with hepatosplenic abscesses had significantly prolonged fever after neutrophil recovery but did not differ from patients without abscesses in any other laboratory or clinical features. Due to the absence of specific alerting clinical and laboratory signs and symptoms of hepatosplenic abscesses, routine ultrasound examination is required for detection of this complication. The presence of hepatic and/or splenic abscesses does not necessarily worsen the prognosis, but it may influence the decision on further chemotherapy and antimicrobial treatment.

Abscess↗