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Biomedical subjects

W Siegert

Publications and source records attributed to W Siegert.

At least 127 records · Page 7Linked to original sources
PubMed1993

Double megatherapy and autologous bone marrow transplantation for advanced neuroblastoma: the LMCE2 study.

In the LMCE1 study using a single course of megatherapy most of the relapses occurred during the first 2 years after autologous bone marrow transplantation. A second pilot study (LMCE2) was therefore set up using a double harvest/double graft approach with two different megatherapy regimens. Objectives were to test the role of increased dose intensity on response status, relapse pattern and overall survival. Thirty-three patients (20 boys, 13 girls) with a median age of 53 months at first megatherapy (range, 17-202 months) entered this study. They were cases either with refractory disease in partial response after second line treatment for stage 4 neuroblastoma (n = 25) or after relapse from stage 4 (n = 5) or stage 3 disease (n = 3). All patients received Etoposid and/or Cisplatinum (or Carboplatin) containing treatments before megatherapy. The first megatherapy regimen was a combination of Tenoposid, Carmustine and Cisplatinum (or Carboplatin), the second applied Vincristin, Melphalan and Total Body Irradiation. The first harvest was scheduled 4 weeks after the last chemotherapy, the second 60 to 90 days after megatherapy. All marrows were purged in vitro by an immunomagnetic technique. Median follow up time since first megatherapy is 56 months. Response rates for evaluable patients were 65% (complete response rate: 16%) for megatherapy 1 and 60% (complete response rate: 25%) for megatherapy 2. Considering that only patients with delayed response or relapse were eligible for this pilot study the overall survival was encouraging with 36% at 2 years and still 32% at 5 years. The costs for these survival rates were high in terms of morbidity (four early and four late toxic deaths; toxic death rate: 24%). Double harvesting may have the disadvantage of delayed engraftments related in part to a disturbance of marrow microenvironment by megatherapy 1. This double megatherapy approach achieved a prolonged relapse free interval (median 11 months, range 2-31 months) in patients reaching megatherapy 2 and justifies further evaluation of concepts with consecutive dose-escalation.

Adolescent↗
PubMed1993

Demonstration of cytomegalovirus by polymerase chain reaction after liver transplantation.

The polymerase chain reaction (PCR) is a highly sensitive and specific technique for detection of cytomegalovirus DNA. With this method we prospectively analyzed buffy coat leukocytes at weekly intervals over 3 months in 60 patients after liver transplantation (LTX). The PCR results were correlated with the pretransplant donor/recipient CMV antibody status and with the occurrence of CMV-induced disease. Thirty-three of 60 (55%) patients became PCR-positive during their posttransplant course. None of the 27 patients with permanent negative PCRs developed CMV disease. Of 33 patients with positive PCRs, 13 (39%) became ill. CMV disease developed in 9 of 22 (41%) antibody-negative recipients but only in 4 of 38 (10%) seropositive graft recipients. The incidence of CMV disease was 75% (9 of 12 patients) in seronegative recipients who converted to positive PCR results and 19% (4 of 21 patients) in seropositive patients with positive PCR findings. The predictive value of a positive PCR was 75% in seronegative patients but it was low (19%) in seropositive recipients. The predictive value of a negative PCR is 100%. Thus, PCR determinations are useful in identifying patients who will not develop CMV disease and in narrowing down the number of individuals who will become sick. Further, PCR is a helpful tool in the follow-up of patients under antiviral treatment.

Adult↗
PubMed1993

Automated processing of human bone marrow grafts for transplantation.

Prior to purging or cryopreservation, we concentrated 21 bone marrow (BM) harvests using a modification of the 'grancollect-protocol' of the Fresenius AS 104 cell separator with the P1-Y set. Within 40-70 min, the initial marrow volume of 1,265 ml (+/- 537 ml) was processed two to three times. A mean of 47% (+/- 21%) of the initial mononuclear cells was recovered in a mean volume of 128 ml (+36 ml). The recovery of clonogenic cells, measured by CFU-GM assays, was 68% (+/- 47%). Red blood cells in the BM concentrates were reduced to 7% (+/- 4%) of the initial number. The procedure was efficient and yielded a BM cell fraction suitable for purging, cryopreservation and transplantation. At this time, 10 of the 21 patients whose BM was processed using this technique have been transplanted. Seven of these 10 patients have been grafted using the BM alone. Three of the 10 patients showed reduced cell viability and colony growth in the thawed BM samples, and therefore obtained BM and peripheral blood-derived stem cells. All transplanted patients showed an evaluable engraftment, achieving 1,000 granulocytes per microliter of peripheral blood in a mean of 18 days.

Automation↗
PubMed1993

Aerosol amphotericin B for prevention of invasive pulmonary aspergillosis.

The pharmacokinetics and applicability of aerosol amphotericin B administrations were studied in 40 neutropenic patients and 4 healthy volunteers. Particle size was measured and pulmonary deposition was demonstrated by radioisotope studies. Inhalations were easy to administer and were well tolerated, with minimal systemic absorption of the drug.

Administration, Inhalation↗
PubMed1993

Serum concentrations of G-CSF during high-dose chemotherapy with autologous stem cell rescue.

In 20 patients treated for refractory germ cell tumors, endogenous G-CSF levels were monitored before and after high-dose chemotherapy with autologous stem cell rescue (ASCR). An inverse relationship was found between endogenous G-CSF levels and peripheral blood leucocyte counts. G-CSF levels were not detectable prior to ASCR, but increased to a maximum of 3400 pg/ml (range 120-15000 pg/ml) thereafter. There was no relationship between peak G-CSF levels and time to engraftment. A decrease in G-CSF levels preceded engraftment and was paralleled by a rise of nadir leucocyte counts.

Adult↗
PubMed1993

Fractionated total body irradiation and high-dose VP-16 with purged autologous bone marrow rescue for children with high risk relapsed acute lymphoblastic leukemia.

Twenty-two children with ALL in high risk second (n = 13), third or subsequent complete remission (n = 9) were treated with high-dose VP-16 60 mg/kg and fractionated total body irradiation (fTBI) 12 Gy, 2 x 2 Gy daily followed by autologous BM rescue. Prior to transplantation all patients had been treated according to intensive German BFM front-line or BFM relapse protocols. In all cases the marrow was purged using monoclonal antibodies attached to magnetic microspheres. All patients engrafted. There was no severe toxicity related to the pre-transplant high-dose chemoradiotherapy. Two patients died in the early course of transplantation from infections (Legionella and Aspergillus). Sixteen patients relapsed within 259 days (median 109 days); 13 died from leukemia. Four patients are alive in CR at a median of 1328 days with a Karnofsky score of 100%. The Kaplan-Meier estimation shows a probability of event-free survival (EFS) of 18% and a probability of relapse of 80%. Considering the otherwise poor prognosis of these children the results are acceptable although the high relapse rate is still disappointing. We conclude that high-dose VP-16 and fTBI combined with ABMT is a curative treatment for some children and should therefore be considered for those who lack an HLA-identical sibling donor. In future better therapy concepts are needed either in pre-transplant conditioning regimens or in post-transplant treatment schedules.

Adolescent↗
PubMed1993

Pneumococcal arthritis after allogeneic bone marrow transplantation.

We report a case of pneumococcal arthritis occurring in a 15-year-old boy following allogeneic BMT. The post-transplant course was complicated by GVHD requiring prolonged immunosuppressive therapy. He experienced recurrent infections, including pneumococcal pneumonia. Thirty-five months after BMT and 12 months after the pneumococcal pneumonia, pneumococcal arthritis of the left knee occurred. This is the first reported case of arthritis caused by Streptococcus pneumoniae after allogeneic BMT. Penicillin prophylaxis may be used to prevent recurrence of pneumococcal infections in patients with chronic GVHD.

Adolescent↗
PubMed1993

Demonstration of chimerism after allogeneic bone marrow transplantation by polymerase chain reaction of Y-chromosome-specific nucleotide sequences--characterization of a new technical approach.

Various techniques are applied to assess chimerism after allogeneic bone marrow transplantation. The polymerase chain reaction (PCR) of donor- and/or host-specific gene sequences provides a rapid and highly sensitive technique. We describe the characterization and application of PCR for the amplification of Y-chromosome-specific DNA in blood cells recovered from stored slides. Four different primer pair combinations were used. PCR can be rapidly performed on stained or unstained slide material with varying sensitivity--depending on the primer combination. The lowest limit of detection is one male cell in 500-1000 female cells. The technique was applied to follow the early post-transplant course of 15 male patients who received grafts from female donors and found a high incidence of mixed chimerism during the first three months after BMT and a striking fluctuation between positive and negative results in the follow-up of individual patients. We conclude that PCR for the detection of male-specific DNA sequences can be successfully performed with high sensitivity on material recovered from stored blood slides.

Adolescent↗
PubMed1992

Treatment of angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma using prednisone with or without the COPBLAM/IMVP-16 regimen. A multicenter study. Kiel Lymphoma Study Group.

OBJECTIVE: To describe the clinical course of patients with angioimmunoblastic lymphadenopathy (AILD)-type lymphoma with a sequential treatment with prednisone and COPBLAM/IMVP-16. DESIGN: A multicenter, prospective, nonrandomized trial. SETTING: University medical centers and community hospitals. PATIENTS: Sixty-seven patients were registered, 28 were excluded, and 39 patients were evaluable for response (median age, 59 years; range, 25 to 82 years) (stages I and II, 10%; stages III and IV, 90%; B symptoms, 74%). MEASUREMENTS: Response, survival, and relapse. INTERVENTION: Patients initially received prednisone and no further treatment if a complete remission was achieved. Relapsing or refractory patients were treated with COPBLAM/IMVP-16. Patients with life-threatening tumor progression or extension received COPBLAM/IMVP-16 initially. Treatments were chosen in accordance with tumor extension and response to prednisone. Treatment modalities were not compared. RESULTS: Twenty-eight patients received primary prednisone, 18 received secondary prednisone, and 11 received primary chemotherapy. The complete response rates (with 95% CIs) were 29% (CI, 12% to 46%), 56% (CI, 33% to 79%), and 64% (CI, 36% to 92%), respectively. The median observation time of surviving patients was 28 months (range, 7 to 53). The median overall survival time was 15 months. The probabilities (with 95% CIs) of overall survival, event-free survival, and relapse at 36 months were 40.5% (CI, 24% to 56%), 32.3% (CI, 17% to 47%), and 34.6% (CI, 14% to 56%), respectively. At the time of evaluation, 22 of 39 patients had died, 7 of noninfectious complications and 14 of infections. CONCLUSIONS: Prednisone with or without COPBLAM/IMVP-16 treatment in AILD-type lymphoma leads to complete remissions in about half of the patients and in long-term, disease-free survival for one third.

Adult↗
PubMed1992

Bone marrow processing with the Fresenius AS 104: initial results.

Prior to purging, cryopreservation, or ABO-incompatible bone marrow (BM) transplantation, we have concentrated 23 BM harvests using a modification of the "grancollect-protocol" and the recently available bone marrow stem cell (BMSC) protocol of the Fresenius AS 104 cell separator with the P1-Y set. Within 40-70 minutes, the initial marrow volume of 922 ml (+/- 408 ml) was processed two to three times. A mean of 59% (+/- 20%) of the initial mononuclear cells was recovered in a mean volume of 119 ml (+/- 31 ml). The recovery of clonogenic cells, measured by CFU-GM assays, was 98% (+/- 80%). Red blood cells in the BM concentrates were reduced to 8% (+/- 4%) of the initial number. The procedure was efficient and yielded a BM cell fraction suitable for purging, cryopreservation, and transplantation. All transplanted patients showed fast and sustained engraftments after autologous or allogeneic BM transplantation.

Bone Marrow Cells↗
PubMed1992

Bone marrow purging prior to autologous transplantation.

Our data suggest that ex vivo bone marrow purging using monoclonal antibodies (MoAbs) and sheep-anti-mouse immunobeads (SAM beads) prior to autologous bone marrow transplantation (ABMT) allows satisfactory tumor cell reduction without critical stem cell losses. Nevertheless, there is only a reduction but no elimination of tumor cells. The consequences will have to be clinically discussed.

Antibodies, Monoclonal↗
PubMed1992

Rearrangements of T-cell receptor delta, gamma and beta genes in acute myeloid leukemia coexpressing T-lymphoid features.

In order to investigate the role of T-cell receptor (TcR)-delta and TcR-gamma gene rearrangements and/or deletions in acute myeloid leukemia (AML) coexpressing T-cell-associated antigens (i.e. CD2 and/or CD4 and/or CD7), we examined blasts from a selected group of 56 AML cases (25 children, 31 adults) coexpressing either of these antigens without cytoplasmic CD3 expression. Forty-four typical AML cases (7 children, 37 adults) without T-cell associated antigens were further studied as controls. Germline configuration of the TcR-delta gene was observed in 91 out of the total of 100 AML cases investigated. Eight of nine cases with rearranged or deleted TcR-delta genes coexpressed T-cell-associated antigens. Blast cells of 7/9 cases were classified as FAB M1, two as FAB M2. In six of these cases TcR-gamma gene rearrangements were also detected. TcR-delta alterations were predominantly found in children whose blasts coexpressed T-lymphoid associated antigens (6/25, 24%), but were rarely detected in adult AML with or without coexpression of T-cell antigens (2/31 and 0/37, respectively).

Acute Disease↗
PubMed1992

Cutaneous toxicity of high-dose carboplatin, etoposide and ifosfamide followed by autologous stem cell reinfusion.

Forty patients with germ cell tumors were treated with carboplatin 1500-2000 mg/m2, etoposide 1200-1600 mg/m2 and ifosfamide 0-10 g/m2 plus mesna followed by autologous stem cell reinfusion. A pruritic maculopapular rash was observed in 10 patients usually starting on the last day of chemotherapy. Lesions remained localized to the extremities in four patients. In six they became confluent and progressed also involving the trunk and face. Facial edema and painful swelling of hands and feet also occurred in this latter group. No ulcerations or bullae formation were seen and changes resolved spontaneously in all patients within 3 weeks leaving marked hyperpigmentation in involved areas. Renal function declined in nine of 10 patients concomitantly with evolving cutaneous changes, but recovered in all except one. Cutaneous side effects were more frequent with increasing doses of etoposide and carboplatin and in patients with deteriorating renal function. Plasma concentrations during high-dose chemotherapy should be monitored to avoid excessive serum levels and toxicity, especially in patients at risk of renal dysfunction.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Antimitochondrial antibodies in patients with chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) and primary biliary cirrhosis (PBC) have many clinical and laboratory features in common. These include scleroderma or lupus erythematosus-like skin lesions, a Sjögren-like sicca syndrome, cholestatic liver disease and a variety of serological autoimmune phenomena. Furthermore, liver histology in both diseases is characterized by lymphocytic infiltration of the portal fields and destruction of small bile ducts. We investigated whether there were also parallels between both diseases in incidence and characteristics of antimitochondrial (AMA) and other autoantibodies. Sera from patients with cGVHD (n = 11, group 1) were examined by immunofluorescence (IFL) and immunoblot (IBL), and the results were compared with sera from patients without cGVHD (n = 21, group 2) and after autologous BMT (n = 16, group 3). In group 1 AMA was detected by IFL in one and by IBL in nine of 11 (81%) patients. Group 2 and 3 patients were AMA-negative by IFL and AMA positive by IBL in statistically lower incidence of 19% and 6% (p less than 0.001), respectively. cGVHD-associated AMA recognized a spectrum of mitochondrial proteins, the most frequent being molecules of 63/60 kD and 22 kD. Follow-up studies showed a temporal correlation between the emergence of AMA and the clinical occurrence of cGVHD. We conclude that patients with cGVHD have a high incidence of AMA similar to patients with PBC, but the reaction pattern of AMA differs between the diseases. The presence of AMA in cGVHD further emphasizes the concept that both diseases may have a related pathogenetic background.

Adolescent↗
PubMed1991

Cisplatin/etoposide/ifosfamide stepwise dose escalation with concomitant granulocyte/macrophage-colony-stimulating factor for patients with far-advanced testicular carcinoma.

In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m2, etoposide 120-150 mg/m2 and ifosfamide 1.2 g/m2 for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died of Clostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/microliters and a thrombocyte nadir of 47,000/microliters. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m2, etoposide 150 mg/m2 and ifosfamide 1.6 g/m2 five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 micrograms/kg on days 6-15. Acute toxicity was severe with a white blood cell nadir of 300/microliters and thrombocyte nadir of 11,000/microliters. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure and Aspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m2, etoposide 200 mg/m2 and ifosfamide 1.6 g/m2 for 5 days and GM-CSF 10 micrograms kg-1 day-1 on days 6-15 s.c.

Antineoplastic Combined Chemotherapy Protocols↗