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F Berthold

Publications and source records attributed to F Berthold.

At least 91 records · Page 5Linked to original sources
PubMed1991

Metaiodobenzylguanidine (mIBG) in treatment of 47 patients with neuroblastoma: results of the German Neuroblastoma Trial.

From 1984 to 1989, 47 children with relapsed, refractory, and/or metastasized neuroblastoma were treated with 131I-metaiodobenzylguanidine (mIBG) in several different treatment combinations. At initial diagnosis, 36 children had Evans stage IV and 11 stage III disease. In 16 of the 47 children, tumor recurred after complete remission prior to mIBG treatment, 26 of 47 progressed from residual or nonresponding tumor, and in 5 of 47 tumor progression during chemotherapy was observed. Altogether the children were treated with a total of 112 courses (range 1-6) with a mean dosage of 8.9 +/- 6.7 mCi/kg body weight/treatment course. Total dose was 283.2 +/- 203.7 mCi for stage III and 388.9 +/- 218.6 mCi for stage IV. Nine of 47 children reached a complete or a very good partial remission (CR and VGPR) from mIBG treatment alone, 13 of 47 achieved partial remission (PR). In an early analysis, 10 patients treated with mIBG in the neuroblastoma trial NB 85 of the German Society of Pediatric Oncology showed no significant difference in survival time compared with 30 conventionally treated children. However, the recent therapy series has been done with higher doses of mIBG, and during improved therapeutic scanning many more bone lesions could be detected than during earlier diagnostic scanning. We conclude that mIBG treatment has not yet fulfilled the expectations for it but still seems for certain indications to be a promising tool to treat neuroblastoma in the future. Moreover, the frontier of neuroblastoma detection is still advancing.

3-Iodobenzylguanidine↗
PubMed1991

Neuroblastoma screening: arguments from retrospective analysis of three German neuroblastoma trials.

The justification for a neuroblastoma screening program has been discussed controversially. The analysis of 701 patients of the German neuroblastoma trials NB 79, 82, and 85 provides additional information on this subject. The basis of our investigation was the good prognosis of stage I and II patients (92% survival 5-10 years after diagnosis) compared with 66% in stage III and 11% in metastatic disease. The correlation of age and stage (p less than 0.0001), a median progression time of 14.6 months (range 3.4-33.5 mo) from localized to metastatic disease as observed in 18 patients, the high incidence of asymptomatic diseases in stages I (49%) and II (30%) patients and the cost-benefit estimation arguments in favor of a screening program. The key problem for the lab part is the lower incidence of abnormal catecholamine metabolite excretion in stage I and II patients. The origin of 89% of metastatic disease from intraabdominal sites suggests that ultrasonography may be of additional value.

Abdomen↗
PubMed1990

MRI of the knee region in leukemic children. Part I. Initial pattern in patients with untreated disease.

The results of MRI studies performed on the medullary cavity in the knee region of 15 children with leukemia and 5 healthy children are reported. By the age of a few years the signal intensities and the relaxation times of bone marrow begin to resemble fat. Early leukemic infiltration can therefore be more easily recognised in the knee region than in the spine using simple T1 weighted Spin-Echo images. We observed an abnormal signal pattern in all our patients which fell into three groups: (a) diffuse uniform (b) diffuse non-uniform and (c) patchy. We have not been able to correlate these into age, sex or the risk factor determined by clinical or laboratory methods. The diffuse patterns seem to dominate in cases of ALL, the patchy forms in AML. No correlation could be found between the blast levels established by the iliac crest biopsy and the results of MRI.

Adolescent↗
PubMed1990

MRI of the knee region in leukemic children. Part II. Follow up: responder, non-responder, relapse.

Part II demonstrates the results of MRI follow up studies of 23 children with leukemia. Differentiation between leukemic cells and normal hematopoiesis by MRI is impossible. The state of disease can only be determined together with bone marrow biopsy. Clinical remission precedes the normalization of bone marrow signal by weeks. In non-responders, however, cytological findings and MRI findings seem to correlate at the same time. During therapy, areas of osteonecrosis may develop. They do not necessarily contradict continuing complete remission. But this does not affect the prognosis and complete remission is still a possibility. Diagnosis of relapse by MRI is only possible in correlation with studies during the different states of disease especially at clinical remission.

Adolescent↗
PubMed1990

Immunoscintigraphic imaging of mIBG-negative metastases in neuroblastoma.

We report a study of seven children with recurrent stage IV neuroblastoma comparing the uptake pattern of 123I-metaiodobenzylguanidine (mIBG) with 99mTc-labeled monoclonal antibody (MAb) BW 575 by the tumor lesions. Immunofluorescence studies of bone marrow had verified specific binding of the antibody to the tumor cells. The majority of tumor sites was detected both by mIBG and MAb scans. However, five of 26 lesions were not detected by mIBG and eight of 26 were false negative by immunoscintigraphy. The false negative lesions by mIBG belonged to five different patients (one of five primary, four of five bone marrow). In conclusion, MAb BW 575 may detect mIBG-negative neuroblastoma sites. The presence of antibody-negative sites suggests the utilization of both scintigraphy methods together.

3-Iodobenzylguanidine↗
PubMed1989

[Lyme borreliosis with erythema chronicum migrans and Garin-Bujadoux-Bannwarth meningopolyneuritis].

A case report is given on a Borrelia burgdorferi infection regarded to be typical because of its clinical course and the diagnosis lately made. The meningopolyneuritis was treated by use of corticosteroids before the serologic detection of Lyme disease. 21 months after infection our patient died of a colon carcinoma. Histological preparation of the brain showed a slight encephalitis we consider as third-stage Lyme borreliosis. We conclude that antibacterial therapy is necessary in the management of Lyme disease, especially after the administration of corticosteroids.

Antibodies, Bacterial↗
PubMed1989

Neuroblastoma consensus deletion maps to 1p36.1-2.

At least 70% of human neuroblastomas display cytogenetically visible aberrations in the short arm of chromosome 1. We have used a panel of probes detecting polymorphic DNA loci, most of which were derived from a library of microdissected distal 1p chromosome fragments, to compare the hybridization pattern of DNA on nine different tumors and the corresponding normal tissue. In eight of the neuroblastomas allelic loss was observed with at least two probes. The deletions were of different size. Since a consensus deletion in all eight tumors included the segment 1p36.1-2, we conclude that genetic information related to neuroblastoma tumorigenesis is located within this approximately 10 megabase segment. Previous studies have revealed the amplification of MYCN in neuroblastomas. Our study did not provide evidence for a correlation between MYCN amplification and the 1p deletion, suggesting that the two genetic alterations result from molecular mechanisms that are not directly related to each other.

Alleles↗
PubMed1989

The impact of preoperative chemotherapy on resectability of primary tumour and complication rate in metastatic neuroblastoma.

231 children with metastatic neuroblastoma prospectively followed up in three clinical trials underwent first look surgery at diagnosis or delayed first look operation after application of chemotherapy and partly second look surgery and were evaluated for resectability and complication rate. More than 85% of the primary tumours were located within the abdomen. The incidence of macroscopically complete removal increased from 30% to 60% after preoperative chemotherapy (p less than 0.001). There was no difference between the efficacy of delayed first look and second look surgery and between children with stage IV and stage IV S neuroblastoma. The mean complication rate was 20% (complication per patient) and 23% (complication per operation). Complications included local problems (7.9%), infections (5.9%), organ dysfunctions (8.3%) and rare other complications (1.3%). No significant difference was found between the three surgical modalities, i.e. preoperative chemotherapy did neither increase the complication rate nor change the complication pattern. The biological meaning of primary tumour control is still unclear. However, a 40% local recurrence rate suggests an aggressive surgical attitude. Our study provides a basis that preoperative chemotherapy may be an effective tool to achieve complete removal of initially non-resectable primary tumours without increasing the complication rate.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Detection of minimal disease in bone marrow of neuroblastoma patients by immunofluorescence.

Indirect immunofluorescence studies were compared with conventional smear cytology in 82 paired bone marrow samples from children with neuroblastoma using monoclonal antibodies (MAbs) BW 575 (neuroblastoma-associated 95 kD glycoprotein) and BW 625 (ganglioside GD2) and tetanus toxin labeling. Congruent results were obtained in 70 of 82, or 85% (positive/positive; negative/negative). In 12 of 82 (15%) patients, bone marrow infiltration was demonstrated by immunofluorescence but not by conventional cytology. As few as 0.01% neuroblastoma cells were reliably detected--in some cases even fewer. Because of antigen heterogeneity, false negative results were obtained in five cases with MAb BW 625, in two cases with MAb BW 575, and in no case with tetanus toxin. No antibodies showed any cross-reactivity to hematopoietic cells in either bone marrow of infants or during regeneration after chemotherapy. We conclude that this panel of antibodies is highly sensitive and specific to detect minimal disease in bone marrow of neuroblastoma patients, which has major implications for the staging procedure, monitoring treatment, early detection of relapse, and assessment of bone marrow status before autologous bone marrow transplantation.

Antibodies, Monoclonal↗
PubMed1989

Bone marrow transplantation in children with neuroblastoma.

Neuroblastoma is the third most frequent malignant tumor in childhood. One-third of the patients over one year of age at the time of diagnosis suffer from the disseminated form (stage IV). Despite highly aggressive chemotherapy survival rates are poor. One hundred and eighty-seven patients with neuroblastoma stage IV have been treated according to the German protocol NB 85. The probability of disease free survival is only 15% after 70 months. Treatment strategy in our protocol includes autologous and allogeneic bone marrow transplantation (BMT) for patients with stage IV (and greater than 1 year old). Twenty-two patients were grafted (7 allogeneic and 15 autologous). The conditioning regimen consisted mainly of high-dose melphalan (180 mg/m2) and total body irradiation (TBI) (3.4 Gy). Survival rates are discussed in the context of the chemotherapy protocol. Our own experience with autologous BMT is poor, despite of different purging methods. For this reason we decided to focus on allogeneic BMT. We have grafted five patients within the last 3 years. Three of them are alive and well, on died from veno-occlusive disease 70 days after BMT, and the remaining patient, grafted from a syngeneic donor, died from relapsing tumor. The main problem in neuroblastoma stage IV is resistance to chemotherapy. Intensification of the conditioning regimen or double autografting leads to a rate of toxic deaths close to 20% (Zucker, EBMT 1987) which is not tolerable. New improvements in the conditioning regimen have to be found to increase the effect of BMT.

Bone Marrow Transplantation↗
PubMed1989

Removal of neuroblastoma cells from bone marrow by a direct monoclonal antibody rosetting technique.

A one-step direct monoclonal antibody rosetting technique is described for removal of neuroblastoma cells from bone marrow. Two monoclonal antibodies (MoAbs) (BW 575, BW 625) were directly coupled to ox red blood cells by use of CrCl3. The IgG1 antibody BW 575 detects a 95-kD neuroblastoma cell-associated glycoprotein and the IgG3 antibody BW 625 recognizes the ganglioside GD 2. After coupling MoAbs to the erythrocytes, specific strong and stable rosettes were formed with neuroblastoma cells and effectively separated from mononuclear cells using density gradient centrifugation. A total of 1.5% IMR5 neuroblastoma cells were reliably removed from mononuclear cells beyond the limit of detection (less than 0.01%) as judged by tetanus toxin labeling. No impairment of stem cell growth (CFU-GM, BFU-E, CFU-GEMM, CFU-M) was observed. Recovery rate of mononuclear cells ranged between 35 and 69%. A red blood cell/nucleated cell ratio more than 50:1 resulted in increased loss of mononuclear cells and a ratio less than 30:1 in incomplete neuroblastoma cell removal. Using indirect rosettes the purging efficacy was lower and the mononuclear cell loss higher. We conclude that the direct monoclonal antibody rosetting technique may be a technically simple and effective alternative purging method for neuroblastoma patients, which is applicable even in cases demonstrating weak expression of one antigen.

Antibodies, Monoclonal↗
PubMed1988

International criteria for diagnosis, staging, and response to treatment in patients with neuroblastoma.

Neuroblastoma is one of the most common tumors in childhood. However, it often has been difficult to compare clinical and laboratory studies of this disease due to a lack of uniform criteria for diagnosis, staging, and response. An international group of conferees addressed each of these issues and reached a consensus. Specific criteria for making a diagnosis of neuroblastoma are defined. A new neuroblastoma staging system is proposed that takes into account the most important elements of current but incompatible systems. Finally, criteria for response to treatment are standardized. The criteria proposed herein represent an international consensus of essentially every major pediatric oncology group or organization in the United States, Europe, and Japan. The staging system should be referred to as the International Neuroblastoma Staging System, and the response criteria as the International Neuroblastoma Response Criteria. Implementation of these criteria will greatly facilitate the comparison of clinical and laboratory studies by different groups and countries. Furthermore, these criteria should serve as a foundation on which future modifications or improvements can be based.

Humans↗
PubMed1987

Effective remission induction in children with recurrent acute myeloid leukemia by mAMSA, Ara-C, and VP 16.

Five children treated for acute myeloid leukemia according to the BFM protocol AML 83 experienced first bone marrow relapse after 7, 10, 14, 18, and 30 months and were retreated for second remission induction. The chemotherapy consisted of mAMSA (100 mg/m2 per day i.v., days 1-3), ARA-C (100 mg/m2, twice daily, days 1-6), and VP 16 (150 mg/m2 per day, days 4-6). Four of the children achieved a complete second remission after one course of chemotherapy, and the fifth child died of pneumonia during bone marrow aplasia. All surviving children received an identical second course within 4-5 weeks, followed by maintenance chemotherapy. Remission duration was 0, 3, 4, 5, and 5 months. Toxicity was confined to heavy bone marrow depression with thrombocytopenia (nadir 2-7000, days 7-13) and leukocytopenia (nadir 0-400, days 8-14). Bleeding episodes could be prevented by substitution with platelets. Four patients experienced infections (pneumonia, septicemia). We conclude that combination chemotherapy using mAMSA, ARA-C, and VP 16 is effective in inducing a second remission in patients with early bone marrow relapse. The main side effect was considerable bone marrow toxicity.

Amsacrine↗
PubMed1987

Alteration of blast phenotype after low-dose cytarabine in children with acute myeloid leukemia.

Two children with acute myeloid leukemia (FAB M1 and M2) experienced bone marrow relapse during maintenance chemotherapy 7 and 10 months after diagnosis. Low-dose ARA-C monotherapy (2 X 10 mg/m2 per day s.c. for 14 days) was then initiated, as suggested by others reporting induction of differentiation and achievement of remission without toxic side effects. In contrast to these reports, remission induction was not observed in the two children after low-dose ARA-C but was achieved by subsequent high-dose chemotherapy. However, blast cell characteristics revealed some alterations. Blast count and chromosome pattern remained unchanged. Cytochemistry revealed the appearance of esterase- (0----11%), 0----21%) and PAS- (0----74%, 0----45%) positive cells in the patients and a remarkable increase (patient 1: 0----71%) and decrease (patient 2: 90----12%) in acid phosphatase positivity. Expression of myeloid marker VIM D5 decreased distinctly (70----4%, 77----11%). However, the biologic relevance of these alterations remains in question. The failure to respond clinically to low-dose ARA-C in both children is discouraging.

Antigens, Ly↗
PubMed1987

Aggressive combination chemotherapy of bone marrow relapse in childhood acute lymphoblastic leukemia containing aclacinomycin-A: a multicentric trial.

An intensive 7-day combination chemotherapy protocol was designed to reinduce children with early bone marrow relapse of acute lymphoblastic leukemia (less than 6 months after the end of or during preceding treatment). This aggressive approach seemed to be justified for a group of patients who were at the highest risk for ultimate treatment failure. In all, 38 children were enrolled for study. The ratio of male (median age, 10 years) to female (median age, 13 years) subjects was 27:11. Thirty patients were treated for their first relapse and eight for their second or subsequent relapse. Isolated bone marrow involvement was present in 24 cases. All patients had received heavy pretreatment including anthracyclines with cumulative doses of between 120 and 240 mg/m2. 22 of these patients, achieved complete remission, ten did not respond to therapy, and six died from the toxicity of the protocol. Cardiac failure was the cause of death in one child (after additional radiotherapy for a mediastinal mass). No further clinical manifestation of cardiomyopathy could be observed. The other five patients died from hemorrhages or infectious complications. The main side effects were fever, gastrointestinal problems, stomatitis, and severe bone marrow aplasia lasting for about 2 weeks with nadirs of platelets and white blood count around days 10-14. The remission rate of 60% was acceptable, though not satisfactory. Only four children survived disease-free for 13+, 14+, 20+, and 22+ months after diagnosis of relapse.

Aclarubicin↗
PubMed1987

No adverse prognostic influence of hepatitis B virus infection in acute childhood lymphoblastic leukemia.

In the years 1980-1985 72 children with acute lymphoblastic leukemia were diagnosed and treated by intensive combination chemotherapy (BFM protocols 79, 81, 83). Of these children 33 acquired a Hepatitis B-virus-carrier state with 1983 as the peak year of incidence. Both groups of patients, the infected and the uninfected ones, were comparable as to prognostic factors. All except 8 patients are off chemotherapy after a total duration of treatment of 1 1/2 or 2 years. Probability for event-free survival (life table analysis, maximum observation time 82 months, minimum 12 months) is equal (0.77 vs. 0.75) in both groups. With 3 exceptions, all HBV-infected patients still carry the HBs-antigen in the serum; 22 of the 30 living patients in the infected group developed anti-HBc.

Acute Disease↗
PubMed1987

Amplification and expression of the N-myc gene in neuroblastoma.

Genomic configuration and expression of the N-myc gene was investigated by Southern and Northern blot analyses in 18 neuroblastomas of different clinical stages. We observed a 4-100-fold amplification of this oncogene in one of six stage III, two of four stage IV as well as one of five stage IVS tumours. Remarkably, an 80-fold N-myc amplification was demonstrated in a patient with stage IV neuroblastoma being in remission for more than 2 years; moreover, a 100-fold amplification could be detected in a stage IVS tumour from a newborn. These data are discussed in view of the recently postulated close association of N-myc amplification with rapid progression of neuroblastomas.

Child↗