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M Schrappe

Publications and source records attributed to M Schrappe.

At least 163 records · Page 9Linked to original sources
PubMed1992

T4+ cell numbers are correlated with plasma glutamate and cystine levels: association of hyperglutamataemia with immunodeficiency in diseases with different aetiologies.

Human immunodeficiency virus type 1 (HIV-1) seropositive individuals suffer from a depletion of T4+ T cells and have elevated plasma glutamate levels. Glutamate is also elevated in cancer patients, and several authors have shown that elevated extracellular glutamate levels inhibit competitively the membrane transport of cystine and cause a decrease of intracellular cystine. We, therefore, tested the hypothesis that high glutamate and/or low cystine levels may generally be associated with low lymphocyte reactivity or low T4+ counts. In three independent studies we tested (i) serum amino acid levels (AAL) versus T4+ counts in healthy individuals, (ii) plasma AAL versus lymphocyte responses in healthy individuals, and (iii) plasma AAL versus T4+ counts in HIV-1 seropositive individuals. When the individuals in each study were divided into four subgroups as defined by median glutamate and cystine levels, the results showed that persons with a combination of low glutamate and high cystine level (LGHC subgroups) had the highest mean T4+ count or highest lymphocyte reactivity. Moreover, the LGHC subgroup in a study of lung cancer patients had a much longer mean survival time than the other three subgroups. In HIV-1 infected patients, hyperglutamataemia is associated with hypocystinaemia and hypocysteinaemia. Azidodeoxythymidine (AZT) treated HIV patients had, on average, lower glutamate levels than patients without AZT.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-Positive T-Lymphocytes↗
PubMed1991

Correlation of chondroitin sulfate proteoglycan expression on proliferating brain capillary endothelial cells with the malignant phenotype of astroglial cells.

Human glioblastomas (five of five), the most malignant astroglial-derived tumors, specifically express a chondroitin sulfate proteoglycan that is recognized by monoclonal antibody 9.2.27 and localized to the glioma cell surface, proliferating endothelial cells, and the perivascular extracellular matrix within the tumor bed. In contrast, the expression of this proteoglycan in normal adult neocortex and white matter is limited to the smooth muscle of small arteries, while normal glia, endothelial cells, and endothelial cell basement membranes are nonreactive. Moreover, two anaplastic astrocytomas, representing medium-grade astroglial-derived tumors, fail to react with monoclonal antibody 9.2.27. In culture, glioblastoma and capillary brain endothelial cells specifically synthesize a 250-kDa core protein and a high-molecular-mass chondroitin sulfate proteoglycan, recognized by monoclonal antibody 9.2.27. These data suggest a correlation between the expression of this chondroitin sulfate proteoglycan on proliferating brain capillary endothelial cells and the malignant phenotype of astroglial cells. The prominent perivascular localization of chondroitin sulfate proteoglycan makes it a marker for both proliferating brain capillary endothelial cells and the most malignant transformed astroglial cells, thus providing an ideal target for the immunotherapy of glioblastoma.

Antibodies, Monoclonal↗
PubMed1988

High-dose methotrexate: pharmacokinetics in children and young adults.

Pharmacokinetics of methotrexate (MTX) was studied in 34 patients (age 1-25 years, median 12 years) predominantly with primary brain tumors and osteosarcoma, who received a total of 64 high-dose infusions (12 g/m2/4 h, maximum dose 20 g), followed by leucovorin rescue (COSS 82). Serum samples were collected over a period of at least 72 h after the end of infusion and MTX was measured by enzyme immunoassay (EMIT). The data were fitted to a biexponential equation using a nonlinear regression analysis. The concentration-time decay of MTX in serum observed in 29/34 patients receiving 4 x 15 mg/m2/d p.o. leucovorin up to 5 days was biphasic with mean half-lives (+/- SD) of 2.42 +/- 0.45 h for t1/2 alpha and 19.9 +/- 7.6 h for t1/2 beta. The steady-state volume of distribution (Vss) was 0.56 +/- 0.18 l/kg and the total body clearance (CL) 71 +/- 20 ml/min/m2 (mean +/- SD). Peak serum concentrations ranged from 674-1778 mumol/l (mean +/- SD, 1201 +/- 293 mumol/l). In 5/34 patients who received a prolonged leucovorin rescue due to a delayed MTX elimination t1/2 alpha was greater than 3.1 h. The data of this study suggest that patients with MTX serum concentrations of less than or equal to 6.3 mumol/l at 24 h, less than or equal to 0.77 mumol/l at 48 h, and less than or equal to 0.33 mumol/l at 72 h after the end of infusion, and a t1/2 alpha of less than or equal to 3.1 h (97.5th percentiles) are at low risk of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1979

Acid- and cryoactivation of renin in human plasma.

Inactive renin in normal human plasma was activated in vitro either by cryoactivation (incubation at 0 degrees C/-5 degrees C up to 3 months) or acid-activation (dialysis to pH 3.0 for 48 h followed by diaylsis to pH 7.5). Plasma-renin-concentration was similar after either activation procedure (96 +/- 50 microU/ml vs 100 +/- 43 microU/ml). There was no further significant acid-activable renin after cryoactivation. These data suggest that conversion of inactive to active renin by optimized procedures is complete. The term "total renin" for activation results under these conditions seems to be valid.

Dialysis↗
PubMedDate not supplied

Foscarnet 5 versus 7 days a week treatment for severe gastrointestinal CMV disease in HIV-infected patients.

In a randomized open trial foscarnet 90 mg/kg b.i.d. 5 days for 3 weeks was compared to 90 mg/kg b.i.d. daily in severe gastrointestinal cytomegalovirus disease in HIV-infected patients. Thirty-eight patients were randomized, 36 were evaluable (all male, age 24-54 years, median 40 years; CD4/microliter 0-150, median 10). Treatment efficacy was evaluated based on a score consisting of symptoms, endoscopic and histologic examination. In the 5-day treatment group 10/16 (62%) patients responded to treatment, in the 7-day treatment group 13/20 (65%), with symptoms resolving in most patients after 1 week. Side effects and adverse events were seen in 13 patients in the 5-day treatment group and in 15 patients in the 7-day treatment group. Laboratory abnormalities were common in both groups, in one patient reversible renal insufficiency developed. Efficacy and safety of treatment 5 days a week was comparable to the standard regimen.

Adult↗
PubMedDate not supplied

Intestinal microsporidiosis in patients with acquired immunodeficiency syndrome--report of three more German cases.

Intestinal microsporidiosis with Enterocytozoon bieneusi was diagnosed in three of 18 HIV-infected patients with chronic diarrhoea. In two cases all known stages of the life cycle of E. bieneusi (merogonial plasmodia, sporogonial plasmodia, sporoblasts, spores) were found in duodenal biopsies by electron microscopical examination, whereas in the third case only merogonial and sporogonial stages were seen. Spores were also visible by light microscopy in semithin sections. Two patients were treated with albendazole (2 x 400 mg/day for 4 weeks) but showed no response. These findings underline the concept of the worldwide distribution of this parasite and verify that it is also frequent in Germany.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Foscarnet and ganciclovir combination therapy for CMV disease in HIV-infected patients.

An open prospective trial of combined ganciclovir and foscarnet therapy for 3 weeks was initiated in 14 episodes of severe CMV-disease in 13 HIV-infected patients (all CDC class IV, age 30-42, median 34 years, CD4+ cell count 0-80, median 10/microliters). In seven episodes of gastrointestinal disease (five colitis, two esophagitis) remission of symptoms and mucosal changes was achieved in five. In seven episodes of retinitis, scarring was achieved in six. Renal toxicity was seen in two patients, moderate hematologic toxicity in eight patients. Overall efficacy was comparable to monotherapy; no new toxicities were seen with the combination of these two drugs.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Seroprevalence and disease association of antineutrophil cytoplasmic autoantibodies and antigens in HIV infection.

This prospective study was designed to determine the role of antineutrophil cytoplasmic autoantibodies (ANCA) in HIV-infected patients. Immunofluorescence tests (IFT) and enzyme-linked immunosorbent assays (ELISA) were applied to sera of 199 consecutive outpatients. In the IFT 20% were positive. An atypical ANCA pattern was demonstrated in 67% of these, 33% revealed a perinuclear staining (pANCA). Specific ELISA revealed proteinase 3 (n = 2), myeloperoxidase (n = 1), lysozyme (n = 2), lactoferrin (n = 1), cathepsin G (n = 1), and human leukocyte elastase (HLE, n = 6). The target antigen remained unidentified in 26 patients. Perinuclear ANCA-positive patients showed atypical antigens in eight of 13 cases; all six patients with anti-HLE revealed a pANCA pattern. The antigens of atypical ANCA-positive patients remained unidentified in 21 of 26 (81%) cases. No signs of vasculitis were present in the ANCA-positive patients. ANCA are frequently found in the sera of HIV-positive patients. They bind to a variety of antigens. No correlation was found between ANCA positivity and autoimmune or opportunistic diseases.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Prophylaxis and treatment of neoplastic meningeosis in childhood acute lymphoblastic leukemia.

The introduction of cranial radiotherapy (CRT) has provided efficient control of overt or subclinical meningeosis in acute leukemia. Especially due to the long-term toxicity of CRT, reduction or elimination of radiotherapy appeared mandatory after cure rates of more than 70% had been achieved in acute lymphoblastic leukemia (ALL). Several large clinical trials of the Berlin-Frankfurt-Münster (BFM) Study Group with more than 3500 patients since 1981 have demonstrated that intensive systemic and intrathecal chemotherapy without or with limited CRT can efficiently prevent central nervous system (CNS) relapses in a large percentage of patients. However, only in low-risk patients prophylactic radiotherapy can be completely and safely replaced by conventional doses of methotrexate. In addition, reduction of chemotherapy in low-risk ALL increased the rate of relapses with CNS involvement. Thus, only a combination of multidrug induction, high-dose methotrexate (HD-MTX) consolidation, and reintensification allowed safe elimination of CRT in low-risk ALL. This approach combined with CRT with 12Gy and 18 Gy in medium and high risk ALL, respectively, reduced the incidence of relapses with CNS involvement to less than 5% (trial ALL-BFM 86). Patients with inadequate response to therapy, or with T-cell ALL, or with overt CNS disease are at particularly high risk for relapse with CNS involvement, and require more systemic and intrathecal chemotherapy combined with cranial irradiation. In B-cell ALL, short intensive chemotherapy pulses including HD-MTX could completely replace radiotherapy. In AML, post-consolidation CRT appears to be advantageous with regard to control of extramedullary as well as systemic relapses.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

[Minimal residual disease analysis in acute lymphoblastic leukemia of childhood within the framework of COALL Study: results of an induction therapy without asparaginase].

UNLABELLED: The detection of minimal residual disease (MRD) is a major prognostic factor for treatment in acute lymphoblastic leukemia (ALL) of childhood. Several groups showed the predictive value of MRD after 5 weeks of chemotherapy (at the end of induction therapy). Patients with more than 1 leukemic cells in 100 cells (> or = 10(-2)) at this time-point have a significantly higher relapse rate. The MRD measurement has been shown to be an independent prognostic factor at several time points in the BFM study (ALL-BFM 90) as well as in the EORTC study. The aim of our investigations was the detection of MRD at the end of induction therapy within the COALL studies which is different from the above studies. In the COALL studies, therapy starts with a 1 week DNR prephase (24 h infusion on day one) and i.th. MTX. Induction therapy consisted of 3 drugs over a period of 4 weeks (Prednisolone, Vincristine and Daunorubicin), asparaginase is given later in consolidation. At the end of induction therapy, bone marrow was obtained for cytomorphologic and molecular analysis. PATIENTS AND METHODS: We investigated bone marrow samples from 76 patients. All patients were in morphologic remission at the end. of induction therapy. For MRD analysis, DNA was isolated from bone marrow mononuclear cells. Clonal T-cell-receptor (TCR) or immunoglobulin gene (IgH) rearrangements were identified by PCR. Monoclonal products were either sequenced directly (TCR) or after excision from high resolution agarose gels. Subsequently patient-specific oligonucleotides for allele-specific PCR were generated. PCR analysis was performed with 1 microgram DNA for each reaction within a semiquantitative matter. This method reached sensitivities down to 10(-5). RESULTS: Eighty-four percent of the analysed samples were MRD positive at the end of induction therapy. 20 out of 76 patient samples (26%) were highly positive (> or = 10(-2)), 28 patients had levels of about 10(-3) (37%), 16 had levels around 10(-4) (21%) and 12 patients had no detectable residual cells (16%). All analysed 15 T-ALL patients had detectable residual disease at this timepoint. Until now, 5/20 patients with very high MRD level at the end of induction therapy suffered a relapse. DISCUSSION: Patients with very high MRD level at the end of induction therapy showed an elevated risk of relapse, but the predictive value is much poorer than for example in the BFM 90 MRD-study. We suggest, that a high MRD level at this timepoint results from a different induction therapy compared to the BFM 90 study. In the COALL studies asparaginase is given only after induction therapy to decrease the risk of thrombosis. We would like to conclude that this differences were compensated later during therapy as the event free survival of both studies is similar. In conclusion, an optimal information from MRD studies is strongly associated with the given therapy. Therefore we initiated an additional MRD time-point after the first chemotherapy block in consolidation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Clinical outcome of patients with childhood acute lymphoblastic leukaemia and an initial leukaemic blood blast count of less than 1000 per microliter.

BACKGROUND: One of the strongest predictive factors for therapy outcome in childhood acute lymphoblastic leukaemia (ALL), treated according to ALL-BFM protocols, is the response to initial prednisone treatment. Prednisone response is characterized by the peripheral leukaemic blast count. The threshold value for the characterisation as good or poor prednisone response is 1000 blasts/microliter on day eight of initial prednisone treatment. It is frequently being discussed, whether patients with ALL that initially present with < 1000 blasts/microliter and still show < 1000 blasts/microliter by day eight of treatment, have the same therapy outcome as prednisone good-responders with initially >/= 1000 blasts/microliter. PATIENTS AND METHODS: We evaluated all patients included in the ALL-BFM 90 study showing good prednisone response. This group included 660 patients presenting with < 1000 blasts/microliter at diagnosis. We compared these patients with the prednisone good-responders that initially presented with >/= 1000 blasts/microliter. In addition we analysed all patients who showed an increasing blast count within the threshold of 1000 blasts/microliter by day eight of treatment. RESULTS: Children presenting with ALL and < 1000 blasts/microliter at diagnosis showed a small but significantly better outcome than prednisone good-responders with initially >/= 1000 blasts/microliter (5 year pEFS 0.86 vs. 0.81, P value 0.0064). If analyzed by treatment group, no significant differences were found. Patients with < 1000 blasts/microliter on day eight of treatment but increasing blast count from diagnosis until day eight did not perform worse. CONCLUSION: The prognostic value of the prednisone response is not restricted to childhood ALL patients presenting with >/= 1000 blasts/microliter at diagnosis, but retains its strength as a strong predictor of treatment outcome also in patients with < 1000 blasts/microliter at diagnosis.

Antineoplastic Agents, Hormonal↗
PubMedDate not supplied

Infants with stage 4 neuroblastoma: the impact of the chimeric anti-GD2-antibody ch14.18 consolidation therapy.

BACKGROUND: Antibody treatment is considered tolerable and potentially effective in the therapy of neuroblastoma. We have analyzed the clinical data of infants < 1 year with stage 4 neuroblastoma with regard to the consolidation treatment. PATIENTS AND METHODS: Infants < 1 year with stage 4 neuroblastoma who completed initial treatment (6-8 chemotherapy cycles followed either by 4 cycles low dose oral chemotherapy or high dose chemotherapy with stem cell transplantation) without event were eligible for this trial. Consolidation therapy consisted of 6 cycles of antibody ch14.18 (20 mg/m(2) x d ch14.18 for 5 days every 2 months) or 12 months oral maintenance chemotherapy (MT). RESULTS: Of 59 evaluable patients, 31 received a total of 159 ch14.18 cycles, 16 received MT instead, and 12 had no further treatment. Fever (47 % of cycles), abnormal CRP without infection (25 %), rash (23 %), cough (16 %), and pain (8 %) were the main side effects. Univariate analysis found no difference in event free survival (3-year-EFS 80.5 +/- 7.1 %, 87.5 +/- 8.3 %, and 75.0 +/- 12.5 % for patients treated with antibody ch14.18, MT, and no further therapy, p = 0.433) and overall survival (3-year-OS 90.1 +/- 5.4 %, 93.8 +/- 6.0 %, and 91.7 +/- 8.0 % for patients treated with antibody ch14.18, MT, and no further therapy, p = 0.931). Multivariate analysis failed to demonstrate an advantage of antibody treatment. CONCLUSION: The outcome of infants with stage 4 neuroblastoma is good. Consolidation treatment with ch14.18 was tolerable but associated with fever, elevated CRP, rash, cough, and pain as side effects. Compared to oral maintenance chemotherapy and no consolidation treatment, ch14.18 treatment had no impact on the patients' outcome which confirms the results found in children > 1 year.

Administration, Oral↗
PubMedDate not supplied

Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: data from the trials ALL-BFM 86, 90, and 95.

Large progress has been made in the treatment of acute lymphoblastic leukemia (ALL) of childhood and adolescence over the past 30 years. Eighty percent of the patients can be cured, but clinical subgroups with a dismal outcome can still be identified. In this study, we investigated the association of age with prognosis in 5 181 patients with ALL under 18 years (y) of age enrolled in the three consecutive treatment trials ALL-BFM 86, 90 and 95 in more than 80 centers. Event-free survival (pEFS) of the total group was significantly associated with age. The most unfavorable outcome was found in infancy and the best results were achieved at toddler and pre-school age. Beyond 5 y of age, survival probability decreased (pEFS at 8 y: < 1 y = 0.45; 1-5 y = 0.82; 6-9 y = 0.75; 10-14 y = 0.63; > or = 15 y = 0.59). The proportion of T-ALL as compared to precursor B-cell ALL (pB-ALL) was lower in younger children, due to an incidence peak of pB-ALL in toddlers and at pre-school age compared to a constant incidence of T-ALL. Within the T-ALL group, no correlation of age with sex, initial white blood cell count, CNS disease, or early treatment response was found. Children under 10 y of age had a slightly lower relapse rate compared to older patients. Within pB-ALL patients, the proportion as well as the absolute incidence of TEL/AML1 rearrangement and DNA index of > or = 1.16 was higher in the younger children. A lower proportion of BCR/ABL-positive ALL was observed in the age group of < 6 y when compared to patients aged > or = 6 y, but the absolute incidence was constant across the age groups after the first year of life. More than half of the infants had a CD10-negative pB-ALL. The incidence was constant after a peak in the first year of life, yet the percentage of CD10 negativity increased with rising age in this subgroup. Adolescents with pB-ALL had a significantly higher proportion of prednisone poor-responders. Accordingly, outcome was worse in older patients. This pattern was also evident in the biologically heterogeneous group of patients with a DNA index of > or = 1.16. In contrast, no significant age-related outcome differences could be shown within TEL/AML1- or BCR/ABL-positive patients, as well as within CD10-negative pB-ALL beyond infant age. Analysis of the pB-ALL group in a Cox's regression model including age and the above-listed biological factors revealed age < 1 year and > or = 10 years as independent risk factors. This is in line with the poorer prognosis of these age groups in the pB-ALL subgroup without specific biological characteristics. This subgroup also had an incidence peak at toddler age, presumably containing other favorable biological subsets. An independent prognostic impact of age in pediatric ALL cannot be excluded by this study. However, our analyses show that the age-associated different prognosis in childhood ALL is at least partly related to the different distribution of relevant prognostic subgroups between the age groups.

Adolescent↗
PubMedDate not supplied

[Treatment of acute lymphoblastic leukemia in childhood and adolescence: results of the multicenter therapy study ALL-BFM 81].

In therapy study ALL-BFM 81 633 previously untreated patients with acute lymphoblastic leukemia (ALL) less than 18 years of age have been recruited from April 1, 1981 to September 30, 1983 and treated in 37 institutions throughout West-Germany and Austria. Here only therapy results of 611 patients with non-B-ALL are presented. Patients with ALL of B-type are described elsewhere. In this fourth consecutive trial of the BFM study group three major questions have been asked: 1. Is it possible to assess the individual risk for relapse more accurately by the use of a risk factor rather than by the risk score which was the discriminator in studies ALL-BFM 76 and ALL-BFM 79? Does this risk factor discriminate more precisely patients at the highest risk for relapse? Offers more intensive risk-adapted therapy to this patient group a better chance for disease-free survival? 2. In patients at a standard risk for relapse with a risk factor below 1.2--approximately 60% of patients with non-B-ALL--can radiotherapy for prevention of CNS disease effectively be replaced by chemotherapy (intermediate dose Methotrexate)? 3. It is possible to reduce duration of maintenance therapy by 6 months to a total duration of 18 months with no unfavorable effect? To assess the radiation problem in standard risk patients and to evaluate the importance of duration of maintenance therapy two randomisations have been utilized. After a median duration of study ALL-BFM 81 of 4 1/2 years and 3 1/4 years after the study had been closed (date of evaluation January 1, 87) the answers are as follows: 1. For the majority of patients risk-adapted therapy had a curative effect. The probability for event-free survival (EFS) in standard risk patients in slightly above 70%, in medium risk patients 67%. In high-risk patients risk-adapted therapy did not improve prognosis, the EFS being still in the order of 50%. A good assessment of the individual risk for relapse is possible by the newly introduced risk factor. This principle is superior to the risk score used in former studies ALL-BFM 76 and ALL-BFM 79 because a low risk group (risk factor below 0.8) could be identified including approximately 25% of all patients with non-B ALL. Selection, quality, and timing of therapy elements remain the decisive prognostic factors, however. 2. Standard risk patients with a risk factor below 0.8 can effectively be protected for CNS relapse by treatment with intermediate dose Methotrexate.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMedDate not supplied

[Corticosteroid-dependent reduction of leukocyte count in blood as a prognostic factor in acute lymphoblastic leukemia in childhood (therapy study ALL-BFM 83)].

In therapy study ALL-BFM 83 a total of 630 patients with acute lymphoblastic leukemia (ALL) have prospectively been evaluated for initial response on therapy with corticosteroids. It was the aim to qualify the in vivo cytoreduction as a new predictor for therapy failure. All patients were exposed for 7 days to prednisone before combination chemotherapy at day 8 has been started. At day 0 one additional dose of Methotrexate was given intrathecally. Therapy for all patients with non-B-ALL has been stratified according to initial tumor burden (risk factor) providing four therapy branches: standard risk low (SR-L), standard risk high (SR-H), medium risk (MR), high risk (HR). After a median duration of study of 21 months, event-free survival (EFS) is for all 630 patients 73%, 81% for SR-L, 76% for SR-H, 69% for MR, and 35% for HR patients (date of evaluation Jan. 1, 1987). In this prospective study, a small subgroup of patients (n = 48; 7.6% of total group) is characterized by greater than 1000 leukemic blasts/mm3 peripheral blood at day 8 after exposure to prednisone. In this subgroup the EFS is only 43% in contrast to 76% in the complementary group of 582 patients with less than 1000 leukemic blasts/mm3 peripheral blood at day 8. Patients of that risk group are derived from therapy branches SR-H, M and HR, the latter contributing relatively most patients. In this negatively selected group all patients with an initial high white blood count, CNS disease at diagnosis, immune subtypes as prae-T-ALL (n = 6), T-ALL (n = 18), null-ALL (n = 5), and males clearly dominate. Of 48 patients with greater than 1000 blasts/mm3 at day 8 4 subsequently failed to enter remission and 8 were qualified as lateresponders. 18 patients relapsed, most of them earlier compared to those of the complementary group. The initial in vivo response on corticosteroid therapy is considered a supplementary prognostic predictor for early failure. It will be utilized in trial ALL/NHL-BFM 86 to qualify patients at the highest risk for relapse. This group of patients is supplemented in addition by non- and lateresponders and children with acute undifferentiated leukemia (AUL). The in vivo corticosteroid test is simple, generates early and reliable results and can be obtained almost always. Thus it may be recommended for use in a multicenter trial.

Antineoplastic Combined Chemotherapy Protocols↗