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H Löffler

Publications and source records attributed to H Löffler.

At least 37 records · Page 2Linked to original sources
PubMed2001

Remission induction therapy: the more intensive the better?

Intensive induction therapy in acute myeloid leukemia (AML) as in some other systemic malignancies is a strategy fundamentally different from post-remission strategies. Approaches such as consolidation treatment, prolonged maintenance, and autologous or allogeneic transplantation in first remission are directed against the minimal residual disease in which a malignant cell population has survived induction treatment and shows resistance due to special genetic or kinetic features. In contrast, induction therapy deals with naive tumor cells possibly different from their counterparts in remission in terms of their kinetic status and sensitivity. Therefore, in AML the introduction of intensification strategies into the induction phase of treatment has been suggested as a new step in addition to intensification in the postremission phase. As expected from the dose effects observed in post-remission treatment with high-dose cytarabine (AraC) or longer treatment, similar dose effects have been found in induction treatment both from the incorporation of high-dose AraC and from the double-induction strategy used in patients up to 60 years of age. As a particular effect, patients with poor-risk AML according to an unfavorable karyotype, high LDH in serum, or a delayed response show longer survival following double induction containing high-dose AraC as compared to standard-dose AraC. A corresponding dose effect in the induction treatment of patients aged 60 years and older has been found with daunorubicin 60 vs 30 mg/m2 as part of the thioguanine/ AraC/daunorubicin (TAD) regimen with the higher dosage significantly increasing the response rate and survival in these older patients who represent a poor-risk group as a whole. Thus we have been able to demonstrate both in younger and older patients that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits cumulative toxicity in that repeated courses containing high-dose AraC in the post-remission period lead to long-lasting aplasias of about 6 weeks. Thus after intensive induction treatment, high-dose chemotherapy in remission may be practicable using stem-cell rescue and may contribute to a further improvement in the outcome in poor-risk as well as average-risk patients with AML. These approaches are currently under investigation by the German AML Cooperative Group (AMLCG). "The more intensive the better" is certainly not the way to go in the management of AML and other systemic malignancies but some increase in intensity may be possible and better.

Acute Disease↗
PubMed2001

Which bioengineering assay is appropriate for irritant patch testing with sodium lauryl sulfate?

For testing with sodium lauryl sulphate (SLS), measurements of transepidermal water loss (TEWL) and cutaneous blood flow with laser Doppler (LD) are considered to be the most reliable methods. The aim of this study was to determine which method of measurement should be preferred when conducting SLS testing under varying conditions. Patch testing with SLS at different concentrations and exposure times was performed. TEWL values were compared with those of LD. TEWL values showed distinct changes at low SLS concentrations and short application periods. By contrast, higher SLS concentrations were necessary to increase LD values. Short application of patches changed TEWL rather than LD values. When evaluating SLS patch testing by bioengineering methods, TEWL measurement appears to be more suitable for a test procedure that provokes mild skin reactions (SLS concentration <1%), whereas LD measurement is more appropriate to evaluate pronounced skin reactions (SLS concentration >or=1%).

Dermatitis, Irritant↗
PubMed2001

Proliferating status of peripheral blood progenitor cells from patients with BCR/ABL-positive chronic myelogenous leukemia.

To investigate the mechanisms behind the leukemic expansion of BCR/ABL-positive chronic myelogenous leukemia (CML), we examined the cell cycle status of hematopoietic progenitor cells from peripheral blood (PB) and bone marrow (BM) of 37 patients with newly diagnosed BCR/ABL-positive CML. We found a high proportion of 12.51 +/- 1.19% of CD34+ peripheral blood progenitor cells (PBPC) in S/G2M phase. Comparison of PB and BM from 19 cases revealed similar proliferation rates (10.74 +/- 1.41% vs 15.97 +/- 1.95%). Furthermore, even primitive CD34+/CD38- PBPC displayed high proliferation rates (17.45 +/- 2.98%) in 10 cases examined. In contrast, PBPC from 11 patients with BCR/ABL-negative myeloproliferative disorders were almost noncycling (S/G2M 1.46 +/- 0.47%). When matched pairs of PB and BM from six patients with BCR/ABL-negative myeloproliferative disorders were examined, only 0.89 +/- 0.41% of the CD34+ PBPC, but 8.29 +/- 3.13% CD34+ cells from BM were in S/G2M phase. Consistently, as compared to 19 patients with newly diagnosed BCR/ABL-positive CML, a significantly lower PB/BM ratio of CD34+ cells in S/G2M phase was found in these six patients with BCR/ABL-negative myeloprolifrative disorders. Administration of the tyrosine kinase inhibitor STI571 to 13 patients with CML in chronic phase, accelerated phase, or blast crisis lead to an inhibition of PBPC proliferation within a few days. Interestingly, CD34+ hematopoietic progenitor cells from BM remained proliferating in five cases examined, indicating that CML PBPC are more easily inhibited by STI571 as compared to CD34+ CML hematopoietic progenitor cells from BM. These data suggest that BCR/ABL leads to an enhanced cell cycle activation of CD34+ cells, which seems to be, at least in part, independent of additional factors provided by the bone marrow microenvironment.

Adult↗
PubMed2001

Irritant patch testing with sodium lauryl sulphate: interrelation between concentration and exposure time.

BACKGROUND: It is well known that the degree of skin reaction to an irritant depends on its concentration and exposure time. OBJECTIVES: To determine the interrelationship between the concentration of sodium lauryl sulphate (SLS) and exposure time in both weak (subclinical) and severe reactions. METHODS: Patch testing with SLS was performed at different concentrations (0.125%, 0.25%, 0.5%, 1.0% and 2.0%) and with different exposure times (3, 6, 12, 24 and 48 h). Evaluation was conducted by measurement of transepidermal water loss and by laser-Doppler flowmetry both 30 min and 24 h after patch removal. RESULTS: We found more reliable and constant skin reactions 24 h after patch removal, and a higher correlation between SLS concentration and skin reaction. CONCLUSIONS: We conclude that the concentration of SLS influences the test outcome to a larger degree than the exposure time. We present formulae by which the outcome of SLS patch testing at various SLS concentrations ranging from 0.125% to 2% and any exposure time between 3 and 24 h can be estimated.

Adolescent↗
PubMed2001

Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients.

The clinical significance of complex chromosome aberrations for adults with acute myeloid leukaemia (AML) was assessed in 920 patients with de novo AML who were karyotyped and treated within the German AML Cooperative Group (AMLCG) trials. Complex chromosome aberrations were defined as three or more numerical and/or structural chromosome aberrations excluding translocations t(8;21)(q22;q22), t(15;17)(q22;q11-q12) and inv(16)(p13q22). Complex chromosome anomalies were detected in 10% of all cases with a significantly higher incidence in patients > or = 60 years of age (17.8% vs. 7.8%, P < 0.0001). Clinical follow-up data were available for 90 patients. Forty-five patients were < 60 years of age and were randomly assigned to double induction therapy with either TAD-TAD [thioguanine, daunorubicin, cytosine arabinoside (AraC)] or TAD-HAM (high-dose AraC, mitoxantrone). Twenty-one patients achieved complete remission (CR) (47%), 20 patients (44%) were non-responders and 9% of patients died during aplasia (early death). The median overall survival (OS) was 7 months and the OS rate at 3 years was 12%. Patients receiving TAD-HAM showed a significantly higher CR rate than patients receiving TAD-TAD (56% vs. 23%, P = 0.04). Median event-free survival was less than 1 month in the TAD-TAD group and 2 months in the TAD-HAM group, respectively (P = 0.04), with a median OS of 4.5 months vs. 7.6 months (P = 0.13) and an OS after 3 years of 7.6% vs. 19.6%. Forty-five patients were > or = 60 years of age: 28 of these patient were treated for induction using one or two TAD courses and 17 cases received TAD-HAM with an age-adjusted reduction of the AraC dose. The CR rate was 44%, 38% were non-responders and 18% experienced early death. The median OS was 8 months and the OS rate at 3 years was 6%. In conclusion, complex chromosome aberrations in de novo AML predicted a dismal outcome, even when patients were treated with intensive chemotherapy. Patients under the age of 60 years with complex aberrant karyotypes may benefit from HAM treatment during induction. However, long-term survival rates are low and alternative treatment strategies for remission induction and consolidation are urgently needed.

Acute Disease↗
PubMed2001

Murine auricular transepidermal water loss -- a novel approach for evaluating irritant skin reaction in mice.

UNLABELLED: The standard method for evaluating contact allergy in mice is the ear swelling technique. However, in experimental irritant contact dermatitis, the epidermal barrier disruption, that represents a predominant effect of irritants, cannot be assayed by this METHOD: An appropriate method to evaluate barrier disruption is the measurement of transepidermal water loss (TEWL) but to date this has so far been possible only on the trunk of hairless or shaved mice. We therefore developed a new technique to measure the TEWL of mice ears (murine auricular TEWL: MATEWL). After patch testing with irritants and allergens, respectively, we found that the ear swelling method is most suitable for evaluating allergic skin reactions, whereas MATEWL is most appropriate for evaluating irritant skin reactions.

Animals↗
PubMed2001

Pitfalls of irritant patch testing using different test chamber sizes.

BACKGROUND: Test chambers for irritant patch testing are usually larger than those used in allergic patch testing. In general, larger areas show stronger skin reactions than smaller areas. OBJECTIVE: This study investigated whether this difference is of practical relevance, when a model irritant is applied in small and large Finn chambers and evaluated by measurement of transepidermal water loss (TEWL). METHODS: Patch testing was performed with 2 concentrations of sodium lauryl sulfate (SLS) (0.25% and 0.5%) on forearms of healthy volunteers. Large (inner diameter, 12 mm) and small (inner diameter, 8 mm) chambers were used. RESULTS: A variance analysis (3 factors, 2-tailed) showed that the test outcome, as assessed by TEWL, was strongly dependent on SLS test concentration and test chamber size. The larger chambers gave approximately 30% to 50% higher values than the smaller. CONCLUSIONS: This may be explained by the fact that with the small chambers, the adjacent small area of nontreated skin was also assessed by the evaporimeter, biasing the results. A formula estimating TEWL value of the large chamber from values of the small chambers has been proposed.

Adolescent↗
PubMed2001

Relationship between depression, anxiety and quality of life: a study of stroke patients compared to chronic low back pain and myocardial ischemia patients.

The prevalence of anxiety disorders and depression is assessed as between 20 and 50% following stroke. Depressive persons tend to give their overall life situation a worse rating than their relatives or physicians because of negative cognitions. Nevertheless, research concerning Quality of Life (QoL) after stroke hardly ever takes into account the methodological bias of assessing QoL only by self-rating. The aim of this study was to point out the important relationship between depression, anxiety and the autoassessment of QoL. QoL was markedly affected in the poststroke patients and in the chronic low back pain and myocardial ischemia patients, and it was rated worst by the most seriously depressed subjects. Clinical studies focusing on the ever more significant evaluation criterion 'health-related QoL' after stroke should take into account the high prevalence of anxiety and depressive symptoms and their major influence on the patients' self-evaluated QoL.

Anxiety Disorders↗
PubMed2000

Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. German AML Cooperative Group.

A prospective multicenter study was performed to investigate the clinical and molecular results of intensified double induction therapy including high-dose cytarabine (ara-C) in combination with ATRA in newly diagnosed acute promyelocytic leukemia (APL), followed by consolidation and 3 years maintenance therapy. Fifty-one patients, diagnosed and monitored from December 1994 to June 1999, were evaluated. The median age was 43 (16-60) years. The morphologic diagnosis was M3 in 40 (78%) and M3v in 11 (22%) patients. In 15 (30%) patients the initial white blood cell counts were > or =5 x 10(9)/l. The cytogenetic or molecular proof of the translocation t(15;17) was a mandatory prerequisite for eligibility. The diagnosis was confirmed by karyotyping in 46 and by RT-PCR of the PML/RARalpha transcript in 45 cases. The rate of complete hematological remission was 92% and the early death rate 8%. Monitoring of minimal residual disease by RT-PCR of PML/RARalpha (sensitivity 10(-4)) showed negativity in 29 of 32 (91%) evaluable cases after induction, in 23 of 25 (92%) after consolidation, and in 27 of 30 (90%) during maintenance, after a median time of 2, 4 and of 18 months after diagnosis, respectively. After a median follow-up of 27 months, the estimated actuarial 2 years overall and event-free survival were both 88% (79, 97), and the 2 years relapse-free survival 96% (90, 100). The high antileukemic efficacy of this treatment strategy is demonstrated by a rapid and extensive reduction of the malignant clone and by a low relapse rate. The results suggest that the intensity of the induction chemotherapy combined with ATRA is one of the factors which may have a critical influence on the outcome of APL. A randomized trial should assess the value of an induction therapy including ATRA and high-dose ara-C in comparison to standard-dose ara-C.

Adolescent↗
PubMed2000

Trend, seasonal and multivariate modelling study of wet precipitation data from the Austrian Monitoring Network (1990-1997).

The aim of the present study was to analyse the data structure of a large data set from rainwater samples collected during a long-term interval (1990-1997) by the Austrian Precipitation Monitoring Network. Eleven sampling sites from the network were chosen as data sources (chemical concentrations of major ions only) covering various location characteristics (height above sea level, rural and urban sampling positions, Alpine rim and Alpine valley disposition, etc.). The analytical results were treated by the application of already classical environmetric approaches, such as linear regression analysis, time-series analysis and principal components analysis (PCA). For most of the sampling sites, a distinct trend of acidity decrease of the wet precipitation was observed. An overall decrease in sulfate concentration for the whole period and all sites of 3.9% year(-1) (2.0 muequiv. L(-1) year(-1)) was found. The free acidity decrease for most of the sites was between 3.5 and 10.9% year(-1). No significant linear trends were found for nitrate. Base cations either decreased (mean percentage decrease for calcium was 5.4% year(-1) and for magnesium 4.4% year(-1)) or did not show any significant change (sodium, potassium). The overall decrease in ammonium concentration was 2.3% year(-1). Further, some typical "rural" (summer minima and winter maxima) and "urban" (winter minima and spring maxima) seasonal behaviour for the majority of the sites in consideration could be defined, indicating the influence of local emission sources. Several latent factors, named "anthropogenic", "crustal" and "mixed salt", were revealed by the multivariate modelling procedure (PCA) possessing a similar structure for most of the sites. The unavoidable exceptions observed were indications of the influence of sporadic local events (construction and agricultural activities, secondary emission sources, etc.), and an effort was made to explain these exceptions.

Acid Rain↗
PubMed2000

Acute myeloid leukemia in adults: is postconsolidation maintenance therapy necessary?

Maintenance treatment for patients with acute myeloid leukemia (AML) in remission has recently been controversially discussed and even abandoned by several groups. An analysis of 14 recently published multicenter trials, however, revealed the highest probabilities of relapse-free survival (RFS), in the range of 35% to 42% at 4 to 5 years, only in patients assigned to maintenance treatment as far as adult age and intent-to-treat conditions were considered. After having demonstrated a superior RFS rate from 3 years of maintenance after standard-dose consolidation compared with that from consolidation alone (P = .00004), the German AMLCG requestioned the effect of maintenance randomly compared with sequential high-dose cytosine arabinoside (Ara-C) and mitoxantrone in patients who received intensified induction treatment. The results show an advantage for maintenance treatment (RFS rate of 32%) versus the sequential Ara-C and mitoxantrone treatment (RFS rate of 25%) (P = .021). We conclude that maintenance treatment continues to substantially contribute to the management of adult patients with AML, even as part of recent strategies using intensified induction treatment, and thus appears necessary in these settings.

Acute Disease↗
PubMed1999

Interferon-alpha before allogeneic bone marrow transplantation in chronic myelogenous leukemia does not affect outcome adversely, provided it is discontinued at least 90 days before the procedure.

The influence of interferon-alpha (IFN) pretreatment on the outcome after allogeneic bone marrow transplantation (BMT) in chronic myelogenous leukemia (CML) is controversial. One goal of the German randomized CML Studies I and II, which compare IFN +/- chemotherapy versus chemotherapy alone, was the analysis of whether treatment with IFN as compared to chemotherapy had an influence on the outcome after BMT. One hundred ninety-seven (23%) of 856 Ph/bcr-abl-positive CML patients were transplanted. One hundred fifty-two patients transplanted in first chronic phase were analyzed: 86 had received IFN, 46 hydroxyurea, and 20 busulfan. Forty-eight patients (32%) had received transplants from unrelated donors. Median observation time after BMT was 4.7 (0.7 to 13.5) years. IFN and chemotherapy cohorts were compared with regard to transplantation risks, duration of treatments, interval from discontinuation of pretransplant treatment to BMT, conditioning therapy, graft-versus-host disease prophylaxis and risk profiles at diagnosis and transplantation, and IFN cohorts also with regard to performance and resistance to IFN. Outcome of patients receiving related or unrelated transplants pretreated with IFN, hydroxyurea, or busulfan was not significantly different. Five-year survival after transplantation was 58% for all patients (57% for IFN, 60% for hydroxyurea and busulfan patients). The outcome within the IFN group was not different by duration of prior IFN therapy more or less than 5 months, 1 year, or 2 years. In contrast, a different impact was observed in IFN-pretreated patients depending on the time of discontinuation of IFN before transplantation. Five-year survival was 46% for the 50 patients who received IFN within the last 90 days before BMT and 71% for the 36 patients who did not (P =.0057). Total IFN dosage had no impact on survival after BMT. We conclude that outcome after BMT is not compromised by pretreatment with IFN if it is discontinued at least 3 months before transplantation. Clear candidates for early transplantation should not be pretreated with IFN.

Adolescent↗
PubMed1999

[Hereditary angioedema. Diagnostic and treatment errors as systemic lupus erythematosus].

BACKGROUND: Symptoms of hereditary angioedema are intermittent edema of subcutaneous tissues, abdominal organs, upper airways, and brain. Because of spontaneous mutation, in 20% of patients a familial history is lacking. Serological hallmarks are diminished complement factor 4 and C1-esterase inhibitor. The heterogenicity of the clinical symptoms frequently leads to false or delayed diagnosis. CASE REPORT: We report on a 50-year-old male patient with intermittent joint swellings, abdominal complaints, pleural effusions, ascites and headaches with disturbances of consciousness since early adulthood. Diagnosis was systemic lupus erythematosus. Immunosuppressive therapy was ineffective over months. Careful re-evaluation of the patient's clinical history and further laboratory examinations led to the diagnosis of an hereditary angioedema. Anamnestic and laboratory exploration of family members disclosed four other cases. Two of them also were symptomatic for decades without adequate diagnosis. CONCLUSION: In case of intermittent swellings, abdominal complaints, laryngeal edema, pleural effusions or ascites, differential diagnosis should involve hereditary angioedema. With early diagnosis and adequate treatment, prognosis is good. Since ACE inhibitors can aggravate the disease they are contraindicated. Diagnosis, pathogenesis, and treatment are discussed by reviewing the literature.

Angioedema↗
PubMed1999

Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group.

Early intensification of chemotherapy with high-dose cytarabine either in the postremission or remission induction phase has recently been shown to improve long-term relapse-free survival (RFS) in patients with acute myeloid leukemia (AML). Comparable results have been produced with the double induction strategy. The present trial evaluated the contribution of high-dose versus standard-dose cytarabine to this strategy. Between March 1985 and November 1992, 725 eligible patients 16 to 60 years of age with newly diagnosed primary AML entered the trial. Before treatment started, patients were randomized between two versions of double induction: 2 courses of standard-dose cytarabine (ara-C) with daunorubicin and 6-thioguanine (TAD) were compared with 1 course of TAD followed by high-dose cytarabine (3 g/m2 every 12 hours for 6 times) with mitoxantrone (HAM). Second courses started on day 21 before remission criteria were reached, regardless of the presence or absence of blast cells in the bone marrow. Patients in remission received consolidation by TAD and monthly maintenance with reduced TAD courses for 3 years. The complete remission (CR) rate in the TAD-TAD compared with the TAD-HAM arm was 65% versus 71% (not significant [NS]), and the early and hypoplastic death rate was 18% versus 14% (NS). The corresponding RFS after 5 years was 29% versus 35% (NS). An explorative analysis identified a subgroup of 286 patients with a poor prognosis representing 39% of the entire population; they included patients with more than 40% residual blasts in the day-16 bone marrow, patients with unfavorable karyotype, and those with high levels of serum lactate dehydrogenase. Their CR rate was 65% versus 49% (p =.004) in favor of TAD-HAM and was associated with a superior event-free survival (median, 7 v 3 months; 5 years, 17% v 12%; P =.012) and overall survival (median, 13 v 8 months; 5 years, 24% v 18%; P =.009). This suggests that the incorporation of high-dose cytarabine with mitoxantrone may contribute a specific benefit to poor-risk patients that, however, requires further substantiation. Double induction, followed by consolidation and maintenance, proved a safe and effective strategy and a new way of delivering early intensification treatment for AML.

Adolescent↗
PubMed1999

[Treatment of adult acute lymphoblastic leukemia].

In patients with adult ALL, substantial progress has been made in the past 20 years. At present a cure rate of 30-40% can be achieved and varies in defined subgroups between 10-51%. ALL does not represent an uniform disease but is formed by biologic subentities, which differ in their natural history, clinical presentation and prognosis. A comprehensive diagnostic examination, including morphology, cytochemistry, immunology, cytogenetic and molecular genetic analysis is a precondition for prognostic assessment and therapeutic stratification. The basic principle of ALL treatment is a combination chemotherapy with sequential administration of induction, consolidation and maintenance therapy. Bone marrow transplantation has become an important part of the treatment strategy and is performed in patients with high risk. In the subgroup of T-ALL a significant progress has been made in the last years with survival rates of 40-50%. In B-ALL the results have been greatly improved to 48-51% by introduction of a specific treatment strategy. However, the results (about 30%) stagnate for the total group of B-lineage-ALL (common ALL, pre-B-ALL, pro-B-ALL). Patients with B-lineage-ALL can be subdivided in a high and low risk group according to the presence of risk factors (age, white blood cell count, time to achieve a complete remission, pro-B-ALL and the translocations t[4;11], t[9;22]). The outcome of the subgroup of adult pro-B-ALL has been substantially improved (50%). An increase of treatment results (20%) appears in outlines for patients above 50 years. The Ph/bcr-abl positive ALL has in spite of improved complete remission rates (60-70%) consistently unfavourable survival rates (10%).

Adult↗
PubMed1999

[Patch testing with sodium lauryl sulfate: benefits and drawbacks in research and practice].

Patch testing with sodium lauryl sulfate (SLS) has been frequently used in the last decade. The evaluation of the SLS test can be performed visually, or with bioengineering methods. Among these, the transepidermal water loss is the most appropriate method, but measurements by laser Doppler flowmetry, colorimetry or corneometry may yield additional relevant data. Various factors such as age, area of testing or climatic conditions may also influence the SLS test, so such factors should be considered when different studies are compared. If correctly used, the SLS test can provide valuable information regarding the skin susceptibility to irritation. An overestimation of the test, just based on objective measurements with bioengineering methods, should be avoided, as the bioengineering data are capable of great precision and reproducibility, but can only define phenomena and not the causal event.

Dermatitis, Irritant↗