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.

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.

Clinical features of inflammatory joint and spine manifestations in Crohn's disease.

167 patients with Crohn's disease were investigated for joint and spine inflammation. Arthritis was observed in 23 patients (14%), sacroiliitis in 24 (14%), and sacroiliitis in combination with arthritis in 11 patients (7%). 15 patients (9%) had ankylosing spondylitis; 9 of them were HLA-B27 positive (60%). A parallel pattern in the course of bowel disease and joint inflammation was observed in 22 out of 34 patients with arthritis (59%). An association between the localization of Crohn's disease and the type of spondylarthritis could not be demonstrated. Patients with arthritis alone developed erythema nodosum (35%) or aphthous stomatitis more often (21%) than patients without spondylarthritis+ (6% and 12%, respectively). Other extra-intestinal manifestations of Crohn's disease did not reveal any association with the development of spondyloarthritis.

[Hypoglycemia in type II diabetic patients]. / Hypoglykämie bei Typ-II-Diabetikern.

The incidence of hypoglycemia was determined in 138 type-2 diabetics treated with insulin (40%) or sulfonylureas (60%). Within one year, ten patients (7%) experienced one severe hypoglycemic episode characterized by a loss of consciousness and the necessity of parenteral glucose administration. Insulin treatment and advanced age increased the risk of hypoglycemia. The knowledge about hypoglycemia was poor. Only 45% of the patients could give a correct definition, 18% knew more than two symptoms, and 15% knew at least one cause of hypoglycemia. 66% would treat hypoglycemia with oral carbohydrates. The risk of hypoglycemia should be considered in the planning of adopted teaching and treatment programs for patients with type-2 diabetes.

[Autonomic neuropathy in diabetes mellitus, chronic renal failure and liver cirrhosis]. / Untersuchungen zur autonomen Neuropathie bei Diabetes mellitus, chronischer Niereninsuffizienz und Leberzirrhose.

Chronic diseases (diabetes mellitus, end stage renal failure on hemodialysis, post-hepatitic liver cirrhosis) caused autonomic neuropathy in 34 of 65 cases. The frequency of autonomic neuropathy was 14 of 30 diabetics (typ I and typ II), twelve of 19 patients on dialysis, and eight of 16 non-alcoholic liver cirrhotics. We did not find a correlation between the tests of the cardiovascular and of the gastrointestinal system. The distribution of the neuropathic changes was undependent of the underlying disorder. Using appropriate tests, alterations of the autonomic functions can be discovered frequently even in asymptomatic patients. At least two pathological test results are necessary to reach a significant difference between patients and healthy controls. This indicates that the diagnosis of autonomic neuropathy should rely on two or more pathological test results. The evidence of autonomic neuropathy identifies a population of high risk patients.

[Toxic liver damage caused by HMG-CoA reductase inhibitor]. / Toxischer Leberschaden durch HMG-CoA-Reduktase-Hemmer.

CASE REPORTS: We report on 4 patients who were referred to the clinic with suspected acute hepatitis and to investigate high transaminase values. After exclusion of specific hepatitis, unspecific virus hepatitis, autoimmune hepatitis, a metabolic disorder damaging the liver and extrahepatic cholestasis, a toxic liver damage remained as the probable cause and was histologically verified. Since other drugs and alcoholics could be eliminated as possible causes of the damage, the toxicity had to be attributed to statin ingestion. CLINICAL COURSE: After discontinuation of the medication with continuation of all other therapeutic agents of the general practitioners, the transaminase values normalized within a few weeks. Renewed administration of statin was not prescribed for ethical reasons. CONCLUSION: Therefore, when prescribing a HMG-CoA-reductase inhibitor, the possibility of liver damage should be mentioned and regular checks of the transaminase values should be performed.

Continuous complete hematological and cytogenetic remission with molecular minimal residual disease 9 years after discontinuation of interferon-alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemia.

Interferon-alpha has been used as standard therapy for patients with Philadelphia-positive chronic myeloid leukemia (CML) for more than 20 years. Recently randomized trials have shown a superiority of the tyrosine kinase inhibitor imatinib in respect to its efficacy to induce complete hematological and cytogenetic remissions and more importantly in overall survival. Although follow-up is much shorter for imatinib than for interferon-alpha, this data changed the treatment algorithms in this disease. At the end of the era of interferon-alpha as a single-drug first-line treatment for most patients we present a case report which exemplifies a rare but exciting property of interferon-alpha in CML: the induction of complete hematological and cytogenetic remissions which can persist over years after discontinuation of the drug. Hence, the enrollment of CML patients in clinical trials which explore a combination treatment of imatinib and interferon-alpha is warranted.

A modified sclerosing needle for the sclerotherapy of upper gastrointestinal bleeding.

A modified instrument that permits simultaneous endoscopic irrigation and sclerotherapy of a bleeding site in the gastrointestinal tract under direct visualisation is presented. To date, the system has been used in 12 patients. Five cases of grade III esophageal varices have been treated and in three cases of acute bleeding, definitive arrest of the bleeding was achieved. In seven cases of acute upper gastrointestinal hemorrhage presenting with gastric ulcer (n = 2 Forrest-Ia and n = 2 Forrest-Ib) and duodenal ulcer (n = 3 Forrest-Ib) bleeding was successfully stopped. The system is easy to handle, reliable in clinical practice, can be employed anywhere and the instrument is inexpensive.