Search Results - (Author, Cooperation:W. K. Hofmann)

2011-05-20

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

ADP-Ribosylation Factor 1/metabolism ; Animals ; Cell Survival/drug effects ; DNA-Binding Proteins/biosynthesis/deficiency/genetics/*metabolism ; *Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl/*antagonists & inhibitors ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug ; therapy/genetics/metabolism/*pathology ; Protein Kinase Inhibitors/*pharmacology/therapeutic use ; Transcription, Genetic ; Tumor Suppressor Protein p53/metabolism

2011-09-13

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Alternative Splicing/genetics ; Exome/genetics ; Hematopoiesis/genetics ; Humans ; Mutation/*genetics ; Myelodysplastic Syndromes/*genetics ; Nuclear Proteins/genetics ; Polymorphism, Single Nucleotide/genetics ; RNA Splice Sites/genetics ; RNA Splicing/*genetics ; Ribonucleoproteins/genetics ; Spliceosomes/genetics

2018-03-30

American Society of Hematology (ASH)

0006-4971

1528-0020

Biology

Medicine

Transplantation, Lymphoid Neoplasia

1432-0584

Key words Myelodysplastic syndrome ; All-trans retinoic acid ; Interferon alpha ; Granulocyte colony-stimulating factor ; Differentiation therapy

Springer Online Journal Archives 1860-2000

Medicine

Abstract  Used as single agents, ATRA, G-CSF, and IFN-α have shown a moderate benefit in patients with low-risk MDS, with a response rate of 10%. The aim of the present study was to evaluate the efficacy of a combination of these agents. The effect on hemoglobin (Hb), platelets, and absolute neutrophil count (ANC), as well as on transfusion frequency, was examined in 25 patients with MDS (11 RA, four RARS, eight RAEB, two CMML). The median age was 61 years (range 44–81), and the male/female ratio was 14/11. Treatment consisted of ATRA at 25 mg/m2/day p.o. for months 1, 3, 5, 7, 9, and 11, IFN-α at 1.5 MIU twice a week s.c. for 52 weeks, and, in patients with initial ANC 〈500/μl, G-CSF at 100–480 μg daily s.c. according to the degree of ANC. The duration of therapy was scheduled for 12 months. Two patients achieved ongoing CR (+19 months; +16 months), one patient with RA after 3 months and one with CMML after 7 months of treatment. In all patients, the mean ANC increased significantly from 1400±200/μl before the start of therapy to 3500±600/μl at the end of treatment (p=0.025). In two patients an increase of Hb was observed, and one patient ceased to require transfusions. In an additional patient with RA and 5q-syndrome, the platelet count normalized following administration of ATRA/IFN-α, increasing from 89,000/μl to 293,000/μl. The eight RAEB patients were nonresponders. We conclude that therapy with ATRA, IFNα, and G-CSF is effective in approximately 35% of low-risk MDS patients (in this study: six of 17) and may induce complete remission in individual cases.

Electronic Resource

1432-0584

Key words AML ; Idarubicin ; HDara-C/DNR consolidation

Springer Online Journal Archives 1860-2000

Medicine

Abstract  The toxicity and outcome after high-dose ara-C/daunorubicin (HDara-C/DNR) consolidation therapy in de novo AML was compared in 11 patients who received an idarubicin-containing induction therapy (IDA; from June 1995 to March 1997) and 16 patients pretreated with daunorubicin (DNR; from July 1990 to May 1995) for induction. The DNR group consisted of two cohorts, one (n=6) of patients who had received, as had the IDA group, two induction and one intermediate-dose ara-C consolidation courses, and another (n=10) of patients who had been pretreated with one induction and one consolidation course prior to HDara-C/DNR. There was no difference in the relative dose between the three cohorts. Following HDara-C/DNR, the IDA-pretreated patients experienced a more prolonged myelosuppression during consolidation therapy compared with the DNR group. Duration of neutropenia (〈500 neutrophils/μl) following HDara-C/DNR was 31.2 ± 16 days (mean ±SEM) in the IDA group compared with 18.7 ± 5 days in the DNR group (p〈.001 Mann-Whitney U-test). The duration of thrombocytopenia (platelets 〈25 000/μl) was 34.8 ± 20 days in the IDA group vs. 18.5 ± 6 days in the DNR group (p〈.005). The more prolonged myelosupression was associated with a longer duration of fever (18.9 ± 24 vs. 6.9 ± 5.2 days). A greater incidence, length (11 ± 8 vs. 1.2 ± 2 days), and severity of diarrhea were observed in the IDA-pretreated group. Three of 11 IDA patients experienced WHO grade III-IV diarrhea. In the IDA group two patients developed severe enterocolitis with Candida septicemia, and one of these patients died. One patient in the IDA group died during prolonged aplasia. In the DNR group 6/16 patients experienced grade I-II diarrhea. Two patients in each group died during consolidation therapy. The CR rate was 87% in the IDA group and 79% in the DNR group. Relapse-free survival after HDara-C is 50% at a median follow-up of 60 months in the DNR group and 45% after a median follow-up of 17 months in the IDA group. Whether the advantage of the superior response rate in the IDA-treated patients may be lost during HDara-C consolidation treatment due to increased toxicity remains to be proven in larger trials.

Electronic Resource

1432-0584

Amifostine ; Myelodysplastic syndrome ; Refractory anemia ; Tumor necrosis factor alpha

Springer Online Journal Archives 1860-2000

Medicine

2 /day three times per week followed by a 2-week interval. Since tumor necrosis factor (TNF)α is a main suppressive cytokine for hematopoiesis in RA patients, serum samples for analyzing endogenous levels of TNFα were collected prior to the study and after four treatment cycles. In three patients (21%), reduced transfusion requirement with prolongation of the transfusion interval from 4 weeks to 8 weeks (two patients) and 4 weeks to 6 weeks was seen. An increase in ANC from 400/μl to 2600/μl and 200/μl to 3400/μl was observed in two patients. Platelets increased from 129,000/μl to 277,000/μl in an additional patient. In one patient, disease progression from RA to RAEB was observed. Serum TNFα levels were increased in MDS patients compared with normal controls (18.8 pg/ml vs 9.1 pg/ml), and there was no change during the treatment with amifostine (17.5 pg/ml). In conclusion, treatment with amifostine as a single agent was of limited benefit in patients with RA. The serum TNFα levels were unchanged during treatment with amifostine in RA patients.

Electronic Resource