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1.
Ann Hematol ; 97(2): 335-342, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29151133

ABSTRACT

In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11). DAC was the first salvage therapy in 16 patients (44%), whereas 20 patients (56%) had previously received 1 to 5 lines of salvage therapy including 16 of them had been treated with Aza. In 22 patients (61%), a median of 2 DLI per patient (range, 1 to 5) was administered in addition to DAC. As a result, overall response rate was 25% including 6 complete remissions (CR, 17%) and 3 partial remissions (PR, 8%). Three patients within the first-line group achieved CR, while also 3 patients receiving DAC as second-line treatment reached CR including 2 patients with previous Aza failure. Median duration of CR was 10 months (range, 2 to 33) and no patient relapsed so far. The 2-year OS rate was 11% (± 6%) without any difference between first-line and pretreated patients. Incidence of acute and chronic graft-versus-host disease was 19 and 5%. Taken together, DAC exerts clinical efficacy in patients with AML or MDS relapsing after allo-SCT and is able to induce durable remissions in individual patients suggesting that DAC may be an alternative to Aza or even a second choice after Aza failure.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/analogs & derivatives , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Lymphocyte Transfusion , Myelodysplastic Syndromes/therapy , Adult , Aged , Azacitidine/therapeutic use , Decitabine , Female , Graft vs Host Disease/prevention & control , Humans , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Myelodysplastic Syndromes/immunology , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/pathology , Recurrence , Remission Induction , Retrospective Studies , Salvage Therapy/methods , Survival Analysis , Transplantation, Homologous , Treatment Outcome
2.
J Transl Med ; 15(1): 174, 2017 08 11.
Article in English | MEDLINE | ID: mdl-28800741

ABSTRACT

BACKGROUND: Red blood cell (RBC) depletion is a standard graft manipulation technique for ABO-incompatible bone marrow (BM) transplants. The BM processing module for Spectra Optia, "BMC", was previously introduced. We here report the largest series to date of routine quality data after performing 50 clinical-scale RBC-depletions. METHODS: Fifty successive RBC-depletions from autologous (n = 5) and allogeneic (n = 45) BM transplants were performed with the Spectra Optia BMC apheresis suite. Product quality was assessed before and after processing for volume, RBC and leukocyte content; RBC-depletion and stem cell (CD34+ cells) recovery was calculated there from. Clinical engraftment data were collected from 26/45 allogeneic recipients. RESULTS: Median RBC removal was 98.2% (range 90.8-99.1%), median CD34+ cell recovery was 93.6%, minimum recovery being 72%, total product volume was reduced to 7.5% (range 4.7-23.0%). Products engrafted with expected probability and kinetics. Performance indicators were stable over time. DISCUSSION: Spectra Optia BMC is a robust and efficient technology for RBC-depletion and volume reduction of BM, providing near-complete RBC removal and excellent CD34+ cell recovery.


Subject(s)
Blood Component Removal/methods , Bone Marrow/metabolism , Erythrocytes/metabolism , Antigens, CD34/metabolism , Bone Marrow Transplantation , Cell Lineage , Feasibility Studies , Hematopoiesis , Humans , Transplantation, Homologous
3.
J Clin Invest ; 124(1): 40-6, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24382388

ABSTRACT

The term epigenetics refers to the heritable changes in gene expression that are not associated with a change in the actual DNA sequence. Epigenetic dysregulation is linked to the pathogenesis of a number of malignancies and has been studied extensively in myelodysplastic syndromes and acute myeloid leukemia. DNA methylation is frequently altered in cancerous cells and likely results in transcriptional silencing of tumor suppressor genes. Re-expression of these genes by inhibition of the DNA methyltransferases has been successful in the treatment of benign and malignant disease. In this Review, we discuss the clinical development of demethylating agents in hematology, with a focus on azacitidine and decitabine.


Subject(s)
DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors , DNA Methylation , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Animals , Antimetabolites, Antineoplastic/pharmacology , Azacitidine/analogs & derivatives , Azacitidine/pharmacology , Clinical Trials as Topic , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA Methyltransferase 3A , Decitabine , Epigenesis, Genetic , Humans , Leukemia, Myeloid, Acute/enzymology , Leukemia, Myeloid, Acute/genetics , Mutation, Missense , Myelodysplastic Syndromes/enzymology , Myelodysplastic Syndromes/genetics
4.
J Occup Med Toxicol ; 4: 29, 2009 Nov 26.
Article in English | MEDLINE | ID: mdl-19941640

ABSTRACT

Although the risk of a herpes B virus (Cercopithecine herpes virus 1) infection is low, the clinical course of the infectious disease is generally unfavourable. A high safety standard can be achieved if people with professional contact to primates apply proper organisational, technical and personal safety precautions. The risk can be considerably reduced if animal keepers, laboratory assistants and scientists receive adequate information about the pathology of herpes B virus and are well trained in the necessary procedures and the precautions. For this reason, comprehensive and regular training, information and instruction must be provided to all primate workers and to laboratory workers who come into contact with potentially infectious material. After potential contamination, the risk for the affected worker must be assessed immediately and post-exposure chemoprophylaxis performed if necessary. This necessitates internal risk assessment. An interdisciplinary group of experts has developed an action plan for Germany.

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