Treatment of relapsed AML and MDS after allogeneic stem cell transplantation with decitabine and DLI —a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group

AbstractIn 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 al so 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, D...
Source: Annals of Hematology - Category: Hematology Source Type: research

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Contributors : Hiroyoshi Kunimoto ; Cem Meydan ; Francine E Garrett-Bakelman ; Caroline Sheridan ; Tak Lee ; Yaseswini Neelamraju ; Ari Melnick ; Ross L LevineSeries Type : Methylation profiling by high throughput sequencingOrganism : Mus musculusRecent studies using next-generation sequencing technology have uncovered mutational landscapes of various myeloid malignancies (Cancer Genome Atlas Research Network, 2013; Yoshida et al., 2011). These genetic data revealed novel classes of mutations that commonly occur in patients with myeloid malignancies, including epigenetic regulators and spliceosomal genes. In addition, co-o...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by high throughput sequencing Mus musculus Source Type: research
Contributors : Hiroyoshi Kunimoto ; Cem Meydan ; Francine E Garrett-Bakelman ; Caroline Sheridan ; Tak Lee ; Yaseswini Neelamraju ; Ari Melnick ; Ross L LevineSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusRecent studies using next-generation sequencing technology have uncovered mutational landscapes of various myeloid malignancies (Cancer Genome Atlas Research Network, 2013; Yoshida et al., 2011). These genetic data revealed novel classes of mutations that commonly occur in patients with myeloid malignancies, including epigenetic regulators and spliceosomal genes. In addition, co-oc...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Background: Azacitidine (Aza) and donor lymphocyte infusions (DLI) confer survival advantage with improved tolerability for patients with relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) following allogenic stem cell transplantation (SCT).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
M, Arnold R, De Witte T, Robin M, Kröger N Abstract No standard exists for the treatment of myelodysplastic syndrome relapsing after allogeneic stem cell transplantation. We performed a retrospective registry analysis of outcome and risk factors in 698 patients, treated with different strategies. Median overall survival from relapse was 4.7 months (4.1-5.3), 2-year survival was 17.7% (14.8-21.2%). Shorter remission after transplantation (p
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Bone Marrow Transplantation, Published online: 11 September 2017; doi:10.1038/bmt.2017.171
Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
Validation of the revised IPSS at transplant in patients with myelodysplastic syndrome/transformed acute myelogenous leukemia receiving allogeneic stem cell transplantation: a retrospective analysis of the EBMT chronic malignancies working party Bone Marrow Transplantation advance online publication, September 11 2017. doi:10.1038/bmt.2017.171 Authors: C Scheid, L de Wreede, A van Biezen, C Koenecke, G Göhring, L Volin, J Maertens, J Finke, J Passweg, D Beelen, J J Cornelissen, M Itälä-Remes, P Chevallier, N Russell, E Petersen, N Milpied, C Richard Espiga, A Peniket, J Sierra, G Mufti, C Crawley, J H Ve...
Source: Bone Marrow Transplantation - Category: Hematology Authors: Source Type: research
ConclusionsOur study shows that HSCT is feasible in the majority of patients with HR-MDS/AML/CMML-2 after AZA treatment. As matched unrelated donor was the most frequent source of donor cells, the time between diagnosis and HSCT needed for donor search could be ‘bridged’ using azacitidine. These data show that AZA prior to HSCT could be a better option than intensive chemotherapy in higher-risk MDS.The trial has been registered with the EudraCT number 2010-019673-1.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 16 March 2017 Source:The Lancet Haematology Author(s): Rick Admiraal, Stefan Nierkens, Moniek A de Witte, Eefke J Petersen, Ger-jan Fleurke, Luka Verrest, Svetlana V Belitser, Robbert G M Bredius, Reinier A P Raymakers, Catherijne A J Knibbe, Monique C Minnema, Charlotte van Kesteren, Jurgen Kuball, Jaap J Boelens Background Anti-thymocyte globulin (ATG) is used to prevent graft-versus-host disease (GvHD) after allogeneic haemopoietic cell transplantation (HCT). However, ATG can also cause delayed immune reconstitution of T cells, negatively affecting survival. We studied the relation be...
Source: The Lancet Haematology - Category: Hematology Source Type: research
We examined chimerism trends post‐HCT in 63 children who underwent HCT for AML or myelodysplastic syndrome (MDS). Mixed T‐cell chimerism at engraftment and absence of chronic graft versus host disease (cGVHD) were associated with relapse (P = 0.04 and P = 0.02, respectively). Mixed T‐cell chimerism at engraftment was predictive in patients without cGVHD (P = 0.03). Patients with engraftment mixed T‐cell chimerism may warrant closer disease monitoring and consideration for early intervention.
Source: Pediatric Blood and Cancer - Category: Cancer & Oncology Authors: Tags: Brief Report Source Type: research
Conclusion SDF-1/CXCR4 axis plays a crucial role in engraftment; however, more studies are warranted to assess their expression post-transplant. Evaluating the ligand (chemokine, SDF-1) or its receptor (CXCR4) may serve as potential surrogate markers for assessment of engraftment.
Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research
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