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Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT

The oral histone deacetylase (HDAC) inhibitor (vorinostat) is safe and results in low incidence of acute graft-versus-host disease (GVHD) after reduced-intensity conditioning, related donor hematopoietic cell transplantation (HCT). However, its safety and efficacy in preventing acute GVHD in settings of heightened clinical risk that use myeloablative conditioning, unrelated donor (URD), and methotrexate are not known. We conducted a prospective, phase 2 study in this higher-risk setting. We enrolled 37 patients to provide 80% power to detect a significant difference in grade 2 to 4 acute GVHD of 50% compared with a reduction in target to 28%. Eligibility included adults with a hematological malignancy to receive myeloablative HCT from an available 8/8-HLA matched URD. Patients received GVHD prophylaxis with tacrolimus and methotrexate. Vorinostat (100 mg twice daily) was started on day –10 and continued through day +100 post-HCT. Median age was 56 years (range, 18-69 years), and 95% had acute myelogenous leukemia or high-risk myelodysplastic syndrome. Vorinostat was safe and tolerable. The cumulative incidence of grade 2 to 4 acute GVHD at day 100 was 22%, and for grade 3 to 4 it was 8%. The cumulative incidence of chronic GVHD was 29%; relapse, nonrelapse mortality, GVHD-free relapse-free survival, and overall survival at 1 year were 19%, 16%, 47%, and 76%, respectively. Correlative analyses showed enhanced histone (H3) acetylation in peripheral blood mononuclear cells...
Source: Blood - Category: Hematology Authors: Tags: Transplantation, Free Research Articles, Clinical Trials and Observations Source Type: research

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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
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 ...
Source: Annals of Hematology - Category: Hematology Source Type: research
Conclusions: Posttransplant MNs have a latency period between that seen in AML/MDS related to alkylators and that associated with topoisomerase II inhibitors. The cytogenetic profile suggests a mutagenic effect on leukemogenesis. The clinical outcome for AML/MDS is dismal, with death occurring at an early phase of treatment. PMID: 29228125 [PubMed - as supplied by publisher]
Source: American Journal of Clinical Pathology - Category: Pathology Authors: Tags: Am J Clin Pathol Source Type: research
Authors: Ertz-Archambault N, Kelemen K Abstract Based on the current WHO Classification of Myeloid Neoplasms, cytogenetic findings play a central role in the diagnostic classification of the myeloid malignancies. Cytogenetic abnormalities detected at primary diagnosis may change over time. Karyotype changes can be characterized as cytogenetic evolution, cytogenetic regression or a combination of both. While the exact mechanism of cytogenetic evolution is not completely understood, the process of cytogenetic evolution is not random, but follows different, and often disease-specific patterns during progression and re...
Source: Panminerva Medica - Category: General Medicine Tags: Panminerva Med 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
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for patients with high-risk hematologic malignancies [1,2]. Common indications for HCT in adults include acute myelogenous leukemia, myeloproliferative neoplasms, myelodysplastic syndromes, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, lymphoma, multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma, and certain solid tumors [2].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
CONCLUSIONSIn the absence of RD transplantation, 8/8 URD transplantation is a viable alternative with similar survival outcomes, whereas 7/8 URD transplantation is associated with poorer overall survival. Cancer 2017. © 2017 American Cancer Society.
Source: Cancer - Category: Cancer & Oncology Authors: Tags: Original Article 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
More News: Acute Leukemia | Acute Myeloid Leukemia | Cancer & Oncology | Chronic Leukemia | Clinical Trials | Hematology | Leukemia | Methotrexate | Myelodysplastic Syndrome | Prograf | Study | Tacrolimus | Transplants