CPX-351 Salvage Therapy Followed by Haplo-Cord Transplant for Relapsed/Refractory Leukemia or Myelodysplastic Syndrome

Conditions:   Myelodysplastic Syndromes;   Leukemia, Myeloid, Acute;   Leukemia, Relapsed Adult Acute Myeloid;   Myelodysplastic Syndromes, Previously Treated Interventions:   Drug: CPX-351;   Drug: Fludarabine;   Drug: Melphalan;   Drug: Rabbit Anti-Human T-Lymphocyte Globulin;   Biological: Haplo-Cord Stem Cell Transplantation Sponsor:   Weill Medical College of Cornell University Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials

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Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, re...
Source: Cancer - Category: Cancer & Oncology Authors: Tags: Review Article Source Type: research
Conclusion: Pulmonary fungal infections are resistant to treatments for hematological malignancies. Since the treatment of the underlying disease is extended and these infections often recur and are exacerbated, surgery should be considered when possible. PMID: 30402396 [PubMed]
Source: Korean Journal of Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Tags: Korean J Thorac Cardiovasc Surg Source Type: research
AbstractShwachman-Diamond syndrome (SDS) is a rare inherited disease mainly caused by mutations in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. However, it has recently been reported that other genes, including DnaJ heat shock protein family (Hsp40) member C21 (DNAJC21), elongation factor-like 1 (EFL1) and signal recognition particle 54 (SRP54) are also associated with an SDS-like phenotype. Interestingly,SBDS, DNAJC21, EFL1 andSRP54 are involved in ribosome biogenesis: SBDS, through direct interaction with EFL1, promotes the release of the eukaryotic initiation factor 6 (eIF6) during ribosome maturation,DNAJC21 stab...
Source: Molecular Diagnosis and Therapy - Category: Molecular Biology Source Type: research
Abstract Clonal hematopoiesis (CH), in which stem cell clones dominate blood production, becomes increasingly common with age and can presage malignancy development. The conditions that promote ascendancy of particular clones are unclear. We found that mutations in PPM1D (protein phosphatase Mn2+/Mg2+-dependent 1D), a DNA damage response regulator that is frequently mutated in CH, were present in one-fifth of patients with therapy-related acute myeloid leukemia or myelodysplastic syndrome and strongly correlated with cisplatin exposure. Cell lines with hyperactive PPM1D mutations expand to outcompete normal cells ...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
Authors: Rahmé R, Adès L Abstract INTRODUCTION: Myelodysplastic syndromes (MDS) are clonal stem cell disorders mostly affecting the elderly. They are classified into lower and higher risk MDS according to prognostic scoring systems. In higher-risk patients, treatments should aim to modify the disease course by avoiding progression to acute myeloid leukemia, and therefore to improve survival. Areas covered: Stem cell transplantation remains the only curative treatment when feasible, but this concerns a small minority of patients. Treatment is principally based on hypomethylating agents (HMAs). Our unde...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
Conclusion: The "Clo-Baltimore regimen" is safe and feasible and provides good survivals for patients with myeloid malignancies and haplo-donors. Methods: Here, we report a variant of the Baltimore regimen, where 1) fludarabine was replaced by clofarabine, 2) bone marrow was replaced by peripheral blood stem cells, and 3) tacrolimus was replaced by cyclosporine, in a "Clo-Baltimore regimen". PMID: 30323896 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Disease relapse after allogeneic hematopoietic cell transplant (allo-HCT) remains the most common cause of mortality for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) (1). Assessment and monitoring of minimal residual disease (MRD) in these patients is often challenging because of heterogeneity of malignant clones, and the absence of well-standardized MRD assays. Chimerism analysis by the characterization of short tandem repeat (STR) markers in subpopulations of peripheral blood (PB) cells is currently widely used to monitor engraftment status and disease relapse after allo-HCT.
Source: Leukemia Research - Category: Hematology Authors: Source Type: research
Purpose of review Myelodysplastic syndromes (MDSs) are rare disorders in children, showing peculiar clinical manifestations and biological features. This review will summarize biological, genetic and clinical features of childhood MDS and will provide an update of the algorithm of treatment of the different disease variants. Recent findings The most recent classification of MDS includes refractory cytopenia of childhood (RCC), advanced and therapy-related MDS. Importantly, in children, these clonal hematopoietic disorders may be often associated with inherited bone marrow failure syndromes, this representing a challen...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: HEMATOLOGIC MALIGNANCIES: Edited by Miguel A. Sanz Source Type: research
Purpose of review The present review focuses on the current management of patients with chronic myelomonocytic leukemia (CMML) and the most recent developments in the field. Recent findings CMML is a heterogeneous malignant myeloid disorder sharing features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms and characterized by peripheral blood monocytosis and increased risk of progression to acute leukemia. Its natural course is highly variable and use of CMML-specific prognostic scoring systems is strongly recommended for tailoring treatment. Multiple recent studies have showed that somatic mutation...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: HEMATOLOGIC MALIGNANCIES: Edited by Miguel A. Sanz Source Type: research
Purpose of review The monitoring of minimal residual disease (MRD) has important clinical implications in both the pre and postallogeneic stem cell transplant (SCT) setting in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Next-generation sequencing (NGS) is a rapidly improving technology whose application to the monitoring of MRD is an active area of research. We aim to describe existing methods of MRD in AML and MDS, with a focus on the utility of NGS in patients undergoing SCT. Recent findings Flow cytometry and quantitative PCR have been recommended by the European Leukemia Net as the preferred m...
Source: Current Opinion in Hematology - Category: Hematology Tags: HEMATOPOIETIC STEM CELL TRANSPLANTATION: Edited by Armand Keating Source Type: research
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