Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization , Heterocyclic Compounds/administration & dosage , Leukemia, Myeloid, Acute/therapy , Stem Cell Transplantation , Adolescent , Adult , Aged , Autografts , Benzylamines , Cyclams , Cytarabine/administration & dosage , Etoposide/administration & dosage , Female , Humans , Male , Middle Aged , Mitoxantrone/administration & dosageABSTRACT
Traditional response criteria in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are based on bone marrow morphology and may not accurately reflect clonal tumor burden in patients treated with non-cytotoxic chemotherapy. We used next-generation sequencing of serial bone marrow samples to monitor MDS and AML tumor burden during treatment with epigenetic therapy (decitabine and panobinostat). Serial bone marrow samples (and skin as a source of normal DNA) from 25 MDS and AML patients were sequenced (exome or 285 gene panel). We observed that responders, including those in complete remission (CR), can have persistent measurable tumor burden (that is, mutations) for at least 1 year without disease progression. Using an ultrasensitive sequencing approach, we detected extremely rare mutations (equivalent to 1 heterozygous mutant cell in 2000 non-mutant cells) months to years before their expansion at disease relapse. While patients can live with persistent clonal hematopoiesis in a CR or stable disease, ultimately we find evidence that expansion of a rare subclone occurs at relapse or progression. Here we demonstrate that sequencing of serial samples provides an alternative measure of tumor burden in MDS or AML patients and augments traditional response criteria that rely on bone marrow blast percentage.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clonal Evolution/genetics , Epigenesis, Genetic/drug effects , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Aged , Aged, 80 and over , Bone Marrow/pathology , Exome , Female , Genes, p53 , High-Throughput Nucleotide Sequencing , Histone Deacetylase Inhibitors/administration & dosage , Humans , Leukemia, Myeloid, Acute/diagnosis , Male , Middle Aged , Mutation , Myelodysplastic Syndromes/diagnosis , Polymorphism, Single Nucleotide , Remission Induction , Treatment Outcome , Tumor BurdenABSTRACT
The nursing and pharmacology literature of 1988 to 1992 generally encouraged a change in nursing practice with regard to maintenance of peripheral intravenous access devices in adults. Although recommendations were based on data, methodological limitations in many studies prevented enthusiastic change from heparinized saline to saline alone. The article describes the quality journey of one community hospital toward practice change in this frequently performed patient care procedure. The success of the change is attributed to pilot outcomes work in the regional tertiary medical center, which demonstrated the credibility of the proposed change. Four organizational processes supported the scientifically based quality change: interdisciplinary efforts of the community hospital instituting the change, a test on one nursing unit, positive recognition of staff undergoing practice change, and publication and dissemination of the clinical procedure change.
