Subject(s)
Bone Marrow Diseases/chemically induced , Dasatinib/therapeutic use , Leukemia, Myeloid, Chronic-Phase/drug therapy , Pyrimidines/adverse effects , Bone Marrow Examination/methods , Female , Humans , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Remission, SpontaneousSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Primary Myelofibrosis/drug therapy , Aged, 80 and over , Azacitidine/administration & dosage , Azacitidine/analogs & derivatives , DNA Modification Methylases/antagonists & inhibitors , Decitabine , Fatigue/prevention & control , Female , Follow-Up Studies , Humans , Male , Middle Aged , Nitriles , Primary Myelofibrosis/pathology , Pyrazoles/administration & dosage , Pyrimidines , Remission Induction , Treatment OutcomeABSTRACT
Peripheral blood progenitor cell mobilization practices vary significantly among institutions. Effective mobilization regimens include growth factor alone, chemotherapy and growth factor combined, and, more recently, incorporation of plerixafor with either approach. Many institutions have developed algorithms to improve stem cell mobilization success rates and cost-effectiveness. However, an optimal stem cell mobilization regimen has not been defined. Practical guidelines are needed to address important clinical questions, including which growth factor is optimal, what chemotherapy and dose is most effective, and when to initiate leukapheresis. We present recommendations, based on a comprehensive review of the literature, from the American Society of Blood and Marrow Transplantation.
Subject(s)
Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation/methods , Stem Cells/metabolism , Transplantation Conditioning/methods , Transplantation, Autologous/methods , Transplantation, Homologous/methods , Guidelines as Topic , Humans , United StatesSubject(s)
Carrier Proteins/genetics , Chromosomes, Human, Pair 17 , Hematologic Neoplasms/genetics , Isochromosomes , Myeloproliferative Disorders/genetics , Nuclear Proteins/genetics , Ribonucleoproteins/genetics , Aged , Carrier Proteins/metabolism , Female , Granulocytes/metabolism , Granulocytes/pathology , Hematologic Neoplasms/metabolism , Hematologic Neoplasms/pathology , Humans , Male , Middle Aged , Mutation , Myeloproliferative Disorders/metabolism , Myeloproliferative Disorders/pathology , Nuclear Proteins/metabolism , Ribonucleoproteins/metabolism , Serine-Arginine Splicing FactorsSubject(s)
Antineoplastic Agents/therapeutic use , Myeloproliferative Disorders/complications , Myeloproliferative Disorders/drug therapy , Pyrazoles/therapeutic use , Renal Insufficiency, Chronic/complications , Aged , Fatal Outcome , Female , Humans , Male , Middle Aged , Myeloproliferative Disorders/diagnosis , Nitriles , Pyrimidines , Renal Insufficiency, Chronic/diagnosis , Treatment OutcomeABSTRACT
We hypothesized that analysis of single nucleotide polymorphism arrays (SNP-A) and new molecular defects may provide new insight in the pathogenesis of systemic mastocytosis (SM). SNP-A karyotyping was applied to identify recurrent areas of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family. Overall survival (OS) was analyzed using the Kaplan-Meier method. We studied a total of 26 patients with SM. In 67% of SM patients, SNP-A karyotyping showed new chromosomal abnormalities including uniparental disomy of 4q and 2p spanning TET2/KIT and DNMT3A. Mutations in TET2, DNMT3A, ASXL1 and CBL were found in 23%, 12%, 12%, and 4% of SM patients, respectively. No mutations were observed in EZH2 and IDH1/IDH2. Significant differences in OS were observed for SM mutated patients grouped based on the presence of combined TET2/DNMT3A/ASXL1 mutations independent of KIT (P = 0.04) and sole TET2 mutations (P<0.001). In conclusion, TET2, DNMT3A and ASXL1 mutations are also present in mastocytosis and these mutations may affect prognosis, as demonstrated by worse OS in mutated patients.
Subject(s)
DNA (Cytosine-5-)-Methyltransferases/genetics , DNA-Binding Proteins/genetics , Gene Expression Regulation , Mastocytosis, Systemic/genetics , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins c-cbl/genetics , Proto-Oncogene Proteins/genetics , Repressor Proteins/genetics , Adolescent , Adult , Aged , DNA Methyltransferase 3A , DNA Mutational Analysis , DNA Primers/genetics , Dioxygenases , Female , Genetic Predisposition to Disease , Humans , Karyotyping , Middle Aged , Mutation , PrognosisABSTRACT
Early and reliable prediction of the likelihood of achieving adequate stem cell collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) would improve collection efficiency, prevent unnecessary aphereses, and permit appropriate treatment alterations. No previous study has reported a threshold CD34+ cell collection quantity on Day 1 or 2 of leukapheresis that could predict successful stem cell collection. We performed a retrospective analysis of all MM patients undergoing first attempt of stem cell collection at our institution from 2001 through 2008. Recursive partitioning analysis was used to identify Day 1 or Day 1+2 CD34+ collection quantity that predicted failure to reach target ≥ 2 × 10(6) CD34+ cells/kg within five days of collection. Totally, 172 patients were included in the analysis. Patients underwent mobilization with G-CSF or G-CSF+ chemotherapy. 23 of 172 patients (13.4%) failed to collect sufficient (≥ 2 × 10(6) CD34+ cells/kg) CD34+ cells after five days of apheresis: 22 of 29 who collected ≤ 0.70 × 10(6) CD34+ cells/kg and 1 of 143 who collected > 0.70 × 10(6) CD34+ cells/kg (75.9% vs. 0.7%, P < 0.001) on Day 1. Collection failure occurred in 23 of 30 patients who collected ≤ 1.54 × 10(6) CD34+ cells/kg and 0 of 142 who collected >1.54 × 10(6) CD34+ cells/kg (76.7% vs. 0%, P < 0.001) on Days 1 + 2. Day 1 CD34+ cell collection quantity identifies patients unlikely to achieve adequate collection for ASCT. Patients who collect ≤ 0.70 × 10(6) CD34+ cells/kg on day 1 could be considered for treatment modifications to improve CD34+ collection, such as early administration of plerixafor or large volume apheresis.
Subject(s)
Antigens, CD34/analysis , Hematopoietic Stem Cell Mobilization/methods , Multiple Myeloma/therapy , Predictive Value of Tests , Adult , Aged , Blood Cell Count , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization/standards , Humans , Leukapheresis/methods , Male , Middle Aged , Practice Guidelines as Topic , Retrospective Studies , Time Factors , Transplantation, Autologous , Treatment FailureABSTRACT
As the overall prognosis and treatment response rate to standard chemotherapy for acute myeloid leukemia (AML) remains poor in the older adult population, there is a need for more effective therapeutic agents with lower toxicity profiles that can be offered to these patients. Gemtuzumab ozogamicin (GO) is an anti-CD33 monoclonal antibody that was approved by the US Food and Drug Administration for use as monotherapy in patients 60 years of age and older with relapsed AML. GO consists of a humanized anti-CD33 antibody (hP67.6) which is linked to N-acetyl-gamma calicheamicin 1,2-dimethyl hydrazine dichloride. Once the antibody attaches to the surface antigen, it is rapidly internalized. Calicheamicin, a potent enediyne, is subsequently released and acts as a cytotoxic anti-tumor agent. In this population, GO has an acceptable toxicity and yields response rates approaching 30%. The efficacy of GO as monotherapy and in combination therapy for treatment of both de novo and relapsed AML continues to be investigated.
