RESUMEN
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.
Asunto(s)
Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre/metabolismo , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Trasplante Homólogo/métodos , Guías como Asunto , Humanos , Estados UnidosRESUMEN
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.
Asunto(s)
Antígenos CD34/análisis , Movilización de Célula Madre Hematopoyética/métodos , Mieloma Múltiple/terapia , Valor Predictivo de las Pruebas , Adulto , Anciano , Recuento de Células Sanguíneas , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Movilización de Célula Madre Hematopoyética/normas , Humanos , Leucaféresis/métodos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Factores de Tiempo , Trasplante Autólogo , Insuficiencia del TratamientoAsunto(s)
Proteínas Portadoras/genética , Cromosomas Humanos Par 17 , Neoplasias Hematológicas/genética , Isocromosomas , Trastornos Mieloproliferativos/genética , Proteínas Nucleares/genética , Ribonucleoproteínas/genética , Anciano , Proteínas Portadoras/metabolismo , Femenino , Granulocitos/metabolismo , Granulocitos/patología , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patología , Humanos , Masculino , Persona de Mediana Edad , Mutación , Trastornos Mieloproliferativos/metabolismo , Trastornos Mieloproliferativos/patología , Proteínas Nucleares/metabolismo , Ribonucleoproteínas/metabolismo , Factores de Empalme Serina-ArgininaRESUMEN
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.
Asunto(s)
ADN (Citosina-5-)-Metiltransferasas/genética , Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica , Mastocitosis Sistémica/genética , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas c-cbl/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Adolescente , Adulto , Anciano , ADN Metiltransferasa 3A , Análisis Mutacional de ADN , Cartilla de ADN/genética , Dioxigenasas , Femenino , Predisposición Genética a la Enfermedad , Humanos , Cariotipificación , Persona de Mediana Edad , Mutación , PronósticoAsunto(s)
Enfermedades de la Médula Ósea/inducido químicamente , Dasatinib/uso terapéutico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Pirimidinas/efectos adversos , Examen de la Médula Ósea/métodos , Femenino , Humanos , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Remisión EspontáneaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mielofibrosis Primaria/tratamiento farmacológico , Anciano de 80 o más Años , Azacitidina/administración & dosificación , Azacitidina/análogos & derivados , Metilasas de Modificación del ADN/antagonistas & inhibidores , Decitabina , Fatiga/prevención & control , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Nitrilos , Mielofibrosis Primaria/patología , Pirazoles/administración & dosificación , Pirimidinas , Inducción de Remisión , Resultado del TratamientoRESUMEN
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.