ABSTRACT
BACKGROUND: While second-generation tyrosine kinase inhibitors (TKI) revolutionized treatment for patients with chronic myeloid leukemia (CML) who developed a suboptimal response to imatinib, many patients in developing countries are fixed to the latter due to socioeconomic barriers. Despite this scenario, scarce information is available to evaluate the clinical prognosis of these patients. METHODS: We conducted a retrospective cohort analysis to compare the overall mortality of patients with CML who developed a suboptimal response to a standard dose of imatinib and were treated with either high-dose imatinib or a second-generation TKI. We created a marginal structural model with inverse probability weighting and stabilized weights. Our primary outcome was overall survival (OS) at 150 months. Our secondary outcomes were disease-free survival (DFS) at 150 months and adverse events. RESULTS: The cohort included 148 patients, of which 32 received high-dose imatinib and 116 a second-generation TKI. No difference was found in the 150-month overall survival risk (RR: 95% CI 0.91, 0.55-1.95, P-value = .77; RD: -0.04, -0.3 to 0.21, P-value = .78) and disease-free survival (RR: 1.02, 95% CI 0.53-2.71, P-value = .96; RD: 0.01, -0.26 to 0.22, P-value = .96). There was also no difference in the incidence of adverse events in either group. CONCLUSION: Ideally, patients who develop a suboptimal response to imatinib should be switched to a second-generation TKI. If impossible, however, our findings suggest that patients treated with high-dose imatinib have a similar overall survival and disease-free survival prognosis to patients receiving a second-generation TKI.
Subject(s)
Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Hispanic or Latino , Imatinib Mesylate/administration & dosage , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Retrospective Studies , Drug SubstitutionABSTRACT
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been developed as an alternative transplant strategy for children with hematological disorders who do not have an HLA-matched donor. We report the analysis of the outcome for 18 consecutive pediatric patients with various hematological diseases, who underwent haplo-HSCT using a reduced-intensity conditioning regimen and CD3/CD19 depletion in an outpatient setting. Twelve of the 18 patients (66.6%) engrafted either transiently or definitively (9 patients engrafted with full donor chimerism and 3 with mixed chimerism). Six patients with acute lymphoblastic leukemia were disease-free between 2 and 35 months (median 25 months) post-HSCT. The overall survival was 33.3% with a median of 25 months (range 2-35). Our results suggest that haplo-HSCT can be a feasible therapeutic alternative for children who do not have a suitable family donor or available cord blood units. These results also demonstrate that it is possible to perform this regimen on an outpatient basis.
Subject(s)
Antigens, CD19/immunology , CD3 Complex/immunology , HLA Antigens/immunology , Hematopoietic Stem Cell Transplantation/methods , Lymphocyte Depletion/methods , Transplantation Conditioning/methods , Adolescent , Adult , Antigens, CD19/analysis , CD3 Complex/analysis , Child , Female , Haploidy , Humans , Male , Middle Aged , Survival Analysis , Transplantation Chimera , Transplantation, Autologous , Young AdultABSTRACT
Objetivo. Determinar los efectos hemodinámicos y metabólicos de la furosemida, comparando la administración en infusión continua versus la intermitente, en pacientes criticamente enfermos. Material y métodos. Estudio prospectivo en pacientes que ingresaron en una unidad de terapia intensiva pediátrica. Fueron divididos en dos grupos; en el grupo A se usó la furosemida a una dosis de o.3 mg/kg/dosis cada ocho horas, y en el grupo B a dosis de impregnación de 0.3 mg/kg/dosis mantenimiento 0.1-0.3 mg/kg/hora, para mantener la diuresis > 1 mL/kg/hora. Se analizaron variables hemodinámicas y metabólicas; se tomaron éstas antes y 24 horas después de instaladas las infusiones, para compararlas de dos modos: el primero, confrotando los valores pre y postinfusión de ambas modalidades entre sí; y el segundo, cotejando los mismos valores en cada manera de administración. Además, se midió el gradiente del gasto urinario en ambos grupos. Resultados. Al comparar los resultados postinfusión, sólo el potasio sérico tuvo significancia (p<0.001) al disminuir éste en el grupo B; al cotejar los resultados pre y postinfusión de cada grupo, la variable significancia estadística, en el grupo A, fue el gasto urinario (p<0.001) que aumentó, y en el grupo B el potasio sérico (p<0.001) que disminuyó. El gradiente urinario, comparando ambos grupos, obtuvo significancia (p<0.01) al resultar mayor en el grupo A. Conclusiones. La infusión continua mantiene mejor la diuresis dentro de márgenes fisiológicos; los bolos de 0.3 mg/kg/dosis parecen ser efectivos para mantener el gasto urinario en valores normales, mientras que se presenta mayor repercusión (con un balance negativo) en el potasio sérico con la infusión continua, por lo que se sugiere individualizar los casos para determinar la forma de administración de este medicamento.
