RESUMO
Resumen: ANTECEDENTES: la fiebre neutropénica es una de las principales complicaciones del tratamiento oncológico y es causa importante de morbilidad y mortalidad; afecta a más de 80% de los pacientes con neoplasias hematológicas durante el primer ciclo de quimioterapia. El tratamiento consiste en antibióticos de amplio espectro con respuestas terapéuticas heterogéneas. OBJETIVO: determinar el tiempo promedio de la desaparición de la fiebre después de la administración de la primera dosis del antibiótico. MATERIAL Y MÉTODO: estudio prospectivo, aleatorizado, doble ciego, efectuado del 1 de mayo al 24 de septiembre de 2014, en el que los pacientes se distribuyeron al azar para recibir tratamiento con ceftazidima-amikacina o imipenem durante 10 días. Se registraron la temperatura y fiebre. Se tomaron hemocultivos previo al tratamiento y a las 48 horas en caso de persistencia de fiebre. Se registraron todos los hemocultivos con crecimiento bacteriano. RESULTADOS: se evaluaron 31 pacientes, de 17 a 61 años de edad (promedio de 33.6 ± 13.9); 15 pacientes recibieron ceftazidima-amikacina (48.4%) y 16 pacientes imipenem (51.6%). El tiempo promedio de remisión de la fiebre fue de 11.2 ± 16.3 vs 9.6 ± 14.8 horas (p = 0.6) en el grupo de ceftazidima-amikacina e imipenem, respectivamente. CONCLUSIONES: no hubo diferencia en el tiempo de mejoría clínica entre los pacientes tratados con imipenem o ceftazidima-amikacina. Ambos esquemas antimicrobianos fueron igual de eficaces para el tratamiento de la fiebre neutropénica secundaria a quimioterapia.
Abstract: BACKGROUND: Neutropenic fever is one of the major complications of cancer treatment and it is an important cause of morbidity and mortality. It occurs in more than 80% of patients with hematologic malignancies during the first cycle of chemotherapy. Treatment consists on broad-spectrum antibiotics with heterogeneous therapeutic responses. OBJECTIVE: To determine the average time for disappearance of fever after the administration of the first dose of antibiotics. MATERIAL AND METHOD: A prospective, randomized, double blind study was conducted. Patients were randomized to receive treatment with ceftazidime/amikacin or imipenem for 10 days. A record of temperature and fever was kept. Blood cultures prior to treatment and at 48 hours were taken in case of persistent fever. All blood cultures were recorded for bacterial growth. RESULTS: Were evaluated 31 patients with ages between 17 and 61 years (mean 33.6 ± 13.9). Fifteen patients received ceftazidime/amikacin (48.4%) and 16 patients imipenem (51.6%). The average time of remission of fever was 11.2±16.3 vs 14.8 ± 9.6 hours (p = 0.6) for the ceftazidime/amikacin and imipenem group, respectively. CONCLUSIONS: There was no difference about the time of clinical improvement among patients treated with imipenem or ceftazidime/amikacin. Both antimicrobials schemes were equally effective for the treatment of secondary neutropenic fever chemotherapy.
RESUMO
Acute lymphoblastic leukemia (ALL) has been recognized as a hematologic neoplasia that originates at the level of a primitive lymphoid stem/progenitor cell. To date, however, the biology of the hematopoietic system in this disorder is still not fully understood. In the present study, we have determined the progenitor cell content (including myeloid, erythroid and multipotent progenitors) in 14 children with ALL and followed the proliferation kinetics of these cells in Dexter-type long-term marrow cultures. We have also characterized some aspects related to the composition and function of the hematopoietic microenvironment developed in vitro. All patients included in this study showed extremely reduced levels of progenitor cells (median of 6.2% of the levels found in normal marrow). Proliferation of these cells in long-term cultures was markedly deficient, since they showed very low numbers - compared to normal cultures - and reached undetectable levels after only a few weeks. Regarding the microenvironment developed in vitro, whereas normal marrow samples contained a median of 8 fibroblastic progenitors/10(5) marrow cells and the stromal cell layers developed in culture contained a median of 341000 adherent cells per well, ALL marrow samples showed no fibroblastic progenitors and the numbers of adherent cells were 21% of those in normal cultures. Interestingly, the levels of TNFalpha and IL-6 in ALL culture supernatants were significantly increased, compared to normal cultures. Bone marrow samples from all 14 children were also analyzed once they reached a complete clinical and hematological remission. Myeloid, erythroid and multipotent progenitor cell levels were significantly increased, compared to patients at diagnosis, and proliferation of myeloid progenitors in long-term cultures was also improved. In contrast, proliferation of erythroid progenitors showed no difference to that in cultures from patients at diagnosis. The numbers of fibroblastic progenitors and adherent cells were significantly increased, compared to patients at diagnosis, and TNFalpha and IL-6 levels returned to normal. In summary, in the present study, we have demonstrated significant in vitro alterations of the hematopoietic system, both in terms of its composition and function, in pediatric patients with ALL. Importantly, most of these alterations are corrected, at least partially, after chemotherapy.
