Comparison of cefepime versus ceftriaxone-amikacin as empirical regimens for the treatment of febrile neutropenia in acute leukemia patients.

BACKGROUND: High-intensity regimes of chemotherapy have led to longer and more severe episodes of neutropenia with a resulting increase in morbidity and mortality due to infections. Which empiric antibiotic regimen to use in these cases is still under debate. METHODS: We performed a randomized comparative study to evaluate the efficacy of cefepime versus ceftriaxone plus amikacin as the initial treatment in an escalating, empirical, antibiotic therapy regimen in febrile neutropenic patients. Both adults and children were included. All patients had less than 500 neutrophils/microl at the time of infection. Patients were randomized to receive either cefepime or ceftriaxone plus amikacin. If infection continued 72 h later, patients in both groups received vancomycin, and if infection had not disappeared 7 days after starting antibiotics, amphotericin B was started. RESULTS: Twenty patients were included in each group. Both treatment and control groups were comparable for age and sex, among other factors. There were 18 cures in the cefepime group and 17 in the ceftriaxone plus amikacin group (p = 0.9). No patient discontinued therapy because of toxicity. CONCLUSIONS: Cefepime is a safe and very effective therapy for patients with acute leukemia and febrile neutropenia; in addition, it is a cheaper regimen in our country, and lacks the potential toxicity of the aminoglycosides.

[Granulocyte colony-stimulating factor in the treatment of febrile neutropenia]. / Factor estimulante de colonias de granulocitos en el tratamiento de neutropenia febril.

PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF) used in addition to antibiotic therapy, in patients with chemotherapy-induced febrile neutropenia shortens the period of fever, neutropenia and hospitalization. PATIENTS AND METHODS: The study was prospective. Patients with lymphoblastic acute leukemia (LAL) were included. They received intensive chemotherapy of induction, intensification, or consolidation. At random, a group received amikacin-ceftriaxone; if no had response after 3 days, we added vancomicin and, after 7 days, amphotericin. The other group received in addition these antibiotics, granulocyte colony-stimulating factor. RESULTS: The groups were comparable in the magnitude of the initial neutropenia (< 0.5 x 10(9)/L), site of the infection, chemotherapy received germs isolated, age, and sex. The patients of the group that received FEC-G were cured in the course of 3.1 days; in the group without FEC-G, this occurred in 7.2 days (p = 0.0001). At the end of the infectious episode, the number of neutrophils, in the group with FEC-G, was of 1.9 x 10(9)/L versus 0.7 x 10(9)/L (p = 0.0009). The mortality was of one and two cases (p = 0.46). The global mortality was 7.5%. CONCLUSIONS: The addition of FEC-G to the treatment with antibiotics, in febrile neutropenia, decreases duration of days with fever, hospitalization and neutropenia. However, the frequency of cure is not augmented.

Neutrophil recovery time and adverse side effects in acute leukemia patients treated with intensive chemotherapy and concomitant G or GM-CSF.

OBJECTIVE: Compare the speed of neutrophil recovery and the unwanted secondary effects in two groups of acute leukemia patients treated with intensive chemotherapy and G or GM-CSF. PATIENTS AND METHODS: Patients were randomly assigned to receive subcutaneous G-CSF at a daily dose of 300 micrograms for adults and 150 micrograms for children or GM-CSF at 400 and 200 micrograms respectively, starting With chemotherapy and stopping when the absolute neutrophil count (ANC) reached 500/microL. Secondary effects were attributed to growth factors only when not coincidental with infection, chemotherapy or hemoderivative transfusion. RESULTS: 34 patients were included in the G-CSF arm and 37 in the GM-CSF arm. Distribution by sex, age, type of acute leukemia, induction or post-induction therapy, as well as initial neutrophil count were comparable among the two groups. Mean time for ANC > 500/microL was 19 days for G-CSF group and 16 days for GM-CSF group (p = 0.08). There were no statistically significant differences in secondary unwanted side effects between the two groups. There were two cases of growth factor-related-fever in the G-CSF group and five in the GM-CSF group (p = 0.25). There was a case of systemic reaction in the G-CSF group. Twenty-nine patients in each group presented febrile neutropenia episodes (p = 0.45). The only factor that showed significance on neutrophil recovery speed was type of leukemia (p = 0.04). CONCLUSIONS: We found no clear advantage of one growth factor over the other for this indication.

[Comparison of 2 regimens of polychemotherapy in refractory acute leukemia or in relapse]. / Comparación de dos regímenes de poliquimioterapia en leucemia aguda refractaria o en recaída.

OBJECTIVE: To compare the effectiveness of two chemotherapy regimens for the treatment of relapsed and refractory acute leukemias. METHODS: We randomly assigned 24 patients in two groups: the LARR1 group received induction with 4 days of etoposide and 4 days of high-dose ara-C; the LARR2 group received induction therapy with 4 days of etoposide plus 3 days of mitoxantrone. Consolidation was given using the same drugs at the same dosage. Maintenance therapy was the same for both groups alternating methotrexate, vincristine, L-asparaginase, carmustine, cyclophosphamide and Ara-C. Every 15 weeks both groups repeated consolidation according to their group. Granulocyte-colony stimulating factor was used in both groups. RESULTS: Median survival for both groups was 5 months (range 1-17). Ten months after starting therapy three patients were disease free in the LARR1 group and two in the LARR2 group. There were no statistically significant differences in complete remission rate (p = 0.62), refractoriness (p = 0.58), deaths in induction (0.14) and other parameters. CONCLUSIONS: Our results were comparable with those of others. The only advantage we found was the possibility of using the LARR1 treatment in patients who have reached or are about to reach cardiotoxic-anthracycline doses.

[Long-term results of 2 therapeutic protocols in children with acute lymphoblastic leukemia of usual risk. Experience at the 20th of November National Medical Center]. / Resultados a largo plazo de dos protocolos terapéuticos, en niños con leucemia linfoblástica aguda de riesgo habitual. Experiencia en el Centro Médico Nacional "20 de Noviembre".

The purpose of this study is to know the disease-free survival in children with acute lymphoblastic leukemia (ALL), submitted to two therapeutic programs. Habitual risk was defined as age older than 2 and younger than 10 years, without neurological, mediastinal or testicular infiltrations, leukocytes < 25 x 10(9)/l and morphologic cell type distinct of L-3. The first group (LAL81) included 30 patients, from 1981 to 1986, and they received: induction with vincristine (VCR) and prednisone (PDN); consolidation with mercaptopurine (MP), cytosine arabinoside (ARA) and doxorubicin (DOX); prophylaxis to the central nervous system (CNS) with radiotherapy and methotrexate (MTX)-ARA-hydrocortisone (HDR) intrathecal, and maintenance with MP and MTX. In the second group (LAL87), 28 patients were included from 1987 to 1993. They received: induction with VCR, PDN and lasparaginase (ASP); consolidation with MP, ARA, DOX, carmustine (BCNU) and cyclophosphamide (CFA); prophylaxis to the (CNS) with intrathecal MTX-ARA-HDR, and maintenance with MP and MTX. There was just one therapeutic failure. In the LAL81, protocol 11 relapses and 9 in LAL87 (p = 0.71) were observed. Of these, two in each group went to the CNS. The disease-free survival in LAL81 was 0.39 at 14 years; in LAL87, was 0.53 at 8 years (p = 0.62).

[Sequential treatment with granulocyte-colony stimulating factor (GCSF) and human recombinant erythropoietin (rH-EPO) in anemia of a patient with myelodysplastic syndrome and high blood transfusion requirements)]. / Tratamiento secuencial con factor estimulante de colonias de granulocitos (FEC-G) y eritropoyetina recombinante humana (EPO-rHu) en la anemia de un paciente con síndrome mielodisplásico y altos requerimientos transfusionales.

We describe the case of a patient with myelodysplastic syndrome (MDS) classified as Refractory Anemia with our Excess blasts, who suffered from high transfusional requirements and who did not respond to the administrations of B12 vitamin, folates, danazol, low dose cytarabine or recombinant human erythropoietin (rHuEPO). The patient was administered two cytokines: granulocyte colony stimulating factor (G-CSF) followed by rHuEPO. The patient remained transfusion free for more than 4 months until his death from causes not related to MDS or the therapy he received. It is the opinion of the authors that the initial G-CSF administration stimulated the early erythroid precursors, making them capable of finishing their maturation when rHuEPO was administered. We believe that this could be a useful therapeutic measure in the treatment of patients with MDS and high transfusional requirements.

Recombinant human granulocyte-macrophage colony-stimulating factor as treatment for chronic leg ulcers.

OBJECTIVE: To evaluate the safety and effectiveness of a single subcutaneous perilesional administration of 300 micrograms of recombinant human granulocyte-macrophage colony stimulating factor (rHGM-CSF) for the treatment of chronic leg ulcers. DESIGN: Prospective, descriptive evaluation in an outpatient group. SETTING: The Centro Médico Nacional 20 de Noviembre, ISSSTE, Mexico City. PATIENTS: 10 patients with chronic leg ulcers. MEASUREMENTS: Ulcer diameter and side effects. RESULTS: After 4 weeks observation, 8 of the 10 ulcers had healed; the other two had a mean diameter decrease of 21%. The only side effect was found in a 58 year old female who complained of moderate perilesional pain two days after having received treatment: it was successfully treated with paracetamol. CONCLUSION: We believe that a single perilesional subcutaneous administration of rhGM-CSF is safe and effective for the treatment of chronic leg ulcers.

[Busulfan versus busulfan-interferon as maintenance therapy in chronic myeloid leukemia]. / Busulfán versus busulfán-interterón como terapia de mantenimiento en leucemia mieloide crónica.

We studied 30 patients in order to evaluate the therapeutic efficacy and toxicity of alfa interferon associated with busulfan as maintenance treatment in de novo chronic granulocytic leukemia. Patients received 0.2 mg/kg of busulfan and reached complete hematological remission (CHR). Patients were then randomized in two groups: one to receive busulfan to be administered when the leukocyte count was above 15 x 10(9)/L, and another to receive subcutaneously 5 million IU of alpha-interferon three times per week (plus busulfan if the leukocyte count went above 15 x 10(9)/L). The duration of CHR was longer in the alfa-interferon group: 31 vs 16 months (p = 0.03) but no cytogenetic remissions were observed. Alfa interferon was well tolerated: no patient was excluded from the study due to toxicity.