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.

[Long-term follow-up of 2 therapeutic programs for the treatment of high-risk childhood acute lymphoblastic leukemia. Experience at the 20 de Noviembre National Medical Center]. / Seguimiento a largo plazo de dos programas terapéuticos para el tratamiento de la leucemia aguda linfoblástica infantil de riesgo alto. Experiencia del Centro Médico Nacional 20 de Noviembre.

This paper reports the long-term, disease-free survival of children with high-risk (HR) acute lymphoblastic leukemia (ALL) treated with two different chemotherapy regimens. HR was defined in children with ALL, younger than 2 or older than 10 years, with or without initial extrahematopoietic disease, with a leukocyte count higher than 25 x 10(9)L, or with L3 FAB type. The first group, LAL1, included 67 patients; they received induction with vincristine (VCR) and prednisone (PDN), early consolidation with 3 cycles of 6-mercaptopurine (6MP), citarabine (ARA) and VCR: central nervous system (CNS) prophylaxis (PFX) consisted of both chemotherapy in induction, consolidation and maintenance, radiotherapy (RT) in consolidation. Maintenance was given with 6MP, methotrexate (MTX), VCR adriamycin (ADR), ARA, cyclophosphamide (CFA) and PDN. The second group, LAL2, with 45 patients, received induction with VCR, PDN, CFA, epirrubicin (EPI), L-Asparaginase (L-ASP); early and late consolidation with 6MP, ARA, VCR, carmustine (BCNU), CFA, EPI, MTX and teniposide 8VM26): CNS PFX consisted of both chemotherapy in induction, consolidation and maintenance, RT in consolidation, maintenance with 6MP, MTX, EPI, CFA, ARA VM26 and BCNU. At the time of diagnosis, both groups were comparable. Disease-free survival probability, for LAL1 group was 0.41 at 14 years and for LAL2 group 0.34 at 8 years (p = 0.45). In the LAL1 group there were three failures and 20 relapses, and in the LAL2 group, there were two failures and 22 relapses. CNS relapses were one and seven in LAL1 and LAL2 groups respectively (p = 0.04). In the LAL2, group relapses were more frequent in patients with dose reduction or difered dose due to marrow toxicity (p = 0.02). We believe that the increase in CNS relapse in the LAL2 group was caused by the late administration of CNS PFX. We also believe that although intensive chemotherapy can increase long-term survival, dose adjustments due to marrow toxicity have a negative effect on long-term, relapse-free survival.

[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).