Micafungin as antifungal prophylaxis in non-transplanted haemotological patients / Micafungina como profilaxis antifúngica en pacientes hematológicos no trasplantados

INTRODUCTION: Fungal infections are a major cause of morbidity and mortality in the haematological patients. These infections are mainly due to Candida spp. and Aspergillus spp. Mortality by these infections is high, but rates have descended in the latest series due to better antifungal agents. Echinocandins are, in vitro, very active against Candida and Aspergillus spp. The objective of the study is to analyse the efficacy and safety of micafungin in the antifungal prophylaxis of haematological patients on chemotherapy. MATERIAL AND METHODS: A multicentre, observational retrospective study was performed in 7 Haematology Departments in Spain. Patients admitted to these departments with chemotherapy or immunosuppressive treatment, and who had received antifungal prophylaxis with micafungin between 1 January 2009 and 31 December 2014 were included. RESULTS: There were 5 cases of probable or proven fungal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 aspergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity. CONCLUSION: Micafungin is an antifungal agent which, used in prophylaxis, has demonstrated good efficacy and an excellent toxicity profile, making it an apparently interesting option in patients requiring antifungal prophylaxis during their hospitalisation episode

INTRODUCCIÓN: Las infecciones fúngicas son una importante causa de morbilidad y mortalidad en los pacientes hematológicos. Estas infecciones son principalmente debidas a Candida spp.y Aspergillus spp. La mortalidad debida a estas infecciones es alta, pero ha descendido a lo largo de las últimas series gracias a los mejores agentes antifúngicos. Las equinocandinas son, in vitro, muy activas contra Candida y Aspergillus spp. El objetivo de este estudio es analizar la eficacia y seguridad de micafungina en la profilaxis antifúngica de pacientes hematológicos en tratamiento quimioterápico. MATERIAL Y MÉTODOS: Un estudio multicéntrico, observacional, retrospectivo se llevó a cabo en 7 servicios de Hematología en España. Se incluyeron los pacientes ingresados con quimioterapia o tratamiento inmunosupresor que hubieran recibido micafungina como profilaxis entre el 1 de enero de 2009 y el 31 de diciembre de 2014. RESULTADOS: Hubo 5 casos de infección fúngica probable o probada (4,8%) según los criterios de la EORTC de 2008: 2 probadas, 3 probables. Las infecciones fúngicas fueron 3 aspergilosis y 2 candidiasis. No hubo ningún abandono de la profilaxis con micafungina debido a toxicidad. CONCLUSIÓN: Micafungina es un agente antifúngico que, usado en profilaxis, ha demostrado buena eficacia y excelente perfil de toxicidad, siendo una opción interesante en pacientes que requieren profilaxis antifúngica durante su hospitalización

Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy.

Risk associated to FLT3 internal tandem duplication (FLT3-ITD) in patients with acute myeloid leukemia (AML) may depend on mutational burden and its interaction with other mutations. We analyzed the effect of FLT3-ITD/FLT3 wild-type (FLT3wt) ratio depending on NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated with intensive chemotherapy. Among NPM1mut patients, FLT3wt and low ratio (<0.5) subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas high ratio (≥0.5) patients had a worse outcome. In NPM1wt AML, FLT3-ITD subgroups showed a comparable outcome, with higher risk of relapse and shortened overall survival than FLT3wt patients. Allogeneic stem cell transplantation in CR1 was associated with a reduced relapse risk in all molecular subgroups with the exception of NPM1mut AML with absent or low ratio FLT3-ITD. In conclusion, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.

Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)].

Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level >0.1% at the end of treatment than in patients with < or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of >10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR >10 compared to 21% for patients with RQ-PCR levels < or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.