Micafungin as antifungal prophylaxis in non-transplanted haemotological patients.

OBJECTIVE: 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. Echinocan-dins 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 haema-tological patients on chemotherapy. METHODS: A multicentre, observational retrospective study was performed in 7 Haematology Depart-ments 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 fun-gal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 as-pergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity. CONCLUSIONS: 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.

Chronic non-spherocytic hemolytic anemia associated with severe neurological disease due to gamma-glutamylcysteine synthetase deficiency in a patient of Moroccan origin.

A previously undescribed mutation of hereditary gamma-glutamylcysteine synthetase (GCS) deficiency was found in a 5 year old boy of Moroccan origin. He presented with chronic haemolytic anaemia, delayed psychomotor development and progressive motor sensitive neuropathy of lower extremities. The parents were third degree relatives. The activity of glycolytic enzymes were found to be normal in the propositus, his parents and a sister, but and a complete lack of GSH was found in the propositus. Accordingly, the measurement of de novo GSH synthetic enzymes was undertaken, and severe GCS deficiency was found in the propositus. Both parents and his sister presented GCS activity ranging from 69% to 90% of normal. GCS gene sequencing showed that the propositus was homozygous for a 1241C>T mutation in exon 11 and both parents and his sister were heterozygous. This mutation predicts a Pro414Leu amino acid substitution. Even though the homology between GCS and crystallographically solved, functionally related proteins is not very high, a three-dimensional model of GCS was derived using Modeller Software. GCS deficiency is a very rare autosomal recessive disorder reported so far in only 8 unrelated probands with severe haemolytic anaemia. In only 3 of these was the anaemia associated with severe neurological dysfunction. We report here the fourth case of GCS deficiency presenting neuropathy, giving further support to the eventual relationship between this enzymopathy and neurological damage.

Progressive external ophthalmoplegia: a paraneoplastic manifestation of lymphoma.

PURPOSE: Paraneoplastic neurological syndromes are well-known sequelae of some malignancies. To our knowledge, a syndrome mimicking progressive external ophthalmoplegia had never been reported preceding the diagnosis of a lymphoma. CASE REPORT: A 63-year-old man developed progressive external ophthalmoplegia, without any other neurological symptoms, as the initial manifestation of a follicular lymphoma grade III. The ophthalmoplegia resolved after two cycles of combination chemotherapy. CONCLUSIONS: The ophthalmologist, when confronted with a progressive external ophthalmoplegia, should consider a neurological paraneoplastic syndrome associated with a tumor as a possible diagnosis.

Splenic involvement by blastic mantle cell lymphoma (large cell/anaplastic variant) mimicking splenic marginal zone lymphoma.

The most cases of splenic marginal zone lymphoma (SMZL) seem to respond favorably to splenectomy. The diagnosis of this lymphoma is mainly based on the recognition of a micronodular pattern of splenic involvement with marginal zone differentiation. However, it is possible to find so-called "marginal zone differentiation" in splenic involvement by other small B-cell lymphomas, particularly mantle cell lymphoma (MCL) and follicular lymphoma. We report a case of blastic MCL, large cell/anaplastic variant with a high level of clinical aggressiveness, showing biphasic cytology and a micronodular pattern which resembles SMZL. A single biopsy corresponding to this case shows two phases of tumoral progression in a MCL, a rare finding in MCL. In conclusion, the differential diagnosis of SMZL must take the possibility of a blastic MCL with biphasic cytology into account, as the case here.

[Monoclonal gammopathies of undetermined significance. Clinical course and biological aspects of 397 cases]. / Gammapatías monoclonales de significado indeterminado. Aspectos clínicos, biológicos y evolutivos de 397 casos.

The diagnostic criteria, incidence, clinical characteristics and outcome of 397 patients with monoclonal gammopathies of undetermined significance, all of them diagnosed and followed-up at the Haematology Service of the Miguel Servet Hospital, in Zaragoza, between January 1970 and December 1988, were revised. The patients' mean age was 64.7 years (range: 2-89). The M/F ratio was 236/161. The mean concentration of the M component (MC) was 1.17 g/dL (range: 0.20-3.50), this being under 0.50 in 65 cases. IgG was the most frequent MC (71.26%), followed by IgA (14.34%) and IgM (10.82%). Multiple MC was present in 14 cases (3.58). Light chains were passed in urine by 33 patients (8.31%). No associated pathology was found in 213 patients (53.65%) upon MC discovery, while 65 other (16.31%) were carriers of different blood disorders, chronic lymphoproliferative diseases being the commonest (11.57%). In 30 patients (7.30%) the MC was associated to nonhaematological malignancies, and 29 others had an underlying chronic infection. Chronic liver disease was present in 25 cases, and autoimmune disease in 14. Transient monoclonal gammopathy was seen in a small group of patients (6.54%), most of them suffering from acute infectious illness. With regard to the group of patients without any associated pathology, their median follow-up was 37.8 months (range: 18-228). Of them, the MC kept unchanged in 134 cases (62.91%); 47(22.06%) died from any unrelated cause, and 10 others evolved into malignant monoclonal gammopathy. The median clinical course of these last expanded to 60 months (range: 11-124), with an accumulated actuarial risk of 4.5% at 5 years, 15% at 10 years and 26% at 15 years.